WO1998027962A2 - Injectable depot gel composition and method of preparing the composition - Google Patents
Injectable depot gel composition and method of preparing the composition Download PDFInfo
- Publication number
- WO1998027962A2 WO1998027962A2 PCT/US1997/023341 US9723341W WO9827962A2 WO 1998027962 A2 WO1998027962 A2 WO 1998027962A2 US 9723341 W US9723341 W US 9723341W WO 9827962 A2 WO9827962 A2 WO 9827962A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- injectable depot
- polymer
- gel composition
- solvent
- beneficial agent
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH] (Somatotropin)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
Definitions
- the present invention relates to a depot gel composition that can be injected into a desired location and which can provide sustained release of a beneficial agent.
- the present invention also relates to a method of preparing the composition.
- Biodegradable polymers have been used for many years in medical applications. Illustrative devices composed of the biodegradable polymers include sutures, surgical clips, staples, implants, and drug delivery systems. The majority of these biodegradable polymers have been based upon glycoside, lactide, caprolactone, and copolymers thereof.
- the biodegradable polymers can be thermoplastic materials which means that they can be heated and formed into various shapes such as fibers, clips, staples, pins, films, etc. Alternatively, they can be thermosetting materials formed by crosslinking reactions which lead to high-molecular-weight materials that do not melt or form flowable liquids at high temperatures.
- thermoplastic and thermosetting biodegradable polymers have many useful biomedical applications, there are several important limitations to their use in the bodies of various animals including humans, animals, birds, fish, and reptiles. Because these polymers are solids, all instances involving their use have required initially forming the polymeric structures outside the body, followed by insertion of the solid structure into the body. For example, sutures, clips, and staples are all formed from thermoplastic biodegradable polymers prior to use. When inserted into the body, they retain their original shape. While this characteristic is essential for some uses, it is a drawback where it is desired that the material flow to fill voids or cavities where it may be most needed. Drug delivery systems using thermoplastic or thermosetting biodegradable polymers also have to be formed outside the body.
- the drug is incorporated into the polymer and the mixture is shaped into a certain form such a cylinder, disc, or fiber for implantation.
- the drug delivery system has to be inserted into the body through an incision. These incisions are sometimes larger than desired by the medical profession and occasionally lead to a reluctance of the patients to accept such an implant or drug delivery system. Nonetheless, both biodegradable and non-biodegradable implantable drug delivery systems have been widely used successfully.
- One reservoir device having a rate-controlling membrane and zero-order release of an agent that is particularly designed for intraoral implantation is described in U.S. Patent No. 5,085,866.
- the device is prepared from a core that is sprayed with a solution having a polymer and a solvent that is composed of a rapidly evaporating, low boiling point first solvent and a slowly evaporating, high boiling second solvent.
- a solution having a polymer and a solvent that is composed of a rapidly evaporating, low boiling point first solvent and a slowly evaporating, high boiling second solvent include those disclosed in U.S. Patent Nos. 3,797,492, 3,987,790, 4,008,719, 4,865,845, 5,057,318, 5,059,423, 5,112,614, 5,137,727, 5,151,093, 5,234,692, 5,234,693, 5,279,608, and 5,336,057.
- Pulsatile delivery devices are also known which deliver a beneficial agent in a pulsatile manner as disclosed in U.S. Patent Nos.
- U.S. Patent No. 5,019,400 describes the preparation of controlled release microspheres via a very low temperature casting process. These materials may or may not contain a drug which can be released into the body. Although these materials can be injected into the body with a syringe, they do not always satisfy the demand for a biodegradable implant. Because they are particulate in nature, they do not form a continuous film or solid implant with the structural integrity needed for certain prostheses.
- microcapsules When inserted into certain body cavities such as a mouth, a periodontal pocket, the eye, or the vagina where there is considerable fluid flow, these small particles, microspheres, or microcapsules are poorly retained because of their small size and discontinuous nature. Further, the particles tend to aggregate and thus their behavior is hard to predict. In addition, microspheres or microcapsules prepared from these polymers and containing drugs for release into the body are sometimes difficult to produce on a large scale, and their storage and injection characteristics present problems. Furthermore, one other major limitation of the microcapsule or small-particle system is their lack of reversibility without extensive surgical intervention. That is, if there are complications after they have been injected, it is considerably more difficult to remove them from the body than with solid implants.
- U.S. Patent No. 4,938,763 and its divisional U.S. Patent No. 5,278,201 relate to a biodegradable polymer for use in providing syringeable, in-situ forming, solid biodegradable implants for animals.
- a thermoplastic system is used wherein a non-reactive polymer is dissolved in a biocompatible solvent to form a liquid which is placed in the animal wherein the solvent dissipates to produce the solid implant.
- thermosetting system is used wherein effective amounts of a liquid acrylic ester- terminated, biodegradable prepolymer and a curing agent are formed and the liquid mixture is placed within the animal wherein the prepolymer cures to form the solid implant.
- the systems provide a syringeable, solid biodegradable delivery system by the addition of an effective level of a biologically active agent to the liquid before the injection into the animal.
- U.S. Patent No. 5,242,910 describes a sustained release composition for treating periodontal disease.
- the composition comprises copolymers of lactide and glycolide, triacetin (as a solvent/plasticizer) and an agent providing relief of oral cavity diseases.
- the composition can take the form of a gel and can be inserted into a periodontal cavity via a syringe using either a needle or a catheter.
- the composition can contain surfactants, flavoring agents, viscosity controlling agents, complexing agents, antioxidants, other polymers, gums, waxes/oils, and coloring agents.
- One illustrative viscosity controlling agent set forth in one of the examples is polyethylene glycol 400.
- compositions need to be non-viscous in order to be injected, a large percentage of drug is released as the system forms by diffusion of the solvent. This effect is referred to as a "burst" effect.
- burst it is typical for solvent-based compositions to have a drug burst wherein 30-75 % of the drug contained in the composition is released within one day of the initial injection.
- the present invention is a significant advance in the art and in one aspect provides an injectable depot gel composition
- an injectable depot gel composition comprising: A) a biocompatible polymer; B) a solvent that dissolves the polymer and forms a viscous gel; C) a beneficial agent; and D) an emulsifying agent in the form of a dispersed droplet phase in the viscous gel.
- the present invention provides a method of preparing an injectable depot gel composition
- a method of preparing an injectable depot gel composition comprising: A) mixing a biocompatible polymer and a solvent whereby the solvent dissolves the polymer and forms a viscous gel; B) dispersing or dissolving a beneficial agent in the viscous gel to form a beneficial agent containing gel; and C) mixing an emulsifying agent with the beneficial agent containing gel, said emulsifying agent forming a dispersed droplet phase in the beneficial agent containing gel so as to provide the injectable depot gel composition.
- the present invention provides a method of preparing an injectable depot gel composition
- a method of preparing an injectable depot gel composition comprising: A) mixing a biocompatible polymer and a solvent whereby the solvent dissolves the polymer and forms a viscous gel; B) dispersing or dissolving a beneficial agent in an emulsifying agent to form a beneficial agent containing emulsifying agent; and C) mixing the beneficial agent containing emulsifying agent with the viscous gel, said beneficial agent containing emulsifying agent forming a dispersed droplet phase in the viscous gel to provide the injectable depot gel composition.
- the invention provides an injectable depot gel composition comprising: A) a biocompatible polymer; B) a solvent that dissolves the polymer and forms a viscous gel; and C) an emulsifying agent in the form of a dispersed droplet phase in the viscous gel.
- the invention provides a kit adapted to provide an injectable depot gel composition
- injectable depot composition comprising as kit components: (a) a biocompatible
- Figure 1 is a graph illustrating the dispense force required to dispense the emulsified and non-emulsified viscous gel compositions through a 20 gauge needle in psig at 2 cc/min
- Figure 2 is a graph illustrating the release profiles of lysozyme from three different compositions in days
- Figure 3 is a graph illustrating the viscosity profiles at different shear rates of water alone and of an aqueous mixture of ethanol, and of the viscous gel without emulsifying agent.
- an injectable depot gel composition comprising: A) a biocompatible polymer; B) a solvent that dissolves the biocompatible polymer and forms a viscous gel; C) a beneficial agent; and D) an emulsifying agent in the form of a dispersed droplet phase in the viscous gel.
- the polymer, solvent and emulsifying agents of the invention must be biocompatible, that is they must not cause irritation or necrosis in the environment of use.
- the environment of use is a fluid environment and may comprise a subcutaneous or intramuscular portion or body cavity of a human or animal.
- Polymers that may be useful in the invention may be biodegradable and may include, but are not limited to polylactides, polyglycolides, polycaprolactones, polyanhydrides, poly amines, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, succinates, poly (malic acid), poly(amino acids), polyvmylpyrrolidone, polyethylene glycol, polyhydroxycellulose, chitin, chitosan, and copolymers, terpolymers and mixtures thereof.
- the polymer may be a polylactide, that is, a lactic acid-based polymer that can be based solely on lactic acid or can be a copolymer based on lactic acid and glycol ic acid which may include small amounts of other comonomers that do not substantially affect the advantageous results which can be achieved in accordance with the present invention.
- lactic acid includes the isomers L-lactic acid, D-lactic acid, DL-lactic acid and lactide while the term "glycolic acid” includes glycolide.
- the polymer may have a monomer ratio of lactic acid/gly colic acid of from about 100:0 to about 15:85, preferably from about 60:40 to about 75:25 and an especially useful copolymer has a monomer ratio of lactic acid/glycolic acid of about 50:50.
- the lactic acid-based polymer has a number average molecular weight of from about 1,000 to about 120,000, preferably from about 10,000 to about 30,000 as determined by gas phase chromatography. As indicated in aforementioned U.S. Patent No. 5,242,910, the polymer can be prepared in accordance with the teachings of U.S. Patent No. 4,443,340.
- the lactic acid-based polymer can be prepared directly from lactic acid or a mixture of lactic acid and glycolic acid (with or without a further comonomer) in accordance with the techniques set forth in U.S. Patent No. 5,310,865. The contents of all of these patents are incorporated by reference. Suitable lactic acid-based polymers are available commercially. For instance, 50:50 lactic acid:glycolic acid copolymers having molecular weights of 10,000, 30,000 and 100,000 are available from Boehringer Ingelheim (Petersburg, VA).
- the biocompatible polymer is present in the composition in an amount ranging from about 5 to about 80% by weight, preferably from about 20 to about 50% by weight and often 35 to 45% by weight of the viscous gel, the viscous gel comprising the combined amounts of the biocompatible polymer and the solvent.
- the solvent Once in place in the environment of use, the solvent will diffuse slowly away from the depot and the polymer will slowly degrade by hydrolysis.
- the solvent must be biocompatible and is selected so as to dissolve the polymer to form a viscous gel that can maintain particles of the beneficial agent dissolved or dispersed and isolated from the environment of use prior to release.
- Illustrative solvents which can be used in the present invention include but are not limited to triacetin, N-methyl-2-pyrrolidone, 2-pyrrolidone, glycerol formal, methyl acetate, benzyl benzoate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid, and l-dodecylazacyclo-heptan-2-one and mixtures thereof.
- the preferred solvents are triacetin and N-methyl-2-pyrrolidone.
- Triacetin provides a high level of polymer dissolution which leads to greater gel viscosities, with attendant higher force needed to dispense the viscous gel when compared with other solvents. These characteristics enable the beneficial agent to be maintained without exhibiting a burst effect, but make it difficult to dispense the gel through a needle.
- a gel prepared from 40% by weight of a 50:50 lactic acid:glycolic polymer and 60% by weight of triacetin required about 40 psig to dispense the gel through a standard 20 gauge needle at 2 cc/min while a gel prepared from the same amount of polymer with 60% by weight of N-methyl-2- pyrrolidone required only about 8 psig.
- Figure 1 further shows that when the emulsifying agent (in this case 33% by weight of a 10% ethanol solution) is added to the viscous gel according to the invention, the dispense force needed is only about 2 psig.
- the shear thinning characteristics of the depot gel compositions of the present invention allow them be readily injected into an animal including humans using standard gauge needles without requiring undue dispensing pressure.
- the solvent is typically present in an amount of from about 95 to about 20% by weight and is preferably present in an amount of from about 80 to about 50% by weight and often 65 to 55% by weight of the viscous gel, that is the combined amounts of the polymer and the solvent.
- the viscous gel formed by mixing the polymer and the solvent typically exhibits a viscosity of from about 1,000 to about 200,000 poise, preferably from about 5 to about 50,000 poise measured at a 1.0 sec " ' shear rate and 25° C using a Haake Viscometer at about 1-2 days after mixing is completed.
- Mixing the polymer with the solvent can be achieved with conventional low shear equipment such as a Ross double planetary mixer for from about 1 to about 2 hours.
- the beneficial agent can be any physiologically or pharmacologically active substance or substances optionally in combination with pharmaceutically acceptable carriers and additional ingredients such as antioxidants, stabilizing agents, permeation enhancers, etc. that do not substantially adversely affect the advantageous results that can be attained by the present invention.
- the beneficial agent may be any of the agents which are known to be delivered to the body of a human or an animal and that are preferentially soluble in water rather than in the polymer-dissolving solvent. These agents include drug agents, medicaments, vitamins, nutrients, or the like. Included among the types of agents which meet this description are nutrients, vitamins, food supplements, sex sterilants, fertility inhibitors and fertility promoters.
- Drug agents which may be delivered by the present invention include drugs which act on the peripheral nerves, adrenergic receptors, cholinergic receptors, the skeletal muscles, the cardiovascular system, smooth muscles, the blood circulatory system, synoptic sites, neuroeffector junctional sites, endocrine and hormone systems, the immunological system, the reproductive system, the skeletal system, autacoid systems, the alimentary and excretory systems, the histamine system and the central nervous system.
- Suitable agents may be selected from, for example, proteins, enzymes, hormones, polynucleotides, nucleoproteins, polysaccharides, glycoproteins, lipoproteins, polypeptides, steroids, analgesics, local anesthetics, antibiotic agents, anti-inflammatory corticosteroids, ocular drugs and synthetic analogs of these species.
- proteins and peptides which include, but are not limited to, bone morphogenic proteins, insulin, colchicine, glucagon, thyroid stimulating hormone, parathyroid and pituitary hormones, calcitonin, renin, prolactin, corticotrophin, thyrotropic hormone, follicle stimulating hormone, chorionic gonadotropin, gonadotropin releasing hormone, bovine somatotropin, porcine somatotropin, oxytocin, vasopressin, GRF, somatostatin, lypressin, pancreozymin, luteinizing hormone, LHRH, LHRH agonists and antagonists, leuprolide, interferons, interleukins, growth hormones such as human growth hormone, bovine growth hormone and porcine growth hormone, fertility inhibitors such as the prostaglandins, fertility promoters, growth factors, coagultion factors, human pancreas hormone releasing factor, analogs and derivatives of these compounds, and pharmaceutically acceptable salts
- the beneficial agents described in aforementioned U.S. Patent No. 5,242,910 can also be used.
- One particular advantage of the present invention is that materials, such as proteins, as exemplified by the enzyme lysozyme, and cDNA, and DNA incorporated into vectors both viral and nonviral, which are difficult to microcapsulate or process into microspheres can be incorporated into the compositions of the present invention without the level of degradation experienced with other techniques.
- the beneficial agent is preferably incorporated into the viscous gel formed from the polymer and the solvent in the form of particles typically having an average particle size of from about 0.1 to about 100 microns, preferably from about 1 to about 25 microns and often from 2 to 10 microns.
- particles having an average particle size of about 5 microns have been produced by spray drying or spray freezing an aqueous mixture containing 50% sucrose and 50% chicken lysozyme (on a dry weight basis). Such particles have been used in certain of the examples illustrated in the figures.
- any conventional low shear device can be used such as a Ross double planetary mixer at ambient conditions. In this manner, efficient distribution of the beneficial agent can be achieved substantially without degrading the beneficial agent.
- the beneficial agent is typically dissolved or dispersed in the composition in an amount of from about 1 to about 50% by weight, preferably in an amount of from about 5 to about 25% and often 10 to 20% by weight of the combined amounts of the polymer, solvent and beneficial agent.
- the beneficial agent is typically dissolved or dispersed in the composition in an amount of from about 1 to about 50% by weight, preferably in an amount of from about 5 to about 25% and often 10 to 20% by weight of the combined amounts of the polymer, solvent and beneficial agent.
- the gel prepared from 40% by weight of a 50:50 lactic acid:glycolic polymer and 60% by weight triacetin is thick and thus difficult to inject but shows little burst (less than 2% of the beneficial agent is delivered in the first eight days).
- the gel prepared from 40% by weight of a 50:50 lactic acid:glycolic polymer and 60% by weight N-methyl-2-pyrrolidone is thin and injectable but shows a large burst (greater than 70% of the beneficial agent is delivered in the first eight days).
- the gel prepared from 27% by weight of a 50:50 lactic acid:glycolic polymer, 40% by weight triacetin and 33 % by weight of a 10% ethanol, 90% isotonic saline solution is thin and injectable and shows little burst (less than 10% of the beneficial agent is delivered in the first eight days).
- lysozyme is the beneficial agent and comprises 20% by weight of the combined beneficial agent, polymer and solvent formulation.
- the emulsifying agent constitutes an important aspect of the present invention.
- the emulsifying agent When the emulsifying agent is mixed with the viscous gel formed from the polymer and the solvent using conventional static or mechanical mixing devices, such as an orifice mixer, the emulsifying agent forms a separate phase composed of dispersed droplets of microscopic size that typically have an average diameter of less than about 100 microns.
- the continuous phase is formed of the polymer and the solvent.
- the particles of the beneficial agent may be dissolved or dispersed in either the continuous phase or the droplet phase.
- the droplets of emulsifying agent elongate in the direction of shear and substantially decrease the viscosity of the viscous gel formed from the polymer and the solvent.
- a viscous gel having a viscosity of from about 5,000 to about 50,000 poise measured at 1.0 sec "1 at 25°C
- the beneficial agent can be mixed with the emulsifying agent just prior to the time of use.
- beneficial agent to be maintained in a dry state prior to use, which may be advantageous in those instances where long term stability of the beneficial agent in the viscous gel is of concern. Additionally, since the beneficial agent will remain in the droplet phase that is entrapped within the viscous gel as it forms, it is possible to select an emulsifying agent in which the drug is optimally stable and thus prolong stability of the beneficial agent in the gel composition. An added benefit is the opportunity to program the release of beneficial agent via diffusion through the porous structure of the implant, rather than by degradation and dissolution of the polymer structure.
- the injectable depot of this invention may be provided as a kit, having kit components comprising (a) a mixture of polymer and solvent, (b) emulsifying agent and (c) beneficial agent.
- kit components comprising (a) a mixture of polymer and solvent, (b) emulsifying agent and (c) beneficial agent.
- the beneficial agent Prior to use the beneficial agent is mixed with the emulsifying agent, and that solution or suspension is mixed with the polymer/solvent mixture to prepare the injectable depot implant for use.
- the emulsifying agent is present in an amount ranging from about 5 to about 80% , preferably from about 20 to about 60% and often 30 to 50% by weight based on the amount of the injectable depot gel composition, that is the combined amounts of polymer, solvent, emulsifying agent and beneficial agent.
- Illustrative emulsifying agents are water, alcohols, polyols, esters, carboxylic acids, ketones, aldehydes and mixtures thereof.
- Preferred emulsifying agents are alcohols, propylene glycol, ethylene glycol, glycerol, water, and solutions and mixtures thereof.
- Especially preferred are water, ethanol, and isopropyl alcohol and solutions and mixtures thereof.
- the type of emulsifying agent affects the size of the dispersed droplets. For instance, ethanol will provide droplets that have average diameters that can be on the order of ten times larger than the droplets obtained with an isotonic saline solution containing 0.9% by weight of sodium chloride at 21°C.
- Figure 3 shows the viscosities at different shear rates using water alone and an aqueous mixture containing 10% by volume of ethanol at a weight ratio of 2: 1 (gel: emulsifying agent) using a viscous gel formed from 50% by weight of a 50:50 lactic acid:glycolic acid copolymer and 50% by weight of triacetin compared to the viscosities of the viscous gel without emulsifying agent.
- the emulsifying agent of the present invention does not constitute a mere diluent that reduces viscosity by simply decreasing the concentration of the components of the composition.
- the use of conventional diluents can reduce viscosity, but can also cause the burst effect mentioned previously when the diluted composition is injected.
- the injectable depot composition of the present invention can be formulated to avoid the burst effect by selecting the emulsifying agent so that once injected into place, the emulsifying agent has little impact on the release properties of the original system.
- Further compositions without beneficial agent may be useful for wound healing, bone repair and other structural support purposes.
- Example 1 Lysozyme particles were made by spray drying 50% sucrose and 50% chicken lysozyme (on a dry weight basis).
- a viscous gel material was prepared by heating 60% by weight of triacetin with 40% by weight of a 50:50 lactic acid:glycolic acid copolymer to 37°C overnight. The viscous gel was allowed to cool to room temperature while mixing continued.
- the lysozyme particles were added to the viscous gel in a ratio of 20:80 lysozyme particles: gel (by weight). The combination was mixed for 5 minutes. Immediately prior to use, a 10% ethanol, 90% isotonic saline solution was added as the emulsifying agent.
- the emulsifying agent comprised 1/3 of the total injectable depot gel composition. 0.5 grams of this injectable depot composition was then injected into a rat.
- Example 2 A viscous gel material is prepared by heating 60 % by weight of triacetin with 40% by weight of a 50:50 lactic acid:glycolic acid copolymer to 37°C overnight. The viscous gel is allowed to cool to room temperature while mixing is continued. Immediately prior to use, lysozyme particles, prepared as in Example 1 and in the same amount, are combined with a 10% ethanol, 90% isotonic saline solution, as an emulsifying agent, in the amount used in Example 1.
- the emulsifying agent-lysozyme solution is mixed with the amount of gel material used in Example 1 to form an injectable depot gel composition.
- the fabricated injectable depot gel composition is suitable for injection into an animal.
- one or more significant advantages can be obtained. More specifically, using simple processing steps, one can obtain a depot gel composition that can be injected into place in an animal without surgery using a low dispensing force through standard needles. Once in place, the composition will quickly return to its original viscosity and may exhibit rapid hardening so as to substantially avoid a burst effect and provide the desired beneficial agent release profile. Furthermore, once the beneficial agent has been fully administered, there is no need to remove the composition since it is fully biodegradable.
- the present invention avoids the use of microparticle or microcapsulation techniques which can degrade certain beneficial agents, like peptide and nucleic acid-based drugs and which microparticles and microcapsules maybe difficult to remove from the environment of use. Since the viscous gel is formed without the need for water, temperature extremes, or other solvents, suspended particles of beneficial agent remain dry and in their original configuration, which contributes to the stability of thereof. Further, since a mass is formed, the injectable depot gel composition may be retrieved from the environment of use if desired.
- the above-described exemplary embodiments are intended to be illustrative in all respects, rather than restrictive, of the present invention. Thus the present invention is capable of many variations in detailed implementation that can be derived from the description contained herein by a person skilled in the art. All such variations and modifications are considered to be within the scope and spirit of the present invention as defined by the following claims.
Abstract
Description
Claims
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002275587A CA2275587C (en) | 1996-12-20 | 1997-12-18 | Injectable depot gel composition and method of preparing the composition |
DK97952507T DK0949905T3 (en) | 1996-12-20 | 1997-12-18 | Injectable depot preparation and method of preparation |
AU56097/98A AU5609798A (en) | 1996-12-20 | 1997-12-18 | Injectable depot gel composition and method of preparing the composition |
DE69705746T DE69705746T2 (en) | 1996-12-20 | 1997-12-18 | INJECTABLE DEPOT GEL PREPARATION AND PRODUCTION METHOD |
EP97952507A EP0949905B1 (en) | 1996-12-20 | 1997-12-18 | Injectable depot gel composition and method of preparing the composition |
AT97952507T ATE203157T1 (en) | 1996-12-20 | 1997-12-18 | INJECTABLE DEPOSIT GEL PREPARATION AND PRODUCTION METHOD |
JP52891698A JP2002512597A (en) | 1996-12-20 | 1997-12-18 | Injectable reservoir gel composition and method of making the composition |
HK99105227A HK1020009A1 (en) | 1996-12-20 | 1999-11-12 | Injectable depot gel composition and method of preparing the composition |
GR20010401458T GR3036599T3 (en) | 1996-12-20 | 2001-09-12 | Injectable depot gel composition and method of preparing the composition |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3343996P | 1996-12-20 | 1996-12-20 | |
US60/033,439 | 1996-12-20 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1998027962A2 true WO1998027962A2 (en) | 1998-07-02 |
WO1998027962A3 WO1998027962A3 (en) | 1998-10-01 |
Family
ID=21870398
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1997/023341 WO1998027962A2 (en) | 1996-12-20 | 1997-12-18 | Injectable depot gel composition and method of preparing the composition |
PCT/US1997/023659 WO1998027963A2 (en) | 1996-12-20 | 1997-12-18 | Gel composition and methods |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1997/023659 WO1998027963A2 (en) | 1996-12-20 | 1997-12-18 | Gel composition and methods |
Country Status (17)
Country | Link |
---|---|
US (6) | US6130200A (en) |
EP (2) | EP0949905B1 (en) |
JP (4) | JP2002512597A (en) |
KR (1) | KR100616793B1 (en) |
CN (1) | CN1146402C (en) |
AT (2) | ATE203157T1 (en) |
AU (2) | AU5609798A (en) |
CA (3) | CA2275525C (en) |
DE (2) | DE69705746T2 (en) |
DK (2) | DK0959873T3 (en) |
ES (2) | ES2158611T3 (en) |
GR (1) | GR3036599T3 (en) |
HK (2) | HK1020009A1 (en) |
IL (1) | IL130532A0 (en) |
NZ (1) | NZ335851A (en) |
PT (2) | PT949905E (en) |
WO (2) | WO1998027962A2 (en) |
Cited By (58)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0950403A2 (en) * | 1998-04-14 | 1999-10-20 | Atrix Laboratories, Inc. | Emulsions for in-situ delivery systems |
WO2000045790A2 (en) * | 1999-02-08 | 2000-08-10 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
WO2000048588A1 (en) * | 1999-02-16 | 2000-08-24 | Farmaceutici Formenti S.P.A. | Pharmaceutical topical compositions containing a non-steroidal antiinflammatory drug |
WO2001003666A2 (en) * | 1999-07-12 | 2001-01-18 | Scimed Life Systems, Inc. | Liquid based vaso-occlusive compositions |
WO2002030393A2 (en) * | 2000-09-21 | 2002-04-18 | Atrix Laboratories, Inc. | Polymeric delivery formulations of leuprolide with improved efficacy |
US6413536B1 (en) | 1995-06-07 | 2002-07-02 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system and medical or surgical device |
WO2003024420A1 (en) * | 2001-09-14 | 2003-03-27 | Novartis Ag | Ophthalmic depot formulations for periocular or subconjunctival administration |
EP1299048A1 (en) * | 2000-06-28 | 2003-04-09 | Atul J. Shukla | Biodegradable vehicles and delivery systems of biologically active substances |
JP2003514006A (en) * | 1999-11-16 | 2003-04-15 | アトリックス ラボラトリーズ,インコーポレイティド | Biodegradable polymer composition |
US6572894B2 (en) | 1995-11-24 | 2003-06-03 | Actipac Biosystems Gmbh | Process for the production of morphologically uniform microcapsules and microcapsules that are produced according to this process |
WO2003045351A1 (en) * | 2001-11-30 | 2003-06-05 | Pfizer Inc. | Controlled release polymeric compositions of bone growth promoting compounds |
WO2004043432A2 (en) * | 2002-11-06 | 2004-05-27 | Alza Corporation | Controlled release depot formulations |
WO2004089335A2 (en) * | 2003-03-31 | 2004-10-21 | Alza Corporation | Non-aqueous single phase vehicles and formulations utilizing such vehicles |
WO2004108111A1 (en) * | 2003-05-30 | 2004-12-16 | Alza Corporation | Implantable elastomeric depot compositions, uses thereof and method of manufacturing |
WO2005009408A2 (en) * | 2003-06-25 | 2005-02-03 | Alza Corporation | Sustained release dosage forms of anesthetics for pain management |
US6878374B2 (en) | 2003-02-25 | 2005-04-12 | Nitto Denko Corporation | Biodegradable polyacetals |
US6899898B2 (en) | 2000-12-21 | 2005-05-31 | Nektar Therapeutics | Induced phase transition method for the production of microparticles containing hydrophobic active agents |
US6992065B2 (en) | 2000-04-19 | 2006-01-31 | Genentech, Inc. | Sustained release formulations |
US7048925B2 (en) | 2003-08-28 | 2006-05-23 | Nitto Denko Corporation | Acid-sensitive polyacetals and methods |
EP1691715A2 (en) * | 2003-11-14 | 2006-08-23 | ALZA Corporation | Surfactant-based gel as an injectable, sustained drug delivery vehicle |
WO2007027289A1 (en) * | 2005-08-30 | 2007-03-08 | Medtronic, Inc. | Shear thinning polymer cell delivery compositions |
US7207982B2 (en) | 2003-03-31 | 2007-04-24 | Alza Corporation | Osmotic pump with means for dissipating internal pressure |
US7258869B1 (en) | 1999-02-08 | 2007-08-21 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle |
EP2030611A1 (en) | 2002-07-31 | 2009-03-04 | Alza Corporation | Injectable multimodal polymer depot compositions and uses thereof |
US7655254B2 (en) | 2005-02-03 | 2010-02-02 | Intarcia Therapeutics, Inc. | Implantable device for continuous delivery of interferon |
US7794696B2 (en) | 2003-09-29 | 2010-09-14 | Nitto Denko Corporation | Biodegradable polyacetals for in vivo polynucleotide delivery |
US7824700B2 (en) | 2001-02-23 | 2010-11-02 | Genentech, Inc. | Erodible polymers for injection |
US7833543B2 (en) | 1995-06-07 | 2010-11-16 | Durect Corporation | High viscosity liquid controlled delivery system and medical or surgical device |
EP2311431A1 (en) | 2002-06-25 | 2011-04-20 | ALZA Corporation | Short duration depot formulations |
US8067020B2 (en) | 2001-06-21 | 2011-11-29 | Genetech, Inc. | Sustained release formulation |
US8114437B2 (en) | 2005-02-03 | 2012-02-14 | Intarcia Therapeutics, Inc. | Solvent/polymer solutions as suspension vehicles |
US8216558B2 (en) | 2005-03-16 | 2012-07-10 | Nitto Denko Corporation | Polymer coating of cells |
US8827884B2 (en) | 2009-08-06 | 2014-09-09 | Koninklijke Philips N.V. | Oncology therapies employing radioactive seeds |
US9303067B2 (en) | 2004-12-21 | 2016-04-05 | Novartis Ag | Sustained release formulation comprising a somatostatin analogue |
US9566336B2 (en) | 2003-06-26 | 2017-02-14 | Psivida Us, Inc. | In situ gelling drug delivery system |
US9604073B2 (en) * | 2010-03-17 | 2017-03-28 | The Board Of Trustees Of The Leland Stanford Junior University | Light-sensitive ion-passing molecules |
US9616055B2 (en) | 2008-11-03 | 2017-04-11 | Durect Corporation | Oral pharmaceutical dosage forms |
US9655861B2 (en) | 2007-12-06 | 2017-05-23 | Durect Corporation | Oral pharmaceutical dosage forms |
US9682127B2 (en) | 2005-02-03 | 2017-06-20 | Intarcia Therapeutics, Inc. | Osmotic delivery device comprising an insulinotropic peptide and uses thereof |
US9724293B2 (en) | 2003-11-17 | 2017-08-08 | Intarcia Therapeutics, Inc. | Methods of manufacturing viscous liquid pharmaceutical formulations |
US9855333B2 (en) | 2013-03-15 | 2018-01-02 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
US9918982B2 (en) | 2002-12-13 | 2018-03-20 | Durect Corporation | Oral drug delivery system |
USD835783S1 (en) | 2016-06-02 | 2018-12-11 | Intarcia Therapeutics, Inc. | Implant placement guide |
US10159714B2 (en) | 2011-02-16 | 2018-12-25 | Intarcia Therapeutics, Inc. | Compositions, devices and methods of use thereof for the treatment of cancers |
US10231923B2 (en) | 2009-09-28 | 2019-03-19 | Intarcia Therapeutics, Inc. | Rapid establishment and/or termination of substantial steady-state drug delivery |
US10300114B2 (en) | 2003-06-26 | 2019-05-28 | Eyepoint Pharmaceuticals Us, Inc. | Bioerodible sustained release drug delivery systems |
USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
US10441528B2 (en) | 2008-02-13 | 2019-10-15 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
US10501517B2 (en) | 2016-05-16 | 2019-12-10 | Intarcia Therapeutics, Inc. | Glucagon-receptor selective polypeptides and methods of use thereof |
US10527170B2 (en) | 2006-08-09 | 2020-01-07 | Intarcia Therapeutics, Inc. | Osmotic delivery systems and piston assemblies for use therein |
US10758623B2 (en) | 2013-12-09 | 2020-09-01 | Durect Corporation | Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same |
US10835580B2 (en) | 2017-01-03 | 2020-11-17 | Intarcia Therapeutics, Inc. | Methods comprising continuous administration of a GLP-1 receptor agonist and co-administration of a drug |
US10925639B2 (en) | 2015-06-03 | 2021-02-23 | Intarcia Therapeutics, Inc. | Implant placement and removal systems |
WO2021081293A1 (en) * | 2019-10-25 | 2021-04-29 | Warsaw Orthopedic, Inc | Compositions for treatment of annular spinal disc injury |
US11083796B2 (en) | 2005-07-26 | 2021-08-10 | Durect Corporation | Peroxide removal from drug delivery vehicle |
US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
US11400019B2 (en) | 2020-01-13 | 2022-08-02 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
Families Citing this family (268)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020183288A1 (en) * | 1995-04-03 | 2002-12-05 | Bone Care International, Inc. | Method for treating and preventing hyperparathyroidism |
ES2158611T3 (en) * | 1996-12-20 | 2001-09-01 | Alza Corp | COMPOSITION IN INJECTABLE GEL WITH RETARD EFFECT AND PROCEDURE FOR THE PREPARATION OF SUCH COMPOSITION. |
US6994851B1 (en) | 1997-07-10 | 2006-02-07 | Mannkind Corporation | Method of inducing a CTL response |
US6977074B2 (en) | 1997-07-10 | 2005-12-20 | Mannkind Corporation | Method of inducing a CTL response |
US6193991B1 (en) | 1997-10-29 | 2001-02-27 | Atul J. Shukla | Biodegradable delivery systems of biologically active substances |
US6733767B2 (en) * | 1998-03-19 | 2004-05-11 | Merck & Co., Inc. | Liquid polymeric compositions for controlled release of bioactive substances |
US7919109B2 (en) | 1999-02-08 | 2011-04-05 | Intarcia Therapeutics, Inc. | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
US7018365B2 (en) | 1999-05-21 | 2006-03-28 | Micro Therapeutics, Inc. | Threaded syringe with quick stop |
EP1949890A3 (en) | 1999-06-04 | 2011-05-18 | ALZA Corporation | Implantable gel compositions and method of manufacture |
JP2003501375A (en) * | 1999-06-04 | 2003-01-14 | アルザ・コーポレーション | Implantable gel composition and method of manufacture |
FR2802923B1 (en) * | 1999-12-28 | 2002-03-08 | Roquette Freres | PROCESS FOR THE PREPARATION OF A LACTIC ACID ESTER COMPOSITION AND ITS USE AS A SOLVENT |
US6465425B1 (en) | 2000-02-10 | 2002-10-15 | Alkermes Controlled Therapeutics, Inc. | Microencapsulation and sustained release of biologically active acid-stable or free sulfhydryl-containing proteins |
US7074803B2 (en) * | 2001-03-02 | 2006-07-11 | Durect Corporation | Opioid formulations |
US20030211974A1 (en) * | 2000-03-21 | 2003-11-13 | Brodbeck Kevin J. | Gel composition and methods |
US6998137B2 (en) * | 2000-04-07 | 2006-02-14 | Macromed, Inc. | Proteins deposited onto sparingly soluble biocompatible particles for controlled protein release into a biological environment from a polymer matrix |
WO2001079354A1 (en) * | 2000-04-12 | 2001-10-25 | Sanko Chemical Industry Co., Ltd. | Antistatic composition |
SG98393A1 (en) | 2000-05-19 | 2003-09-19 | Inst Materials Research & Eng | Injectable drug delivery systems with cyclodextrin-polymer based hydrogels |
US20060177416A1 (en) * | 2003-10-14 | 2006-08-10 | Medivas, Llc | Polymer particle delivery compositions and methods of use |
US7666445B2 (en) * | 2000-10-20 | 2010-02-23 | The Trustees Of The University Of Pennsylvania | Polymer-based surgically implantable haloperidol delivery systems and methods for their production and use |
US20020106406A1 (en) * | 2000-12-08 | 2002-08-08 | Mchugh Anthony J. | Crystallizable/non-crystallizable polymer composites |
US7088002B2 (en) * | 2000-12-18 | 2006-08-08 | Intel Corporation | Interconnect |
US20020114795A1 (en) | 2000-12-22 | 2002-08-22 | Thorne Kevin J. | Composition and process for bone growth and repair |
US6500408B2 (en) | 2001-01-27 | 2002-12-31 | Jc Technologies, Inc. | Enamel-safe tooth bleach and method for use |
CA2439472A1 (en) * | 2001-02-27 | 2002-09-06 | University Of Rochester | Methods and compositions for modifying apolipoprotein b mrna editing |
US20040185101A1 (en) * | 2001-03-27 | 2004-09-23 | Macromed, Incorporated. | Biodegradable triblock copolymers as solubilizing agents for drugs and method of use thereof |
US6590059B2 (en) | 2001-05-11 | 2003-07-08 | Ap Pharma, Inc. | Bioerodible polyorthoesters from dioxolane-based diketene acetals |
EP1408876A4 (en) | 2001-06-22 | 2004-09-22 | Durect Corp | Zero-order prolonged release coaxial implants |
US7342089B2 (en) * | 2001-07-11 | 2008-03-11 | Palatin Technologies, Inc. | Cyclic peptides for treatment for cachexia |
US7345144B2 (en) * | 2001-07-11 | 2008-03-18 | Palatin Technologies, Inc. | Cyclic peptides for treatment of cachexia |
US7718802B2 (en) | 2001-08-10 | 2010-05-18 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
US7732451B2 (en) * | 2001-08-10 | 2010-06-08 | Palatin Technologies, Inc. | Naphthalene-containing melanocortin receptor-specific small molecule |
US7655658B2 (en) * | 2001-08-10 | 2010-02-02 | Palatin Technologies, Inc. | Thieno [2,3-D]pyrimidine-2,4-dione melanocortin-specific compounds |
WO2003013571A1 (en) * | 2001-08-10 | 2003-02-20 | Palatin Technologies, Inc. | Peptidomimetics of biologically active metallopeptides |
US7456184B2 (en) * | 2003-05-01 | 2008-11-25 | Palatin Technologies Inc. | Melanocortin receptor-specific compounds |
GB2404865B (en) * | 2001-09-11 | 2005-09-28 | Caretek Medical Ltd | Novel drug delivery technology |
ITMI20012060A1 (en) * | 2001-10-05 | 2003-04-05 | Recordati Chem Pharm | NEW N-ACYLATED HETEROCYCLES |
MXPA04004664A (en) * | 2001-11-14 | 2004-09-10 | Alza Corp | Injectable depot composition. |
NZ533435A (en) * | 2001-11-14 | 2007-10-26 | Alza Corp | Injectable depot compositions and uses thereof |
CA2467239A1 (en) * | 2001-11-14 | 2003-05-22 | Alza Corporation | Catheter injectable depot compositions and uses thereof |
DK1484054T3 (en) * | 2002-02-22 | 2012-11-26 | Santen Pharmaceutical Co Ltd | Drug delivery system for subconjunctival administration of fine grains |
ES2207387B1 (en) * | 2002-02-28 | 2005-07-16 | Consejo Sup. Investig. Cientificas | CHEMICAL COMPOSITION OF IGF-I FOR THE TREATMENT AND PREVENTION OF NEURODEGENERATIVE DISEASES. |
US6960346B2 (en) * | 2002-05-09 | 2005-11-01 | University Of Tennessee Research Foundation | Vehicles for delivery of biologically active substances |
US7432245B2 (en) * | 2002-06-07 | 2008-10-07 | Abbott Laboratories Inc. | Pharmaceutical formulation comprising a peptide angiogenesis inhibitor |
US7649023B2 (en) * | 2002-06-11 | 2010-01-19 | Novartis Ag | Biodegradable block copolymeric compositions for drug delivery |
US7160551B2 (en) * | 2002-07-09 | 2007-01-09 | The Board Of Trustees Of The University Of Illinois | Injectable system for controlled drug delivery |
JP4723244B2 (en) * | 2002-07-19 | 2011-07-13 | オメロス コーポレイション | Biodegradable triblock copolymers, methods for their synthesis, and hydrogels and biomaterials made therefrom |
IL166418A0 (en) * | 2002-07-31 | 2006-01-15 | Alza Corp | Injectable depot compositions and uses thereof |
US20050287648A1 (en) * | 2002-08-05 | 2005-12-29 | University Of Rochester | Protein Transducing Domain/Deaminase Chimeric Proteins, Related Compounds, and Uses Thereof |
GB0222522D0 (en) | 2002-09-27 | 2002-11-06 | Controlled Therapeutics Sct | Water-swellable polymers |
AU2003267763A1 (en) * | 2002-10-25 | 2004-05-13 | Pfizer Products Inc. | Depot formulations of arylheterocyclic active agents in the form of a suspension |
EP1562626B1 (en) * | 2002-10-29 | 2007-11-28 | ALZA Corporation | Stabilized, solid-state polypeptide particles |
US6918561B2 (en) * | 2002-10-31 | 2005-07-19 | Yon So Chong | Shell assembly for winding tire cord strip or belt cord strip |
JP2004196787A (en) * | 2002-12-04 | 2004-07-15 | Santen Pharmaceut Co Ltd | Drug delivery system with subconjunctival depot |
CN101336887A (en) * | 2002-12-04 | 2009-01-07 | 参天制药株式会社 | Drug delivery system using subconjunctival depot |
BR0317421A (en) * | 2002-12-19 | 2005-11-08 | Alza Corp | Stable non-aqueous single phase gels and formulations for release from an implantable device |
WO2004057959A2 (en) | 2002-12-20 | 2004-07-15 | Generipharm, Inc. | Intracutaneous injection |
ES2282529T3 (en) * | 2003-02-03 | 2007-10-16 | Hans-Dietrich Dr.Techn. Polaschegg | COMPOSITION FOR THE PREVENTION OF AN INFECTION DUE TO A PERMANENT DEVICE. |
EP1622540A4 (en) * | 2003-03-11 | 2009-12-30 | Qlt Usa Inc | Formulations for cell- schedule dependent anticancer agents |
DE10314082A1 (en) * | 2003-03-28 | 2004-10-21 | Mcs Micro Carrier Systems Gmbh | Biodegradable injectable implant |
AU2004227986A1 (en) * | 2003-03-31 | 2004-10-21 | Alza Corporation | Osmotic delivery system and method for decreasing start-up times for osmotic delivery systems |
TW584939B (en) * | 2003-04-23 | 2004-04-21 | Nanya Technology Corp | Method of forming bottle-shaped trench and the method for fabricating bottle-shaped trench capacitors |
US7968548B2 (en) | 2003-05-01 | 2011-06-28 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine compounds with diamine groups |
US7727990B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine and keto-piperazine compounds |
US7727991B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific single acyl piperazine compounds |
MY146351A (en) * | 2003-05-29 | 2012-08-15 | Schering Plough Ltd | Compositions for treating infection in cattle and swine |
US20070184084A1 (en) * | 2003-05-30 | 2007-08-09 | Guohua Chen | Implantable elastomeric caprolactone depot compositions and uses thereof |
US20060286173A1 (en) * | 2003-08-20 | 2006-12-21 | Kazuhito Yamada | Drug delivery system for sub-tenon s capsule adminstration of fine grains |
EP1670895A4 (en) * | 2003-09-03 | 2007-11-14 | Univ Rochester | Cytidine deaminase activators, deoxycytidine deaminase activators, vif antagonists, and methods of screening for molecules thereof |
EP1677781A4 (en) * | 2003-10-29 | 2008-11-19 | Idexx Lab Inc | Salts of pharmacologically active compounds |
CN1889929B (en) * | 2003-11-14 | 2013-04-10 | 阿尔萨公司 | Excipients in drug delivery vehicles |
US20050106214A1 (en) * | 2003-11-14 | 2005-05-19 | Guohua Chen | Excipients in drug delivery vehicles |
US20050281879A1 (en) * | 2003-11-14 | 2005-12-22 | Guohua Chen | Excipients in drug delivery vehicles |
CA2553254C (en) * | 2004-01-12 | 2013-12-17 | The Trustees Of The University Of Pennsylvania | Long-term delivery formulations and methods of use thereof |
US8329203B2 (en) * | 2004-01-12 | 2012-12-11 | The Trustees Of The University Of Pennsylvania | Drug-containing implants and methods of use thereof |
US8221778B2 (en) * | 2005-01-12 | 2012-07-17 | The Trustees Of The University Of Pennsylvania | Drug-containing implants and methods of use thereof |
AU2005207002B2 (en) | 2004-01-21 | 2011-03-17 | University Of Utah Research Foundation | Mutant sodium channel Nav1.7 and methods related thereto |
US7429391B2 (en) * | 2004-01-30 | 2008-09-30 | Access Business Group International Llc | Holistic composition and method for reducing skin pigmentation |
US8048086B2 (en) | 2004-02-25 | 2011-11-01 | Femasys Inc. | Methods and devices for conduit occlusion |
US8048101B2 (en) | 2004-02-25 | 2011-11-01 | Femasys Inc. | Methods and devices for conduit occlusion |
US8052669B2 (en) | 2004-02-25 | 2011-11-08 | Femasys Inc. | Methods and devices for delivery of compositions to conduits |
US9238127B2 (en) | 2004-02-25 | 2016-01-19 | Femasys Inc. | Methods and devices for delivering to conduit |
US7709484B1 (en) | 2004-04-19 | 2010-05-04 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
US20080248465A1 (en) * | 2004-04-26 | 2008-10-09 | Uab Research Foundation | Polymorphisms in the Fcgr2b Promoter and Uses Thereof |
WO2005115410A2 (en) * | 2004-05-06 | 2005-12-08 | University Of Rochester | Context dependent inhibitors of cytidine deaminases and uses thereof |
NZ550926A (en) * | 2004-05-17 | 2010-01-29 | Ares Trading Sa | Hydrogel interferon formulations |
US20050266087A1 (en) * | 2004-05-25 | 2005-12-01 | Gunjan Junnarkar | Formulations having increased stability during transition from hydrophobic vehicle to hydrophilic medium |
UA92146C2 (en) * | 2004-06-01 | 2010-10-11 | Эйрэс Трейдинг С.А. | Stabilized interferon liquid formulations |
US7858115B2 (en) * | 2004-06-24 | 2010-12-28 | Idexx Laboratories | Phospholipid gel compositions for drug delivery and methods of treating conditions using same |
US7854943B2 (en) * | 2004-06-24 | 2010-12-21 | Idexx Laboratories | Phospholipid gel compositions for drug delivery and methods of treating conditions using same |
GB0417401D0 (en) | 2004-08-05 | 2004-09-08 | Controlled Therapeutics Sct | Stabilised prostaglandin composition |
LT2767292T (en) | 2004-09-17 | 2016-12-12 | Durect Corporation | Sustained Local Anesthetic Composition Containing SAIB |
CA2581143C (en) * | 2004-09-21 | 2015-03-31 | Shandong Luye Pharmaceutical Co., Ltd. | Long acting sustained-release formulation containing dopamine receptor agonist and the preparation method thereof |
EP3173072A1 (en) * | 2004-10-01 | 2017-05-31 | Ramscor, Inc. | Conveniently implantable sustained release drug compositions |
US9993558B2 (en) | 2004-10-01 | 2018-06-12 | Ramscor, Inc. | Sustained release eye drop formulations |
US8541413B2 (en) * | 2004-10-01 | 2013-09-24 | Ramscor, Inc. | Sustained release eye drop formulations |
US20080038316A1 (en) * | 2004-10-01 | 2008-02-14 | Wong Vernon G | Conveniently implantable sustained release drug compositions |
AR052155A1 (en) * | 2004-12-14 | 2007-03-07 | Novartis Ag | ORGANIC COMPOUNDS |
US20060141040A1 (en) * | 2004-12-23 | 2006-06-29 | Guohua Chen | Injectable non-aqueous suspension |
CN100425233C (en) * | 2005-01-12 | 2008-10-15 | 复旦大学 | Nimodipine gel for nasal cavity |
US20060216242A1 (en) * | 2005-02-03 | 2006-09-28 | Rohloff Catherine M | Suspending vehicles and pharmaceutical suspensions for drug dosage forms |
WO2006084083A2 (en) * | 2005-02-03 | 2006-08-10 | Duramed Pharmaceuticals, Inc. | Devices for delivering agents to a vaginal tract |
US7959938B2 (en) | 2005-03-15 | 2011-06-14 | Intarcia Therapeutics, Inc. | Polyoxaester suspending vehicles for use with implantable delivery systems |
US20060253068A1 (en) * | 2005-04-20 | 2006-11-09 | Van Bilsen Paul | Use of biocompatible in-situ matrices for delivery of therapeutic cells to the heart |
US20070015689A1 (en) * | 2005-06-23 | 2007-01-18 | Alza Corporation | Complexation of metal ions with polypeptides |
EP1741440A1 (en) * | 2005-07-08 | 2007-01-10 | Mellitus S.L. | Use of BPI protein for the treatment of disorders of the metabolism and cardiovascular disorders |
EP1909774A2 (en) * | 2005-08-04 | 2008-04-16 | Angiotech International Ag | Block copolymer compositions and uses thereof |
WO2007038246A2 (en) * | 2005-09-22 | 2007-04-05 | Medivas, Llc | Solid polymer delivery compositions and methods for use thereof |
JP5192384B2 (en) | 2005-09-22 | 2013-05-08 | メディバス エルエルシー | Bis- (α-amino) -diol-diester-containing poly (ester amide) and poly (ester urethane) compositions and methods of use |
US8852638B2 (en) | 2005-09-30 | 2014-10-07 | Durect Corporation | Sustained release small molecule drug formulation |
US7669732B2 (en) * | 2005-10-25 | 2010-03-02 | Imi Cornelius Inc. | Cup lid dispenser |
JP5153340B2 (en) * | 2005-11-16 | 2013-02-27 | 学校法人東海大学 | Drug release control composition and drug release medical device |
EP1962894A4 (en) * | 2005-12-07 | 2012-11-14 | Medivas Llc | Method for assembling a polymer-biologic delivery composition |
US20070142287A1 (en) * | 2005-12-20 | 2007-06-21 | Biomed Solutions, Llc | Compositions And Methods For Treatment Of Cancer |
US20070184087A1 (en) | 2006-02-06 | 2007-08-09 | Bioform Medical, Inc. | Polysaccharide compositions for use in tissue augmentation |
US8580746B2 (en) * | 2006-03-30 | 2013-11-12 | Palatin Technologies, Inc. | Amide linkage cyclic natriuretic peptide constructs |
CA2647146A1 (en) * | 2006-03-30 | 2007-10-11 | Palatin Technologies, Inc. | Linear natriuretic peptide constructs |
BRPI0709427A2 (en) * | 2006-03-30 | 2011-07-12 | Palatin Technologies Inc | "Cyclic construct, pharmaceutical composition and use of a compound |
JP5445130B2 (en) * | 2006-05-02 | 2014-03-19 | メディバス エルエルシー | Delivery of ophthalmic drugs to the exterior or interior of the eye |
EP2021141A4 (en) * | 2006-05-09 | 2013-07-03 | Medivas Llc | Biodegradable water soluble polymers |
CN101453982B (en) | 2006-05-30 | 2011-05-04 | 精达制药公司 | Two-piece, internal-channel osmotic delivery system flow modulator |
GB0613333D0 (en) | 2006-07-05 | 2006-08-16 | Controlled Therapeutics Sct | Hydrophilic polyurethane compositions |
GB0613638D0 (en) | 2006-07-08 | 2006-08-16 | Controlled Therapeutics Sct | Polyurethane elastomers |
CN101500430B (en) | 2006-08-07 | 2014-02-19 | 诺维信公司 | Enzyme granules for animal feed |
US20080031998A1 (en) * | 2006-08-07 | 2008-02-07 | Novozymes A/S | Enzyme Granules for Animal Feed |
US20080038332A1 (en) * | 2006-08-10 | 2008-02-14 | Cai Gu Huang | Stable pharmaceutical formulation comprising atorvastatin calcium |
US7834017B2 (en) | 2006-08-11 | 2010-11-16 | Palatin Technologies, Inc. | Diamine-containing, tetra-substituted piperazine compounds having identical 1- and 4-substituents |
GB0620685D0 (en) | 2006-10-18 | 2006-11-29 | Controlled Therapeutics Sct | Bioresorbable polymers |
US8999317B2 (en) | 2006-11-01 | 2015-04-07 | University Of Rochester | Methods and compositions related to the structure and function of APOBEC3G |
US8337883B2 (en) | 2006-11-03 | 2012-12-25 | Durect Corporation | Transdermal delivery systems |
US7718616B2 (en) | 2006-12-21 | 2010-05-18 | Zimmer Orthobiologics, Inc. | Bone growth particles and osteoinductive composition thereof |
KR100825519B1 (en) * | 2007-01-05 | 2008-04-25 | 주식회사 바이오폴리메드 | A chitosan based polymer conjugate and a method for producing the same |
DK2167039T3 (en) * | 2007-05-18 | 2017-01-09 | Durect Corp | Improved depot formulations |
MX337286B (en) | 2007-05-25 | 2016-02-22 | Indivior Uk Ltd | Sustained delivery formulations of risperidone compounds. |
US10092524B2 (en) | 2008-06-11 | 2018-10-09 | Edge Therapeutics, Inc. | Compositions and their use to treat complications of aneurysmal subarachnoid hemorrhage |
US9364432B2 (en) * | 2007-06-11 | 2016-06-14 | Edge Therapeutics, Inc. | Intraventricular drug delivery system for improving outcome after a brain injury affecting cerebral blood flow |
WO2009015143A1 (en) * | 2007-07-24 | 2009-01-29 | Medivas, Llc | Biodegradable cationic polymer gene transfer compositions and methods of use |
US8470360B2 (en) * | 2008-04-18 | 2013-06-25 | Warsaw Orthopedic, Inc. | Drug depots having different release profiles for reducing, preventing or treating pain and inflammation |
KR20100067684A (en) * | 2007-11-05 | 2010-06-21 | 보오슈 앤드 롬 인코포레이팃드 | Water-immiscible materials as vehicles for drug delivery |
WO2009060473A2 (en) * | 2007-11-06 | 2009-05-14 | Panacea Biotec Limited | Injectable compositions, processes and uses thereof |
CA2705520C (en) * | 2007-11-13 | 2016-06-28 | Surmodics Pharmaceuticals, Inc. | Viscous terpolymers as drug delivery platform |
WO2009080699A2 (en) * | 2007-12-20 | 2009-07-02 | Merck Serono S.A. | Peg-interferon-beta formulations |
US20090181068A1 (en) * | 2008-01-14 | 2009-07-16 | Dunn Richard L | Low Viscosity Liquid Polymeric Delivery System |
KR20100121484A (en) * | 2008-02-15 | 2010-11-17 | 본 테라퓨틱스 소시에테아노님 | Pharmaceutical composition for use in the treatment or prevention of osteoarticular diseases |
BRPI0905369C8 (en) | 2008-02-15 | 2021-05-25 | Bone Therapeutics | pharmaceutical composition, use of pharmaceutical composition and compartmentalized kit |
US8828354B2 (en) | 2008-03-27 | 2014-09-09 | Warsaw Orthopedic, Inc. | Pharmaceutical gels and methods for delivering therapeutic agents to a site beneath the skin |
US8956636B2 (en) | 2008-04-18 | 2015-02-17 | Warsaw Orthopedic, Inc. | Methods and compositions for treating postoperative pain comprosing ketorolac |
US9132085B2 (en) | 2008-04-18 | 2015-09-15 | Warsaw Orthopedic, Inc. | Compositions and methods for treating post-operative pain using clonidine and bupivacaine |
US20090264489A1 (en) * | 2008-04-18 | 2009-10-22 | Warsaw Orthopedic, Inc. | Method for Treating Acute Pain with a Formulated Drug Depot in Combination with a Liquid Formulation |
US9125917B2 (en) * | 2008-04-18 | 2015-09-08 | Warsaw Orthopedic, Inc. | Fluocinolone formulations in a biodegradable polymer carrier |
US8722079B2 (en) | 2008-04-18 | 2014-05-13 | Warsaw Orthopedic, Inc. | Methods for treating conditions such as dystonia and post-stroke spasticity with clonidine |
US20090264477A1 (en) * | 2008-04-18 | 2009-10-22 | Warsaw Orthopedic, Inc., An Indiana Corporation | Beta adrenergic receptor agonists for treatment of pain and/or inflammation |
US8524267B2 (en) * | 2008-04-18 | 2013-09-03 | Warsaw Orthopedic, Inc. | Dexamethasone formulations in a biodegradable material |
US9132119B2 (en) | 2008-04-18 | 2015-09-15 | Medtronic, Inc. | Clonidine formulation in a polyorthoester carrier |
US8420114B2 (en) | 2008-04-18 | 2013-04-16 | Warsaw Orthopedic, Inc. | Alpha and beta adrenergic receptor agonists for treatment of pain and / or inflammation |
US20090263443A1 (en) * | 2008-04-18 | 2009-10-22 | Warsaw Orthopedics, Inc. | Methods for treating post-operative effects such as spasticity and shivering with clondine |
US9072727B2 (en) | 2008-04-18 | 2015-07-07 | Warsaw Orthopedic, Inc. | Alpha adrenergic receptor agonists for treatment of degenerative disc disease |
US8846068B2 (en) * | 2008-04-18 | 2014-09-30 | Warsaw Orthopedic, Inc. | Methods and compositions for treating post-operative pain comprising a local anesthetic |
US9289409B2 (en) * | 2008-04-18 | 2016-03-22 | Warsaw Orthopedic, Inc. | Sulindac formulations in a biodegradable material |
US8889173B2 (en) * | 2008-04-18 | 2014-11-18 | Warsaw Orthopedic, Inc. | Alpha adrenergic receptor agonists for treatment of pain and/or inflammation |
US8557273B2 (en) | 2008-04-18 | 2013-10-15 | Medtronic, Inc. | Medical devices and methods including polymers having biologically active agents therein |
USRE48948E1 (en) | 2008-04-18 | 2022-03-01 | Warsaw Orthopedic, Inc. | Clonidine compounds in a biodegradable polymer |
US8956641B2 (en) | 2008-04-18 | 2015-02-17 | Warsaw Orthopedic, Inc. | Alpha adrenergic receptor agonists for treatment of inflammatory diseases |
US8629172B2 (en) | 2008-04-18 | 2014-01-14 | Warsaw Orthopedic, Inc. | Methods and compositions for treating post-operative pain comprising clonidine |
US20090264478A1 (en) * | 2008-04-18 | 2009-10-22 | Warsaw Orthopedic, Inc. | Sulfasalazine formulations in a biodegradable polymer carrier |
US8883768B2 (en) * | 2008-04-18 | 2014-11-11 | Warsaw Orthopedic, Inc. | Fluocinolone implants to protect against undesirable bone and cartilage destruction |
US20100015049A1 (en) * | 2008-07-16 | 2010-01-21 | Warsaw Orthopedic, Inc. | Methods and compositions for treating postoperative pain comprising nonsteroidal anti-inflammatory agents |
US20100016808A1 (en) * | 2008-07-17 | 2010-01-21 | Bioform Medical, Inc. | Thin-Walled Delivery System |
US9492375B2 (en) | 2008-07-23 | 2016-11-15 | Warsaw Orthopedic, Inc. | Foam carrier for bone grafting |
CN102186484A (en) * | 2008-08-13 | 2011-09-14 | 梅迪沃什有限公司 | Aabb-poly(depsipeptide) biodegradable polymers and methods of use |
US10070888B2 (en) | 2008-10-03 | 2018-09-11 | Femasys, Inc. | Methods and devices for sonographic imaging |
US9554826B2 (en) | 2008-10-03 | 2017-01-31 | Femasys, Inc. | Contrast agent injection system for sonographic imaging |
NZ592113A (en) * | 2008-10-15 | 2012-04-27 | Intarcia Therapeutics Inc | Highly concentrated drug particles, formulations, suspensions and uses thereof |
US20100098746A1 (en) * | 2008-10-20 | 2010-04-22 | Warsaw Orthopedic, Inc. | Compositions and methods for treating periodontal disease comprising clonidine, sulindac and/or fluocinolone |
US9161903B2 (en) | 2008-10-31 | 2015-10-20 | Warsaw Orthopedic, Inc. | Flowable composition that hardens on delivery to a target tissue site beneath the skin |
CA2780624A1 (en) | 2008-11-11 | 2010-05-20 | Signum Biosciences, Inc. | Isoprenyl derivatives useful as agents to modulate inflammation |
WO2010065801A1 (en) | 2008-12-04 | 2010-06-10 | Palatin Technologies, Inc. | Amine substituted piperazine melanocortin receptor-specific compounds |
WO2010065802A2 (en) | 2008-12-04 | 2010-06-10 | Palatin Technologies, Inc. | Substituted pyrrolidine or imidazolidine melanocortin receptor-specific compounds |
WO2010065799A2 (en) | 2008-12-04 | 2010-06-10 | Palatin Technologies, Inc. | Amine substituted piperidine melanocortin receptor-specific compounds |
US20100168807A1 (en) * | 2008-12-23 | 2010-07-01 | Burton Kevin W | Bioactive terpolymer compositions and methods of making and using same |
US8980317B2 (en) | 2008-12-23 | 2015-03-17 | Warsaw Orthopedic, Inc. | Methods and compositions for treating infections comprising a local anesthetic |
US9480643B2 (en) | 2008-12-23 | 2016-11-01 | Surmodics Pharmaceuticals, Inc. | Implantable composites and implants comprising same |
US9415197B2 (en) * | 2008-12-23 | 2016-08-16 | Surmodics, Inc. | Implantable suction cup composites and implants comprising same |
US8951546B2 (en) * | 2008-12-23 | 2015-02-10 | Surmodics Pharmaceuticals, Inc. | Flexible implantable composites and implants comprising same |
US8974808B2 (en) | 2008-12-23 | 2015-03-10 | Surmodics, Inc. | Elastic implantable composites and implants comprising same |
US20100226959A1 (en) * | 2009-03-04 | 2010-09-09 | Warsaw Orthopedic, Inc. | Matrix that prolongs growth factor release |
US20100228097A1 (en) * | 2009-03-04 | 2010-09-09 | Warsaw Orthopedic, Inc. | Methods and compositions to diagnose pain |
US20100239632A1 (en) * | 2009-03-23 | 2010-09-23 | Warsaw Orthopedic, Inc. | Drug depots for treatment of pain and inflammation in sinus and nasal cavities or cardiac tissue |
JP5805632B2 (en) | 2009-06-08 | 2015-11-04 | パラティン テクノロジーズ, インコーポレイテッドPalatin Technologies, Inc. | Peptides specific for the melanocortin receptor |
US8617583B2 (en) | 2009-07-17 | 2013-12-31 | Warsaw Orthopedic, Inc. | Alpha adrenergic receptor agonists for prevention or treatment of a hematoma, edema, and/or deep vein thrombosis |
US8653029B2 (en) | 2009-07-30 | 2014-02-18 | Warsaw Orthopedic, Inc. | Flowable paste and putty bone void filler |
US8231891B2 (en) | 2009-07-31 | 2012-07-31 | Warsaw Orthopedic, Inc. | Implantable drug depot for weight control |
US20110097375A1 (en) | 2009-10-26 | 2011-04-28 | Warsaw Orthopedic, Inc. | Formulation for preventing or reducing bleeding at a surgical site |
US20110097380A1 (en) * | 2009-10-28 | 2011-04-28 | Warsaw Orthopedic, Inc. | Clonidine formulations having antimicrobial properties |
US9504698B2 (en) * | 2009-10-29 | 2016-11-29 | Warsaw Orthopedic, Inc. | Flowable composition that sets to a substantially non-flowable state |
US8597192B2 (en) | 2009-10-30 | 2013-12-03 | Warsaw Orthopedic, Inc. | Ultrasonic devices and methods to diagnose pain generators |
EP2498603B1 (en) | 2009-11-12 | 2016-07-13 | Signum Biosciences, Inc. | Use of anti-bacterial agents for the treatment of epithelial-related conditions |
US9993441B2 (en) | 2009-12-30 | 2018-06-12 | Surmodics, Inc. | Controlled release matrix barrier structure for subcutaneous medical devices |
US8475824B2 (en) * | 2010-01-26 | 2013-07-02 | Warsaw Orthopedic, Inc. | Resorbable matrix having elongated particles |
US8758791B2 (en) * | 2010-01-26 | 2014-06-24 | Warsaw Orthopedic, Inc. | Highly compression resistant matrix with porous skeleton |
US9125902B2 (en) * | 2010-01-28 | 2015-09-08 | Warsaw Orthopedic, Inc. | Methods for treating an intervertebral disc using local analgesics |
US9050274B2 (en) * | 2010-01-28 | 2015-06-09 | Warsaw Orthopedic, Inc. | Compositions and methods for treating an intervertebral disc using bulking agents or sealing agents |
US9486500B2 (en) | 2010-01-28 | 2016-11-08 | Warsaw Orthopedic, Inc. | Osteoimplant and methods for making |
US20110229457A1 (en) * | 2010-03-12 | 2011-09-22 | Surmodics, Inc. | Injectable drug delivery system |
US10335366B2 (en) | 2010-05-31 | 2019-07-02 | Laboratorios Farmacéuticos Rovi, S.A. | Risperidone or paliperidone implant formulation |
US10350159B2 (en) | 2010-05-31 | 2019-07-16 | Laboratories Farmacéuticos Rovi, S.A. | Paliperidone implant formulation |
US10285936B2 (en) | 2010-05-31 | 2019-05-14 | Laboratorios Farmacéuticos Rovi, S.A. | Injectable composition with aromatase inhibitor |
ES2589106T3 (en) | 2010-05-31 | 2016-11-10 | Laboratorios Farmaceuticos Rovi, S.A. | Injection controlled antipsychotic composition |
US10881605B2 (en) | 2010-05-31 | 2021-01-05 | Laboratorios Farmaceuticos Rovi, S.A. | Methods for the preparation of injectable depot compositions |
SI2394663T1 (en) | 2010-05-31 | 2022-02-28 | Laboratorios Farmaceuticos Rovi, S.A. | Compositions for injectable in-situ biodegradable implants |
US10463607B2 (en) | 2010-05-31 | 2019-11-05 | Laboratorios Farmaceutics Rofi S.A. | Antipsychotic Injectable Depot Composition |
WO2011161531A1 (en) * | 2010-06-24 | 2011-12-29 | Torrent Pharmaceuticals Limited | Pharmaceutical composition containing goserelin for in-situ implant |
WO2012012460A1 (en) | 2010-07-19 | 2012-01-26 | Xeris Pharmaceuticals, Inc. | Stable glucagon formulations for the treatment of hypoglycemia |
US8246571B2 (en) | 2010-08-24 | 2012-08-21 | Warsaw Orthopedic, Inc. | Drug storage and delivery device having a retaining member |
EP2611868B1 (en) | 2010-08-30 | 2020-01-08 | Surmodics Pharmaceuticals, Inc. | Biodegradable terpolymers and terpolymer blends as pressure-sensitive adhesives |
US11291483B2 (en) | 2010-10-20 | 2022-04-05 | 206 Ortho, Inc. | Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants |
US10525169B2 (en) | 2010-10-20 | 2020-01-07 | 206 Ortho, Inc. | Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications |
US11207109B2 (en) | 2010-10-20 | 2021-12-28 | 206 Ortho, Inc. | Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications |
US10525168B2 (en) | 2010-10-20 | 2020-01-07 | 206 Ortho, Inc. | Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications |
US11484627B2 (en) | 2010-10-20 | 2022-11-01 | 206 Ortho, Inc. | Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications |
US20120101593A1 (en) | 2010-10-20 | 2012-04-26 | BIOS2 Medical, Inc. | Implantable polymer for bone and vascular lesions |
US11058796B2 (en) | 2010-10-20 | 2021-07-13 | 206 Ortho, Inc. | Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications |
US8740982B2 (en) | 2010-10-26 | 2014-06-03 | Kyphon Sarl | Devices containing a chemonucleolysis agent and methods for treating an intervertebral disc or spinal arachnoiditis |
US8404268B2 (en) | 2010-10-26 | 2013-03-26 | Kyphon Sarl | Locally targeted anti-fibrotic agents and methods of use |
US9414930B2 (en) | 2010-10-26 | 2016-08-16 | Kyphon SÀRL | Activatable devices containing a chemonucleolysis agent |
CA2817584C (en) | 2010-11-15 | 2018-01-02 | Zimmer Orthobiologics, Inc. | Bone void fillers |
WO2012075447A2 (en) | 2010-12-03 | 2012-06-07 | Warsaw Orthopedic, Inc. | Compositions and methods for delivering clonidine and bupivacaine to a target tissue site |
WO2012075451A2 (en) | 2010-12-03 | 2012-06-07 | Warsaw Orthopedic, Inc. | Clonidine and gaba compounds in a biodegradable polymer carrier |
US9060978B2 (en) | 2011-01-24 | 2015-06-23 | Warsaw Orthopedic, Inc. | Method for treating an intervertebral disc disorder by administering a dominant negative tumor necrosis factor antagonist |
US9717779B2 (en) | 2011-01-31 | 2017-08-01 | Warsaw Orthopedic, Inc. | Implantable matrix having optimum ligand concentrations |
CN105853348B (en) | 2011-03-10 | 2019-08-30 | Xeris药物公司 | Parenteral injection stablizing solution |
US9592243B2 (en) | 2011-04-25 | 2017-03-14 | Warsaw Orthopedic, Inc. | Medical devices and methods comprising an anabolic agent for treatment of an injury |
US9511077B2 (en) | 2011-04-25 | 2016-12-06 | Warsaw Orthopedic, Inc. | Medical devices and methods comprising an anabolic agent for wound healing |
US9873765B2 (en) | 2011-06-23 | 2018-01-23 | Dsm Ip Assets, B.V. | Biodegradable polyesteramide copolymers for drug delivery |
CN103748139B (en) | 2011-06-23 | 2016-08-17 | 帝斯曼知识产权资产管理有限公司 | For delivering the micron particle comprising biodegradable polyester-amide copolymer or the nano-particle of bioactivator |
US9132194B2 (en) | 2011-07-12 | 2015-09-15 | Warsaw Orthopedic, Inc. | Medical devices and methods comprising an adhesive sheet containing a drug depot |
US9205241B2 (en) | 2011-07-12 | 2015-12-08 | Warsaw Orthopedic, Inc. | Medical devices and methods comprising an adhesive material |
EP2773331B1 (en) | 2011-10-31 | 2016-02-10 | Xeris Pharmaceuticals, Inc. | Formulations for the treatment of diabetes |
KR20230104761A (en) * | 2012-01-23 | 2023-07-10 | 알러간, 인코포레이티드 | Time released biodegradable or bioerodible microspheres or microparticles suspended in a solidifying depot-forming injectable drug formulation |
WO2013130877A1 (en) | 2012-02-29 | 2013-09-06 | 206 Ortho, Inc. | Method and apparatus for treating bone fractures, including the use of composite implants |
US9534018B2 (en) | 2012-03-13 | 2017-01-03 | Tensive Controls Inc. | Melanocortin analogs having enhanced activity and transport |
US9511018B2 (en) | 2012-04-05 | 2016-12-06 | Warsaw Orthopedic, Inc. | Clonidine compounds in a biodegradable matrix |
US8735504B2 (en) | 2012-05-02 | 2014-05-27 | Warsaw Orthopedic, Inc. | Methods for preparing polymers having low residual monomer content |
US9125805B2 (en) | 2012-06-27 | 2015-09-08 | Xeris Pharmaceuticals, Inc. | Stable formulations for parenteral injection of small molecule drugs |
US8835601B2 (en) * | 2012-12-21 | 2014-09-16 | Mayo Foundation For Medical Education And Research | Natriuretic polypeptide delivery systems |
US9066853B2 (en) | 2013-01-15 | 2015-06-30 | Warsaw Orthopedic, Inc. | Clonidine compounds in a biodegradable fiber |
US9018162B2 (en) | 2013-02-06 | 2015-04-28 | Xeris Pharmaceuticals, Inc. | Methods for rapidly treating severe hypoglycemia |
EA033537B1 (en) | 2013-03-11 | 2019-10-31 | Durect Corp | Injectable controlled release composition comprising high viscosity liquid carrier |
US20140308352A1 (en) | 2013-03-11 | 2014-10-16 | Zogenix Inc. | Compositions and methods involving polymer, solvent, and high viscosity liquid carrier material |
MX352907B (en) | 2013-03-15 | 2017-12-13 | Heron Therapeutics Inc | Compositions of a polyorthoester and an aprotic solvent. |
EP3795635A1 (en) | 2013-05-23 | 2021-03-24 | 206 ORTHO, Inc. | Apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants |
US9775978B2 (en) | 2014-07-25 | 2017-10-03 | Warsaw Orthopedic, Inc. | Drug delivery device and methods having a retaining member |
US9764122B2 (en) | 2014-07-25 | 2017-09-19 | Warsaw Orthopedic, Inc. | Drug delivery device and methods having an occluding member |
WO2016022831A1 (en) | 2014-08-06 | 2016-02-11 | Xeris Pharmaceuticals, Inc. | Syringes, kits, and methods for intracutaneous and/or subcutaneous injection of pastes |
WO2016044683A1 (en) | 2014-09-19 | 2016-03-24 | Tensive Controls, Inc. | Anti-microbial peptides |
EP3233067B1 (en) | 2014-12-18 | 2019-11-06 | DSM IP Assets B.V. | Drug delivery system for delivery of acid sensitive drugs |
EP3240585A1 (en) * | 2014-12-29 | 2017-11-08 | Boston Scientific Scimed Inc. | Compositions, devices and methods for multi-stage release of chemotherapeutics |
WO2016168388A2 (en) | 2015-04-14 | 2016-10-20 | Palatin Technologies, Inc. | Therapies for obesity, diabetes and related indications |
US9649364B2 (en) | 2015-09-25 | 2017-05-16 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic formulations in aprotic polar solvents |
US11590205B2 (en) | 2015-09-25 | 2023-02-28 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic glucagon formulations in aprotic polar solvents |
US10076650B2 (en) | 2015-11-23 | 2018-09-18 | Warsaw Orthopedic, Inc. | Enhanced stylet for drug depot injector |
USD802755S1 (en) | 2016-06-23 | 2017-11-14 | Warsaw Orthopedic, Inc. | Drug pellet cartridge |
CN109477044B (en) | 2016-07-19 | 2021-10-08 | 艺康美国股份有限公司 | Method and cleaning solution for removing chewing gum and other sticky food |
US10434261B2 (en) | 2016-11-08 | 2019-10-08 | Warsaw Orthopedic, Inc. | Drug pellet delivery system and method |
KR20240036128A (en) | 2017-06-02 | 2024-03-19 | 엑스에리스 파머수티클스, 인크. | Precipitation resistant small molecule drug formulations |
CN107595765A (en) * | 2017-09-22 | 2018-01-19 | 沈阳兴齐眼药股份有限公司 | A kind of ophthalmically acceptable sustained release drug delivery system and preparation method thereof |
CN112516372A (en) * | 2020-11-12 | 2021-03-19 | 盐城工学院 | Composite drug-loaded fiber for absorbable surgical suture |
CA3231500A1 (en) | 2021-09-09 | 2023-03-16 | Xeris Pharmaceuticals, Inc. | Injectable high concentration pharmaceutical formulations and methods of manufacturing and use thereof |
WO2023046731A1 (en) | 2021-09-21 | 2023-03-30 | Laboratorios Farmacéuticos Rovi, S.A. | Antipsychotic injectable extended-release composition |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990003768A1 (en) * | 1988-10-03 | 1990-04-19 | Southern Research Institute | Biodegradable in-situ forming implants |
WO1991005544A1 (en) * | 1989-10-23 | 1991-05-02 | Medinvent | Drug delivery system, method for preparing the same, and use thereof |
EP0539751A1 (en) * | 1991-10-28 | 1993-05-05 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
US5242910A (en) * | 1992-10-13 | 1993-09-07 | The Procter & Gamble Company | Sustained release compositions for treating periodontal disease |
US5318780A (en) * | 1991-10-30 | 1994-06-07 | Mediventures Inc. | Medical uses of in situ formed gels |
EP0640647A2 (en) * | 1993-08-26 | 1995-03-01 | Collagen Corporation | Ionically crosslinked glycosaminoglycan gels for soft tissue augmentation and drug delivery |
WO1995027481A1 (en) * | 1994-04-08 | 1995-10-19 | Atrix Laboratories, Inc. | Liquid delivery compositions |
WO1997015287A1 (en) * | 1995-10-25 | 1997-05-01 | Macromed, Inc. | Thermosensitive biodegradable polymers based on poly(ether-ester) block copolymers |
Family Cites Families (82)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US35338A (en) * | 1862-05-20 | Improvement in catamenial and urinal bandages and receptacles | ||
FR2065764A5 (en) * | 1969-10-29 | 1971-08-06 | Dev Investisse | Controlled emission insecticidal vapourisingstrips |
FR2077679A7 (en) * | 1970-02-04 | 1971-11-05 | Boullenger Yvette | Volatile pesticide dispensers - with evaporation rate controlled with hydrophobic esters |
BE758156R (en) * | 1970-05-13 | 1971-04-28 | Ethicon Inc | ABSORBABLE SUTURE ELEMENT AND ITS |
US3714228A (en) * | 1970-08-14 | 1973-01-30 | Universal Oil Prod Co | Preparation of esters |
US3792010A (en) * | 1972-03-27 | 1974-02-12 | Ethicon Inc | Plasticized polyester sutures |
US3797492A (en) * | 1972-12-27 | 1974-03-19 | Alza Corp | Device for dispensing product with directional guidance member |
US3923939A (en) * | 1974-06-07 | 1975-12-02 | Alza Corp | Process for improving release kinetics of a monolithic drug delivery device |
US3987790A (en) * | 1975-10-01 | 1976-10-26 | Alza Corporation | Osmotically driven fluid dispenser |
US4008719A (en) * | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
US4675189A (en) * | 1980-11-18 | 1987-06-23 | Syntex (U.S.A.) Inc. | Microencapsulation of water soluble active polypeptides |
US4443340A (en) * | 1981-10-09 | 1984-04-17 | Betz Laboratories, Inc. | Control of iron induced fouling in water systems |
DE3324192A1 (en) * | 1983-07-05 | 1985-01-17 | Troponwerke Gmbh & Co Kg | DEPOT ANTIPHLOGISTICS |
US4708861A (en) * | 1984-02-15 | 1987-11-24 | The Liposome Company, Inc. | Liposome-gel compositions |
US4985404A (en) * | 1984-10-04 | 1991-01-15 | Monsanto Company | Prolonged release of biologically active polypeptides |
EP0226061B1 (en) | 1985-12-17 | 1994-02-16 | United States Surgical Corporation | High molecular weight bioresorbable polymers and implantation devices thereof |
US4865845A (en) * | 1986-03-21 | 1989-09-12 | Alza Corporation | Release rate adjustment of osmotic or diffusional delivery devices |
US4962091A (en) | 1986-05-23 | 1990-10-09 | Syntex (U.S.A.) Inc. | Controlled release of macromolecular polypeptides |
US5227157A (en) | 1986-10-14 | 1993-07-13 | Board Of Regents, The University Of Texas System | Delivery of therapeutic agents |
DE3635679A1 (en) * | 1986-10-21 | 1988-05-05 | Dynamit Nobel Ag | Surgical suture material |
US4981696A (en) | 1986-12-22 | 1991-01-01 | E. I. Du Pont De Nemours And Company | Polylactide compositions |
US4853218A (en) * | 1987-02-24 | 1989-08-01 | Schering Corporation | Zinc-protamine-alpha interferon complex |
US5229422A (en) * | 1987-09-07 | 1993-07-20 | Teijin Limited | Extemporaneous preparation type kit of a pharmaceutical substance-containing fat emulsion |
GB2209937B (en) | 1987-09-21 | 1991-07-03 | Depiopharm S A | Water insoluble polypeptides |
US5725491A (en) | 1988-10-03 | 1998-03-10 | Atrix Laboratories, Inc. | Method of forming a biodegradable film dressing on tissue |
US5702716A (en) | 1988-10-03 | 1997-12-30 | Atrix Laboratories, Inc. | Polymeric compositions useful as controlled release implants |
US5632727A (en) | 1988-10-03 | 1997-05-27 | Atrix Laboratories, Inc. | Biodegradable film dressing and method for its formation |
US5633002A (en) | 1988-10-04 | 1997-05-27 | Boehringer Ingelheim Gmbh | Implantable, biodegradable system for releasing active substance |
US5085866A (en) * | 1988-12-02 | 1992-02-04 | Southern Research Institute | Method of producing zero-order controlled-released devices |
US5057318A (en) * | 1988-12-13 | 1991-10-15 | Alza Corporation | Delivery system for beneficial agent over a broad range of rates |
US5059423A (en) * | 1988-12-13 | 1991-10-22 | Alza Corporation | Delivery system comprising biocompatible beneficial agent formulation |
US5019400A (en) | 1989-05-01 | 1991-05-28 | Enzytech, Inc. | Very low temperature casting of controlled release microspheres |
US5487897A (en) * | 1989-07-24 | 1996-01-30 | Atrix Laboratories, Inc. | Biodegradable implant precursor |
US5077049A (en) * | 1989-07-24 | 1991-12-31 | Vipont Pharmaceutical, Inc. | Biodegradable system for regenerating the periodontium |
US5112614A (en) * | 1989-09-14 | 1992-05-12 | Alza Corporation | Implantable delivery dispenser |
US5091188A (en) | 1990-04-26 | 1992-02-25 | Haynes Duncan H | Phospholipid-coated microcrystals: injectable formulations of water-insoluble drugs |
US5733566A (en) * | 1990-05-15 | 1998-03-31 | Alkermes Controlled Therapeutics Inc. Ii | Controlled release of antiparasitic agents in animals |
EP0489743A1 (en) | 1990-07-03 | 1992-06-17 | Vipont Pharmaceutical, Inc. | Intragingival delivery systems for treatment of periodontal disease |
US5234693A (en) * | 1990-07-11 | 1993-08-10 | Alza Corporation | Delivery device with a protective sleeve |
US5234692A (en) * | 1990-07-11 | 1993-08-10 | Alza Corporation | Delivery device with a protective sleeve |
US5151093A (en) * | 1990-10-29 | 1992-09-29 | Alza Corporation | Osmotically driven syringe with programmable agent delivery |
US5620700A (en) | 1990-10-30 | 1997-04-15 | Alza Corporation | Injectable drug delivery system and method |
GB9027422D0 (en) * | 1990-12-18 | 1991-02-06 | Scras | Osmotically driven infusion device |
US5292782A (en) * | 1991-02-20 | 1994-03-08 | Novamont S.P.A. | Biodegradable polymeric compositions based on starch and thermoplastic polymers |
SE9100610D0 (en) * | 1991-03-04 | 1991-03-04 | Procordia Ortech Ab | BIORESORBABLE MATERIAL FOR MEDICAL USE |
US5137727A (en) * | 1991-06-12 | 1992-08-11 | Alza Corporation | Delivery device providing beneficial agent stability |
US5288214A (en) * | 1991-09-30 | 1994-02-22 | Toshio Fukuda | Micropump |
AU2605592A (en) * | 1991-10-15 | 1993-04-22 | Atrix Laboratories, Inc. | Polymeric compositions useful as controlled release implants |
KR970007322B1 (en) * | 1991-12-19 | 1997-05-07 | 미쓰이도오아쓰 가가쿠 가부시키가이샤 | Polyhydroxy carboxylic acid and production thereof |
US5209746A (en) * | 1992-02-18 | 1993-05-11 | Alza Corporation | Osmotically driven delivery devices with pulsatile effect |
US5308348A (en) * | 1992-02-18 | 1994-05-03 | Alza Corporation | Delivery devices with pulsatile effect |
US5456679A (en) * | 1992-02-18 | 1995-10-10 | Alza Corporation | Delivery devices with pulsatile effect |
US5656297A (en) | 1992-03-12 | 1997-08-12 | Alkermes Controlled Therapeutics, Incorporated | Modulated release from biocompatible polymers |
EP0560014A1 (en) | 1992-03-12 | 1993-09-15 | Atrix Laboratories, Inc. | Biodegradable film dressing and method for its formation |
EP0633907A1 (en) | 1992-03-30 | 1995-01-18 | Alza Corporation | Additives for bioerodible polymers to regulate degradation |
GB9211268D0 (en) * | 1992-05-28 | 1992-07-15 | Ici Plc | Salts of basic peptides with carboxyterminated polyesters |
US5711968A (en) * | 1994-07-25 | 1998-01-27 | Alkermes Controlled Therapeutics, Inc. | Composition and method for the controlled release of metal cation-stabilized interferon |
US5716644A (en) | 1992-06-11 | 1998-02-10 | Alkermes, Inc. | Composition for sustained release of non-aggregated erythropoietin |
US5674534A (en) | 1992-06-11 | 1997-10-07 | Alkermes, Inc. | Composition for sustained release of non-aggregated erythropoietin |
EP0674506B1 (en) * | 1992-12-02 | 2000-08-23 | Alkermes Controlled Therapeutics, Inc. | Controlled release growth hormone containing microspheres |
US5447725A (en) * | 1993-06-11 | 1995-09-05 | The Procter & Gamble Company | Methods for aiding periodontal tissue regeneration |
US5681873A (en) | 1993-10-14 | 1997-10-28 | Atrix Laboratories, Inc. | Biodegradable polymeric composition |
US5650173A (en) | 1993-11-19 | 1997-07-22 | Alkermes Controlled Therapeutics Inc. Ii | Preparation of biodegradable microparticles containing a biologically active agent |
JPH07188059A (en) * | 1993-12-28 | 1995-07-25 | Rohto Pharmaceut Co Ltd | Therapeutic agent for periodontosis |
US5556905A (en) * | 1994-03-30 | 1996-09-17 | Reilly Industries, Inc. | Physically-modified degradable thermoplastic compositions |
DE69530919T2 (en) | 1994-04-08 | 2004-05-13 | Atrix Laboratories, Inc., Fort Collins | ASSOCIATED POLYMER SYSTEM FOR USE WITH A MEDICAL DEVICE |
FR2718642B1 (en) * | 1994-04-15 | 1996-07-12 | Pf Medicament | Biodegradable controlled release microspheres and their preparation process. |
US5626862A (en) * | 1994-08-02 | 1997-05-06 | Massachusetts Institute Of Technology | Controlled local delivery of chemotherapeutic agents for treating solid tumors |
SE503644C2 (en) * | 1994-10-14 | 1996-07-22 | Eka Chemicals Ab | Ways to determine the content of organic material in effluents from pulp and paper mills |
WO1996021427A1 (en) | 1995-01-09 | 1996-07-18 | Atrix Laboratories, Inc. | Liquid polymer delivery system |
DE69637733D1 (en) * | 1995-02-13 | 2008-12-11 | Intertrust Tech Corp | SYSTEMS AND METHOD FOR SAFE TRANSMISSION |
US5736152A (en) | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
US5980945A (en) * | 1996-01-16 | 1999-11-09 | Societe De Conseils De Recherches Et D'applications Scientifique S.A. | Sustained release drug formulations |
WO1998007412A1 (en) | 1996-08-21 | 1998-02-26 | Alkermes Controlled Therapeutics, Inc. | Controlled release microparticles with a hydrophobic material |
US6978370B1 (en) * | 1996-09-03 | 2005-12-20 | Cryptography Research, Inc. | Method and system for copy-prevention of digital copyright works |
ES2158611T3 (en) * | 1996-12-20 | 2001-09-01 | Alza Corp | COMPOSITION IN INJECTABLE GEL WITH RETARD EFFECT AND PROCEDURE FOR THE PREPARATION OF SUCH COMPOSITION. |
US7233948B1 (en) * | 1998-03-16 | 2007-06-19 | Intertrust Technologies Corp. | Methods and apparatus for persistent control and protection of content |
US6697944B1 (en) * | 1999-10-01 | 2004-02-24 | Microsoft Corporation | Digital content distribution, transmission and protection system and method, and portable device for use therewith |
US7213005B2 (en) * | 1999-12-09 | 2007-05-01 | International Business Machines Corporation | Digital content distribution using web broadcasting services |
US6366907B1 (en) * | 1999-12-15 | 2002-04-02 | Napster, Inc. | Real-time search engine |
IL135555A0 (en) * | 2000-04-09 | 2001-05-20 | Vidius Inc | Preventing unauthorized access to data sent via computer networks |
US6947909B1 (en) * | 2000-05-12 | 2005-09-20 | Hoke Jr Clare L | Distribution, recognition and accountability system for intellectual and copy written properties in digital media's |
-
1997
- 1997-12-18 ES ES97952507T patent/ES2158611T3/en not_active Expired - Lifetime
- 1997-12-18 DK DK97952575T patent/DK0959873T3/en active
- 1997-12-18 WO PCT/US1997/023341 patent/WO1998027962A2/en active IP Right Grant
- 1997-12-18 CA CA2275525A patent/CA2275525C/en not_active Expired - Fee Related
- 1997-12-18 NZ NZ335851A patent/NZ335851A/en not_active IP Right Cessation
- 1997-12-18 EP EP97952507A patent/EP0949905B1/en not_active Expired - Lifetime
- 1997-12-18 DE DE69705746T patent/DE69705746T2/en not_active Expired - Lifetime
- 1997-12-18 DK DK97952507T patent/DK0949905T3/en active
- 1997-12-18 CN CNB971807957A patent/CN1146402C/en not_active Expired - Fee Related
- 1997-12-18 JP JP52891698A patent/JP2002512597A/en not_active Withdrawn
- 1997-12-18 AT AT97952507T patent/ATE203157T1/en active
- 1997-12-18 AU AU56097/98A patent/AU5609798A/en not_active Abandoned
- 1997-12-18 EP EP97952575A patent/EP0959873B1/en not_active Expired - Lifetime
- 1997-12-18 AU AU56154/98A patent/AU739469B2/en not_active Ceased
- 1997-12-18 KR KR1019997005514A patent/KR100616793B1/en not_active IP Right Cessation
- 1997-12-18 PT PT97952507T patent/PT949905E/en unknown
- 1997-12-18 US US08/993,208 patent/US6130200A/en not_active Expired - Lifetime
- 1997-12-18 US US08/993,031 patent/US6331311B1/en not_active Expired - Lifetime
- 1997-12-18 WO PCT/US1997/023659 patent/WO1998027963A2/en active IP Right Grant
- 1997-12-18 AT AT97952575T patent/ATE318580T1/en active
- 1997-12-18 PT PT97952575T patent/PT959873E/en unknown
- 1997-12-18 ES ES97952575T patent/ES2256898T3/en not_active Expired - Lifetime
- 1997-12-18 JP JP52902098A patent/JP4642946B2/en not_active Expired - Fee Related
- 1997-12-18 IL IL13053297A patent/IL130532A0/en unknown
- 1997-12-18 DE DE69735384T patent/DE69735384T2/en not_active Expired - Lifetime
- 1997-12-18 CA CA002275587A patent/CA2275587C/en not_active Expired - Fee Related
- 1997-12-18 CA CA2591581A patent/CA2591581C/en not_active Expired - Fee Related
-
1999
- 1999-11-12 HK HK99105227A patent/HK1020009A1/en not_active IP Right Cessation
-
2000
- 2000-03-21 US US09/532,337 patent/US6673767B1/en not_active Expired - Fee Related
- 2000-06-01 HK HK00103307A patent/HK1023950A1/en not_active IP Right Cessation
- 2000-07-13 US US09/615,568 patent/US6468961B1/en not_active Expired - Fee Related
-
2001
- 2001-09-12 GR GR20010401458T patent/GR3036599T3/en unknown
- 2001-11-25 US US09/947,421 patent/US20020034532A1/en not_active Abandoned
-
2002
- 2002-08-19 US US10/224,444 patent/US20060013879A9/en not_active Abandoned
-
2010
- 2010-01-29 JP JP2010018875A patent/JP2010095544A/en active Pending
- 2010-01-29 JP JP2010018276A patent/JP2010120952A/en active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990003768A1 (en) * | 1988-10-03 | 1990-04-19 | Southern Research Institute | Biodegradable in-situ forming implants |
WO1991005544A1 (en) * | 1989-10-23 | 1991-05-02 | Medinvent | Drug delivery system, method for preparing the same, and use thereof |
EP0539751A1 (en) * | 1991-10-28 | 1993-05-05 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
US5318780A (en) * | 1991-10-30 | 1994-06-07 | Mediventures Inc. | Medical uses of in situ formed gels |
US5242910A (en) * | 1992-10-13 | 1993-09-07 | The Procter & Gamble Company | Sustained release compositions for treating periodontal disease |
EP0640647A2 (en) * | 1993-08-26 | 1995-03-01 | Collagen Corporation | Ionically crosslinked glycosaminoglycan gels for soft tissue augmentation and drug delivery |
WO1995027481A1 (en) * | 1994-04-08 | 1995-10-19 | Atrix Laboratories, Inc. | Liquid delivery compositions |
WO1997015287A1 (en) * | 1995-10-25 | 1997-05-01 | Macromed, Inc. | Thermosensitive biodegradable polymers based on poly(ether-ester) block copolymers |
Cited By (110)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6413536B1 (en) | 1995-06-07 | 2002-07-02 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system and medical or surgical device |
US7833543B2 (en) | 1995-06-07 | 2010-11-16 | Durect Corporation | High viscosity liquid controlled delivery system and medical or surgical device |
US7053209B1 (en) | 1995-06-07 | 2006-05-30 | Durect Corporation | High viscosity liquid controlled delivery system and medical or surgical device |
US6572894B2 (en) | 1995-11-24 | 2003-06-03 | Actipac Biosystems Gmbh | Process for the production of morphologically uniform microcapsules and microcapsules that are produced according to this process |
EP0950403A3 (en) * | 1998-04-14 | 2000-04-12 | Atrix Laboratories, Inc. | Emulsions for in-situ delivery systems |
EP0950403A2 (en) * | 1998-04-14 | 1999-10-20 | Atrix Laboratories, Inc. | Emulsions for in-situ delivery systems |
EP1666026B2 (en) † | 1999-02-08 | 2015-02-25 | Intarcia Therapeutics, Inc | Non-aqueous single phase biocompatible viscous vehicles and methods for preparing the same |
AU775904B2 (en) * | 1999-02-08 | 2004-08-19 | Intarcia Therapeutics, Inc. | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
US7258869B1 (en) | 1999-02-08 | 2007-08-21 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle |
WO2000045790A2 (en) * | 1999-02-08 | 2000-08-10 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
EP1666026A2 (en) | 1999-02-08 | 2006-06-07 | Alza Corporation | Non-aqueous single phase biocompatible viscous vehicles and methods for preparing the same |
US8048438B2 (en) | 1999-02-08 | 2011-11-01 | Intarcia Therapeutics, Inc. | Stable non- aqueous single phase viscous vehicles and formulations utilizing such vehicles |
EP1666026A3 (en) * | 1999-02-08 | 2007-08-08 | Alza Corporation | Non-aqueous single phase biocompatible viscous vehicles and methods for preparing the same |
WO2000045790A3 (en) * | 1999-02-08 | 2000-12-07 | Alza Corp | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
WO2000048588A1 (en) * | 1999-02-16 | 2000-08-24 | Farmaceutici Formenti S.P.A. | Pharmaceutical topical compositions containing a non-steroidal antiinflammatory drug |
WO2001003666A2 (en) * | 1999-07-12 | 2001-01-18 | Scimed Life Systems, Inc. | Liquid based vaso-occlusive compositions |
WO2001003666A3 (en) * | 1999-07-12 | 2001-07-26 | Scimed Life Systems Inc | Liquid based vaso-occlusive compositions |
JP2003514006A (en) * | 1999-11-16 | 2003-04-15 | アトリックス ラボラトリーズ,インコーポレイティド | Biodegradable polymer composition |
US6992065B2 (en) | 2000-04-19 | 2006-01-31 | Genentech, Inc. | Sustained release formulations |
EP1299048A4 (en) * | 2000-06-28 | 2005-09-28 | Atul J Shukla | Biodegradable vehicles and delivery systems of biologically active substances |
EP1299048A1 (en) * | 2000-06-28 | 2003-04-09 | Atul J. Shukla | Biodegradable vehicles and delivery systems of biologically active substances |
WO2002030393A3 (en) * | 2000-09-21 | 2002-06-27 | Atrix Lab Inc | Polymeric delivery formulations of leuprolide with improved efficacy |
AU2010201645B2 (en) * | 2000-09-21 | 2012-07-12 | Tolmar Therapeutics, Inc. | Polymeric delivery formulations of leuprolide with improved efficacy |
WO2002030393A2 (en) * | 2000-09-21 | 2002-04-18 | Atrix Laboratories, Inc. | Polymeric delivery formulations of leuprolide with improved efficacy |
EP2158900A1 (en) * | 2000-09-21 | 2010-03-03 | QLT USA, Inc. | Polymeric delivery formulations of leuprolide with improved efficacy |
EP1586309A1 (en) * | 2000-09-21 | 2005-10-19 | Atrix Laboratories, Inc. | Polymeric delivery formulations of leuprolide with improved efficacy |
AU2001292931B2 (en) * | 2000-09-21 | 2006-08-24 | Tolmar Therapeutics, Inc. | Polymeric delivery formulations of leuprolide with improved efficacy |
KR100831113B1 (en) * | 2000-09-21 | 2008-05-20 | 큐엘티 유에스에이, 인코포레이티드 | Polymeric delivery formulations of leuprolide with improved efficacy |
CZ303134B6 (en) * | 2000-09-21 | 2012-04-25 | Atrix Laboratories, Inc. | Leuprolide polymeric delivery formulation with improved efficacy |
US7252842B2 (en) | 2000-12-21 | 2007-08-07 | Alrise Biosystems Gmbh | Induced phase transition method for the production of microparticles containing hydrophilic active agents |
US6899898B2 (en) | 2000-12-21 | 2005-05-31 | Nektar Therapeutics | Induced phase transition method for the production of microparticles containing hydrophobic active agents |
US8501216B2 (en) | 2001-02-23 | 2013-08-06 | Genentech, Inc. | Bioerodible polymers for injection |
US7824700B2 (en) | 2001-02-23 | 2010-11-02 | Genentech, Inc. | Erodible polymers for injection |
US8067020B2 (en) | 2001-06-21 | 2011-11-29 | Genetech, Inc. | Sustained release formulation |
WO2003024420A1 (en) * | 2001-09-14 | 2003-03-27 | Novartis Ag | Ophthalmic depot formulations for periocular or subconjunctival administration |
WO2003045351A1 (en) * | 2001-11-30 | 2003-06-05 | Pfizer Inc. | Controlled release polymeric compositions of bone growth promoting compounds |
EA011350B1 (en) * | 2001-11-30 | 2009-02-27 | Пфайзер Инк. | Controlled release polymeric compositions of bone growth promoting compounds |
US8017144B2 (en) | 2001-11-30 | 2011-09-13 | Pfizer Inc. | Controlled release polymeric compositions of bone growth promoting compounds |
US11179326B2 (en) | 2002-06-25 | 2021-11-23 | Durect Corporation | Short duration depot formulations |
US10201496B2 (en) | 2002-06-25 | 2019-02-12 | Durect Corporation | Short duration depot formulations |
EP2311431A1 (en) | 2002-06-25 | 2011-04-20 | ALZA Corporation | Short duration depot formulations |
EP2316421A1 (en) | 2002-06-25 | 2011-05-04 | ALZA Corporation | Bupivacaine-containing injectable depot composition |
US10471001B2 (en) | 2002-06-25 | 2019-11-12 | Durect Corporation | Short duration depot formulations |
US10471002B2 (en) | 2002-06-25 | 2019-11-12 | Durect Corporation | Short duration depot formulations |
EP2030611A1 (en) | 2002-07-31 | 2009-03-04 | Alza Corporation | Injectable multimodal polymer depot compositions and uses thereof |
US7368126B2 (en) | 2002-11-06 | 2008-05-06 | Guohua Chen | Controlled release depot formulations |
WO2004043432A3 (en) * | 2002-11-06 | 2004-07-08 | Alza Corp | Controlled release depot formulations |
WO2004043432A2 (en) * | 2002-11-06 | 2004-05-27 | Alza Corporation | Controlled release depot formulations |
US9918982B2 (en) | 2002-12-13 | 2018-03-20 | Durect Corporation | Oral drug delivery system |
US6878374B2 (en) | 2003-02-25 | 2005-04-12 | Nitto Denko Corporation | Biodegradable polyacetals |
US8496943B2 (en) | 2003-03-31 | 2013-07-30 | Durect Corporation | Non-aqueous single phase vehicles and formulations utilizing such vehicles |
AU2010212478B2 (en) * | 2003-03-31 | 2011-06-23 | Alza Corporation | Non-aqueous single phase vehicles and formulations utilizing such vehicles |
WO2004089335A2 (en) * | 2003-03-31 | 2004-10-21 | Alza Corporation | Non-aqueous single phase vehicles and formulations utilizing such vehicles |
US7207982B2 (en) | 2003-03-31 | 2007-04-24 | Alza Corporation | Osmotic pump with means for dissipating internal pressure |
WO2004089335A3 (en) * | 2003-03-31 | 2005-02-10 | Alza Corp | Non-aqueous single phase vehicles and formulations utilizing such vehicles |
WO2004108111A1 (en) * | 2003-05-30 | 2004-12-16 | Alza Corporation | Implantable elastomeric depot compositions, uses thereof and method of manufacturing |
WO2005009408A3 (en) * | 2003-06-25 | 2006-01-19 | Alza Corp | Sustained release dosage forms of anesthetics for pain management |
EP2067468A1 (en) * | 2003-06-25 | 2009-06-10 | ALZA Corporation | Sustained release dosage forms of anesthetics for pain management |
WO2005009408A2 (en) * | 2003-06-25 | 2005-02-03 | Alza Corporation | Sustained release dosage forms of anesthetics for pain management |
US10300114B2 (en) | 2003-06-26 | 2019-05-28 | Eyepoint Pharmaceuticals Us, Inc. | Bioerodible sustained release drug delivery systems |
US9566336B2 (en) | 2003-06-26 | 2017-02-14 | Psivida Us, Inc. | In situ gelling drug delivery system |
US7048925B2 (en) | 2003-08-28 | 2006-05-23 | Nitto Denko Corporation | Acid-sensitive polyacetals and methods |
US8383091B2 (en) | 2003-09-29 | 2013-02-26 | Nitto Denko Corporation | Biodegradable polyacetals for in vivo polynucleotide delivery |
US7794696B2 (en) | 2003-09-29 | 2010-09-14 | Nitto Denko Corporation | Biodegradable polyacetals for in vivo polynucleotide delivery |
EP1691715A2 (en) * | 2003-11-14 | 2006-08-23 | ALZA Corporation | Surfactant-based gel as an injectable, sustained drug delivery vehicle |
EP1691715A4 (en) * | 2003-11-14 | 2007-09-26 | Alza Corp | Surfactant-based gel as an injectable, sustained drug delivery vehicle |
US9724293B2 (en) | 2003-11-17 | 2017-08-08 | Intarcia Therapeutics, Inc. | Methods of manufacturing viscous liquid pharmaceutical formulations |
US9303067B2 (en) | 2004-12-21 | 2016-04-05 | Novartis Ag | Sustained release formulation comprising a somatostatin analogue |
US10363287B2 (en) | 2005-02-03 | 2019-07-30 | Intarcia Therapeutics, Inc. | Method of manufacturing an osmotic delivery device |
US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
US8206745B2 (en) | 2005-02-03 | 2012-06-26 | Intarcia Therapeutics, Inc. | Solvent/polymer solutions as suspension vehicles |
US9682127B2 (en) | 2005-02-03 | 2017-06-20 | Intarcia Therapeutics, Inc. | Osmotic delivery device comprising an insulinotropic peptide and uses thereof |
US7655254B2 (en) | 2005-02-03 | 2010-02-02 | Intarcia Therapeutics, Inc. | Implantable device for continuous delivery of interferon |
US8114437B2 (en) | 2005-02-03 | 2012-02-14 | Intarcia Therapeutics, Inc. | Solvent/polymer solutions as suspension vehicles |
US8216558B2 (en) | 2005-03-16 | 2012-07-10 | Nitto Denko Corporation | Polymer coating of cells |
US11083796B2 (en) | 2005-07-26 | 2021-08-10 | Durect Corporation | Peroxide removal from drug delivery vehicle |
WO2007027289A1 (en) * | 2005-08-30 | 2007-03-08 | Medtronic, Inc. | Shear thinning polymer cell delivery compositions |
US10527170B2 (en) | 2006-08-09 | 2020-01-07 | Intarcia Therapeutics, Inc. | Osmotic delivery systems and piston assemblies for use therein |
US10206883B2 (en) | 2007-12-06 | 2019-02-19 | Durect Corporation | Oral pharamaceutical dosage forms |
US9655861B2 (en) | 2007-12-06 | 2017-05-23 | Durect Corporation | Oral pharmaceutical dosage forms |
US10441528B2 (en) | 2008-02-13 | 2019-10-15 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
US10328068B2 (en) | 2008-11-03 | 2019-06-25 | Durect Corporation | Oral pharmaceutical dosage forms |
US9884056B2 (en) | 2008-11-03 | 2018-02-06 | Durect Corporation | Oral pharmaceutical dosage forms |
US9616055B2 (en) | 2008-11-03 | 2017-04-11 | Durect Corporation | Oral pharmaceutical dosage forms |
US8827884B2 (en) | 2009-08-06 | 2014-09-09 | Koninklijke Philips N.V. | Oncology therapies employing radioactive seeds |
US10231923B2 (en) | 2009-09-28 | 2019-03-19 | Intarcia Therapeutics, Inc. | Rapid establishment and/or termination of substantial steady-state drug delivery |
US10869830B2 (en) | 2009-09-28 | 2020-12-22 | Intarcia Therapeutics, Inc. | Rapid establishment and/or termination of substantial steady-state drug delivery |
US9604073B2 (en) * | 2010-03-17 | 2017-03-28 | The Board Of Trustees Of The Leland Stanford Junior University | Light-sensitive ion-passing molecules |
US10159714B2 (en) | 2011-02-16 | 2018-12-25 | Intarcia Therapeutics, Inc. | Compositions, devices and methods of use thereof for the treatment of cancers |
US9907851B2 (en) | 2013-03-15 | 2018-03-06 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US10300142B2 (en) | 2013-03-15 | 2019-05-28 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US9855333B2 (en) | 2013-03-15 | 2018-01-02 | Durect Corporation | Compositions with a rheological modifier to reduce dissolution variability |
US11529420B2 (en) | 2013-12-09 | 2022-12-20 | Durect Corporation | Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same |
US10758623B2 (en) | 2013-12-09 | 2020-09-01 | Durect Corporation | Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same |
US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
US10583080B2 (en) | 2014-09-30 | 2020-03-10 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
US10925639B2 (en) | 2015-06-03 | 2021-02-23 | Intarcia Therapeutics, Inc. | Implant placement and removal systems |
US10501517B2 (en) | 2016-05-16 | 2019-12-10 | Intarcia Therapeutics, Inc. | Glucagon-receptor selective polypeptides and methods of use thereof |
US11214607B2 (en) | 2016-05-16 | 2022-01-04 | Intarcia Therapeutics Inc. | Glucagon-receptor selective polypeptides and methods of use thereof |
US11840559B2 (en) | 2016-05-16 | 2023-12-12 | I2O Therapeutics, Inc. | Glucagon-receptor selective polypeptides and methods of use thereof |
USD912249S1 (en) | 2016-06-02 | 2021-03-02 | Intarcia Therapeutics, Inc. | Implant removal tool |
USD835783S1 (en) | 2016-06-02 | 2018-12-11 | Intarcia Therapeutics, Inc. | Implant placement guide |
USD962433S1 (en) | 2016-06-02 | 2022-08-30 | Intarcia Therapeutics, Inc. | Implant placement guide |
USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
US10835580B2 (en) | 2017-01-03 | 2020-11-17 | Intarcia Therapeutics, Inc. | Methods comprising continuous administration of a GLP-1 receptor agonist and co-administration of a drug |
US11654183B2 (en) | 2017-01-03 | 2023-05-23 | Intarcia Therapeutics, Inc. | Methods comprising continuous administration of exenatide and co-administration of a drug |
WO2021081293A1 (en) * | 2019-10-25 | 2021-04-29 | Warsaw Orthopedic, Inc | Compositions for treatment of annular spinal disc injury |
US11400019B2 (en) | 2020-01-13 | 2022-08-02 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
US11771624B2 (en) | 2020-01-13 | 2023-10-03 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0949905B1 (en) | Injectable depot gel composition and method of preparing the composition | |
CA2466642C (en) | Injectable depot composition | |
US20030211974A1 (en) | Gel composition and methods | |
US20030170289A1 (en) | Injectable depot compositions and uses thereof | |
WO2004043432A2 (en) | Controlled release depot formulations | |
AU2002346406A1 (en) | Injectable depot composition | |
AU2002359406A1 (en) | Injectable depot compositions and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
AK | Designated states |
Kind code of ref document: A3 Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): GH GM KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref document number: 2275587 Country of ref document: CA Ref country code: CA Ref document number: 2275587 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1997952507 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1997952507 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWG | Wipo information: grant in national office |
Ref document number: 1997952507 Country of ref document: EP |