Sustained-release formulation containing an amino acid polymer with a lower alkyl (C.sub.1 -C.sub.4) polar solvent

• US 4,713,244 A
• Filed: 08/16/1985
• Issued: 12/15/1987
• Est. Priority Date: 08/16/1985
• Status: Expired due to Fees

• Current Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Original Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Inventors: Bawa, Rajan, Deichert, William G.
• Primary Examiner(s): Griffin, Ronald W.
• Application Number:
  US06/766,734
• Time in Patent Office: 851 Days
• Field of Search: 424/19, 424/21, 424/486, 424/487, 424/429, 604/893, 604/894, 604/895, 351/160 R, 351/160 H, 351/177, 523/106, 523/107, 523/108, 514/912, 514/913, 514/954
• US Class Current: 424/429
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants

Abstract

A sustained-release polymeric hydrogel dosage form useful for topical, systemic or transdermal administration of a medicinal agent comprising a cross-linked, polymerized hydrophilic polymer, an amino acid polymer, a cross-linking agent, and an optional hydrophobic monomer and/or a chain regulator in conjunction with a lower alkyl (C₁ -C₄), polar solvent and said medicinal agent in a therapeutically effective amount.

Claims

1. A sustained-release polymeric hydrogel dosage form useful for topical, systemic or transdermal administration of a medicinal agent comprising a cross-linked, polymerized hydrophilic polymer including an amino acid moiety in the polymer, in conjunction with a lower alkyl (C₁ -C₄) polar solvent and said medicinal agent in a therapeutically effective amount.

2. The sustained-release dosage form of claim 1 wherein the polymer includes therein a hydrophobic component:

3. The sustained-release dosage form of claim 1 or 2 wherein the amino acid moiety is derived from an aliphatic monocarboxylic acid, an aliphatic dicarboxylic acid, an aromatic dicarboxylic acid, an aromatic tricarboxylic acid or an aromatic tetracarboxylic acid.

4. The sustained-release dosage form of claim 1 or 2 wherein the amino acid moiety is derived from methacroyl glycine, methacroyl glutamate, methacroyl desmosine or methacroyl isodesmosine.

5. The sustained-release dosage form of claim 1 or 2 wherein the polar solvent is a lower alkyl (C₁ -C₄) alcohol, an unmodified ketone, a modified ketone, a mixture of a lower alkyl (C₁ -C₄) alcohol and water in any proportion or a mixture of an unmodified ketone and a modified ketone in any proportion.

6. The sustained-release dosage form of claim 1 or 2 wherein said medicinal agent is an antibiotic, an antiviral, an anti-inflammatory, a steroid, a peptide, a polypeptide, a cardiotonic, an antihypertensive, an antiallergic, an alpha-adrenergic blocking agent, a beta-adrenergic blocking agent, an anticataract agent, an ophthalmic medicament, an ophthalmic lubricating agent or an ophthalmic anesthetic agent.

7. The sustained-release dosage form of claim 1 or 2 wherein said medicinal agent is selected from the group consisting of pilocarpine, idoxuridine, carbachol, bethanechol, timolol, tetracycline, epinephrine, phenylephrine, eserine, phospholine, demecarium, cyclopentolate, homatropine, scopolamine, nitroglycerin, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, gentamycin, penicillin, erythromycin, sulfacetamide, polymyxin B, tobramycin, isofluorophate, fluoromethalone, dexamethasone, hydrocortisone, fluorocinolone, medrysone, prednisolone, methyl prednisolone, betamethasone, triamcinolone, interferon, cromolyn, all-trans-retinoic acid and a nontoxic, pharmaceutically acceptable salt thereof.

8. The sustained-release dosage form of claim 1 or 2 wherein said medicinal agent is an ophthalmic lubricating agent selected from the group consisting of polyvinyl alcohol, a cellulose polymer and a polylactam.

9. The sustained-release dosage form of claim 1 or 2 wherein said medicinal agent is an ophthalmic anesthetic agent.

10. The sustained-release dosage form of claim 1 or 2 wherein said dosage form is molded as a contact lens or ocular insert for ophthalmic administration of a systemic medicament, an ophthalmic medicament or an ophthalmic lubricating agent.

11. The sustained-release dosage form of claim 1 or 2 wherein said dosage form is molded as a contact lens for opthalmic administration of a systemic medicament, an ophthalmic medicament or an ophthalmic lubricating agent and retains the ability to correct vision.

12. The sustained-release dosage form of claim 2 wherein a polymeric hydrogel is prepared from a polymerizable hydrophilic monomer present in the amount of about 50% to about 90% w/w, an amino acid monomer present in the amount of about 5% to about 27% w/w, a cross-linking agent present in the amount of about 3% to about 30% w/w and a hydrophobic monomer present in the amount of about 8% to about 20% w/w, the weight percent being based on the total weight of the polymeric hydrogel.

13. A method of administering a therapeutically effective amount of a medicinal agent over an extended period of time to a mammal in need of the medicinal agent for local or systemic effect which comprises contacting a tissue of said mammal with the sustained-release dosage form of claim 1 or 2 for a prolonged period of time.

14. A method of administering a therapeutically effective amount of an ophthalmic medicament over an extended period of time to a mammal in need of the medicament which comprises contacting an eye tissue of said mammal with the sustained-release dosage form of claim 1 or 2 for a prolonged period of time, wherein said medicinal agent is the opthalmic medicament.

15. A method of administering a therapeutically effective amount of an ophthalmic lubricating agent over an extended period of time to a mammal in need of the agent which comprises contacting an eye tissue of said mammal with the sustained-release dosage form of claim 1 or 2 for a prolonged period of time, wherein said medicinal agent is the ophthalmic lubricating agent.

16. A method of administering a therapeutically effective amount of an ophthalmic anesthetic agent over an extended period of time to a mammal in need of ophthalmic anesthesia which comprises contacting an eye tissue of said mammal with the sustained-release dosage form of claim 1 or 2 for a prolonged period of time, wherein said medicinal agent is the ophthalmic anesthetic agent.

17. A method of treating glaucoma in a mammal suffering from glaucoma which comprises contacting an eye tissue of said mammal with the sustained-release dosage form of claim 1 or 2, wherein said medicinal agent is an agent for reducing intraocular pressure for a prolonged period of time.

18. A method of treating glaucoma in a mammal suffering from glaucoma which comprises contacting an eye tissue of said mammal with the sustained-release dosage form of claim 1 or 2, wherein said medicinal agent is timolol, pilocarpine or a nontoxic, pharmaceutically acceptable salt thereof for a prolonged period of time.

19. A method of inducing natural lacrimation or creating artificial lacrimation in a mammal suffering from deficient lacrimation which comprises contacting an eye tissue of said mammal with the sustained-release dosage form of claim 1 or 2 for a prolonged period of time, wherein said medicinal agent is an ophthalmic lubricating agent.

20. A process for the preparation of the sustained-release dosage form of claim 1 which comprises mixing a hydrophilic monomer, an amino acid monomer, a cross-linking agent and a lower alkyl (C₁ -C₄), polar solvent, polymerizing at room temperature, adding a medicinal agent and cross-linking.

21. A process for the preparation of the sustained-release dosage form of claim 2 which comprises mixing a hydrophilic monomer, an amino acid monomer, a cross-linking agent, a hydrophobic monomer and a lower alkyl (C₁ -C₄), polar solvent, polymerizing at room temperature, adding a medicinal agent and cross-linking.

22. The process of claim 20 or 21 wherein a catalyst is used.

23. The process of claim 20 or 21 wherein a chain regulator is added.

24. The process of claim 20 or 21 wherein a catalyst is used and a chain regulator is added.