|Publication number||US3625214 A|
|Publication date||Dec 7, 1971|
|Filing date||May 18, 1970|
|Priority date||May 18, 1970|
|Publication number||US 3625214 A, US 3625214A, US-A-3625214, US3625214 A, US3625214A|
|Original Assignee||Alza Corp|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (4), Referenced by (217), Classifications (24) |
|External Links: USPTO, USPTO Assignment, Espacenet|
US 3625214 A
United States Patent 3,184,386 5/1965 Stephenson 3,416,530 12/1968 Ness ABSTRACT: A drug-delivery device for prolongedly delivering drugs to patients according to any predetermined time release profile, e.g., increasing, decreasing, constant, pulsing, sinusoidal, and like patterns of release, is fabricated by applying a drug coating of varying or uniform thickness to a relatively drug-impermeable film soluble in body fluids and thence rolling said coated film about itself in spiral or jeliyroli fashion. Upon administration to the body, the outermost extremities of the film gradually erode at a predetermined rate in body fluids thus exposing coextensive extremities of the drug coating, also soluble in body fluids, and drug is released to the tissues of the body. Suitable design of the drug coating along the spiral, e.g., of varying thickness, etc. provides for the aforesaid release patterns as the device disintegrates.
PATENTEDDEC nan 35251214 INVENTOR. Takeru Higuchi Attorney nnuc-nnuvnav DEVICE BACKGROUND OF THE INVENTION This invention relates to a device for delivering drugs to patients according to a programmed schedule and, more especially, to a device which can deliver drugs according to any desired program of release which may be therapeutically desired.
In the pharmaceutical field, most prolonged or sustained action medicators have had as their objective to release medication at a constant rate. However, many programs of therapy require that the quantity of medication administered vary with time. For example, in antibiotic therapy, it is common to administer a large initial dose of drug followed by smaller doses. Conversely, in desensitizing against allergens, therapeutic regimes often call for dose of the allergen to progressively increase over the time of treatment. More complex regimes, in which the dose of medication varies through periodic high and low points, are also known. In general, these therapeutic programs are practiced by periodically administering different amounts of medication in separate dosage forms. Such practice requires frequent acts by the patient or trained attendant and departures from the therapeutic program often occur. Thus, a need exists for a drug-delivery device that can provide any desired time profile for drug administration.
SUMMARY OF THE INVENTION Accordingly, it is a primary object of this invention to pro vide a device for delivering drugs to patients according to any predetermined time release profile.
In attaining the objects of this invention, one feature resides in the application of a drug coating of varying or uniform thickness to a relatively impermeable film soluble in body fluids. To provide the drug-delivery unit, the coated film is spirally wound or rolled about itself in jellyroll fashion. When the device is physically inserted or implanted in the body or administered via the gastrointestinal tract, the film gradually erodes or dissolves at a predetennined rate in body fluids thus exposing the drug coating. By suitable design of the film and of the drug coating, which itself dissolves in body fluids, one can obtain any desired release pattern including increasing, decreasing, pulsing, constant, sinusoidal, etc.
Other objects, features and advantages of this invention will become more apparent from the following description when taken in conjunction with the accompanying drawings, and wherein like reference numerals are used to indicate like or equivalent parts.
BRIEF DESCRIPTION OF THE DRAWINGS In the drawings:
FIG. 1 is a side view of the coated substrate precursor structure of a drug-delivery device of this invention;
FIG. la is a top view of a drug-delivery device of this invention, formed from the structure of FIG. 1;
FIG. lb is a side view of the structure of FIG. la;
FIG. 2 is a side view of a coated substrate precursor structure of another drug-delivery device of this invention;
FIG. 2a is a top view of another drug-delivery device of this invention, formed from the structure of FIG. 2;
FIG. 2b is a top view of another drug-delivery device of this invention, also formed from the structure of FIG. 2;
FIG. 20 is a side view of the structures of both FIG. 2a and FIG. 2b;
FIG. 3 is a side view of a coated substrate precursor structure of yet another drug-delivery device of this invention;
FIG. 3a is a top view of yet another drug-delivery device of this invention, formed from the structure of FIG. 3;
FIG. 3b is a side view of the structure of FIG. 3a;
FIG. 4 is a side view of a coated substrate precursor structure of still another drug-delivery device of this invention;
FIG. 4a is a top view of still another drug-delivery device of this invention, formed from the structure of FIG. 4;
FIG. 4b is a side view of the structure of FIG. 4a;
DETAILED DESCRIPTION OF THE INVENTION This invention has for its essence an assemblage of relatively impermeable film separating slowly soluble, medicament-containing matrix composition. Referring particularly to FIGS. I and la, a relatively impermeable film 10 is shown which dissolves at a slow predetermined rate in body fluids. The film 10 is coated with a medicament Ill containing matrix composition 12 of constant thickness, which matrix is soluble in body fluids (FIG. I).
The coated film is next spirally wound or rolled about itself in jellyroll" fashion to provide the drug-delivery device 13 of FIGS. Ia and lb.
To use the drug-delivery device of this invention, it is either physically inserted or surgically implanted in the body or is administered via the gastrointestinal tract. As the film is eroded away by the action of either gastrointestinal tissue or other body fluids, the drug matrix layer becomes exposed and it too erodes, thus releasing the drug to the tissues of the body. When the matrix layer is thin, relatively small amounts of medication are released per amount of film eroded. Conversely, if the matrix layer is thick the amount of medicament released will be enhanced. By adjusting the thickness of the matrix or the concentration of drug therein, any desired time release profile can be programmed.
By use of the drug-delivery device of FIGS. la and lb which is comprised of a drug-matrix coating of constant thickness, there is provided a drug dosage unit which can exhibit a constant slow rate of release of drug.
In FIG. 2 a relatively impenneable film I0 is also shown which dissolves very slowly in body fluids. However, in this embodiment the said film I0 is coated with a medicament I1 containing matrix composition 12 of uniformly varying thickness, namely, the drug or matrix layer is spread thin at a proximal end of the surface of the film but uniformly progressively thicker across to the distal end of the surface of the film.
It will thus be appreciated that, depending upon from which end the assemblage is wound about itself, there can be conveniently prepared drug-delivery devices which will provide constantly decreasing slow rate of release of drug (FIG. 2a) or constantly increasing slow rate of release of drug (FIG. 2b). In either event such devices would be identical in side plan view (FIG. 2c).
As described and illustrated above, the drug-delivery device of this invention may be comprised of a drug-matrix layer such as to program any desired time release profile, and two other of such forms are illustrated in FIGS. 3, 3a, 3b, 4, 4a and 4b, with the FIGS. 3 depicting a unit which provides a pulsing release pattern and the FIGS. 41 a unit which provides a sinusoidal release pattern.
Moreover, even though in the FIGS. of the drawing cylindrical structures are shown, it is apparent that flattened (FIG. 5) or other configurations can be easily provided. The drugdelivery device of the invention is also advantageously capped at either end with a material 14 slowly soluble in body fluids so as to prevent even the slightest amount of drug from prematurely exuding out of said ends (see FIG. 6).
In many instances, it is desirable to provide for release of the drug immediately upon administration of the device. This can be achieved by coating the preformed device, as illustrated in any of FIGS. 10, 2a, 2b, 3a, da and 5, with a layer of the matrix 112 containing drug 11. Alternatively, as illustrated in FIG. '7, film It) can be coated with medicament 11 containing matrix composition 12 on both face surfaces thereof. Upon rolling this coated film about itself, the resulting device will bear a drug-containing coating on its exterior surface (FIG. 7a). In either event, the resulting device initially will release drug by dissolution of the exteriorly exposed coating of the matrix. Thereafter, the film will dissolve, eventually releasing drug disposed within the interior of the spirally wound device.
The film or carrier materials 10 are flexible and relatively resistant to erosion in body fluids to provide for medicating action over a prolonged period of time and are preferably polymeric in nature. Exemplary materials include polymers of the following three general classes: (1 those which slowly dissolve in body fluids, for example, gelatin, glycerinated gelatin, formalin treated gelatin, collagen, polyvinylalcohol, and the like; (2) those which hydrolyze in body fluids, for example, the polymeric, essentially linear, dibasic acid anhydrides of the formula:
especially the polyanhydride polymers of sebacic and azelaic acids, polyhydroxyacetic acid such as described in U.S. Pat. Nos. 2,668,162 and 2,676,945, and polysulfite polymers; and (3) polymers cleaved by enzymes present in body fluids. for example, chitin, which is enzymatically cleaved by lysozyme.
The polyanhydride polymers of theabove type (2) can be conveniently prepared by condensing the respective dibasic acids in the presence of SOCl,, benzene and ethyl acetate.
The film or carrier material should be relatively impermeable to passage of the drug by difiusion or leaching. Otherwise, the rate of release of the drug will depend, at least in part, upon diffusion through the film rather than upon erosion of the film and matrix. Selection of appropriate membrane materials will be dependent on the particular drug to be used, and those skilled in the art can readily make the appropriate choices.
Matrix materials used in fabricating the drug coating of constant or varying thickness are soluble in body fluids. The drug matrix substance must erode faster than the film such that, when physically inserted or implanted in the body or administered via the gastrointestinal tract, the film first erodes or dissolves in body fluids thus exposing the drug coating which thence itself erodes or dissolves and hence provides a slow rate of release of drug, albeit the erosion or dissolution is more rapid than that of the film material. In this manner, erosion or dissolution of the film is the rate controlling step for drug administration; for once the film erodes at its predetennined rate, the drug is released relatively rapidly by dissolution of the matrix. Exemplary matrix materials include polyvinylpyrrolidone, water soluble starch, gum acacia, gum tragacanth, or the like, or even those film materials hereinbefore delineated, so long as the requirement is observed that the selected drug matrix substance must erode or dissolve faster than the selected film.
Any of the drugs used to treat the body can be incorporated in the drug layer of the drug-delivery device of this invention. Drug is used herein in its broadest sense as including any composition or substance that will produce a pharmacologic response.
Suitable drugs for use in therapy with the device of the invention include without limitation:
l. Protein drugs such as insulin;
2. Desensitizing agents such as ragweed pollen antigens, hay fever pollen antigens, dust antigen and milk antigen;
3. Vaccines such as smallpox, yellow fever, distemper, hog cholera, fowl pox, antivenom, scarlet fever, dyptheria toxoid, tetanus toxoid, pigeon pox, whooping cough, influenzae, rabies, mumps, measles, poliomyelitis, Newcastle disease, etc.;
4. Antiinfectives, such as antibiotics, including penicillin, tetracycline, chlortetracycline bacitracin, nystatin, streptomycin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, and erythromycin; sulfonamides, including sulfacetamide, sulfamethizole, sulfamethazine, sulfadiazine, sulfamerazine, and sulfisoxazole; anti-virals including idoxuridine; and other antiinfectives including nitrofurazone and sodium propionate;
5. Antiallergenics such as antazoline, methapyrilene, chlorpheniramine, pyrilamine and prophenpyridamine;
6. Antiallergenics such as hydrocortisone, cortisone, hydrocortisone acetate, dexamethasone, dexamethasone 2lphosphate, fluocinolone, triamcinolone, medrysone, prednisolone, prednisolone 2l-phosphate, and prednisolone acetate;
7. Decongestants such as phenylcphrine, naphazoline, and tetrahydrazoline;
8. Miotics and anticholinesterases such as pilocarpine, eserine salicylate, carbachol, diisopropyl fluorophosphate, phospholine iodide, and demecarium bromide;
such as atropine sulfate, cyclopentolate, homatropine, scopolamine, tropicamide, eucatropine, and hydroxyamphetamine;
l0. Sympathomimetics such as epinephrine;
l l. Sedatives and Hypnotics such as pentabarbital sodium, phenobarbital, secobarbital sodium, codeine, (abromoisovaleryl) urea, carbromal;
l2. Psychic Energizers such as 3-(2-aminopropyl) indole acetate and 3-(2-aminobutyl) indole acetate;
13. Tranquilizers such as reserpine, chlorpromayline, and thiopropazate;
l4. Androgenic steroids such as methyltestosterone and fluorymesterone;
15. Estrogens such as estrone, l7 B-estradiol, ethinyl estradiol, and diethyl stilbesterol;
l6. Progestational agents such as progesterone, megestrol, melengestrol, chlormadinonc, ethisterone, norethynodrel, l9- nor-progesterone, norethindrone, medroxyprogesterone and 17 B-hydroxy-progesterone;
l7. Humoral agents such as the prostaglandins, for example PGE PGE and PGF l8. Antipyretics such as aspirin, sodium salicylate, and salicylamide;
l9. Antispasmodics such as atropine, mcthantheline, papaverine, and methscopolamine bromide;
20. Antimalarials such as the 4-aminoquinolines, 8- aminoquinolines, chloroquine, and pyrimethamine;
21. Antihistamines such as diphenhydramine, dimenhydrinate, tripelennamine, perphenazine, and chlorophenazine;
22. Cardioactive agents such as dibenzhydroflumethiazide, flumethiazide, chlorothiazide, and aminotrate;
23. Nutritional agents such as vitamins, essential amino acids and essential fats.
Other drugs having the same or different physiological activity as those recited above can be employed in drug-delivery devices within the scope of the present invention.
Drugs can be in various forms, such as uncharged molecules, components of molecular complexes, or nonirritating, pharmacologically acceptable salts such as hydrochloride, hydrobromide, sulfate, phosphate, nitrate, borate, acetate, maleate, tartrate, salicylate, etc. For acidic drugs, salts of metals, amines, or organic cations (e.g., quaternary ammonium) can be employed. Furthermore, simple derivatives of the drugs (such as ethers, esters, amides, etc.) which have desirable retention and release characteristics but which are easily hydrolyzed by body pH, enzymes, etc., can be employed.
The amount of drug incorporated in the drug-delivery device varies widely depending on the particular drug, the desired therapeutic elTect, and the time span for which it takes the film barrier and matrix material to erode or dissolve. Since a variety of devices in a variety of sizes and shapes are intended to provide complete dosage regimes for therapy for a variety of maladies, there is no critical upper limit on the amount of drug incorporated in the device. The lower limit too will depend on the activity of the drug and the time span of its release from the device. Thus it is not practical to define a range for the therapeutically effective amount of drug to be released by the device.
To prepare the drug-delivery device of the invention, the drug is mixed with the matrix material either at ambient or elevated temperatures to form a settable mixture. The settable mixture, whether a dispersion or true solution, is then simply spread on the film substrate in constant or varying thicknesses (see the FIGS. of the drawing) and allowed to set, for example, by drying or hardening. The coated film is next spirally wound or rolled about itself in jellyroll to provide the subject device.
In applying the drug-containing matrix to the film, the drug release profile of the device is determined. in most instances, a matrix of uniform drug concentration is applied over one entire surface of the film, at a constant or varying thickness. However, the matrix can be printed onto the film in various patterns, providing different rates of drug release. In addition, different portions of the film can be coated with matrix portions having different drug concentration. in each of these ways, the rate of release of drug from the device can be controlled and a wide variety of release patterns obtained.
The drug-delivery device can be fabricated in any convenient shape for either physical insertion or implantation in the body or for administration via the gastrointestinal tract. Dimensions of the device can thus vary widely and are not of controlling importance. The lower limit of the size of the device is governed by the amount of the particular drug to be supplied to the body to elicit the desired pharmacologic response, as well as by the form the dosage unit takes, for example, implantate, suppository, peroral pellet, oral bolus, vaginal pessory, buccal or sublingual lozenge, ocular insert (e.g. as described in US. Pat. No. 3,416,530), the like. Likewise with respect to the upper limit on the size of the device. One of the prime advantages of the dosage form of the invention over the capsule types of the prior art is that any inadvertent flaw in the protective film barrier will not suddenly release the entire drug content. Another advantage, if used as an implantate or the like, is the total disappearance of the film barrier when its function has been completed. Likewise as regards the drug matrix material.
It too will be appreciated that the principle of providing any predetermined time release profile can be embodied in devices other than drug-delivery devices, namely, in any device where it is desired to provide for the prolonged release of any active ingredient according to any desired release pattern.
While there have been shown and described and pointed out the fundamental novel features of the invention as applied to the preferred embodiment, those skilled in the art will appreciate that various modifications, changes, and omissions in the drug-delivery device illustrated and described can be made without departing from the spirit of the invention. It is the intention, therefore, to be limited only by the scope of the following claims.
What is claimed is:
l. A drug-delivery device for prolongedly delivering drugs according to any predetermined time release profile comprised of a spirally rolled substrate, said substrate being comprised of a relatively drug impermeable, flexible film erodible in body fluids and being coated with a drug-containing matrix composition, which matrix itself is erodible in body fluids.
2. The drug-delivery device as defined by claim 1, wherein the matrix composition is more rapidly erodible in body fluids than said film.
3. The drug-delivery device as defined by claim 1, wherein the drug is uniformly distributed throughout the matrix composition.
4. The drug-delivery device as defined by claim 3, wherein the drug coating is of constant thickness along the spiral.
5. The drugelivery device as defined by claim 3, wherein the drug coating is of varying thickness.
6. The drug-delivery device as defined by claim 3, wherein the thickness of the drug coating increases along the spiral.
7. The drug-delivery device as defined by claim 3, wherein the thickness of the drug coating decreases along the spiral.
8. The drug-delivery device as defined by claim 3, wherein the drug coating is of sinusoidal thickness along the spiral.
9. The drug-delivery device as defined by claim 5, wherein the film is comprised of a polymeric material which slowly dissolves in body fluids.
10. The drug-delivery device as defined by claim 3, wherein the film is comprised of polymeric material which hydrolyzes in body fluids.
11. The drugdelivery device as defined by claim 3, wherein the membrane is comprised of polymeric material which is cleaved by enzymes present in body fluids.
112. The drug-delivery device as defined by claim 1 bearing an external coating of said drug-containing matrix composition.
13. A device for prolongedly delivering active ingredient to a given fluid environment according to any predetermined time release profile comprised of a spirally rolled substrate said substrate being comprised of a relatively active ingredient impermeable, flexible film erodible in a given fluid environment, said fllm being coated with an active ingredient containing matrix composition, which matrix itself is erodible in said given fluid environment.
14. The method of prolongedly delivering drug to a patient according to any predetermined time release profile comprising administering to said patient the drug-delivery device as defined by claim ll.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US2099402 *||Jan 17, 1934||Nov 16, 1937||Pratt Food Company||Pill or tablet|
|US2928770 *||Nov 28, 1958||Mar 15, 1960||Bardani Frank M||Sustained action pill|
|US3184386 *||Aug 29, 1962||May 18, 1965||Burroughs Wellcome Co||Prolonged action medicinal tablets|
|US3416530 *||Mar 2, 1966||Dec 17, 1968||Richard A. Ness||Eyeball medication dispensing tablet|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US3826258 *||Feb 7, 1972||Jul 30, 1974||Abraham S||Gradual release medicine carrier|
|US3887699 *||Dec 29, 1970||Jun 3, 1975||Yolles Seymour||Biodegradable polymeric article for dispensing drugs|
|US3888975 *||Dec 27, 1972||Jun 10, 1975||Alza Corp||Erodible intrauterine device|
|US3892238 *||Jan 14, 1974||Jul 1, 1975||Abbott Lab||Drug supporting anchor|
|US3898986 *||Dec 27, 1972||Aug 12, 1975||Alza Corp||Biotransformable intrauterine device|
|US3926188 *||Nov 14, 1974||Dec 16, 1975||Alza Corp||Laminated drug dispenser|
|US3960150 *||Sep 15, 1975||Jun 1, 1976||Alza Corporation||Bioerodible ocular device|
|US3961628 *||Apr 21, 1975||Jun 8, 1976||Alza Corporation||Ocular drug dispensing system|
|US3971367 *||Jun 4, 1975||Jul 27, 1976||Alza Corporation||Intrauterine device having means for changing from uterine-retentive shape to nonuterine-retentive shape|
|US3981303 *||Jul 31, 1975||Sep 21, 1976||Alza Corporation||Bioerodible ocular device|
|US3986510 *||Aug 1, 1975||Oct 19, 1976||Alza Corporation||Bioerodible ocular device|
|US3993071 *||Jul 24, 1975||Nov 23, 1976||Alza Corporation||Bioerodible ocular device|
|US3993073 *||Mar 3, 1975||Nov 23, 1976||Alza Corporation||Novel drug delivery device|
|US4083741 *||Jul 27, 1976||Apr 11, 1978||Hoffmann-La Roche, Inc.||Novel dosage form|
|US4126502 *||Apr 29, 1977||Nov 21, 1978||Hoffmann-La Roche Inc.||Manufacture of pharmaceutical dosage forms|
|US4126503 *||Apr 29, 1977||Nov 21, 1978||Hoffmann-La Roche Inc.||Manufacture of pharmaceutical dosage forms|
|US4135514 *||Mar 9, 1977||Jan 23, 1979||Alza Corporation||Osmotic releasing system for administering ophthalmic drug to eye of animal|
|US4142526 *||Mar 9, 1977||Mar 6, 1979||Alza Corporation||Osmotic releasing system with means for changing release therefrom|
|US4228149 *||May 30, 1978||Oct 14, 1980||Beecham Group Limited||Sustained release compositions|
|US4308250 *||Dec 9, 1980||Dec 29, 1981||Beecham Group Limited||For oral administration to ruminants|
|US4439183 *||May 13, 1982||Mar 27, 1984||Alza Corporation||Parenteral agent dispensing equipment|
|US4521211 *||Feb 3, 1984||Jun 4, 1985||Alza Corporation||Parenteral agent dispensing equipment|
|US4540408 *||Apr 29, 1982||Sep 10, 1985||Smith And Nephew Associated Companies Limited||Applicators for pharmacologically active agents, their preparation and use|
|US4548598 *||Feb 3, 1984||Oct 22, 1985||Alza Corporation||Parenteral agent dispensing equipment|
|US4576604 *||Mar 4, 1983||Mar 18, 1986||Alza Corporation||Osmotic system with instant drug availability|
|US4673405 *||Jan 8, 1986||Jun 16, 1987||Alza Corporation||Osmotic system with instant drug availability|
|US4698062 *||Oct 30, 1985||Oct 6, 1987||Alza Corporation||Medical device for pulsatile transdermal delivery of biologically active agents|
|US4883666 *||Apr 29, 1987||Nov 28, 1989||Massachusetts Institute Of Technology||Controlled drug delivery system for treatment of neural disorders|
|US4886870 *||Feb 15, 1985||Dec 12, 1989||Massachusetts Institute Of Technology||Bioerodible articles useful as implants and prostheses having predictable degradation rates|
|US4891225 *||Jan 21, 1986||Jan 2, 1990||Massachusetts Institute Of Technology||Sustained release|
|US4906474 *||May 21, 1984||Mar 6, 1990||Massachusetts Institute Of Technology||Bioerodible polyanhydrides for controlled drug delivery|
|US4946929 *||Jun 15, 1987||Aug 7, 1990||Massachusetts Institute Of Technology||Biocompatible polyanhydrides|
|US5079006 *||Jul 13, 1988||Jan 7, 1992||Aprex Corporation||Pharmaceutical compositions containing a magnetically detectable material|
|US5114719 *||Sep 14, 1989||May 19, 1992||Sabel Bernhard A||Polymer matrix for drug delivery of biologically active molecules|
|US5167962 *||Aug 8, 1991||Dec 1, 1992||Southwest Research Institute||Release at desired location in intestine|
|US5236734 *||Mar 16, 1992||Aug 17, 1993||Fuisz Technologies Ltd.||Method of preparing a proteinaceous food product containing a melt spun oleaginous matrix|
|US5238696 *||May 6, 1992||Aug 24, 1993||Fuisz Technologies Ltd.||Method of preparing a frozen comestible|
|US5268110 *||Aug 27, 1992||Dec 7, 1993||Fuisz Technologies Ltd.||Oil removing method|
|US5279849 *||May 12, 1992||Jan 18, 1994||Fuisz Technologies Ltd.||Melt spinning|
|US5286513 *||Jun 22, 1993||Feb 15, 1994||Fuisz Technologies Ltd.||Proteinaceous food product containing a melt spun oleaginous matrix|
|US5326568 *||Apr 30, 1992||Jul 5, 1994||Giampapa Vincent C||Implanting insert having drug-containing, biodegradable concentric shells|
|US5348758 *||Oct 20, 1992||Sep 20, 1994||Fuisz Technologies Ltd.||Controlled melting point matrix formed with admixtures of a shearform matrix material and an oleaginous material|
|US5374447 *||Dec 6, 1993||Dec 20, 1994||Fuisz Technologies Ltd.||Exchanging a portion of fat in meat product with oleaginous containing matrix formed by vegetable oils or animal fats and oils and sugar|
|US5380473 *||Oct 23, 1992||Jan 10, 1995||Fuisz Technologies Ltd.||Process for making shearform matrix|
|US5387431 *||Mar 5, 1992||Feb 7, 1995||Fuisz Technologies Ltd.||Saccharide-based matrix|
|US5407676 *||Dec 24, 1992||Apr 18, 1995||Fuisz Technologies Ltd.||Hydrophilic form of perfluoro compounds and a method of manufacture|
|US5427804 *||Mar 15, 1994||Jun 27, 1995||Fuisz Technologies Ltd.||Low-fat edible proteins with maltodextrins and low-saturate oils|
|US5429836 *||Jul 29, 1993||Jul 4, 1995||Fuisz Technologies Ltd.||Maltodextrin and emulsifier feed and matrix for foods|
|US5445769 *||Jun 27, 1994||Aug 29, 1995||Fuisz Technologies Ltd.||Spinner head for flash flow processing|
|US5456932 *||Apr 22, 1994||Oct 10, 1995||Fuisz Technologies Ltd.||Adding fructose to reduce heat needed to create flash flow conditions|
|US5464935 *||Feb 6, 1995||Nov 7, 1995||Centocor, Inc.||Peptide inhibitors of selectin binding|
|US5472731 *||Mar 22, 1995||Dec 5, 1995||Fuisz Technologies Ltd.||Protein based food product|
|US5490993 *||Mar 24, 1995||Feb 13, 1996||Fuisz Technologies Ltd.||Method of preparing a proteinaceous food product containing a melt spun matrix and product thereof|
|US5494677 *||Jun 28, 1993||Feb 27, 1996||Giampapa; Vincent C.||Tissue-specific implantable therapeutic agent delivery system|
|US5501858 *||Sep 10, 1993||Mar 26, 1996||Fuisz Technologies Ltd.||Rapidly dispersable compositions containing polydextrose|
|US5503862 *||May 26, 1995||Apr 2, 1996||Fuisz Technologies Ltd.||Reducing temperature by mixing in fructose, maltodextrin and/or polydextrose|
|US5516537 *||May 4, 1993||May 14, 1996||Fuisz Technologies Ltd.||Frozen comestibles|
|US5518551 *||Sep 10, 1993||May 21, 1996||Fuisz Technologies Ltd.||Spheroidal crystal sugar and method of making|
|US5518730 *||Jun 3, 1992||May 21, 1996||Fuisz Technologies Ltd.||Biodegradable controlled release flash flow melt-spun delivery system|
|US5520859 *||Apr 8, 1994||May 28, 1996||Fuisz Technologies Ltd.||Method for flash flow processing having feed rate control|
|US5545409 *||Apr 5, 1994||Aug 13, 1996||Massachusetts Institute Of Technology||Shaped matrix of polyanhydride or polyorthoester and a chondrogenic or osteogenic bioactive protein|
|US5549917 *||Jun 7, 1995||Aug 27, 1996||Fuisz Technologies Ltd.||Flash flow formed solloid delivery systems|
|US5556652 *||Aug 5, 1994||Sep 17, 1996||Fuisz Technologies Ltd.||Comestibles containing stabilized highly odorous flavor component delivery systems|
|US5567439 *||Nov 4, 1994||Oct 22, 1996||Fuisz Technologies Ltd.||Delivery of controlled-release systems(s)|
|US5576042 *||Mar 2, 1994||Nov 19, 1996||Fuisz Technologies Ltd.||High intensity particulate polysaccharide based liquids|
|US5582855 *||Jul 1, 1994||Dec 10, 1996||Fuisz Technologies Ltd.||Flash flow formed solloid delivery systems|
|US5587198 *||May 31, 1995||Dec 24, 1996||Fuisz Technologies Ltd.||Positive hydration method of preparing confectionery and product therefrom|
|US5593502 *||Jun 6, 1995||Jan 14, 1997||Fuisz Technologies Ltd.||Method of making crystalline sugar and products resulting therefrom|
|US5597416 *||Oct 7, 1993||Jan 28, 1997||Fuisz Technologies Ltd.||Method of making crystalline sugar and products resulting therefrom|
|US5597608 *||Dec 28, 1994||Jan 28, 1997||Fuisz Technologies Ltd.||Feedstock subjected to force and heating conditions to induce flash flow; foods, drugs|
|US5601076 *||Jun 5, 1995||Feb 11, 1997||Fuisz Technologies Ltd.||Spheroidal polycrystallite having continuous three-dimensional structure comprising small crystallites arranged around spheroidal center|
|US5601835 *||Jan 12, 1994||Feb 11, 1997||Massachusetts Institute Of Technology||Insertion into central nervous system|
|US5602230 *||May 10, 1995||Feb 11, 1997||Centocor, Inc.||Peptide inhibitors of selectin binding|
|US5618785 *||Jun 1, 1995||Apr 8, 1997||Centocor, Inc.||Antiischemic agents, antitumor agents, antiarthritic agents|
|US5622719 *||May 23, 1996||Apr 22, 1997||Fuisz Technologies Ltd.||Mixing additive with uncured shearform carrier matrix, molding, crystallization|
|US5624684 *||May 13, 1992||Apr 29, 1997||Fuisz Technologies Ltd.||Enzyme systems|
|US5629009 *||Aug 7, 1996||May 13, 1997||Massachusetts Institute Of Technology||Inducing chondrogenesis and osteogenesis by implanting shaped polyanhydride or polyorthoester matrix with bioactive substance, i.e., demineralized bone protein, tgf-beta, egf, fgf or pdgf|
|US5633027 *||Jun 7, 1995||May 27, 1997||Fuisz Technologies Ltd.||Solid delivery system; mixture of flavored oils and triglycerides|
|US5651987 *||Aug 27, 1993||Jul 29, 1997||Fuisz Technologies Ltd.||Ulcer prevention and treatment composition|
|US5654003 *||Feb 10, 1994||Aug 5, 1997||Fuisz Technologies Ltd.||Process and apparatus for making tablets and tablets made therefrom|
|US5654273 *||Sep 22, 1994||Aug 5, 1997||Children's Medical Center Corporation||Synducin mediated modulation of tissue repair|
|US5660848 *||Nov 2, 1994||Aug 26, 1997||The Population Council, Center For Biomedical Research||Subdermally implantable device|
|US5660851 *||Jun 5, 1995||Aug 26, 1997||Yissum Research Development Company Of The Hebrew Univ. Of Jerusalem||Covalent attachmentof a carboxylic acid-containing active material through anhydride bonds to a polymer that contains pendant carboxylic acid groups; drug delivery|
|US5695993 *||Aug 12, 1994||Dec 9, 1997||Oklahoma Medical Research Foundation||Cloning and regulation of an endothelial cell protein C/activated protein C receptor|
|US5709876 *||Jun 7, 1995||Jan 20, 1998||Fuisz Technologies Ltd.||Saccharide-based matrix|
|US5710123 *||Dec 13, 1993||Jan 20, 1998||Centocor, Inc.||Peptide inhibitors of selectin binding|
|US5713852 *||Jun 7, 1995||Feb 3, 1998||Alza Corporation||Oral dosage and method for treating painful conditions of the oral cavity|
|US5728397 *||Feb 4, 1997||Mar 17, 1998||Fuisz Technologies Ltd.||Polydextrose product and process|
|US5733577 *||Aug 16, 1996||Mar 31, 1998||Fuisz Technologies Ltd.||Crystallization of a quick-dissolving shearform matrix, mixing with a time-release drug delivery system to form flowable microparticles and compacting|
|US5744180 *||Oct 23, 1996||Apr 28, 1998||Fuisz Technologies Ltd.||Comestibles containing stabilized highly odorous flavor component delivery systems|
|US5753617 *||Sep 8, 1993||May 19, 1998||Centocor, Inc.||Peptide inhibitors of cellular adhesion|
|US5756115 *||Jun 7, 1995||May 26, 1998||The Population Coucil, Center For Biomedical Research||Contraceptive method using a subdermally implantable device|
|US5759539 *||Jun 6, 1995||Jun 2, 1998||Georgia Research Foundation, Inc.||Oxidizing ethanol to acetate in the blood|
|US5804247 *||Dec 20, 1996||Sep 8, 1998||Fuisz Technologies Ltd.||Mixing together a saccharide based shearform matrix comprising magnesium and calcium salt and hydrated hydrobonding agent selected from food grade gums, gelatin and mixture, hydration to provide cohesiveness and lubricity|
|US5824342 *||Apr 9, 1996||Oct 20, 1998||Fuisz Technologies Ltd.||Flash flow formed solloid delivery systems|
|US5827563 *||Jan 13, 1997||Oct 27, 1998||Fuisz Technologies Ltd.||Fondant cream containing polycrystalline sugar having uniform controlled particle size and three-dimensional structure|
|US5843884 *||Nov 15, 1995||Dec 1, 1998||Oklahoma Medical Research Foundation||C9 complement inhibitor|
|US5843922 *||Jun 11, 1996||Dec 1, 1998||Fuisz Technologies Ltd.||Preparation of oligosaccharides and products therefrom|
|US5849900 *||Mar 28, 1995||Dec 15, 1998||Max-Planck-Gesellschaft Zur Forderung Der Wissenschafter E.V.||Inhibition of viruses by antisense oligomers capable of binding to polypurine rich tract of single-stranded RNA or RNA-DNA hybrids|
|US5851552 *||Aug 16, 1996||Dec 22, 1998||Fuisz Technologies, Ltd.||Delivery of controlled-release system(s)|
|US5851553 *||Dec 19, 1996||Dec 22, 1998||Fuisz Technologies, Ltd.||Process and apparatus for making rapidly dissolving dosage units and product therefrom|
|US5853760 *||Dec 2, 1994||Dec 29, 1998||Lts Lohmann Therapie-Systeme Gmbh & Co. Kg||Device for the controlled release of active substances|
|US5853762 *||Aug 16, 1996||Dec 29, 1998||Fuisz Technologies Ltd||Delivery of controlled-release system(s)|
|US5858385 *||Jul 21, 1997||Jan 12, 1999||The Trustees Of The Stevens Institute Of Technology||Microporous hollow fiber membrane having pores filled with water or solvent, fiber lumen filled with solvent or water and pest control substance or fragrance which partitions in pores and diffuses out|
|US5859227 *||Feb 20, 1997||Jan 12, 1999||Bearsden Bio, Inc.||Binding sites for proteins involved in post-transcriptional regulation in eukaryotic cells; for potential drug targets and cloning of heterologous proteins|
|US5866163 *||Dec 19, 1996||Feb 2, 1999||Fuisz Technologies Ltd.||Quick dissolving active material|
|US5871781 *||Dec 19, 1996||Feb 16, 1999||Fuisz Technologies Ltd.||Apparatus for making rapidly-dissolving dosage units|
|US5888982 *||Mar 31, 1997||Mar 30, 1999||President And Fellows Of Harvard College||Regulation of vascular smooth muscle cell heme oxygenase-1|
|US5895664 *||Jun 14, 1994||Apr 20, 1999||Fuisz Technologies Ltd.||Process for forming quickly dispersing comestible unit and product therefrom|
|US5898066 *||Aug 26, 1994||Apr 27, 1999||Children's Medical Center Corporation||Trophic factors for central nervous system regeneration|
|US5916876 *||Dec 22, 1994||Jun 29, 1999||Centocor, Inc.||Peptide inhibitors of leukocyte adhesion|
|US5925333 *||Nov 15, 1995||Jul 20, 1999||Massachusetts Institute Of Technology||Screening for compounds that alter the binding by scavengers|
|US5962322 *||Nov 15, 1996||Oct 5, 1999||Massachusetts Institute Of Technology||Methods for modulation of cholesterol transport|
|US6001990 *||Jun 7, 1995||Dec 14, 1999||The General Hospital Corporation||Antisense inhibition of hepatitis C virus|
|US6004749 *||Jul 31, 1997||Dec 21, 1999||Message Pharmaceuticals||Detection of interactions between rna binding proteins and each of amyloid precursor protein untranslated region|
|US6020002 *||Nov 5, 1997||Feb 1, 2000||Fuisz Technologies Ltd.||Delivery of controlled-release system(s)|
|US6107029 *||Jul 31, 1996||Aug 22, 2000||Message Pharmaceticals, Inc.||Detecting protein bound nucleic acids; forming binding solution, heating solution, denaturing the nucleic acids in solution, cooling solution, adding proteins, detecting interactions between the proteins and ribonucleic acids|
|US6110481 *||Mar 4, 1994||Aug 29, 2000||Trustees Of The Stevens Institute Of Technology||A controlled release dispenser employing microporous membranes with or without a nonporous coating and aqueous-organic partitioning of the bioreactive substances such as pesticides, hormones, nutrients and fragrances to humans or animals|
|US6124267 *||Apr 20, 1998||Sep 26, 2000||Southpac Trust Internationals, Inc.||O-glycan inhibitors of selectin mediated inflammation derived from PSGL-1|
|US6129926 *||May 13, 1992||Oct 10, 2000||Fuisz Technologies Ltd.||Flash flow processing of thermoplastic polymers and products made therefrom|
|US6196993||Apr 19, 1999||Mar 6, 2001||Eyelab Group, Llc||Ophthalmic insert and method for sustained release of medication to the eye|
|US6200751||Nov 7, 1997||Mar 13, 2001||Oklahoma Medical Research Foundation||Cell preferential regulatory sequences; for the control of transcription from heterologous nucleotide sequences; for use in gene therapy|
|US6203813||Oct 9, 1998||Mar 20, 2001||Lance L. Gooberman||Opiate antagonist, steroidal antiinflammatory agent and carrier; sustained release; drug abuse treatment|
|US6284729||May 6, 1998||Sep 4, 2001||Children's Medical Center Corporation||Methods and reagents for regulating obesity|
|US6299875||Jun 4, 1998||Oct 9, 2001||Panacea Pharmaceuticals, Llc||Methods to block IGE binding to cell surface receptors of mast cells|
|US6306428||Apr 13, 1998||Oct 23, 2001||Roehm Gmbh Chemische Fabrik||Controlled active substance release is accomplished with rolled or folded layers of a polymer film, that contain a pharmaceutically active substance|
|US6309639||Aug 9, 2000||Oct 30, 2001||The Board Of Regents Of The University Of Oklahoma||Administering an antibody to a protein component or to a carbohydrate-protein component of p-selectin glycoprotein ligand, the glycoprotein ligand comprising a fucosylated sialylated glycoprotein containing sialyl lewis x antigen|
|US6350859||Feb 2, 1999||Feb 26, 2002||Massachusetts Institute Of Technology||Class BI and CI scavenger receptors|
|US6399064||Oct 29, 1998||Jun 4, 2002||Oklahoma Medical Research Foundation||Cloning endothelial cells and protein c|
|US6407236||Aug 23, 1999||Jun 18, 2002||Medco Research, Inc.||Tumor diagnosis; antiinflammatory agents; antiischemic agents; antidepressants|
|US6410508||Oct 7, 1999||Jun 25, 2002||Med College Georgia Res Inst||Glucose-dependent insulinotropic peptide for use as an osteotropic hormone|
|US6448253||Sep 16, 1998||Sep 10, 2002||King Pharmaceuticals Research And Development, Inc.||Adenosine A3 receptor modulators|
|US6506382||Oct 29, 2001||Jan 14, 2003||The Board Of Regents Of The University Of Oklahoma||Method for inhibiting reperfusion injury using antibodies to P-selectin glycoprotein ligand|
|US6667036||Nov 18, 2002||Dec 23, 2003||The Board Of Regents Of The University Of Oklahoma||Administering antibody to a protein component or to a carbohydrate-protein component of P-selectin glycoprotein ligand for therapy of rheumatoid arthritis|
|US6919373||Feb 19, 1999||Jul 19, 2005||Alza Corporation||Methods and devices for providing prolonged drug therapy|
|US6921825||Apr 26, 2002||Jul 26, 2005||King Pharmaceuticuals Research & Development, Inc.||Pyrazolo-triazolo- pyrimidine, triazolo-triazolo-pyrimidine and imidazolo-triazolo-pyrimidine derivatives useful for the treatment of hypertension, inflammation, mast cell degranulation, cardiac hypoxia, and ischemia|
|US6930129||Mar 8, 2001||Aug 16, 2005||Alza Corporation||Orally administering a dosage form containing a central nervous system-acting drug in a pharmaceutically acceptable carrier, wherein said dosage release the drug at an ascending release rate for an extended time period|
|US6953568||Aug 25, 1998||Oct 11, 2005||Oklahoma Medical Research Foundation||Administering biological conjugates that bind preferentially to endothelial protein C receptor(EPCR), to endothelial cells of vascular systems; genetic translocation; drug delivery|
|US7045350||Aug 29, 2002||May 16, 2006||Mount Sinai School Of Medicine Of New York University||Alternatively spliced circulating tissue factor|
|US7063843||Aug 20, 1999||Jun 20, 2006||Oklahoma Medical Research Foundation||Cloning and regulation of an endothelial cell protein C/activated protein C receptor|
|US7078511||Jun 19, 1995||Jul 18, 2006||Massachusette Institute Of Technology||nucleic acid molecule encoding Hamster scavenger receptor BI (HaSR-BI) which has high affinity for low density lipoproteins (LDL) and acylated LDL, expressed in adipocytes; antilipemic, anticholesterol agents; receptor binding assay; drug screening|
|US7166568||Feb 9, 1998||Jan 23, 2007||Oklahoma Medical Research Foundation||Compositions and methods to inhibit formation of the C5b-9 complex of complement|
|US7208467||Jun 7, 2002||Apr 24, 2007||Monty Krieger||Administering a compound altering transfer of cholesterol or cholesteryl ester from high density lipoprotein or other lipoproteins via SR-BI to liver or steroidogenic tissues or compounds blocking oxidative modification of LDL|
|US7241457 *||Sep 29, 2004||Jul 10, 2007||Alza Corporation||Osmotically driven active agent delivery device providing an ascending release profile|
|US7306580||Apr 16, 2003||Dec 11, 2007||Cook Incorporated||Medical device with therapeutic agents|
|US7361684||May 16, 2002||Apr 22, 2008||Massachusetts Institute Of Technology||Screening of compounds for treatment of atherosclerosis and heart attack|
|US7514592||Apr 5, 2005||Apr 7, 2009||Massachusetts Institute Of Technology||transgenic rodents genetically engineered to knock out gene expression of active scavenger receptor class BI (SR-BI) and having apolipoprotein E activity or expression decreased to 2-5% of normal levels; models of cardiovascular disoders induced by feeding a lipid enriched diet|
|US7780647||Oct 31, 2007||Aug 24, 2010||Cook Incorporated||Medical device with therapeutic agents|
|US7785632||Sep 15, 2004||Aug 31, 2010||Ordway Research Institute, Inc.||angiogenesis inhibitors; tetraiodothyroacetic acid conjugated to glycolide-lactide copolymer; binds cell surface receptor for thyroid hormone on integrin alpha at cell membrane level and does not activate signal transduction|
|US7786090||Mar 1, 2007||Aug 31, 2010||President And Fellows Of Harvard College||Methods and compositions for treating and preventing neurologic disorders|
|US7824704||Aug 15, 2005||Nov 2, 2010||Surmodics, Inc.||Controlled release bioactive agent delivery device|
|US7960606||Jun 19, 2007||Jun 14, 2011||The J. David Gladstone Institutes||Mouse model of chronic heart failure and coronary atherosclerosis regression|
|US7976862||Aug 15, 2005||Jul 12, 2011||Surmodics, Inc.||Longitudinal body; polymeric coating of polyalkyl(meth)acrylate and/or aromatic poly(meth)acrylate; and poly(ethylene-co-vinyl acetate); triamcinolone acetonide; drug delivery to eye|
|US8021680||Apr 29, 2004||Sep 20, 2011||Surmodics, Inc.||Controlled release bioactive agent delivery device|
|US8034369||Sep 12, 2005||Oct 11, 2011||Surmodics, Inc.||Controlled release bioactive agent delivery device|
|US8071134||Sep 15, 2005||Dec 6, 2011||Ordway Research Institute, Inc.||treating subjects having conditions related to angiogenesis; thyroid hormone, thyroid hormone analog, or polymeric forms thereof|
|US8084059||Sep 15, 2006||Dec 27, 2011||Alza Corporation||Antidepressant dosage form|
|US8163798||Aug 12, 2003||Apr 24, 2012||Alza Corporation||Administering methylphenidate at an ascending release rate over an extended time period; therapeutic affect over long time period; hyperactivity/attention deficit disorder|
|US8211401||Dec 4, 2009||Jul 3, 2012||Molecular Insight Pharmaceuticals, Inc.||Technetium- and rhenium-bis(heteroaryl) complexes and methods of use thereof for inhibiting PSMA|
|US8211402||Dec 4, 2009||Jul 3, 2012||Molecular Insight Pharmaceuticals, Inc.||CA-IX specific radiopharmaceuticals for the treatment and imaging of cancer|
|US8235047||Mar 30, 2006||Aug 7, 2012||Conceptus, Inc.||Methods and devices for deployment into a lumen|
|US8246974||Apr 8, 2005||Aug 21, 2012||Surmodics, Inc.||Medical devices and methods for producing the same|
|US8268887||Oct 8, 2009||Sep 18, 2012||Feng Xu||Drug conjugates and methods of use thereof|
|US8518451||Nov 25, 2009||Aug 27, 2013||Albany College of Pharmacy and Health Services||Thyroid hormone analogs and methods of use|
|US8562945||Dec 4, 2009||Oct 22, 2013||Molecular Insight Pharmaceuticals, Inc.||Technetium- and rhenium-bis(heteroaryl) complexes and methods of use thereof|
|US8629179||Oct 19, 2009||Jan 14, 2014||Alza Corporation||Methods and devices for providing prolonged drug therapy|
|US8668926||Apr 11, 2007||Mar 11, 2014||Shaker A. Mousa||Nanoparticle and polymer formulations for thyroid hormone analogs, antagonists, and formulations thereof|
|US8673344 *||Nov 12, 2007||Mar 18, 2014||AbbVie Deutschland GmbH & Co. KG||Solid dosage form with a film containing an active substance, as well as its method of production|
|US8707958||Aug 1, 2012||Apr 29, 2014||Bayer Essure Inc.||Methods and devices for deployment into a lumen|
|US8802240||Jan 6, 2012||Aug 12, 2014||Nanopharmaceuticals Llc||Uses of formulations of thyroid hormone analogs and nanoparticulate forms thereof to increase chemosensitivity and radiosensitivity in tumor or cancer cells|
|US8821835||Jun 13, 2013||Sep 2, 2014||Microspherix Llc||Flexible and/or elastic brachytherapy seed or strand|
|US8840865||Sep 30, 2013||Sep 23, 2014||Molecular Insight Pharmaceuticals, Inc.||Technetium- and rhenium-bis(heteroaryl) complexes and methods of use thereof|
|US8877970||Jan 8, 2009||Nov 4, 2014||Molecular Insight Pharmaceuticals, Inc.||Inhibitors of carbonic anhydrase IX|
|US8932558||Sep 29, 2008||Jan 13, 2015||Plaxgen Inc||Multi-subunit biological complexes for treatment of plaque-associated diseases|
|US20100119583 *||Nov 12, 2007||May 13, 2010||Abbott Gmbh & Co. Kg||Solid dosage form with a film containing an active substance, as well as its method of production|
|US20130189342 *||Mar 16, 2011||Jul 25, 2013||Titan Pharmaceuticals, Inc.||Heterogeneous implantable devices for drug delivery|
|US20130195950 *||Mar 13, 2013||Aug 1, 2013||Titan Pharmaceuticals, Inc.||Heterogeneous implantable devices for drug delivery|
|US20130195951 *||Mar 13, 2013||Aug 1, 2013||Titan Pharmaceuticals, Inc.||Heterogeneous implantable devices for drug delivery|
|US20130202673 *||Mar 13, 2013||Aug 8, 2013||Titan Pharmaceuticals, Inc.||Heterogeneous implantable devices for drug delivery|
|DE2656387A1 *||Dec 13, 1976||Jun 30, 1977||Hoffmann La Roche||Feste pharmazeutische einheitsdosierungsform als darreichunsform eines medikaments sowie verfahren und anlage zu ihrer herstellung|
|DE3124981A1 *||Jun 25, 1981||Jan 13, 1983||Ruhland Nachf Gmbh Dr||Wirkstoffhaltige kollageneinlage zum einfuehren in knochen oder weichteile und verfahren zu deren herstellung|
|EP0010987A1 *||Nov 5, 1979||May 14, 1980||Beecham Group Plc||Device for oral administration to a ruminant animal|
|EP0021758A1 *||Jun 16, 1980||Jan 7, 1981||Beecham Group Plc||Veterinary preparations for ruminant animals|
|EP0064841A1 *||Apr 29, 1982||Nov 17, 1982||Smith and Nephew Associated Companies p.l.c.||Applicators for pharmaceutically active agents, their preparation and use|
|EP0714912A2||Jul 17, 1991||Jun 5, 1996||The Board Of Regents Of The University Of Oklahoma||GMP-140 derived lektin-like domain peptides and their ligands|
|EP0872234A2 *||Apr 7, 1998||Oct 21, 1998||Röhm Gmbh||Laminar medical formulation|
|EP1920768A1 *||Nov 10, 2006||May 14, 2008||Abbott GmbH & Co. KG||Solid dosage form with a film containing an active substance, as well as its method of production|
|EP2133365A2||Dec 26, 2007||Dec 16, 2009||Emory University||Compositions and methods for the treatment of infections and tumors|
|EP2194144A1||Nov 15, 2005||Jun 9, 2010||Trustees Of Boston University||Roles for dual Endothelin-1/Angiotensin II receptor (DEAR) in hypertension and angiogenesis|
|EP2335694A1||Sep 15, 2004||Jun 22, 2011||Ordway Research Institute, Inc.||Thyroid hormone analogs and methods of use.|
|EP2380872A1||Jun 15, 2005||Oct 26, 2011||Polymedix, Inc.||Polycationic compounds and uses thereof|
|EP2397155A1||Jun 8, 2006||Dec 21, 2011||Dana Farber Cancer Institute||Methods and compositions for the treatment of persistent infections and cancer by inhibiting the programmed cell death 1 (pd-1)pathway|
|EP2397156A1||Jun 8, 2006||Dec 21, 2011||Dana-Farber Cancer Institute, Inc.||Methods and compositions for the treatment of persistent infections and cancer by inhibiting the programmed cell death 1 (PD-1)pathway|
|EP2423331A2||Mar 31, 2005||Feb 29, 2012||The General Hospital Corporation||Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments|
|EP2439284A1||Mar 31, 2005||Apr 11, 2012||The General Hospital Corporation||Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments|
|EP2439285A1||Mar 31, 2005||Apr 11, 2012||The General Hospital Corporation||Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments|
|EP2444038A2||Feb 28, 2007||Apr 25, 2012||Conceptus, Inc.||Devices for deployment into a lumen|
|EP2447375A2||Mar 31, 2005||May 2, 2012||The General Hospital Corporation||Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments|
|EP2468883A1||Dec 22, 2010||Jun 27, 2012||Pangaea Biotech S.L.||Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer|
|EP2476707A1||Nov 15, 2004||Jul 18, 2012||Children's Medical Center Corporation||Self-cleaving ribozymes and uses thereof|
|EP2492688A1||Feb 23, 2011||Aug 29, 2012||Pangaea Biotech, S.A.||Molecular biomarkers for predicting response to antitumor treatment in lung cancer|
|EP2662079A1||May 10, 2012||Nov 13, 2013||Ordway Research Institute, Inc.||Uses of formulations of thyroid hormone antagonists and nanoparticulate forms thereof to increase chemosensivity and radiosensitivity in tumor or cancer cells|
|EP2706057A1||Dec 4, 2009||Mar 12, 2014||Molecular Insight Pharmaceuticals, Inc.||Bis(imidazolyl)compounds and radionuclide complexes|
|WO1991017745A1 *||May 22, 1991||Nov 28, 1991||Southwest Res Inst||Filament system for delivering a medicament and method|
|WO1993021859A1 *||Apr 26, 1993||Nov 11, 1993||Vincent Carmine Giampapa||Tissue-specific implantable therapeutic agent delivery system|
|WO1995023598A1 *||Feb 28, 1995||Sep 8, 1995||Stevens Inst Technology||Controlled release microporous membranes|
|WO2001022947A2 *||Sep 16, 2000||Apr 5, 2001||Krumme Markus||Preparation containing active ingredients and/or auxiliary agents with a controlled release of these substances and the use and production of the same|
|WO2003097019A1 *||Apr 29, 2003||Nov 27, 2003||Cuine-Backert Marie Elisabeth||Multilamellar system for the administration of active agents by means of ingestion|
|WO2004093962A1 *||Mar 24, 2004||Nov 4, 2004||Cook Inc||Medical device with therapeutic agents.|
|WO2007097867A1 *||Jan 25, 2007||Aug 30, 2007||Boston Scient Scimed Inc||Extendable rolled delivery system|
|WO2008056001A1 *||Nov 12, 2007||May 15, 2008||Abbott Gmbh & Co Kg||Solid dosage form with a film containing an active substance, as well as its method of production|
|WO2010075332A1||Dec 22, 2009||Jul 1, 2010||Charitable Leadership Foundation||Small molecule ligands of the integrin rgd recognition site and methods of use|
|WO2011058164A1||Nov 15, 2010||May 19, 2011||Pangaea Biotech, S.A.||Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer|
|WO2011061625A2||Nov 19, 2010||May 26, 2011||Solis Biodyne||Compositions for increasing polypeptide stability and activity, and related methods|
|WO2012085229A1||Dec 22, 2011||Jun 28, 2012||Pangaea Biotech, S.L.||Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer|
|WO2012113819A1||Feb 22, 2012||Aug 30, 2012||Pangaea Biotech, S.L.||Molecular biomarkers for predicting response to antitumor treatment in lung cancer|
|WO2012149326A1 *||Apr 27, 2012||Nov 1, 2012||Massachusetts Institute Of Technology||Layer processing for pharmaceuticals|
| || |
|U.S. Classification||424/424, 424/484, 424/472, 424/443, 424/433, 424/426, 424/436, 424/427, 424/434, 424/435|
|International Classification||A61K9/70, A61M31/00, A61K9/20, A61D7/00|
|Cooperative Classification||A61D7/00, A61M31/002, A61K9/2072, A61K9/2086, A61K9/70|
|European Classification||A61M31/00D, A61D7/00, A61K9/20K4, A61K9/70, A61K9/20K|