# US 12,758,576 B2 · Hydroxypropyl beta-cyclodextrin compositions and methods > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,758,576 B2 - Document ID: US12758576B2 - Status: Granted - Kind: B2 - Application number: 19/406,402 - Filed: 2025-12-02 - Published: 2026-04-09 - Granted: 2026-10-13 - Earliest claimed: 2015-06-10 - Assignees: Mandos LLC - Applicants: Mandos LLC - Inventors: Bernardus Nicolaas Machielse; Allan Darling - Web page: https://patentgrep.com/patent/US12758576B2 ## CPC - A61K 31/724: Cyclodextrins - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/0085: {Brain, e.g. brain implants; Spinal cord} - 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) ## Abstract This disclosure provides mixtures of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, the mixture optionally including unsubstituted beta-cyclodextrin molecules, for use as a pharmaceutically active ingredient; methods of making such mixtures; methods of qualifying such mixtures for use in a pharmaceutical composition suitable for intrathecal or intracerebroventricular administration; pharmaceutical compositions suitable for intrathecal or intracerebroventricular administration comprising such mixtures; and methods of using the pharmaceutical compositions for treatment of Niemann-Pick disease Type C. ## Claims ### Claim 1 A method of treating Niemann Pick in a human patient in need thereof comprising administering a composition comprising a mixture of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, wherein: the mixture comprises unsubstituted beta-cyclodextrin (“DS-0”) and beta-cyclodextrin substituted with one hydroxypropyl group (“DS-1”), and, the mixture comprises from 15% to 30% beta-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”), and wherein the composition comprises less than 5 International Units (IU) of endotoxins per gram. ### Claim 2 (depends on 1) The method of claim 1, wherein the mixture comprises less than 0.5% DS-0. ### Claim 3 (depends on 1) The method of claim 1, wherein the mixture comprises less than 0.2% DS-0. ### Claim 4 (depends on 1) The method of claim 1, wherein the mixture comprises less than 4.0% DS-1. ### Claim 5 (depends on 1) The method of claim 1, wherein the mixture comprises less than 3.0% DS-1. ### Claim 6 (depends on 1) The method of claim 1, wherein the composition comprises less than 1.5 International Units (IU) of endotoxins per gram. ### Claim 7 (depends on 1) The method of claim 1, wherein the composition comprises less than 1 International Units (IU) of endotoxins per gram. ### Claim 8 (depends on 1) The method of claim 1, wherein the mixture has an average molar substitution (“MS”) in the range of 0.40-0.80. ### Claim 9 (depends on 1) The method of claim 1, wherein the mixture has an average degree of substitution (“DSa”) of about 3 to about 7. ### Claim 10 (depends on 1) The method of claim 1, wherein the mixture has an average degree of substitution (“DSa”) of about 6 to about 7. ### Claim 11 (depends on 1) The method of claim 1, wherein the composition comprises no more than 1 ppm propylene oxide. ### Claim 12 (depends on 1) The method of claim 1, wherein the total amount of other unspecified impurities is less than or equal to 0.05%. ### Claim 13 (depends on 1) The method of claim 1, wherein the patient is a pediatric patient. ### Claim 14 (depends on 1) The method of claim 1, wherein the patient is an adult patient. ### Claim 15 (depends on 1) The method of claim 1, wherein the composition further comprises a pharmaceutically acceptable diluent. ### Claim 16 (depends on 1) The method of claim 1, wherein the mixture comprises at least 17% DS-5. ### Claim 17 (depends on 1) The method of claim 1, wherein the mixture comprises at least 19% DS-5. ### Claim 18 (depends on 1) The method of claim 1, wherein the mixture comprises no more than 25% DS-5. ### Claim 19 A method of treating Niemann Pick in a human patient in need thereof comprising administering a composition comprising a mixture of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, wherein: the mixture comprises unsubstituted beta-cyclodextrin (“DS-0”), beta-cyclodextrin substituted with one hydroxypropyl group (“DS-1”), and at least 15% beta-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”), and wherein the composition comprises less than 5 International Units (IU) of endotoxins per gram. ### Claim 20 (depends on 19) The method of claim 19, wherein the mixture comprises less than 0.5% 2.0% DS-0. ### Claim 21 (depends on 19) The method of claim 19, wherein the mixture comprises less than 0.2% 1.5% DS-0. ### Claim 22 (depends on 19) The method of claim 19, wherein the mixture comprises less than 4.0% DS-1. ### Claim 23 (depends on 19) The method of claim 19, wherein the composition comprises less than 1.5 International Units (IU) of endotoxins per gram. ### Claim 24 A method of treating Niemann Pick in a human patient in need thereof comprising administering a composition comprising a mixture of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, wherein: the mixture comprises unsubstituted beta-cyclodextrin (“DS-0”), beta-cyclodextrin substituted with one hydroxypropyl group (“DS-1”), and no more than 30% beta-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”), and wherein the composition comprises less than 5 International Units (IU) of endotoxins per gram. ### Claim 25 (depends on 24) The method of claim 24, wherein the mixture comprises no more than 25% DS-5. ### Claim 26 (depends on 24) The method of claim 24, wherein the mixture comprises less than 0.5% DS-0. ### Claim 27 (depends on 24) The method of claim 24, wherein the mixture comprises less than 0.2% DS-0. ### Claim 28 (depends on 24) The method of claim 24, wherein the composition comprises less than 1.5 International Units (IU) of endotoxins per gram. ### Claim 29 (depends on 24) The method of claim 24, wherein the composition comprises less than 0.2% propylene glycol. ### Claim 30 A method of treating Niemann Pick in a human patient in need thereof comprising administering a composition comprising a mixture of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, wherein: the mixture comprises from 15% to 30% beta-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”), wherein the composition comprises less than 0.4% propylene glycol, and wherein the composition comprises less than 1.5 International Units (IU) of endotoxins per gram.