# US 11,440,975 B2 · Cross-linked starch-based polymers for drug-delivery > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,440,975 B2 - Document ID: US11440975B2 - Status: Granted - Kind: B2 - Application number: 17/049,185 - Filed: 2019-04-19 - Published: 2021-08-05 - Granted: 2022-09-13 - Earliest claimed: 2018-04-20 - Assignees: Roquette Freres - Applicants: Roquette Freres - Inventors: Francesco Trotta; Fabrizio Caldera - Web page: https://patentgrep.com/patent/US11440975B2 ## CPC - A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof - C08B 37/0012: {Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof} - A61K 9/4816: {Wall or shell material} - A61K 47/40: Cyclodextrins; Derivatives thereof - A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)} - C08B 31/006: {Crosslinking of derivatives of starch} - C08B 37/0015: {Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes} - C08B 37/0018: {Pullulan, i.e. (alpha-1,4)(alpha-1,6)-D-glucan; Derivatives thereof} - C08L 3/02: Starch; Degradation products thereof, e.g. dextrin - C08L 3/04: Starch derivatives {, e.g. crosslinked derivatives} - C08L 5/00: Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00 - C08L 5/16: Cyclodextrin; Derivatives thereof - 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) - C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21) - C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06) ## Abstract The invention relates a process for preparing a cross-linked starch-based polymer comprising the following steps: 1) dissolving a starchy material in a suitable solvent to form a starchy material solution; and 2) adding a episulfide of formula (I), wherein R1, R2, R3 and R4 are independently selected from hydrogen and (C1-C3)alkyl in the starchy material solution in order to obtain the disulfide crosslinked starch-based polymer. In another aspect the invention concerns a disulfide-cross-linked starch-based polymer obtainable by the process of the invention, that is characterized by only disulfide bridges. ## Claims ### Claim 1 A process for preparing a disulfide cross-linked starch-based polymer comprising the following steps: 1) dissolving a starchy material in a suitable solvent to form a starchy material solution; and 2) adding an episulfide of formula (I) wherein R1, R2, R3 and R4 are independently selected from hydrogen and (C1-C3)alkyl in the starchy material solution in order to obtain the disulfide crosslinked starch-based polymer, and wherein the starchy material is selected from the group consisting of a cyclodextrin, a dextrin, a maltodextrin, and a combination thereof. ### Claim 2 (depends on 1) The process according to claim 1, wherein the starchy material is a cyclodextrin selected from α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. ### Claim 3 (depends on 1) The process according to claim 1, wherein the starchy material is a maltodextrin derived from cereal starch, legume starch, or waxy maize starch. ### Claim 4 (depends on 1) The process according to claim 1, wherein the starchy material is a maltodextrin derived from pea starch. ### Claim 5 (depends on 4) The process according to claim 4, wherein the maltodextrin derived from pea starch has an amylose content in the range from 25% to 50% dry weight relative to the dry weight of starch. ### Claim 6 (depends on 1) The process according to claim 1, wherein in step 1) the solvent is selected from organic aprotic polar solvents and water. ### Claim 7 (depends on 1) The process according to claim 1, wherein step 2) is carried out at room temperature. ### Claim 8 (depends on 1) The process according to claim 1, wherein step 2) is carried out at pH in the range from 12 to 14. ### Claim 9 (depends on 8) The process according to claim 8, wherein the molar ratio between starchy material and the episulfide is in the ratio from 1:2 to 1:20. ### Claim 10 (depends on 9) The process according to claim 9, wherein when the starchy material is a cyclodextrin, the ratio is 1:10, and the final disulfide cross-linked starch-based polymer is obtained by precipitation. ### Claim 11 (depends on 9) The process according to claim 9, wherein the starchy material is a maltodextrin or a dextrin, and the ratio is 1:10. ### Claim 12 (depends on 1) The process according to claim 1, wherein in the episulfide of formula (I), R1, R2, R3 and R4 are independently selected from H and CH3. ### Claim 13 (depends on 12) The process according to claim 12, wherein the episulfide of formula (I) is propylene disulfide. ### Claim 14 (depends on 1) A disulfide cross-linked starch-based polymer obtainable by the process of claim 1. ### Claim 15 (depends on 14) A method for encapsulation/inclusion/entrapment of an organic compound, wherein the method comprises the step of adding the disulfide cross-linked starch-based polymer of claim 14 with an excess of the organic compound dissolved in a solvent thus obtaining the organic compound encapsulated, included, or entrapped in the disulfide cross-linked starch-based polymer. ### Claim 16 (depends on 14) A method for encapsulating and delivering a drug, wherein said method comprises the steps of: adding using the disulfide cross-linked starch-based polymer according to claim 14 with an excess of the drug dissolved in a solvent thus obtaining the drug encapsulated in the disulfide cross-linked starch-based polymer; and delivering the encapsulated drug. ### Claim 17 (depends on 14) A method for hosting and delivering an anticancer drug in chemoresistant cancer cells, wherein said method comprises the steps of: adding the disulfide cross-linked starch-based polymer according to claim 14 with an excess of the anticancer drug dissolved in a solvent thus obtaining the anticancer drug hosted in the disulfide cross-linked starch-based polymer; and delivering the hosted anticancer drug in chemoresistant cancer cells.