# US 2019/0167689 A1 · Modulation of the nitric oxide synthase pathway for oral health > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0167689 A1 - Document ID: US20190167689A1 - Status: Published application - Kind: A1 - Application number: 16/213,894 - Filed: 2018-12-07 - Published: 2019-06-06 - Earliest claimed: 2016-06-13 - Assignees: Meharry Medical College - Applicants: Meharry Medical College - Inventors: Janet H. SOUTHERLAND; Pandu R. GANGULA - Web page: https://patentgrep.com/patent/US20190167689A1 ## CPC - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 9/0056: {Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals} - A61K 9/0058: {Chewing gums (non-medicinal aspects, preparing chewing gum A23G4/00; chewing gum for care of the teeth or oral cavity, e.g. with breath freshener A61Q11/00)} - A61K 9/0063: {Periodont} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 9/10: Dispersions; Emulsions - A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis - A61P 5/48: of the pancreatic hormones - 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 Pharmaceutical compositions and methods of treatment or prevention of diseases and conditions associated with or characterized by at least one of xerostomia and periodontal disease by modulation of the nitric oxide synthase pathway are provided, as are animal models and drug screening methods. Such modulation may be achieved by the administration of tetrahydrobiopterin (BH4) or its prodrugs and/or salts. Treating and preventing xerostomia can have the downstream effect of also preventing periodontitis, dental caries, parotid gland enlargement, inflammation and fissuring of the lips (chelitis), inflammation or ulcers of the tongue and buccal mucosa, oral candidiasis, salivary gland infection (sialadenitis), halitosis, and cracking and fissuring of oral mucosa. ## Claims ### Claim 1 A method of treatment or prevention of a disease state or condition associated with or characterized by at least one of xerostomia and periodontal disease in a subject in need thereof, the method comprising administering an agent selected from tetrahydrobiopterin (BH4), a prodrug of BH4, or a pharmaceutically acceptable salt of any of the foregoing to the subject in a therapeutically effective amount. ### Claim 2 (depends on 1) The method of claim 1, wherein the prodrug of BH4 is sepiapterin. ### Claim 3 (depends on 1) The method of claim 1, comprising delivering the BH4 to a salivary gland of the subject. ### Claim 4 (depends on 1) The method of claim 1, comprising administering the agent locally to the subject's mouth. ### Claim 5 (depends on 1) The method of claim 1, in which the agent is administered in a dentifrice, film, oral spray, lozenge, or a gum. ### Claim 6 (depends on 1) The method of claim 1, in which the agent is administered in an oral rinse, a paste, a gel, or a varnish. ### Claim 7 (depends on 1) The method of claim 1, further comprising treating the subject for at least one of: head and neck cancer, Sjogren's syndrome, diabetes mellitus, dental caries, parotid gland enlargement, inflammation and fissuring of the lips (chelitis), inflammation or ulcers of the tongue and buccal mucosa, oral candidiasis, salivary gland infection (sialadenitis), halitosis and cracking and fissuring of oral mucosa. ### Claim 8 (depends on 1) The method of claim 1, wherein the amount is about 3.18-635 μmol agent per kg weight of the subject. ### Claim 9 (canceled) ### Claim 10 (depends on 1) The method of claim 1, wherein the amount is about 31.8-63.5 μmol agent per kg weight of the subject. ### Claim 11 (depends on 1) The method of claim 1, wherein the amount is selected from about 31.8 and about 63.5 μmol agent per kg weight of the subject. ### Claim 12 (depends on 1) The method of claim 1, wherein the amount is about 3.2-3200 μmol. ### Claim 13 (depends on 1) The method of claim 1, wherein the amount is about 180-640 μmol. ### Claim 14 (depends on 1) The method of claim 1, wherein the amount is about 320 μmol. ### Claim 15 (depends on 1) The method of claim 1, wherein the amount is effective to achieve a concentration of 10-1000 μM BH4 at a salivary gland of the subject. ### Claim 16 (depends on 1) The method of claim 1, wherein the amount is effective to achieve a concentration of 50-200 μM BH4 at the salivary gland of the subject. ### Claim 17 (depends on 1) The method of claim 1, wherein the amount is effective to achieve a concentration of 100 μM BH4 at the salivary gland of the subject. ### Claim 18 A pharmaceutical composition for the treatment or prevention of a disease state or condition associated with or characterized by at least one of xerostomia and periodontal disease, comprising a dentifrice, gum, film, spray, or lozenge; an agent selected from tetrahydrobiopterin (BH4), a prodrug of BH4, or a pharmaceutically acceptable salt of any of the foregoing, in a therapeutically effective amount; and a pharmaceutically acceptable carrier. ### Claim at position 19 -58. (canceled) ### Claim 59 (depends on 1) The method of claim 1, wherein the disease state or condition is xerostomia. ### Claim 60 (depends on 1) The method of claim 1, wherein the disease state or condition is periodontitis. ### Claim 61 (depends on 1) The method of claim 1, wherein the disease state or condition is selected from the group consisting of: dental caries, parotid gland enlargement, inflammation and fissuring of the lips (chelitis), inflammation or ulcers of the tongue and buccal mucosa, oral candidiasis, salivary gland infection (sialadenitis), halitosis and cracking and fissuring of oral mucosa.