# US 10,307,350 B2 · Morphogenetically active amorphous calcium polyphosphate nanoparticles for therapeutic applications > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,307,350 B2 - Document ID: US10307350B2 - Status: Granted - Kind: B2 - Application number: 15/527,479 - Filed: 2015-11-10 - Published: 2017-11-09 - Granted: 2019-06-04 - Earliest claimed: 2014-11-17 - Assignees: NanotecMARIN GmbH - Applicants: NanotecMARIN GmbH - Inventors: Werner Ernst Ludwig Georg Müller - Web page: https://patentgrep.com/patent/US10307350B2 ## CPC - A61K 8/24: Phosphorous; Compounds thereof - A61K 8/0283: {Matrix particles} - A61K 8/671: {Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal} - A61L 27/12: Phosphorus-containing materials, e.g. apatite - A61Q 19/08: Anti-ageing preparations - A61K 2800/413: Nanosized, i.e. having sizes below 100 nm - A61L 2300/624: Nanocapsules - A61L 2400/12: Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces - A61L 2430/02: for reconstruction of bones; weight-bearing implants - 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) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS ## Abstract This invention concerns a calcium polyphosphate material consisting of amorphous nanoparticles with a diameter of approximately between about 45 nm to about 0.25 μm that displays a considerable hardness (elastic modulus) of about 1.3 GPa. The inventive noncrystalline and biodegradable material that is produced under mild conditions, at room temperature, is morphogenetically active and preferably induces bone formation and the expression of the marker gene for osteoblast activity, alkaline phosphatase. In a preferred aspect, the invention concerns a method for producing amorphous retinol/calcium-polyphosphate nanospheres (retinol/aCa-polyP-NS) that show several unexpected properties and can be used in the treatment or prophylaxis of a variety of dermatological conditions, including photoaging. ## Claims ### Claim 1 A method for the production of solid, degradable amorphous polyphosphate nanospheres having calcium counterions, wherein said method comprises the steps of: i) dissolving a polyphosphate salt in an aqueous solvent to create a solution and adjusting the pH value of the solution to an alkaline value, ii) adding a calcium salt solution to said polyphosphate salt solution, and adjusting the pH value to an alkaline value, wherein amorphous polyphosphate nanospheres are formed under the alkaline pH, iii) optionally, washing with a solvent and iv) collecting the nanospheres formed, wherein steps i) to iii) are performed at ambient temperature, and wherein said nanospheres have a hardness between 0.8 GPa and 1.8 GPa, and is morphogenetically active. ### Claim 2 (depends on 1) The method, according to claim 1, used to prepare degradable amorphous retinoid/calcium-polyphosphate (Ca-polyP) nanospheres, wherein a) in step i) a lubricating coating material is co-dissolved in said aqueous solvent, b) in step ii) a retinoid salt is co-dissolved in said solvent, and c) nanospheres as formed are collected. ### Claim 3 (depends on 2) The method according to claim 2, wherein the said retinoid is retinol. ### Claim 4 (depends on 2) The method according to claim 2, wherein the retinoid/Ca-polyp nanospheres are obtained by addition of one part of a solution containing 2 g/L of retinol and 56 g/L of calcium chloride in absolute ethanol to two parts of a solution containing 10 g/L of sodium polyphosphate and 20 g/L of poly(ethylene glycol) in water. ### Claim 5 (depends on 2) The method according to claim 2, wherein said retinoid/Ca-polyP nanospheres are obtained in an essentially homogenous size suitable for cellular uptake by clathrin-mediated endocytosis. ### Claim 6 (depends on 2) The method, according to claim 2, wherein in step i) the lubricating coating is a poly(ethylene glycol) polymer. ### Claim 7 (depends on 2) The method, according to claim 2, wherein the retinoid/Ca-polyP nanospheres are formulated for use in dermatology. ### Claim 8 (depends on 7) The method, according to claim 7, wherein the retinoid/Ca-polyP nanospheres are formulated as a crème or ointment. ### Claim 9 (depends on 1) The method according to claim 1, wherein said calcium salt is calcium chloride. ### Claim 10 (depends on 1) The method according to claim 1, wherein said polyphosphate salt is sodium polyphosphate. ### Claim 11 (depends on 1) The method according to claim 1, wherein the polyphosphate has a chain length of about 3 to about 1000 phosphate units. ### Claim 12 (depends on 1) The method according to claim 1, wherein the pH is adjusted to 10. ### Claim 13 (depends on 1) The method according to claim 1, wherein the polyphosphate salt is sodium polyphosphate and the calcium salt is calcium chloride at a stoichiometric ratio of 0.1 to 10 (phosphate to calcium). ### Claim 14 (depends on 1) The method according to claim 1, wherein the calcium salt solution is a solution containing 14 g/L of calcium chloride or 28 g/L of calcium chloride and the polyphosphate salt solution is a solution containing 10 g/L of sodium polyphosphate. ### Claim 15 (depends on 1) The method according to claim 1, wherein an emulsifier is added to the polyphosphate solution in order to avoid phase separation. ### Claim 16 (depends on 1) The method according to claim 1, further comprising the step of producing hard amorphous and morphogenetically active polyphosphate nanospheres, and/or a material containing such nanospheres. ### Claim 17 (depends on 1) The method, according to claim 1, wherein the aqueous solvent is water. ### Claim 18 (depends on 1) The method, according to claim 1, wherein the solid, degradable amorphous nanospheres are formulated for use in dermatology or dentistry or for regenerating bone.