# US 2019/0167598 A1 · A novel treatment regimen involving sapropterin dihydrochloride > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0167598 A1 - Document ID: US20190167598A1 - Status: Published application - Kind: A1 - Application number: 16/321,197 - Filed: 2017-07-27 - Published: 2019-06-06 - Earliest claimed: 2016-07-29 - Assignees: Dipharma S.p.A. - Applicants: Dipharma S.A. - Inventors: Gilles PAIN; Fabio CANNATA; Bareket GELBHART - Web page: https://patentgrep.com/patent/US20190167598A1 ## CPC - A61K 9/2086: {Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat (active cores with a complete drug-free outer coat A61K9/28)} - A61K 9/2013: {Organic compounds, e.g. phospholipids, fats} - A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates} - A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 31/375: Ascorbic acid, i.e. vitamin C; Salts thereof - A61K 31/4965: Non-condensed pyrazines - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - 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 The invention relates to an improved tetrahydrobiopterin formulation for treating patients affected by hyperphenylalaninemia. More specifically, the formulation of the invention permits a prolonged residence of tetrahydrobiopterin in the plasma, and/or a higher concentration of sapropterin in the plasma, enabling notably the treatment of HPA patients that would usually not be classified as responders to tetrahydrobiopterin loading test, and therefore left without any pharmacological treatment opportunity, but only with a strictly controlled protein diet. ## Claims ### Claim at position 1 -13. (canceled) ### Claim 14 A method of treating hyperphenylalaninemia, comprising administering daily: a) once only, a first fast-release formulation containing from 5 mg/kg to 20 mg/kg of sapropterin and a stabilizing agent, the stabilizing agent being present in an amount of up to about 5% w/w of the sapropterin; and b) a second formulation containing from 2 mg/kg to 20 mg/kg of an antioxidant; to a patient in need thereof. ### Claim 15 (depends on 14) The method of claim 14, wherein the stabilizing agent of the first fast-release formulation is selected from the group consisting of antioxidants, chelating agents, moisture retaining agents, disaccharides or higher polyols, hydrophobic agents and the like, cyclodextrins, and combinations thereof. ### Claim 16 (depends on 14) The method of claim 14, wherein the antioxidant of the second formulation is selected from the group consisting of: citric acid, tartaric acid, vitamin C, plant polyphenols, anthocyanins, flavonoids, isoflavonoids, glutathione and mixtures thereof. ### Claim 17 (depends on 16) The method of claim 16, wherein the second formulation is administered from 2 to 6 times per day in an amount of between 0.33 mg/kg to 10 mg/kg per dose, with the first dose being administered within 30 minutes before or after the administration of the first fast-release formulation. ### Claim 18 (depends on 17) The method of claim 17 wherein the second dose of the second formulation is administered after 2 hours from the first dose of the second formulation, and then any subsequent doses, if any, at regular intervals. ### Claim 19 (depends on 17) The method of claim 17, wherein the dose of the first fast-release formulation and the first dose of the second formulation are administered in a fasting state. ### Claim 20 (depends on 17) The method of claim 17, wherein the antioxidant of the second formulation is ascorbic acid. ### Claim 21 (depends on 16) The method of claim 16, wherein the first fast-release formulation and the second formulation are administered simultaneously. ### Claim 22 (depends on 14) The method of claim 14, wherein the patient has phenylketonuria (PKU). ### Claim 23 (depends on 16) The method of claim 16, wherein the second formulation is an extended release formulation, releasing the antioxidant for up to 24 hours after administration. ### Claim 24 (depends on 23) The method of claim 23, wherein the second formulation releases the antioxidant from 6 to 12 hours after administration. ### Claim 25 (depends on 23) The method of claim 23, wherein the first fast-release formulation and the second formulation are administered simultaneously. ### Claim 26 (depends on 25) The method of claim 25, wherein the first fast-release formulation and the second formulation are administered in a single dosage form. ### Claim 27 (depends on 23) The method of claim 23, wherein the antioxidant of the second formulation is ascorbic acid. ### Claim 28 (depends on 26) The method of claim 26, wherein the first fast-release formulation and the second formulation are formulated as a tablet, capsule, pill, dragee, powder, microparticulate system or in granule form. ### Claim 29 (depends on 26) The method of claim 26, wherein single dosage form is administered in a fasting state. ### Claim 30 (depends on 23) The method of claim 23, wherein the first fast-release formulation and the second formulation are administered sequentially, the second formulation being administered within 30 minutes before or after the administration of the first fast-release formulation. ### Claim 31 (depends on 30) The method of claim 30, wherein the second formulation is administered within 30 minutes before the administration of the first fast-release formulation.