# US 9,040,105 B2 · Nanocrystals and amorphous nanoparticles and method for production of the same by a low energy process > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,105 B2 - Document ID: US9040105B2 - Status: Granted - Kind: B2 - Application number: 13/649,470 - Filed: 2012-10-11 - Published: 2013-04-18 - Granted: 2015-05-26 - Earliest claimed: 2011-10-17 - Assignees: The Pharmasol Corporation - Applicants: PharmaSol GmbH - Inventors: Cornelia Keck - Web page: https://patentgrep.com/patent/US9040105B2 ## CPC - A61K 9/145: {with organic compounds} - A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)} - A61K 36/87: Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine - A61P 35/00: Antineoplastic agents - Y10S 977/773: Nanoparticle, i.e. structure having three dimensions of 100 nm or less - Y10S 977/90: having step or means utilizing mechanical or thermal property, e.g. pressure, heat - 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 - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## Abstract A process for the production of nanocrystals or amorphous nanoparticles of actives (nanomaterials), especially from the peels of grapes. A dispersion of a micrometer-sized material in a solution of surfactant or a steric stabilizer is first provided. The macrosuspension is then stirred for at least 1 minute at a rotational speed above 500 rpm using a rotor-stator mixer. The stirred mixture is passed through a jet stream or piston-gas type high pressure homogenizer. The nanomaterials produced can be incorporated into formulations for use as nutraceutical, nutritional supplement, or as supportive treatment in medical therapy. The active can be derived from the peels of grapes. ## Claims ### Claim 1 A process for the preparation of nanocrystals or amorphous nanoparticles of an active comprising: i) providing a macrosuspension comprising a dispersion of a micrometer-sized material comprising an active in a solution of a surfactant or a steric stabiliser, wherein the active is in the solid state and remains in the solid state during the process; ii) stirring the macrosuspension for at least 1 minute at a rotational speed above 500 rounds per minute (rpm) using a rotor-stator mixer; and iii) passing the macrosuspension through a jet stream or piston-gap type high pressure homogenizer to produce nanocrystals or amorphous nanoparticles of the active wherein the homogenization in step iii) takes place at a pressure below 1,500 bar applying up to 20 homogenization cycles maximum. ### Claim 2 (depends on 1) The process according to claim 1, wherein the rotational speed in step ii) is above 5000 rpm. ### Claim 3 (depends on 1) The process according to claim 1, wherein the rotational speed in step ii) is above 10,000 rpm ### Claim 4 (depends on 1) The process according to claim 1, wherein the rotational speed in step ii) is above 12,000 rpm ### Claim 5 (depends on 1) The process according to claim 1, wherein the rotational speed in step ii) is above 15,000 rpm. ### Claim 6 (depends on 1) The process according to claim 1, wherein the rotational speed in step ii) is above 20,000 rpm. ### Claim 7 (depends on 1) The process according to claim 1, wherein the rotational speed in step ii) is 20,000 to 40,000 rpm ### Claim 8 (depends on 1) The process according to claim 1, wherein the rotational speed in step ii) is about 24,000 rpm. ### Claim 9 (depends on 1) The process according to claim 1, wherein the gaps of the rotor of the rotor-stator mixer as used in step ii) are 1 mm or less wide. ### Claim 10 (depends on 1) The process according to claim 1, wherein the gaps of the rotor of the rotor-stator mixer as used in step ii) are 0.8 mm or less. ### Claim 11 (depends on 1) The process according to claim 1, wherein the gaps of the rotor of the rotor-stator mixer as used in step ii) are 0.6 mm or less. ### Claim 12 (depends on 1) The process according to claim 1, wherein the gaps of the rotor of the rotor-stator mixer as used in step ii) are about 0.5 mm. ### Claim 13 (depends on 1) The process according to claim 1, wherein the gap between rotor and stator in the rotor-stator mixer used in step ii) is 0.5 mm or less wide. ### Claim 14 (depends on 1) The process according to claim 1, wherein the gap between rotor and stator in the rotor-stator mixer used in step ii) is 0.4 mm or less wide. ### Claim 15 (depends on 1) The process according to claim 1, wherein the gap between rotor and stator in the rotor-stator mixer used in step ii) is 0.3 mm or less wide. ### Claim 16 (depends on 1) The process according to claim 1, wherein the gap between rotor and stator in the rotor-stator mixer used in step ii) is about 0.2 mm wide. ### Claim 17 (depends on 1) The process according to claim 1, wherein step ii) is effected batch-wise in a discontinuous mode or in a flow-through chamber. ### Claim 18 (depends on 1) The process according to claim 1, wherein the homogenization in step iii) takes place at a pressure below 1,001 bar applying up to 8 homogenization cycles maximum. ### Claim 19 (depends on 1) The process according to claim 1, wherein the homogenization in step iii) takes place at a pressure below 501 bar applying up to 5 homogenization cycles maximum. ### Claim 20 (depends on 1) The process according to claim 1, wherein the homogenization in step iii) takes place at a pressure at 300 bar or below 300 bar applying 1-2 homogenization cycles maximum. ### Claim 21 (depends on 1) The process according to claim 1, wherein the active is derived from peels of grapes. ### Claim 22 A process for the preparation of nanocrystals or amorphous nanoparticles of an active comprising: i) providing a macrosuspension comprising a dispersion of a micrometer-sized material comprising an active in a solution of a surfactant or a steric stabiliser, wherein the active is in the solid state and remains in the solid state during the process; ii) stirring the macrosuspension for at least 1 minute at a rotational speed above 500 rounds per minute (rpm) using an ART-MICCRA-type rotor-stator mixer; and iii) passing the macrosuspension through a jet stream or piston-gap type high pressure homogenizer to produce nanocrystals or amorphous nanoparticles of the active.