Claims for Patent: 5,756,552

Summary for Patent: 5,756,552

Title:	Lyophilized pharmaceutical preparations capable of providing aqueous drug composition having property of reversible thermosetting gelation
Abstract:	Herein disclosed is a lyophilized pharmaceutical preparation obtained by lyophilizing an aqueous composition having property of reversible thermosetting gelation and comprising an effective amount of a drug, 0.2 to 2.1 (W/V)% of methylcellulose (the content of methoxyl group is within the range of 26 to 33%), 1.2 to 2.3 (w/v)% of citric acid and 0.5 to 13 (W/V)% of polyethylene glycol. The lyophilized pharmaceutical preparation makes it possible to stably store drugs unstable to water till they are put into practical use and, upon therapeutic use, an aqueous composition having property of reversible thermosetting gelation which can undergo gelation when locally applied can easily and immediately be reconstituted from the preparation by addition of a proper amount of a solvent for reconstitution.
Inventor(s):	Takeuchi; Masanobu (Nihonbashi-Muromachi, JP), Suzuki; Hiroe (Nihonbashi-Muromachi, JP), Takahashi; Toshie (Nihonbashi-Muromachi, JP), Maruyama; Hiroki (Nihonbashi-Muromachi, JP), Sasaki; Miyako (Nihonbashi-Muromachi, JP), Naito; Keiko (Nihonbashi-Muromachi, JP), Oguma; Touru (Nihonbashi-Muromachi, JP), Maeda; Makoto (Nihonbashi-Muromachi, JP)
Assignee:	Wakamoto Pharmaceutical Co., Ltd. (Tokyo, JP)
Application Number:	08/809,604
Patent Claims:	1. A lyophilized pharmaceutical preparation having property of reversible thermosetting gelation obtained by lyophilizing an aqueous composition comprising an effective amount of a drug, 0.2 to 2.1 (W/V)% of methylcellulose wherein the methoxyl group of the methylcellulose is within the range of 26 to 33%, 1.2 to 2.3 (W/V)% of citric acid and 0.5 to 13 (W/V)% of polyethylene glycol. 2. The lyophilized pharmaceutical preparation according to claim 1 for ophthalmic use wherein the pharmaceutically effective drug is selected from the group consisting of antiviral agents, antifungal agents, antibacterial substances, antiallergic agents, anti-inflammatory agents, miotics, vitamins, antiglaucoma drugs, anticataract drugs, carbonic anhydrase inhibitors, immunosuppressive agents, amino acids, adjuvants for surgery, anti-proliferative agents for fibroblast and mixture thereof. 3. The lyophilized pharmaceutical preparation according to claim 2 wherein the drug is selected from the group consisting of adenosine arabinoside, interferons, Amphotericin B, Nystatin, Carbenicillin, Penicillin G, Cefazolin, Tetracycline, Polymyxin B, Vancomycin, Amikacin, Erythromycin, Aspirin, Indomethacin, Acetylcholine, Physostigmine, Cocarboxylase, Cobamamide, Dipivefrine, Glutathione, Pirenoxine, Acetazolamide, Methotrexate, Cyclophosphamide, cysteine, hyaluronidase, .alpha.-Chymotrypsin, Mitomycin C and pharmaceutically acceptable salts thereof. 4. The lyophilized pharmaceutical preparation according to claim 3 wherein the drug is Mitomycin C. 5. The lyophilized pharmaceutical preparation according to claim 1 for local or dermatological use wherein the pharmaceutically effective drug is selected from the group consisting of antifungal agents, antibacterial substances and anti-inflammatory agents. 6. The lyophilized pharmaceutical preparation according to claim 5 wherein the drug is selected from the group consisting of Nystatin, Tetracycline, Amikacin, Polymyxin B, Erythromycin, Aspirin, Indomethacin and pharmaceutically acceptable salts thereof. 7. The lyophilized pharmaceutical preparation according to claim 1 to be administered into body cavities wherein the pharmaceutically effective drug is selected from the group consisting of antiviral agents, antifungal agents, antibacterial substances, antipyretics, analgesics, anti-inflammatory agents and antineoplastics. 8. The lyophilized pharmaceutical preparation according to claim 7 wherein the drug is selected from the group consisting of interferons, Nystatin, Tetracycline, Amikacin, Erythromycin, Aspirin, Indomethacin, Doxorubicin, Asparaginase and pharmaceutically acceptable salts thereof. 9. The lyophilized pharmaceutical preparation according to claim 1 wherein a 2.0% aqueous solution of the methylcellulose has a viscosity, as determined at 20.degree. C., ranging from 13 to 12000 millipascal.multidot.sec. 10. The lyophilized pharmaceutical preparation according to claim 1 wherein the polyethylene glycol has a weight-average molecular weight ranging from 1000 to 50,000. 11. The lyophilized pharmaceutical preparation according to claim 1 wherein the aqueous composition having property of reversible thermosetting gelation reconstituted with a solvent for reconstitution has a gelling temperature of from about 20.degree. C. to about 40.degree. C. and the composition is liquid at a temperature lower than the gelling temperature. 12. The lyophilized pharmaceutical preparation according to claim 1 wherein it includes at least one of pharmaceutically acceptable buffers, preservatives and solubilizing agents. 13. The lyophilized pharmaceutical preparation according to claim 1 wherein the solvent for reconstitution is water or water containing at least one of pharmaceutically acceptable buffers, preservatives and solubilizing agents. 14. A lyophilized pharmaceutical preparation comprising about 1 to about 50% by weight of methylcellulose, about 5 to about 60% by weight of citric acid or a salt thereof (expressed in terms of the reduced amount of citric acid), about 3 to about 88% by weight of polyethylene glycol and about 0.004 to about 70% by weight of a drug.

Details for Patent 5,756,552

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	05/05/2004		2039-02-26
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	12/02/2004		2039-02-26
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	10/26/2004		2039-02-26
Akorn, Inc.	HYDASE	hyaluronidase	Injection	021716	10/25/2005		2039-02-26
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2039-02-26