# US 5,708,025 A · Methods for promoting wound healing > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,708,025 A - Document ID: US5708025A - Status: Granted - Kind: A - Application number: 08/465,835 - Filed: 1995-06-06 - Granted: 1998-01-13 - Earliest claimed: 1991-10-21 - Assignees: The United States of America as represented by the Department of Health and Human Services - Inventors: Dvorit Samid - Web page: https://patentgrep.com/patent/US5708025A ## CPC - A61K 31/7076: containing purines, e.g. adenosine, adenylic acid - A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) - A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)} - A61K 31/20: having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids - A61K 31/35: having six-membered rings with one oxygen as the only ring hetero atom - A61K 31/365: Lactones - A61K 31/70: Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047) - A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - 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 Compositions and methods of treating anemia, cancer, AIDS, or severe .beta.-chain hemoglobinopathies by administering a therapeutically effective amount of phenylacetate or pharmaceutically acceptable derivatives thereof or derivatives thereof alone or in combination or in conjunction with other therapeutic agents. Pharmacologically-acceptable salts alone or in combinations and methods of preventing AIDS and malignant conditions, and inducing cell differentiation are also aspects of this invention. ## Claims ### Claim 1 A method of inducing the production of TGF.alpha. in a cell comprising contacting the cell with a TGF.alpha. inducing amount of a compound of the formula: ##STR3## wherein R.sub.0 is aryl, phenoxy, substituted aryl or substituted phenoxy; R.sub.1 and R.sub.2 are, independently, H, hydroxy, lower alkoxy, lower straight or branched chain alkyl or halogen; R.sub.3 and R.sub.4 are, independently, H, lower alkoxy, lower straight or branched chain alkyl or halogen; and n is an integer from 0 to 2; a salt thereof; a stereoisomer thereof; and a mixture thereof. ### Claim 2 (depends on 1) The method of claim 1, wherein the induction is in a wound of a subject and the induction is sufficient to promote wound healing. ### Claim 3 (depends on 1) The method of claim 1, wherein the compound is sodium phenylacetate. ### Claim 4 (depends on 1) The method of claim 1, wherein the compound is sodium phenylbutyrate. ### Claim 5 (depends on 1) The method of claim 1, wherein the TGF-.alpha. inducing mount is from 50 to 1000 mg/kg/day. ### Claim 6 (depends on 1) The method of claim 1, wherein the TGF-.alpha. inducing mount is from 300 to 500 mg/kg/day. ### Claim 7 (depends on 1) The method of claim 1, wherein the TGF-.alpha. inducing mount is from 150 to 250 mg/kg/day. ### Claim 8 (depends on 1) The method of claim 1, wherein R.sub.0 is aryl or phenoxy, the aryl and phenoxy being unsubstituted or substituted width, independently, one or more halogen, hydroxy or lower alkyl. ### Claim 9 (depends on 1) The method of claim 1, wherein R.sub.0 is phenyl, naphthyl, or phenoxy, the phenyl, naphthyl and phenoxy being unsubstituted or substituted with, independently, one or more moieties of halogen, hydroxy or lower alkyl. ### Claim 10 (depends on 1) The method of claim 1, wherein R.sub.0 is phenyl, naphthyl, or phenoxy, the phenyl, naphthyl and phenoxy being unsubstituted or substituted with, independently, from 1 to 4 moieties of halogen, hydroxy or lower alkyl of from 1 to 4 carbon atoms; R.sub.1 and R.sub.2 are, independently, H, hydroxy, lower alkoxy of from 1 to 2 carbon atoms, lower straight or branched chain alkyl of from 1 to a carbon atoms or halogen; and R.sub.3 and R.sub.4 are, independently, H, lower alkoxy of from 1 to 2 carbon atoms, lower straight or branched chain alkyl of from 1 to 4 carbon atoms or halogen. ### Claim 11 (depends on 1) The method of claim 1, wherein n is 0 or 2; R.sub.0 is aryl or substituted aryl; and R.sub.1 and R.sub.2 are H, lower alkoxy, or lower alkyl. ### Claim 12 (depends on 11) The method of claim 11, wherein n is 0. ### Claim 13 The method of wherein the compound is .alpha.-methylphenylacetic acid, .alpha.-ethylphenylacetic acid, .alpha.-hydroxyphenylacetic acid, .alpha.-methoxyphenylacetic acid, 1-naphthylacetic acid, 4-chlorophenylacetic acid, 4-iodophenylacetic acid, 4-fluorophenylacetic acid, 3-chlorophenylacetic acid, 2-chlorophenylacetic acid, 2,6-dichlorophenylacetic acid, 2-methylphenylacetic acid, 3-methylphenylacetic acid, 4-methylphenylacetic acid, phenoxypropionic acid, 4-chlorophenylbutyric acid, 4-iodophenylbutyric acid, 4-fluorophenylbutyric acid, 3-chlorophenylbutyric acid, or 2-chlorophenylbutyric acid. ### Claim 14 A method of promoting the healing of a wound in a subject comprising administering to a wound in the subject a would healing mount of a compound of the formula: ##STR4## wherein R.sub.0 is aryl, phenoxy, substituted aryl or substituted phenoxy; R.sub.1 and R.sub.2 are, independently, H, hydroxy, lower alkoxy, lower straight or branched chain alkyl or halogen; R.sub.3 and R.sub.4 are, independently, H, lower alkoxy, lower straight or branched chain alkyl or halogen; and n is an integer from 0 to 2; a salt thereof; a stereoisomer thereof; and a mixture thereof. ### Claim 15 (depends on 14) The method of claim 14, wherein the compound is sodium phenylacetate. ### Claim 16 (depends on 14) The method of claim 14, wherein the compound is sodium phenylbutyrate. ### Claim 17 (depends on 14) The method of claim 14, wherein the wound healing mount is from 50 to 1000 mg/kg/day. ### Claim 18 (depends on 14) The method of claim 14, wherein the wound healing mount is from 300 to 500 mg/kg/day. ### Claim 19 (depends on 14) The method of claim 14, wherein the wound healing mount is from 150 to 250 mg/kg/day. ### Claim 20 (depends on 14) The method of claim 14, wherein the wound healing mount is an amount sufficient to induce the production of TGF-.alpha. around the locality of the wound. ### Claim 21 (depends on 20) The method of claim 20, wherein the compound is sodium phenylacetate. ### Claim 22 (depends on 20) The method of claim 20, wherein the compound is sodium phenylbutyrate. ### Claim 23 (depends on 14) The method of claim 14, wherein R.sub.0 is aryl or phenoxy, the aryl and phenoxy being unsubstituted or substituted with, independently, one or more halogen, hydroxy or lower alkyl. ### Claim 24 (depends on 14) The method of claim 14, wherein R.sub.0 is phenyl, naphthyl, or phenoxy, the phenyl, naphthyl and phenoxy being unsubstituted or substituted with, independently, one or more moieties of halogen, hydroxy or lower alkyl. ### Claim 25 (depends on 14) The method of claim 14, wherein R.sub.0 is phenyl, naphthyl, or phenoxy, the phenyl, naphthyl and phenoxy being unsubstituted or substituted with, independently, from 1 to 4 moieties of halogen, hydroxy or lower alkyl of from 1 to 4 carbon atoms; R.sub.1 and R.sub.2 are, independently, H, hydroxy, lower alkoxy of from 1 to 2 carbon atoms, lower straight or branched chain alkyl of from 1 to 4 carbon atoms or halogen; and R.sub.3 and R.sub.4 are, independently, H, lower alkoxy of from 1 to 2 carbon atoms, lower straight or branched chain alkyl of from 1 to 4 carbon atoms or halogen. ### Claim 26 (depends on 14) The method of claim 14, wherein n is 0; R.sub.0 is aryl or substituted aryl; and R.sub.1 R.sub.2 are H, lower alkoxy, or lower alkyl. ### Claim 27 (depends on 26) The method of claim 26, wherein n is 0. ### Claim 28 (depends on 14) The method of claim 14, wherein the compound is .alpha.-methylphenylacetic acid, .alpha.-ethylphenylacetic acid, .alpha.-hydroxyphenylacetic acid, .alpha.-methoxyphenylacetic acid, 1-naphthylacetic acid, 4-chlorophenylacetic acid, 4-iodophenylacetic acid, 4-fluorophenylacetic acid, 3-chlorophenylacetic acid, 2-chlorophenylacetic acid, 2,6-dichlorophenylacetic acid, 2-methylphenylacetic acid, 3-methylphenylacetic acid, 4-methylphenylacetic acid, phenoxypropionic acid, 4-chlorophenylbutyric acid, 4-iodophenylbutyric acid, 4-fluorophenylbutyric acid, 3-chlorophenylbutyric acid, or 2-chlorophenylbutyric acid. ### Claim 29 (depends on 14) The method of claim 14, wherein the compound is administered topically. ### Claim 30 (depends on 29) The method of claim 29, wherein the compound is applied at a concentration of from about 0.1 mM to about 10 mM. ### Claim 31 (depends on 14) The method of claim 14, wherein the compound is administered ocularly. ### Claim 32 (depends on 14) The method of claim 14, wherein the compound is administered orally. ### Claim 33 (depends on 14) The method of claim 14, wherein the compound is administered in the form of a suppository. ### Claim 34 (depends on 14) The method of claim 14, wherein the compound is administered parenterally. ### Claim 35 (depends on 14) The method of claim 14, wherein the compound is administered intermittently. ### Claim 36 (depends on 14) The method of claim 14, wherein the compound is administered continuously.