# US 11,896,715 B2 · In vivo bulking agent, injection comprising same, and preparation method therefor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,896,715 B2 - Document ID: US11896715B2 - Status: Granted - Kind: B2 - Application number: 17/621,587 - Filed: 2020-06-11 - Published: 2022-11-10 - Granted: 2024-02-13 - Earliest claimed: 2019-06-21 - Assignees: Korea University Research and Business Foundation - Applicants: Korea University Research and Business Foundation - Inventors: Kwang Dae Hong; Jihun Seo; Joon Bum Lee - Web page: https://patentgrep.com/patent/US11896715B2 ## CPC - A61K 9/1641: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers} - A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} - A61K 8/0241: {Containing particulates characterized by their shape and/or structure (see also A61K8/04, A61K8/11, and A61K8/14, further aspects are classified in A61K2800/40 and subcodes)} - A61K 8/8158: {Homopolymers or copolymers of amides or imides, e.g. (meth) acrylamide; Compositions of derivatives of such polymers} - A61K 8/8188: {Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bonds, and at least one being terminated by a bond to sulfur or by a hertocyclic ring containing sulfur; Compositions of derivatives of such polymers} - A61K 8/891: saturated, e.g. dimethicone, phenyl trimethicone, C24-C28 methicone or stearyl dimethicone - 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 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin - A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) - A61L 27/48: with macromolecular fillers - A61L 27/52: Hydrogels or hydrocolloids - A61Q 19/00: Preparations for care of the skin - A61B 2017/00792: {Plastic surgery} - A61B 2017/00805: {Treatment of female stress urinary incontinence} - A61K 2800/624: by macromolecular compounds - A61K 2800/654: The particulate/core comprising macromolecular material - A61L 2400/06: Flowable or injectable implant compositions - A61L 2430/34: for soft tissue reconstruction - 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 - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) ## Abstract The present invention relates to an in-vivo bulking agent which can be used as a medicinal agent for prevention or treatment of at least one disease selected from the group consisting of urinary incontinence, fecal incontinence, and gastroesophageal reflux or as a filler for use in a plastic surgery procedure, and to a preparation method therefor. The in-vivo bulking agent can exhibit a bulking effect when injected into the body and particularly, is highly biocompatible because a first composition in which silicone particles are coated with a zwitterionic polymer having a surfactant property is introduced into a second composition, whereby the bulking agent can inhibit inflammatory reactions in vivo. ## Claims ### Claim 1 An in-vivo bulking agent formulated as an injectable composition, comprising: a first composition including polydimethylsiloxane (PDMS) particles and a zwitterionic polymer surrounding a surface of the polydimethylsiloxane particles; and a second composition having a viscosity of 100 to 1500 cps at room temperature, wherein the zwitterionic polymer of the first composition has a surfactant property, and wherein the zwitterionic polymer is included in an amount of 0.1 to 5 parts by weight of based on 100 parts by weight of the polydimethylsiloxane particles and the zwitterionic polymer is a random copolymer including a first monomer having a zwitterion ion and a second monomer containing an acrylic acid ester, wherein the first monomer is one or more selected from the group consisting of methacryloyloxyethyl phosphorylcholine (MPC), carboxybetaine methacrylate (CBMA), and sulfobetaine methacrylate (SBMA). ### Claim 2 (depends on 1) The in-vivo bulking agent of claim 1, wherein the in-vivo bulking agent satisfies the following Equation 1: V2−V1|×1/100≤0.1 [Equation 1] wherein, V1 refers to a volume occupied by the in-vivo bulking agent when the in-vivo bulking agent is injected into a subject, and V2 refers to a volume occupied by the in-vivo bulking agent in the body 4 weeks after injection of the in-vivo bulking agent into the subject. ### Claim 3 (depends on 1) The in-vivo bulking agent of claim 1, wherein the first composition is in the form of particles having an average particle diameter in the range of 50 to 500 μm. ### Claim 4 (depends on 1) The in-vivo bulking agent of claim 1, wherein the second monomer is one or more selected from the group consisting of butyl methacrylate (BMA), 3-[tris(trimethylsiloxy)silyl]propyl methacrylate (TRIS) and dodecyl methacrylate (DMA). ### Claim 5 (depends on 1) The in-vivo bulking agent of claim 1, wherein the second composition is hyaluronic acid (HA) or collagen. ### Claim 6 (depends on 1) The in-vivo bulking agent of claim 1, wherein the second composition is added in an amount of 55 to 65% (v/v) based on the total in-vivo bulking agent. ### Claim 7 (depends on 1) The in-vivo bulking agent of claim 1, wherein the agent is used for prevention or treatment of sphincter-related diseases. ### Claim 8 (depends on 7) The in-vivo bulking agent of claim 7, wherein the sphincter-related disease is at least one disease selected from the group consisting of a urinary incontinence disease, fecal incontinence, gastroesophageal reflux, and vesicoureteral reflux. ### Claim 9 (depends on 1) The in-vivo bulking agent of claim 1, wherein the agent is used for a plastic surgery procedure. ### Claim 10 (depends on 1) An injection including the in-vivo bulking agent according to claim 1. ### Claim 11 (depends on 1) A method for preventing or treating a sphincter-related disease, the method comprising injecting the in-vivo bulking agent according to claim 1 into a subject. ### Claim 12 (depends on 11) The method of claim 11, wherein the sphincter-related disease is at least one disease selected from the group consisting of fecal incontinence, rectal incontinence, gastroesophageal reflux, a urinary incontinence disease, and vesicoureteral reflux. ### Claim 13 A method for preparing an in-vivo bulking agent formulated as an injectable composition, the method comprising: mixing polydimethylsiloxane particles and a zwitterionic polymer to prepare a first composition in which the zwitterionic polymer is surrounded on a surface of the polydimethylsiloxane particles; and dispersing the first composition in a second composition having a viscosity of 100 to 1500 cps at room temperature; wherein the first composition includes 0.1 to 5 parts by weight of the zwitterionic polymer based on 100 parts by weight of the polydimethylsiloxane particles and the zwitterionic polymer is a random copolymer including a first monomer having a zwitterion ion and a second monomer containing an acrylic acid ester, wherein the first monomer is one or more selected from the group consisting of methacryloyloxyethyl phosphorylcholine (MPC), carboxybetaine methacrylate (CBMA), and sulfobetaine methacrylate (SBMA). ### Claim 14 (depends on 13) The method of claim 13, wherein the preparation of the first composition includes: preparing a mixed solution by adding the polydimethylsiloxane particles and the zwitterionic polymer to a solvent; dispersing the polydimethylsiloxane particles and the zwitterionic polymer in the solvent by ultrasonicating the mixed solution; and centrifuging the ultrasonicated mixed solution, and then obtaining powder to prepare the first composition in which the zwitterionic polymer is surrounded on the surface of the polydimethylsiloxane particles.