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Publication numberUS3797492 A
Publication typeGrant
Publication dateMar 19, 1974
Filing dateDec 27, 1972
Priority dateDec 27, 1972
Publication numberUS 3797492 A, US 3797492A, US-A-3797492, US3797492 A, US3797492A
InventorsPlace V
Original AssigneeAlza Corp
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Device for dispensing product with directional guidance member
US 3797492 A
Abstract
A drug product dispensing device is comprised of a product compartment having a metering means for dispensing its product in a body cavity, and a propellant compartment communicating with the product compartment for producing a propellant. In one embodiment, a self actuated valve is positioned between the product and the propellant compartment for directing the flow of propellant into the product compartment. In another embodiment, a slidable piston is positioned in the product compartment for receiving the flow of propellant moving into the product compartment. A collapsed bag is joined to the propellant compartment with the bag capable of being inflated by a propellant from the propellant compartment to maintain the device in a product receptive area. The device is optionally housed in a bioerodible container and released therefrom prior to its dispensing a product. In both embodiments of the device, product is moved through the metering means by propellant either moving through the valves or against the piston to urge product through the means.
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Description  (OCR text may contain errors)

United States Patent Place Mar. 19, 1974 [75] Inventor: Virgil A. Place, Palo Alto, Calif.

[73] Assignee: Alza Corporation, Palo Alto, Calif.

[22] Filed: Dec. 27, 1972 21 Appl. No.: 318,900

[52] U.S. Cl. 128/260, 128/214 F, 128/1 R [51] Int. Cl. A61m 5/00 [58] Field of Search 128/2 R, 260, 214 F, 1 R, 128/213; ZZZ/386.5

[56] References Cited UNITED STATES PATENTS 1,957,564 5/1934 West 128/272 2,485,235 12/1969 Felson 128/2 3,604,417 9/1971 Stolzenberg 128/213 3,692,027 9/1972 Ellinwood, Jr.... 128/260 3,731,681 5/1973 Blackshear 128/214 F 3,701,351 10/1972 Harvey 128/260 Primary Examiner-Aldrich F. Medbery [57] ABSTRACT A drug product dispensing device is comprised of a product compartment having a metering means for dispensing its product in a body cavity, and a propellant compartment communicating with the product compartment for producing a propellant. In one embodiment, a self actuated valve is positioned between the product and the propellant compartment for directing the flow of propellant into the product compartment. In another embodiment, a slidable piston is positioned in the product compartment for receiving the flow of propellant moving into the product compartment. A collapsed bag is joined to the propellant compartment with the bag capable of being inflated by a propellant from the propellant compartment to maintain the device in a product receptive area, The device is optionally housed in a bioerodible container and released therefrom prior to its dispensing a product. In both embodiments of the device, product is moved through the metering means by propellant either moving through the valves or against the piston to urge product through the means.

13 Claims, 6 Drawing Figures PATENTEDIAR l 9 m4 SHtEI 2 BF 2 FIG.4

DEVICE FOR DISPENSING PRODUCT WITI-I DIRECTIONAL GUIDANCE MEMBER BACKGROUND OF THE INVENTION This invention relates to a novel and useful drug type product delivery device for delivering a product at a controlled rate for a prolonged period of time to produce a local or systemic physiological or pharmacological effect. The device is comprised of a wall surrounding an internal space with the space consisting of a product compartment for containing a product and a propellant compartment for storing a propellant or propellant producing agent. The product compartment has a discharge flow control means that communicates with the compartment for releasing the product to the environment. In one embodiment of the invention, a self actuated valve is positioned between the product and propellant compartments for guiding propellant into the product compartment to move the product through the flow control means. In another embodiment of the invention the product and propellant compartment are separated by a slidable piston that moves in response to propellant generating in the propellant compartment to move the product through the flow control means. A collapsed bag is fixed to the propellant compartment with the bag expandable to an inflated state by propellant flowing therein prior to the delivery of product from the device, for keeping the device in a product receptive area during delivery of the product. The device leaves the product receptive area after delivery of the product by the bag returning to a collapsed position by release of its propellant or by biodegradation of a part of the whole device. The device is optionally initially internally housed in a container and released therefrom in the environment of use prior to its delivery of the product.

A long felt need exists, especially in the medical and the veterinary arts for a product dispensing device that can effectively administer a product, for example, a drug, vitamin, nutrient, antibiotic or the like to a drug receptor environment, such as the stomach, reliably at a controlled and continuous rate over a prolonged period of time In many instances, such a rate of product release from a product dispensing device should have a preferred zero order time dependence, that is, the rate of drug release is independent of time. In some instances it is also desirable to have a delivery system with a programmed delivery rate.

Different approaches have been tried by the'pharmaceutical and manufacturing arts to obtain such a product dispensing device that can achieve these goals, but the results obtained have not led to their acceptance by the medical and veterinary arts for the management of health and disease. One approach, which has received attention comprises administering a product to the environment of use, such as a drug to the gastrointestinal tract, by first mixing the drug with a pharmaceutical carrier material to give a product that is gradually broken down by the body fluids such as gastrointestinal fluids with the drug released as the carrier disintegrates. Numerous drug carriers have been used for this purpose including waves, oils, fats, soluble polymers and the like. While some of these products have provided a slow release of drug, the desired, constant release rate for a prolonged period has not been achieved. One reason for this is that as the carrier disintegrates the surface area of the product decreases, concomitantly exposing increasingly smaller quantities of the carrier and the drug to the surrounding fluids that inherently results in a decline in the release rate over time. Another approach for dispensing a drug to the environment of use, particularly to the gastrointestinal tract, has been to enclose the drug within a single, dispensing capsule having a permeable wall through which the drug canpass by diffusion. An approach of this kind is set forth in United States Pat. No. 3,279,996. These dispensing devices too have inherent difficulties. For example, one difficulty associated with the prior art is that different devices having different drug release rates cannot readily be made bcause the only variable parameter for the device is the thickness of the material used to make the device. Additionally, the structure of these prior art devices generally is based merely on the high permeability of a single material as the diffusion control for some important drug molecules without a consideration of release rate controlling properties over a large number of hours which can defeat the primary object of an acceptable drug dispensing device.

Another method widely used to obtain a necessary and beneficial product or drug level in a drug receptor over a number of hours comprises administering a number of pills or tablets at regular time intervals to achieve a dose frequency response relationship. However, this method has certain inherent limitations that tend to defeat its purpose. For example, the pills often are rapidly cleared, for example, from the gastrointestinal tract before they are fully utilized, or an excessive amount of fluid present in the tract can unfavorably affect the drug reaching the desired drug level. Also, the administration of a number of pills at set times requires attention and frequently a particular administration is inadvertently overlooked which diminishes the results of this method. Thus, a graphic illustration of the drugs concentration in the blood during a dosage schedule for this method has the appearance of a series of peaks and valleys; and often these valleys may fall below the drug concentration needed to achieve the desired beneficial effects.

One other approach used by the art to obtain a controlled rate of product release over a prolonged period is through the use of coated slow release bead technique. In this technique, the dose of drug is divided into a group of pellets about 1 to 2 milli-meters in diameter, and each group coated with a material resistant to gastric and/or intestinal fluids. To time control the release, each group is coated with an increased number of coats, that is, the first group one coat, the second group two coats and so forth. However, this technique, as with the dose frequency response relationship technique described above, has those certain, common inherent limitations that tend to diminish its purpose. Therefore, these types of coated slow release beads are not suitable for releasing drug at a controlled rate for a prolonged period of time.

SUMMARY OF THE INVENTION Accordingly, it is an immediate object of this invention to provide a drug type product dispensing device for the delivery of locally active or systemically active products that produce a physiologic or pharmacologic effect, which device essentially overcomes the aforesaid disadvantages associated with the prior art dispensing devices.

Still another important object of the invention is to provide a bioerodible product dispensing device for releasing a product at a controlled and continuous rate for a prolonged period of time.

Still yet another object of this invention is to provide a reliable and easily used product delivery device for administering a product such as a drug to a drug receptor area and remain in the area during the administration of drug from the device.

Yet still another object of the present invention is to make available to the art a product dispensing device for continuously administering controlled quantities of drug to the environment of use, such as the stomach and the gastrointestinal tract to produce a beneficial effect and then pass from the environment after a predetermined amount of drug is released in the environment.

A further object of this invention is to provide a device that provides a complete dosage regimen for administering a drug to a drug receptor site for a particular time period, the use of which requires intervention only for initiation of the regimen.

Still a further object of the invention is to provide a drug delivery device suitable for oral administration for continuously administering drug in the gastro-intestinal tract and remaining therein until the desired dosage regimen is essentially complete before the device is eliminated from the gastrointestinal tract either by passing through the tract or by bioeroding, then passing through the tract.

Yet still a further object of the invention is to provide an administerable drug delivery device that is selfcontained and self-powered and will remain in the environment of use, such as the uterus, vagina or the stomach for an extended time while administering drug from the device through a drug self actuated flow control outlet in response to energy produced in the drug delivery device.

In attaining the objects, features and advantages of this invention, a novel and useful product dispensing device is provided for the controlled and the continuous dispensing of a product in the environment of use by using a propellant as the driving force for dispensing the product from the device. The device is comprised of a product chamber and a propellant chamber separated by either a self actuated single directional valve or a piston. The product chamber is a reservoir for containing a drug, a vitamin, a nutrient or other beneficial product or useful agent, and it is suitably equipped with a discharge passage for conveying product at a metered rate from the chamber to the environment of use. The propellant chamber is positioned next to the product chamber and it contains a fluid with a vapor pressure in excess of one atmosphere at the temperature of use. Product is discharged from the device by the action of vapor pressures arising in the propellant chamber that pass through the valve into the product chamber, or against the piston, to exert a constant and positive pressure against the product to urge the product through the metering passage. A collapsed hollow balloon is suitably joined to the propellant chamber, and a passageway communicates between the chambers. The balloon is inflated by vapors from the propellant chamber that move into and fill the balloon for keeping the device in the environment of use during the period of product administration. At the end of this period, the balloon collapses as vapors leave the balloon to permit the devices passage from the environment. In another embodiment the devices length of stay in the environment can be controlled by fabricating the entire device of material that biodegrades after an extended period of time to let the device pass from the environment of use. The product dispensing device optionally is internally housed in a container and it is released therefrom prior to its product dispension operation in the environment of use.

Other objects, features and advantages of the invention will be apparent to those skilled in the art from the following detailed description of the invention, taken in conjunction with the drawings and the accompanying claims.

BREIF DESCRIPTION OF THE DRAWINGS In the drawings which are not drawn to scale, but rather are set forth to illustrate various embodiments of the invention, the drawings are as follows:

FIG. 1 is a plan side view of drug delivery device of the invention initially optionally housed in a container.

FIG. 2 is an enlarged, detailed perspective side view illustrating a drug delivery device of the invention housed in a container with a section of the container removed.

FIG. 3 is an enlarged, detailed isometric view illustrating another drug delivery device confined in a container with a section removed illustrating a directional member.

FIG. 4 is an enlarged, detailed view of another device of the invention showing a device having a piston member.

FIG. 5 is a view diagrammatically illustrating a drug delivery device descending through a body passage into an environment of use.

FIG. 6 is a side view diagrammatically illustrating a drug delivery device in use in the environment of use, such as in the stomach.

In the drawings and specification, like parts in related figures are identified by like numbers. The terms appearing earlier in the specification and in the description of the drawings, as well as embodiments thereof, are further described elsewhere in the disclosure.

DETAILED DESCRIPTION OF THE INVENTION Turning now to the drawings in detail, which are examples of various drug delivery devices of the invention, and which examples are not to be construed as limiting, one general example of a novel drug delivery device is indicated in FIG. 1 by numeral 10. Drug delivery device 10 is illustrated in side perspective view and it is comprised of a bioerodible container 12 housing a drug delivery device 14 affixed to a collapsed hollow balloon 16. In FIG. 1 drug delivery device 10 is depicted in miniature to exemplify one general operative embodiment of the invention suitable for passing through a body opening or positioning in a body drug receptor area. An enlarged detailed description of FIG. 1 is set forth in FIG. 2.

Referring to FIG. 2, a drug delivery device 10 is generally seen in a bioerodible container 12 with a section removed to illustrate the operative drug delivery device 14 housed in the container 12. Container 12 is advantageously formed of two parts each made of bioerodible materials and designed to telescope into each other for easily housing device 14 in container 12. Device 14 in another embodiment can optionally be housed in a container of single unit construction also made of a bioerodible material. Container 12 in one embodiment is made from gelatin or the like because it can move quickly and easily through body passages such as the alimentary canal and also because it can quickly disintegrate when it reaches a drug receptor area such as the stomach to free device 14. Containers made of other non-toxic bioerodible materials can also be used for releasing the device in animals, humans, avians and the like. Drug delivery device 14 is comprised of a wall 15 surrounding an internal space divided into a product chamber 11 and a propellant chamber 17. Propellant chamber 17 is suitably joined to a collapsed balloon 16 that communicates through a passageway 19 with propellant chamber 17. Product chamber 11 is separated from propellant chamber 17 by a valve 20 for directing the flow of a propellant from chamber 17 into product chamber 11 and also to prevent a product in chamber 11 from moving into propellant chamber 17.

Drug delivery device 14 as seen in FIG. 2 is made of materials that are essentially impermeable to fluids and gases in the environment of use such as water, gastric juice, carbon dioxide and the like. Device 14 is made by conventional manufacturing techniques, such as casting, lamination and interface sealing, stamping accompanied with adhesive or thermal joining of parts into a composite device and the like. Device 14 can be made of naturally occurring or synthetic materials of the kinds commerically available to the art. Device 14 can be made of rigid, semi-rigid or flexible materials and they can be non-biodegradable or biodegradable. In one embodiment a part of device 14 can be made of bioerodible material that bioerodes in the environment of use to facilitate removal from the environment. In another embodiment, all of device 14 including wall 15 can be made of bioerodible material that bioerodes in the environment of use, such as the stomach, to facilitate the passage of the device from the stomach through the gastrointestinal tract.

Collapsed balloon 16 in sealed relation with drug delivery device 14 is in one embodiment suitably joined to device 14 by sealing balloon 16 with an adhesive, such as an epoxy, a-cyanoacrylic, polyvinyl chloride adhesives or the like to device 14, or balloon 14 can be heat sealed or cast on device 14. in another embodi-,

ment it can be fitted over a communicating conduit 12a integrally formed on one end of device 14. Collapsable balloon 16 is made of naturally occurring or synthetic flexible, polymeric materials that lend themselves to changes in shape and size, that is, changes in volume from collapsed to inflated and returnable to collapsed position after a prolonged period of time. Balloon or member 16 can in one embodiment be made of amaterial that is biodegradable in the environment of use, or in another embodiment member 16 can be made of a material that is permeable to a gas at a slow rate, or member 16 can be equipped with an erosion plug, not shown in FIG. 2, that erodes after a predetermined time to release gas from an inflated balloon thereby deflating it to a collapsed state to let it pass from the environment of use, such as the stomach. In other embodiments, member 16 can have other designs and shapes such as flat bags, tubes, foldable bagsand the like, which can be used for the purpose of the invention.

Drug delivery device 14 consists of a product chamber 16 that contains a product 22 such as a drug or the like and a propellant chamber 17 that contains a means for producing a gas, such as a gas stored in liquified form at ambient temperatures but a gas at physiological temperature. The two chambers communicate through a valve 20 that is a conventional self actuated valve, or a one way flap valve or the like. Valve 20 is a unidirectional valve that suitably guides the flow of propellant into the product chamber, and it is suitably positioned between product chamber 16 and propellant chamber 17. Valve 20 is positioned by adhesively or thermally joining it to wall 15 or a wall 15a that separates the chambers prior to the closure of device 14. Valve 20 is made of commerically available plastics, metals, laminates of plastics and metals or the like. In FIG. 2, valve 20 is a one way flap valve, and it is sealed on the product side of the device. Valve 20 acts to tightly close and substantially prevent the backflow of gas that passed into product chamber 11 back into chamber 17. It also serves to prevent the movement of product 22 in product chamber 11 into propellant chamber 17; and, it further serves to guide the flow of gas from the propellant chamber 17 into the product chamber 11 where the gas functions as the pressure driving force for moving product 22 from chamber 11 through .a metering outlet 21 for releasing product 22 to the environment of use. Metering outlet 21 is initially closed with an erodible plug, not shown in FIG. 2, that quickly erodes after device 14 is freed from container 12 upon its entry into the environment of use, such as the stomach.

In operation, in one example of the invention that is not to be construed as limiting the scope of the invention, device 10 is orally administered through the esophagus into the stomach where drug delivery device 14 is freed from container 12. Next, collapsed balloon l6 inflates in the stomach to keep drug delivery device 14 therein during the period of drug administration. Drug administration is affected by the production of a gas in propellant chamber 17 that inflates collapsed balloon l6 and also moves through valve 20 into product chamber 11 to urge drug 22 through discharge outlet 21 at a controlled and constant rate into the external environment, the stomach. At the end of the drug administration period, inflated balloon 16 collapses by erosion of its plug, of the whole device biodegrades to permit passage of device 14 from the stomach.

In FIG. 3, another embodiment of the invention is illustrated comprised of an assembled drug delivery device 10 consisting of a swallowable bioerodible container 12 made of two telescopically associated nontoxic envelopes having an interior cavity housing a drug delivery device 14. Container 12 has a 'size and shape for swallowing and for passage by humans, farm animals such as cows and steers, household pets such as dogs and sport animals to their stomach by normal peristalsis. In the stomach container 12 is made from gelatin, gelatin cocoa butter mixtures. or the like, and it quickly and easily disintegrates to release drug delivery device 14 for discharging a medicament 22, a mixture of medicaments, or a beneficial agent such as a vitamin, nutrient or the like into the stomach.

Device 14 of FIG. 3 is a self actuated, self powered vapor pressure activated device and it is comprised of an outer wall 15 surrounding an internal space defining a product chamber 11 and a propellant chamber 17.

. Wall 15, optionally called a housing or shell, in this embodiment is made from a material essentially impermeable to fluids and gases, preferably biodegradable and digestable, and it has a deformable hollow member 16 fixed to one end of said shell 15. Deformable bladder member 16 is optionally integrally formed, cemented or sealed to shell at a passageway 24 that connects with propellant chamber 17. A one way valve allows gas to enter collapsed bag 16 and it also acts to essentially prevent the flow back of gas into propellant chamber 17. The inflated size of deformable member 16 is controlled by predetermined dimension that corresponds to the size of the environment of use, or of the host and also to limit its expansion to assure a flow of gas into product chamber 11. Deformable member 16,

as shown in FIG. 3, is a collapsed bag folded or having a plurality of staggered folds 18a and it is made from a flexible, elastic material to allow it to freely expand and then return to a collapsed state. Member 16 is manufactured with a bioerodible plug 23 that erodes to vent the gas or it is made ofa material permeable to gas to allow the gas to slowly diffuse therethrough over a period of time to deflate member 16 to let it pass from the environment of use, such as the stomach. Product chamber 11 is a means for storage of drug 22, that is, a drug reservoir, and it also functions as a chamber for communicating with propellant chamber 17 through valve 20 for receiving gas for moving drug 22 through a flow control means 21 to the exterior of the device. Flow control means 21 can be of different structures, such as a porous inert plate, sintered ceramics, a calibrated aperture, a capillary, a hollow stainless steel tube having an internal diameter corresponding to 15 gauge to gauge surgical needles, or the like for conveying a drug 22 through shell 15 to the exterior of the device. In another embodiment element 21 can be made of a material that is essentially impermeable to a selected gas but permeable as by diffusion to a selected drug. Element 21 can also be of pores of minute diameter that gas cannot pass through under normal presure, but readily let drug diffuse threrethrough. Valve 20 can also operate in cooperation with element 21 by valve 20 extending to the wall of the device to move drug into element 21. The flow control means acts to release drug at a metered rate, for example, according to the Hagen-Poiseuille equation, and at a constant rate over a period of time, despite the decreasing volume of drug 22 in chamber 11 during the discharge of the drug. Propellant chamber 17 is a vapor pressure generating chamber and it contains a gas stored in a chemical state, for example, a solid or liquified form that produces a gas with a vapor pressure in excess of one atmosphere at the temperature of use, that is, the temperature of the stomach, to cause collapsed member 16 to inflate to a predetermined size and shape by the movement of gas into it. The dimension of inflated balloon 16 in the inflated state will of course be different for different animals but it should be large enough to retain the device, for example, in the selected drug receptor area, such as the stomach. Generally, the dimensions of the device are slightly larger than the diameter of the body cavity or opening which dimensions are of recorded size in standard textbooks. The device will be slightly larger than the pyloric canal which is about 1 cm to 4 cm, usually 2 cm in humans, and the device maintains these dimensions until completion of the prescribed therapeutic regimen. Vapor pressures arising in propellant chamber 17 also exert their pressure against drug 22 in product chamber 11 to urge drug 22 through flow control means 21 to the exterior of the device at a controlled rate for a prolonged period of time. At the end of the pressurized therapeutic regimen, bioerodible plug 23 erodes to vent balloon 16 into the stomach causing it to collapse to a size smaller than the pyloric canal. Device 14 then passes through the lower gastrointestinal tract and out of the body. Alternatively, drug delivery device 14 can bioerode or be digested by the action of gastric juices, enzymes and the like into fragments that pass from the stomach.

FIG. 4 represents another novel and useful drug delivery device of the invention. In FIG. there is seen a device 14 structurally similar to device 14 of FIG. 3 with the device of FIG. 4 illustrated free of the optional container 12. Device 14 of FIG. 4 is manufactured with a piston 30 positioned between propellant chamber 17 and drug reservoir chamber 11. Piston 30 is made from a material that is essentially impermeable to gas and drug and one of its functions is to keeppropellant in the propellant chamber for propellant to exert energy against it to push it against drug to urge drug from the device. Piston 14 is slidably mounted and it can be a sliding barrier, a disk or sliding seal so constructed as to movably provide and maintain a gas drug barrier between the compartments. Piston 30 is substantially frictionally disposed and it is free to move within the device by sliding while maintaining an impenetrable barrier therebetween. The size of the balloon to the device can vary depending on the mass of the product charge, and generally, the size may be alike, or the size of the balloon may be the larger size. The desired size can easily be determined by test floating various devices in known liquids and then selecting the appropriate size and shape for the particular drug regimen.

FIG. 5 and FIG. 6 diagrammatically illustrate the use of the drug delivery device 14 of the invention. In FIG. 5 there is seen a device being administered into an environment of use, such as, the outline of a human 39 with a container 12 moving through the esophagus 40 and on into a drug receptor area, the stomach 41. In FIG. 5 the device 14 is seen in operation in the drug receptor site, the stomach 41 administering a drug at a controlled and continuous rate for a prolonged period of time to the stomach.

DETAILS OF THE INVENTION Drug delivery device 14 of this invention can be made into assorted sizes and shapes with these dimensions adapted for administering a drug to a particular animal, human or avian and to the ease of manufacture. The shape of the device is usually tubular but other shapes such as cylindrical, oblong, oblate, prolate, spherical and the like can be made. The device is usually fabricated for administration into a body cavity such as oraladministration into the stomach and the size of the deformable hollow member 16 of the device in the inflated state will be slightly larger than the diameter of the body passageway or cavity to maintain the device in a drug receptor area. The size of-various body cavities are recorded in standard medical references, and for the purpose of illustrating the spirit of the invention the size of the device needed in the inflated state to keep the device in a human stomach will be slightly larger than the size of the pyloric canal. For example, for humans the size of the inflated member will be in the range of 3 cm in diameter to about 10 cm in length, usually about 2 cm by 4 cm. Of course, the devices of various sizes such as 2 cm by 5 cm, 3.14 cm by 5 cm, 4 cm by 4 cm, and the like are also within the mode and manner of the invention.

Wall 15 of the device defining chambers 11 and 17 and housing the drug and gas in liquified form can be flexible, semi-flexible or rigid or modifications thereof. Wall 15 is initially essentially impermeable to the gas in liquified form and to the drug, and it can be made from a wide variety of materials commercially available such as thin aluminum, teflon, poly(ethylene), laminates of poly(propylene), poly(methylmethacrylate); poly(formaldehyde), nylon, laminates of polystyrene, thin metal foils such as thin aluminum foil, tin foils, poly(vinylidene chloride) coated tin foil and the like. In an economical aspect, the devices of this invention are made of materials that lend themselves to single use devices and as such they are made from relatively inexpensive materials. The thickness of the shell can vary over a whole range, usually from 0.2 mils to 200 mils, generally in the range of 1 mil to mils and the like.

Collapsable bag 16 attached to housing at propellant chamber 17 is made from flexible, polymeric materials. In one embodiment the material can be substantially impermeable to gases. In the embodiment wherein the material is impermeable to gas, an erodible plug is used to deflate an inflated member, and it has a size and shape corresponding to the volume of gas employed and to the animals stomach. In another embodiment the material can be permeable to gas to let gas slowly diffuse through the material to collapse an inflated balloon to let the device pass from the environment of use. The bag 16 is made from commercially available naturally occurring or synthetic materials and it is about 0.2 mils to 20 mils thick, or more, usually 0.4 to 2.0 mils and the like. Bag 16 can be made ofa single material, a combination of materials in laminated form such as elastomric materials bonded on foils and the like. Illustrative materials include commercially available materials such as natural rubber, silicones, poly- (urethanes), poly(acrylonitriles), poly(ethylene), poly(propylene), poly(vinylidene chloride), poly(- vinylidene fluoride), acrylic elastomers, ethylene propylene terpolymers, laminates such as poly(ethylene)- poly(vinylidene chloride), nylonpoly(vinylidene chloride), nylon-poly(vinylidene chloride), poly(ethylene)-poly(vinylidene)-poly(ethylene), poly(ethylene)- poly(vinyl alcohol)-poly(vinylidene)chloride, other laminates such as extra thin metal foils such as tin foil coated on a polymer, aluminum foil coated on a polymer, plastic coated foils such as poly(ethylene) on tin foil, poly(vinylidene chloride) on stainless steel foil and the like.

Exemplary materials suitable for exerting a vapor pressure to inflate a collapsed bag and to act as the driving power to enable the device to function as a constant rate vapor pressure powered device are inorganic and organic compounds whose vapor is in equilibrium with its liquid phase to exert a constant pressure at a given temperature regardless of volume. Representative of compounds are those that are liquids at ambient temperatures, usually 20C to C or less, and have a boiling point, 8?, above this temperature to exert a vapor pressure greater than one atmosphere at physiological temperatures. Exemplary materials useful for exerting a vapor pressure and also for inflating deformable hollow member 18 are halogenated hydrocarbons, fluorochlorinated lower saturated aliphatic hydrocarbons, halogenated unsaturated hydrocarbons, halogenated lower alkanes of 1 to 4 carbon atoms and the like, such as diethyl ether BP 34.6C, methyl formate BP 31.5C, isopentane BP 279C, tetramethyl silane BP 265C, perfluoropentane isomers BP 31.0C, npentane 360C, diethenyl ether 28C, mixtures thereof and the like. Usually, the amount of gas stored in the liquified phase in the propellant chamber 18 will be about 0.2 cc to 5.0 cc or higher, and the volume of the vapor phase will be from 40 percent to percent of the inflated member or the volume of the chamber.

Materials suitable for use as bioerodible plug 23 or for forming bioerodibles when the device is credible in the environment of use, are those materials that bioerode in the environment of use, such as the stomach, at a predetermined given time or over a period of time. The materials are those that erode by known biological processes, such as chemical degradation, acidic hydrolysis,enzymatic action, oxidation, reduction, dissolution, slow solubilization, and the like. The bioerosion rate for suitable materials can be determined by standard assay procedures consisting of placing a section of material in natural or artificial body juice, such as gastric juice at normal body temperatures and observing the rate of erosion over a period of time. By prolonged period of time is meant, for the present purposes, 8 hours to 30 days, usually 1 day to 8 days.

Representative materials for making plug 23 and wall 15 comprise hydrophilic polymers of uncross-linked hydroxylalkyl acrylates and methacrylates, hydrolytically biodegradable poly(anhydride)polymers as described in United States Pat. Nos. 2,073,799; 2,668,162; and 2,676,945; and in Introduction to Polymer Chemistry, Stille, J. K., Chapter 6, 1962, published by Wiley Publishing Co., bioerodible polyesters as described in Industrial and Engineering Chemistry, Vol. 36, No. 3, pages 223 to 228, 1964; Macrmol Chem, Vol. 75, pages 211 to 214, 1964; United States Pat. Nos. 2,703,316; 2,668,162; 3,297,033; and 2,676,945, cross-linked gelatin prepared with a cross-linking agent reactive with the hydroxyl, carboxyl or amino functional groups of the gelatin molecule as described in J. Polymer Science, Part A-l V0]. 5, No. l, 1967, J. Polymer Science, Vol. 54, pages 321-335, 1961; Advances in Protein Chemistry, Vol. VI, Cross Linkage in Protein Chemistry, 1961, published by Academic Press, Inc.

Other materials include proteins and hydrocolloides of animal and plant origins such as. modified collagen, elastin, keratin, fibrin, karaya, algin, pectin, carrageenin, chitin, heparin, locust bean gum and the like. Also, synthetic polymers such as poly(ethylene oxide), poly(vinylpyrrolidone), poly(ethyl eneimine), poly(acrylic acid) copolymers of acrylamide and methacrylamide up to 40 percent by weight of N-methylene bisacrylamide or N,N-dimethylol urea, synthetic poly amino acid polymers, and the like.

The active product or agent that can be released by the device are those that give a beneficial effect to an animal, human, and the like including the environment. The term product and agent are considered equivalents for the purpose of this invention and it includes active drugs that can be administered with the delivery device of the invention. These drugs are administered in accordance with their known use and dose, and combinations of these drugs, as described in The Pharmacological Basis of Therapeutics, 14th Edition, Goodman, L. S., and Gilman, A., 1970, The Macmillan Co., Physicians Desk Reference, 25th Edition, 1971, Medical Economics, Inc.; and, Remingtons Pharmaceutical Sciences, 14th Edition, 1970, Mack Publishing Co., include without limitation, for example, drugs acting on the central nervous system such as hypnotics and sedatives such as pentobarbital sodium, phenobarbital, secobarbital, thiopental, etc.; heterocyclic hypnotics such as dioxopiperidines, and glutarimides; hypnotics and sedatives such as amides and ureas exemblified by diethylisovaleramide and oz-bromoisovaleryl urea and the like; hypnotics and sedative alcohols such as carbomal, naphthoxyethanol, methylparaphenol and the like; and hypnotic and sedative urethanes, disulfanes and the like; psychic energizers such as isocarboxazid, nialamide, phenelzine, imipramine, tranylcypromine, pargylene and the like; tranquilizers such as chloropromazine, promazine, fluphenazine reserpine, deserpidine, meprobamate, benzodiazepines such as chloridiazepoxide, and the like; anticonvulsants such as primidone, diphenylhydantoin, ethotoin, pehneturide, ethosuximide and the like; muscle relaxants and anti-parkinson agents such as mephenesin, methocarbomal, trihexylphenidyl, biperiden, levo-dopa, also known as L-dopa and Las -mammary phenylalanine, and the like; analgesics such as morphine, codeine, meperidine, nalorphine and the like; antipyretics and anti-inflammatory agents such as aspirin, salicylamide, sodium salicylamide and the like; local anesthetics such as procaine, lidocaine, naep'aine, piperocaine, tetracaine, dibucaine and the like; antispasmodics and anti-ulcer agents such as atropine, scopolamine, methscopolamine, oxyphenonium, papaverine, prostaglandins such as PGE PGE PGF a, PGA

and the like; anti-microbials such as penicillin, tetracycline, oxytetracycline, chlorotetracycline, chloramphenicol, sulfonamides and the like; anti-malarials such as 4-aminoquinclines, -tininoquinmines and pyrimethamine; hormonal agents such as prednisolone, cortisone, cortisol and triamcinolone; androgenic steroids, for example, methyltestosterone, fluoximesterone and the like; estrogenic steroids, for example, 178- estradiol and ethinyl estradiol; progestational steroids, for example 1704- hydroxyprogesteron e acetate, l9-nor-progesterone, norethindrone and the like; sympathomimetic drugs such as epinephrine, amphetamine, ephedrine, norepinephrine and the like; cardiovascular drugs, for example, procainamide, amyl nitrate, nitroglycerin, dipyridamole, sodium nitrate, mannitol nitrate and the like; diuretics, for example, chlorothiazide, flumethiazide and the like; antiparasitic agents such as bephenium hydroxynaphthoate and dichlorophen, dapsone and the like; neoplastic agents such as mechlorethamine, uracil mustard, 5- fluorouracil, 6-thioquanine, procarbazine and the like; hypoglycemic drugs such as sulfonylureas such as tolbutamide, acetohexamide, tolazamide, and chlorpropamide, the biguanides and the like; nutritional agents such as vitamins, essential amino acids, essential fats and the like; and other physiologically or pharmacologically active agents. Also, the drugs can be present as the pharmacologically acceptable derivatives, such as ethers, esters, amides, acetals and the like that lend themselves to passage into the circulatory system. These derivatives can be prepared by art known techniques and then used in the practice of the invention.

Of course, the drug derivative should be such as to convert to the active drug within the body through the action of body enzymes assisted transformations, pH, specific organ activites and the like. Other agents that can be released by the device include without limitation insecticides, bactericides, germicides, animal feeds, cosmetics, fish pond foods, perfumes and like agents that can be charged into the reservoir and metered at a controlled rate from the device to the environment of use.

The above and other beneficial agents can be used per se or they are conveniently formulated into a pharmaceutical form by mixing with a non-toxic carrier. Carriers acceptable for the purpose of this invention are the art known carriers that do not adversely affect the active agent, the host, or the material comprising the delivery device. For example, suitable pharmaceutical carriers include sterile water; saline, dextrose; dextrose in water or saline; condensation products of castor oil and ethylene oxide combining about 30 to about 35 moles of ethylene oxide per mole of castor oil; liquid glyceryl triester of a lower molecular weight fatty acid; lower alkanols; oils such as corn oil; peanut oil; sesame oil and the like, with emulsifiers such as monoor diglyceride of a fatty acid, or a phosphatide, for example, lecithin, and the like; glycols; polyalkylene glycols; aqueous media in the presence of a suspending agent, for example, sodium carboxymethylcellulose; sodium alginate; poly(vinylpyrrolidone); and the like, alone or with suitable dispensing agents such as lecithin; polyoxyethylene stearate; and the like. The carrier may also contain adjuvants such as preserving, stabilizing, wetting, emulsifying, viscosity modifying agents, and the like.

The amount of active agent incorporated in the device varies depending on the particular agent, the desired effect, and the time span over which it is desired to have the agent released. Since devices of different sizes and shapes are intended to provide complete dosage regimen, there is no critical upper limit on the amount of drug incorporated in the device. The lower limit will depend on the activity of the drug and the time span of its release from the device. In general, therefore, the amount of the drug incorporated in the device is non-limited and it is an amount equal to, or larger than, the amount of drug that on release from the device is effective for bringing about the drugs physiological or pharmacological local or systemic effects. For example, the amount of drug present in the delivery device for large farm animals will vary with the size of the animal, while the amount in the device when it is used for adult humans for a period of time of 4 hours to 6 days to achieve local or system effect is for various drugs, such as propantheline 120 to 300 mg in the device; for glutamic acid hydrochloride an amount in the device of 50 to 300 mg; for pargyline hydrochloride 50 to 100 mg; for erythrityl tetranitrate 50 to 100 mg; mannitol hexanitrate to mg; ephedrine sulfate 40 to 500 mg; nylidrin hydrochloride 12 to 48 mg; bethanechol chloride to 480 mg; phentolamine 100 to 400 mg; guanethidene 100 to 1000 mg; methyl dopa 3 to 12 gms; atropine 100 mcg to 1250 mcg; and the tive elements that are essentially self actuated, that is, no external intervention is needed to initiate the flow of drug. Numerous flow resistive means are commercially available, such as porous plugs, microporous membranes, capillaries, etched polymers, perforated polymers, and the like. The flow resistive means can be made from a variety of materials such as poly(ethylene), nylon, teflon, expoxies, poly(methyl methacrylate), metals, alloys, ceramics, sintered ceramics, stainless steel capillaries of 0.1 to 1 cm in length with a diameter of 0.1 to 20 microns, a stainless steel porous disk having a thickness of 0.1 cm, a diameter of 0.1 cm, a pore size of 0.1 micron, a porosity of 20 percent and a tortuosity of 0.5, and the like. The rate of flow through the resistive means is governed by the Hagen- Poisseuille equation wherein Q 5 rrD APII ZS L, where Q equals flow in ml/sec, D equals diameter in cm, p. equals viscosity in poise, AP equals pressure in dynes/cm, and L equals length of the means. The use of this equation allows the flow rate to be easily predicted and readily adjusted by changing the length and diameter parameters of the flow resistive means. Also, by altering the viscosity of the carrier the flow rate can easily be varied without altering the specifications of the flow resistive means. The viscosity of any carrier can easily be ascertained by employing standard viscometers, such as the Wclls-Brookfield viscometer. The device of this invention can effectively meter from 0.001 ml/hour to 0.5 ml/hour, smaller or larger for various times such as 4 hours, 6 hours, a day or longer. The viscosity of the carrier medium used to convey the drug can vary over a range of l to 10 centipoise at physiological temperature for administering a drug to a host.

A typical example of a novel and useful product delivery device for the administration of drug is prepared by first manufacturing a device comprised of a spherical collapsable balloon approximately 4 cm in diameter fabricated from commercially available poly(ethylene terephthlate) by standard vacuum forming and heat sealing processes. Passing through one place of the balloon at the point of a final heat seal is a water solubel poly(urethane) erodible seal. Next, a housing formed of polymeric material of tubular shape is divided into two compartments with one compartmentadhesively sealed by means of a cyanoacrylate adhesive to the collapsed balloon. The two compartments are separated by a sliding pistion, and the compartment communicating with the balloon is charged with 1.25 cm of isopentane. The compartment distant from the balloon is charged with drug and it is closed and equipped with a flow control means consisting of a porous poly(ethylene) plug 0.9 mm in diameter and 1.0 mm long which has a porosity of percent, an average pore size of 1 micron, and a tortuosity factor of about 2. The device is filled with 1 cm of drug formulation containing 16 mg of the commercially available diuretic, bendroflumethiazide in 95 percent ethanol to which carboxymethyl cellulose has been added to give a viscosity of 10,000 centipoise at 37C. The porous flow control element is sealed with the water soluble commercially available polymer, sodium poly(styrene sulfonate). The collapsed balloon is folded around the delivery device and the whale assembly is placed in a two piece gelatin capsule. On ingestion, the capsule freely dissolves and the balloon self inflates by virtue of vaporization of the isopentane at the physiologic temperature. The sodium poly(styrene sulfonate) seal is dissolved and the device delivers 2 mg of bendroflumethiazide per day for seven days. At the end of the continuous, controlled and prolonged drug delivery period, the dissolution of the water soluble poly(urethane) seal is completed which allows for collapse of the poly( ethylene terephthalate) balloon. The whole assembly is then eliminated from the gastrointestinal tract, that is, the environment of use.

Among the advantages of the device of the invention are the ease of construction by standard manufacturing technique devices into units of different sizes, especially of a miniaturized size, also of shapes and forms that are suitable for delivering a drug internally to an animal or human. Another important advantage of the claimed delivery device is its ability to dispense at a controlled rate, a beneficial agent having a wide variety of chemical and physical properties and over a wide range of release rates. Still another important advantage of the invention resides in the devices ability to effectively control the rate of release of the drug from the device throughout the major portion of drug administration in a substantial zero order release rate. A further advantage of the device resides in the use of low cost materials for the power, and for the device to give a unit suitable for disposal, after comparatively short periods of use, for example, eight hours, a day or Week without undue economic hardship on the user, yet providing a continuous and controlled administration of drug without any external energy source. And, although the invention has been described in detail, it will be understood that certain changes and modifications can be made without departing from the spirit and scope of the invention.

I claim:

1. A drug type product delivery device for the continuous administration of a product, said device comprising,

a. a wall surrounding an internal space, the space housing,

b. a product compartment which. serves as a reservoir for containing a beneficial product with the product compartment adjacent to,

c. a propellant compartment which serves as a means for containing an agent for producing a gas having avapor pressure above one atmosphere at the term perature of product administration,

d. a valve between the compartments for directing the flow of a gas from the propellant compartment to the product compartment,

e. a discharge metering means communicating with the product chamber and the exterior of the device for metering a product at a controlled and continu' ous rate from the product chamber,

f. a hollow deformable member comprised of a flexible distendable material joined to the propellant compartment,

g. the hollow deformable member freely movable from a collapsed position to an expanded position and movable from an expanded position to a collapsed position after a period of time,

h. and wherein the device when positioned in the environment of use, the deformable member is moved from a collapsed to an expanded position by gas produced in the propellant compartment that moves into the deformable member and on release of the gas therefrom it subsequently returns to a collapsed position and while in the environment of use and when charged with product, said product is metered through the discharge means on movement of gas through the valve into the product compartment to continuously move a therapeutically effective amount of product from the product delivery device.

2. A product delivery device for the continuous administration of a product according to claim 1 wherein the hollow deformable member is provided with a bioerodible plug that on bioerosion vents the interior of the member to its exterior.

3. A product delivery device for the continuous administration of a product according to claim 1 wherein the hollow deformable member is formed of an elastic material permeable to an inflating gas that slowly let the gas diffuse through the material to move the member from an expanded to collapsed position.

4. A product delivery device for the continuous administration of a product according to claim 1 wherein drug is metered through the discharge means in response to gas filling the product compartment to increase its volume while reducing the volume of drug in the product compartment.

5. A product delivery device for the continuous and controlled administration of a product according to Claim 1 wherein the device is contained in a bioerodible container.

6. A product delivery device for the continuous and controlled administration of a product according to claim 1 wherein a valve is positioned between the propellant compartment and the hollow deformable member. l

7. A drug type delivery device for the continuous and controlled administration of a product for producing a beneficial effect, wherein the device comprises:

a. a wall surrounding an internal space and formed of a material substantially impermeable to product, the space containing b. a reservoir compartment for containing a beneficial product, and

c. a propellant compartment as a means for containing a chemical agent for producing a gas having a vapor pressure in excess of one atmosphere, at the temperature of product administration from the device,

d. a piston slidably positioned between the reservoir compartment and the propellant compartment, the piston movable in response to gas produced in the propellant compartment,

e. a metering means communicating with the reservoir and the exterior of the device for metering an effective amount of product at a controlled rate from the reservoir,

f. a hollow deformable member comprised of a distendable material joined to the propellant compartment,

g. the hollow deformable member movable from a collapsed to an expanded position and returnable to a collapsed position after a period of time,

h. a passageway communicating with the propellant compartment and the deformable member,

i. and wherein the device when positioned in the environment of use and when charged with product, the deformable member is inflated by gas flowing from the propellant compartment into the member, and product is urged through the metering means by the movement of the piston into the product compartment in response to gas produced in the propellant compartment to progressively decrease the volume of the reservoir as product is administered from the device.

8. A product delivery device for the continuous administration of a product according to claim 7 wherein the hollow deformable member is provided with a bioerodible plug that is capable of bioerosion in the environment of use to vent the interior of the member to its exterior.

9. A product delivery device for the continuous administration of a product according to claim 7 wherein the hollow deformable member is formed of an elastic material permeable to an inflating gas and slowly lets the gas diffuse through the material to move an expanded member to a collapsed member.

10. A product delivery device for thecontinuous administration of a product according to claim 7 wherein the product is a beneficial drug that can produce a local or systemic effect.

11. A product delivery device for the continuous administration of a product according to claim 7 wherein the device is contained in a bioerodible container formed of a material that can bioerode at a physiological temperature in a physiological environment.

12. A product delivery device for the continuous and controlled administration of a product according to claim 7 wherein a unidirectional valve is positioned between the propellant compartment and the deformable member.

13. A product delivery device for the continuous and controlled administration of a product according to claim 1 wherein the product delivery device is made of a material that can bioerode at biological temperatures over a period of time.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US1957564 *Nov 23, 1932May 8, 1934West Aubra TExpanding capsule body
US2485235 *Aug 17, 1945Oct 18, 1949Container CorpMethod and apparatus for closing and sealing cartons
US3604417 *Mar 31, 1970Sep 14, 1971American Cyanamid CoOsmotic fluid reservoir for osmotically activated long-term continuous injector device
US3692027 *Apr 23, 1971Sep 19, 1972Ellinwood Everett H JrImplanted medication dispensing device and method
US3701351 *Jun 28, 1971Oct 31, 1972Harvey Douglas GInflatable intravaginal applicator for animals
US3731681 *Jan 14, 1972May 8, 1973Univ MinnesotaImplantable indusion pump
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3901232 *Oct 26, 1973Aug 26, 1975Alza CorpIntegrated device for administering beneficial drug at programmed rate
US3952741 *Jan 9, 1975Apr 27, 1976Bend Research Inc.Controlled release delivery system by an osmotic bursting mechanism
US4203439 *Oct 11, 1978May 20, 1980Alza CorporationOsmotic system with volume amplifier for increasing amount of agent delivered therefrom
US4203441 *Dec 18, 1978May 20, 1980Alza CorporationOsmotically triggered device with gas generating means
US4217894 *May 4, 1978Aug 19, 1980Siemens AktiengesellschaftApparatus for supplying medication to the human or animal body
US4629449 *Mar 21, 1985Dec 16, 1986Alza CorporationVaginal dispenser for dispensing beneficial hormone
US4687480 *Sep 9, 1985Aug 18, 1987Commonwealth Scientific And Industrial Research OrganizationFor insertion into the rumen of an animal through the oesophagus
US4718430 *Sep 20, 1985Jan 12, 1988Walter HolzerProcedure and device for the administering of insulin or similar long-term medicaments
US4735804 *May 7, 1987Apr 5, 1988Merck & Co., Inc.Sustained release from polymer rod
US4758436 *May 7, 1987Jul 19, 1988Merck & Co., Inc.Drug delivery device which can be retained in the stomach for a controlled period of time
US4767627 *May 1, 1987Aug 30, 1988Merck & Co., Inc.Drug delivery device which can be retained in the stomach for a controlled period of time
US4861268 *Jun 13, 1988Aug 29, 1989Transpharm GroupTooth-anchored beneficial agent delivery device
US4911707 *Aug 10, 1988Mar 27, 1990Ciba-Geigy CorporationMonolithic user-activated transdermal therapeutic system
US4917676 *Sep 27, 1988Apr 17, 1990Ciba-Geigy CorporationUser-activated transdermal therapeutic system
US4961931 *Sep 9, 1988Oct 9, 1990Alza CorporationMethod for the management of hyperplasia
US5194003 *Jan 3, 1992Mar 16, 1993Transpharm Group, Inc.Removable device for delivering beneficial agents orally
US5198222 *Aug 31, 1990Mar 30, 1993Agribiotech, Inc.Time release bolus
US5198229 *Jun 5, 1991Mar 30, 1993Alza CorporationSelf-retaining gastrointestinal delivery device
US5219334 *May 24, 1989Jun 15, 1993Tsukada Medical Research Co., Ltd.Infuser with balloon for continuously infusing liquid drug
US6132420 *Nov 14, 1997Oct 17, 2000Alza CorporationOsmotic delivery system and method for enhancing start-up and performance of osmotic delivery systems
US6171298Mar 11, 1998Jan 9, 2001Situs CorporationIntravesical infuser
US6179118 *Apr 12, 1999Jan 30, 2001Glaxo Wellcome Inc.Method and package for storing a pressurized container containing a drug
US6183461Sep 14, 1999Feb 6, 2001Situs CorporationMethod for delivering a medication
US6238067 *May 17, 1999May 29, 2001Eric HirschIlluminated balloon apparatus
US6283943 *Feb 19, 1999Sep 4, 2001Minimed Inc.Negative pressure pump
US6315112Jun 22, 2000Nov 13, 2001Smithkline Beecham CorporationMethod and package for storing a pressurized container containing a drug
US6352152Jun 20, 2000Mar 5, 2002Smithkline Beecham CorporationMethod and package for storing a pressurized container containing a drug
US6390291May 15, 2000May 21, 2002Smithkline Beecham CorporationMixture of drug and propellants
US6607512 *Jan 9, 2001Aug 19, 2003Genzyme CorporationDevice for delivery of liquid and gel-like surgical materials and methods for use thereof
US6679374Feb 7, 2002Jan 20, 2004Smith Kline Beecham CorporationPackage for storing a pressurized container containing a drug
US6974587May 8, 2002Dec 13, 2005Aircom Manufacturing, Inc.Sustained release of drug; fluid bladder; hermetic sealing; pressurization
US7207982Mar 31, 2004Apr 24, 2007Alza CorporationOsmotic pump with means for dissipating internal pressure
US7368126Nov 4, 2003May 6, 2008Guohua ChenControlled release depot formulations
US7445616 *Mar 17, 2004Nov 4, 2008Petrakis Dennis NTemperature responsive systems
US7476224Apr 9, 2008Jan 13, 2009Petrakis Dennis NTemperature responsive systems
US7655001 *Sep 29, 2008Feb 2, 2010Petrakis Dennis NTemperature responsive systems
US7655257Aug 20, 2003Feb 2, 2010Intarcia Therapeutics, Inc.Impermeable reservoir divided into water-swellable agent/drug chambers; fluid from environment imbibed through semipermeable plug into the water-swellable agent chamber releasing drug through a back-diffusion regulating outlet; delivering leuprolide acetate for advanced prostate cancer for 2 years
US7749191Mar 20, 2008Jul 6, 2010Beutlich Lp, PharmaceuticalsDevice and method for drug delivery
US7828150Jun 5, 2001Nov 9, 2010Glaxosmithkline LlcContainer for medicament powder
US7829109Nov 14, 2002Nov 9, 2010Durect CorporationCatheter injectable depot compositions and uses thereof
US7854745 *Feb 19, 2010Dec 21, 2010Obalon Therapeutics, Inc.Intragastric device
US8080259Dec 29, 2009Dec 20, 2011Intarcia Therapeutics, Inc.Sustained delivery of an active agent using an implantable system
US8114437Feb 3, 2006Feb 14, 2012Intarcia Therapeutics, Inc.Solvent/polymer solutions as suspension vehicles
US8162969Oct 15, 2009Apr 24, 2012Obalon Therapeutics, Inc.Intragastric device
US8172458Sep 29, 2008May 8, 2012Petrakis Dennis NTemperature responsive systems
US8206745Jun 10, 2011Jun 26, 2012Intarcia Therapeutics, Inc.Solvent/polymer solutions as suspension vehicles
US8211467Nov 1, 2010Jul 3, 2012Intarcia Therapeutics, Inc.Osmotic drug delivery devices containing suspension formulations comprising particles having active agents and nonaqueous single-phase vehicles
US8226597Mar 21, 2008Jul 24, 2012Baxter International, Inc.Fluid delivery system and flow control therefor
US8231566Mar 21, 2008Jul 31, 2012Baxter International, Inc.Fluid delivery system and flow control therefor
US8252303Nov 14, 2002Aug 28, 2012Durect CorporationA biodegradable, biocompatible polymer, a water-immiscible solvent to plasticize the polymer and form a gel, a thixotropic agent and a beneficial agent; drug delivery; improved shear thinning and reduced injection
US8278330Sep 27, 2010Oct 2, 2012Durect CorporationShort duration depot formulations
US8292911Jan 21, 2011Oct 23, 2012Obalon Therapeutics, Inc.Intragastric device
US8298562May 26, 2011Oct 30, 2012Intarcia Therapeutics, Inc.Sustained delivery of an active agent using an implantable system
US8440226Jun 18, 2012May 14, 2013Intarcia Therapeutics, Inc.Solvent/polymer solutions as suspension vehicles
US8460694Oct 8, 2012Jun 11, 2013Intarcia Therapeutics, Inc.Solvent/polymer solutions as suspension vehicles
US8496943Jul 18, 2005Jul 30, 2013Durect CorporationNon-aqueous single phase vehicles and formulations utilizing such vehicles
US8501215Jul 28, 2003Aug 6, 2013Guohua ChenHaving a solvent with a miscibility in water of less than or equal to 7 wt. % at 25 degrees C., to plasticize the polymer and form a gel therewith; improved shear thinning behavior and reduced injection force
US8535701Oct 4, 2012Sep 17, 2013Intarcia Therapeutics, Inc.Sustained delivery of an active agent using an implantable system
US8647358Jan 21, 2011Feb 11, 2014Obalon Therapeutics Inc.Intragastric device
US8672876Mar 21, 2008Mar 18, 2014Baxter International Inc.Fluid delivery system and flow control therefor
US8740927Jan 21, 2011Jun 3, 2014Obalon Therapeutics Inc.Intragastric device
US20090182303 *Dec 18, 2008Jul 16, 2009Steven WalakTargeted Therapeutic Agent Release for Weight Loss Therapy
CN101010114BAug 24, 2005May 26, 2010皇家飞利浦电子股份有限公司Electronically and remotely controlled pill and system for delivering at least one medicament
EP0075062A1 *Sep 18, 1981Mar 30, 1983Anton Dr. SadjakImplantable device for the constant delivery of a substance
EP0089548A1 *Mar 8, 1983Sep 28, 1983Merck & Co., Inc.Osmotic drug delivery system
EP0091621A1 *Mar 31, 1983Oct 19, 1983Milliken Research CorporationLow flow constant rate pump
EP2030611A1Jul 28, 2003Mar 4, 2009Alza CorporationInjectable multimodal polymer depot compositions and uses thereof
EP2311431A1Jun 25, 2003Apr 20, 2011ALZA CorporationShort duration depot formulations
EP2316421A1Jun 25, 2003May 4, 2011ALZA CorporationBupivacaine-containing injectable depot composition
WO1998020930A1Nov 7, 1997May 22, 1998Alza CorpOsmotic delivery system and method for enhancing start-up and performance of osmotic delivery systems
WO2004089457A1Mar 31, 2004Oct 21, 2004Alza CorpOsmotic pump with means for dissipating internal pressure
WO2006021932A1 *Aug 24, 2005Mar 2, 2006Koninkl Philips Electronics NvElectronically and remotely controlled pill and system for delivering at least one medicament
WO2006025013A1 *Aug 29, 2005Mar 9, 2006Koninkl Philips Electronics NvElectronically controlled pill and system for delivering at least one medicament
WO2006077529A2 *Jan 16, 2006Jul 27, 2006Koninkl Philips Electronics NvSystem for controlling traversal of an ingested capsule
WO2010022716A1 *Aug 28, 2009Mar 4, 2010Hochschule OffenburgElectronic pill for dispensing a substance, in particular a drug, in a human or animal body in a controllable manner
Classifications
U.S. Classification604/890.1, 206/522, 424/453
International ClassificationA61M31/00, A61K9/00, A61M37/00
Cooperative ClassificationA61M31/002, A61M37/00, A61K9/0004
European ClassificationA61M37/00, A61M31/00D, A61K9/00L4