# US 2018/0021435 A1 · Hypotonic hydrogel formulations for enhanced transport of active agents at mucosal surfaces > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2018/0021435 A1 - Document ID: US20180021435A1 - Status: Published application - Kind: A1 - Application number: 15/546,772 - Filed: 2016-01-26 - Published: 2018-01-25 - Earliest claimed: 2015-01-27 - Assignees: The Johns Hopkins University - Applicants: The Johns Hopkins University - Inventors: Katharina Maisel; Laura Ensign; Justin Hanes; Richard Cones - Web page: https://patentgrep.com/patent/US20180021435A1 ## CPC - A61K 9/0031: {Rectum, anus} - A61K 8/90: Block copolymers (A61K8/89 takes precedence) - A61K 9/0034: {Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides} - A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)} - A61K 31/09: having two or more such linkages - A61K 31/352: condensed with carbocyclic rings, e.g. methantheline {(cannabinoids A61K31/658)} - A61K 31/365: Lactones - A61K 31/52: Purines, e.g. adenine - A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61P 31/18: for HIV - A61K 8/72: containing organic macromolecular compounds - A61K 9/0012: {Galenical forms characterised by the site of application} - A61K 9/08: Solutions {(composition of solutions A61K47/00)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Hypotonic formulations of hydrogel forming polymers, preferably poloxamers, have been developed for enhanced delivery through mucosa of therapeutic, diagnostic, prophylactic or other agents, to epithelial tissues, especially those having a mucosal coating. The polymers are administered at a concentration above, at or less than their critical gelling concentration (CGC) under isotonic conditions. The hypotonicity of the formulation is adjusted so that the polymer gels at the lower concentration. A Poloxamer gel administered into the vagina or colorectum at its CGC will form a “plug” of gel in the lumen. ## Claims ### Claim 1 An aqueous polymeric formulation for use as a barrier and/or in the delivery of a therapeutic, prophylactic, diagnostic or nutraceutical agent to a mucosal or epithelial tissue comprising a gel-forming polymer at a concentration which is less than the critical gel concentration of the polymer at the time of application to mucosal or epithelial tissues, and increases in concentration as water is absorbed from the formulation to or above the critical gel concentration (CGC) of the polymer under isotonic conditions and a temperature between room temperature and body temperature, optionally comprising excipients to form a hypotonic formulation of the polymer. ### Claim 2 (depends on 1) The formulation of claim 1, wherein the gel-forming polymer is present at a concentration above the minimum gel concentration of the polymer (MGC). ### Claim 3 (depends on 1) The formulation of claim 1, wherein the gel-forming polymer is a thermosensitive gel-forming polymer. ### Claim 4 (depends on 3) The formulation of claim 3, wherein the thermosensitive gel-forming polymer has a critical solution temperature that is below 30° C. ### Claim 5 (depends on 1) The formulation of claim 1 wherein the polymer is a poloxamer. ### Claim 6 (depends on 1) The formulation of claim 1, wherein the polymer in combination with excipient forms a depo or barrier gel on a mucosal or epithelial surface selected from the group consisting of oral, pharyngeal, esophogeal, pulmonary, ocular, aural, nasal, buccal, lingual, vaginal, cervical, genitourinary, alimentary, anorectal, and skin surfaces. ### Claim 7 (depends on 6) The formulation of claim 6, wherein the epithelial surface is the vaginal surface and the prophylactic effect is contraception, protection against sexually-transmitted disease, or treatment of abnormal proliferation such as cancer or endometriosis. ### Claim 8 (depends on 1) The formulation of claim 1, wherein the hypotonic solution further comprises a therapeutic, prophylactic, or diagnostic agent. ### Claim 9 (depends on 8) The formulation of claim 8, wherein the gel releases the therapeutic, prophylactic, or diagnostic agent at the epithelial surface over a period of at least 24 hours. ### Claim 10 (depends on 1) The formulation of claim 1, wherein the gel-forming polymer is between greater than 12 and less than 24% F98 in an aqueous excipient. ### Claim 11 (depends on 1) The formulation of claim 1, wherein the gel-forming polymer is between 10 and 18% F127. ### Claim 12 (depends on 1) The formulation of claim 1, wherein the gel forms a uniform layer on the epithelial surface. ### Claim 13 (depends on 1) The formulation of claim 1, wherein the gel causes no significant signs of irritation at the epithelial surface. ### Claim 14 (depends on 1) The formulation of claim 1 in the form of a dry powder, gel, or liquid. ### Claim 15 (depends on 1) The formulation of claim 1, wherein the polymer formulation is provided in a single or multiple dosage unit administration ### Claim 16 (depends on 1) A method for administering an agent to a mucosal or epithelial surface comprising administrating to a site in need thereof the formulation of claim 1. ### Claim 17 (depends on 16) The method of claim 16 wherein the concentration of polymer in the formulation at the time of administration to mucosal or epithelial tissue is less than the critical gel concentration of the polymer, and increases in concentration as water is absorbed from the formulation to or above the critical gel concentration (CGC) of the polymer under isotonic conditions and a temperature between room temperature and body temperature. ### Claim 18 (depends on 16) The method of claim 16 wherein the formulation is administered with a polymer concentration below the critical gel concentration (CGC) of the polymer under isotonic conditions and a temperature between room temperature and body temperature. ### Claim 19 (depends on 16) The method of claim 16 for delivery of a therapeutic, prophylactic, diagnostic or nutraceutical. ### Claim 20 (depends on 16) The method of claim 16 for formation of a barrier.