# US 10,369,110 B2 · Treatment method and product for uterine fibroids using purified collagenase > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,369,110 B2 - Document ID: US10369110B2 - Status: Granted - Kind: B2 - Application number: 14/213,957 - Filed: 2014-03-14 - Published: 2014-09-18 - Granted: 2019-08-06 - Earliest claimed: 2013-03-15 - Assignees: BioSpecifics Technologies Corp.; Duke University - Applicants: BioSpecifics Technologies Corp.; Duke University - Inventors: Phyllis Carolyn Leppert; Thomas L. Wegman - Web page: https://patentgrep.com/patent/US10369110B2 ## CPC - A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)} - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - 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 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)} - A61K 9/0034: {Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants} - A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)} - A61K 38/43: Enzymes; Proenzymes; Derivatives thereof - A61K 38/4886: {Metalloendopeptidases (3.4.24), e.g. collagenase} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C12Y 304/24003: Microbial collagenase (3.4.24.3) - C12Y 304/24007: Interstitial collagenase (3.4.24.7), i.e. matrix metalloprotease 1 or MMP1 - 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 - C12Y: ENZYMES ## Abstract The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid. ## Claims ### Claim 1 A method for the treatment of uterine fibroids in a patient comprising administering into the uterine fibroid a composition comprising an amount of collagenase from Clostridium histolyticum sufficient to cleave disordered collagen fibrils of types I, III and V in said uterine fibroids, wherein said administering is by injecting or inserting into the fibroid about 0.06 to about 1 mg of said collagenase per 1 cm3 uterine fibroid tissue. ### Claim 2 (depends on 1) The method of claim 1, wherein the collagenase is a mixture of collagenase I and collagenase II. ### Claim 3 (depends on 1) The method of claim 1, wherein about 0.1 mg to about 0.8 mg collagenase is administered per cm3 of tissue to be treated. ### Claim 4 (depends on 1) The method of claim 1, wherein about 0.2 mg to about 0.6 mg collagenase is administered per cm3 of tissue to be treated. ### Claim 5 (depends on 1) The method of claim 1, wherein said composition is injected or inserted into said fibroid transabdominally. ### Claim 6 (depends on 1) The method of claim 1, wherein said composition is injected or inserted into said fibroid transvaginally. ### Claim 7 (depends on 1) The method of claim 1, wherein said composition is injected or inserted into said fibroid under image guidance. ### Claim 8 (depends on 7) The method of claim 7, wherein said image is at least one of a direct visual image and a non-direct visual image. ### Claim 9 (depends on 8) The method of claim 8, wherein said direct visual image is a scope image. ### Claim 10 (depends on 8) The method of claim 8, wherein said non-direct visual image is an MRI image. ### Claim 11 (depends on 10) The method of claim 10, wherein said composition comprises an MRI contrast agent. ### Claim 12 (depends on 8) The method of claim 8, wherein said non-direct visual image is an ultrasound image. ### Claim 13 (depends on 12) The method of claim 12, wherein said composition comprises an ultrasound contrast agent. ### Claim 14 (depends on 8) The method of claim 8, wherein said non-direct visual image is a fluoroscopic image. ### Claim 15 (depends on 14) The method of claim 14, wherein said composition comprises an x-ray contrast agent. ### Claim 16 (depends on 1) The method of claim 1, wherein said composition further comprises a chemical ablation agent, a non-steroidal anti-inflammatory drug, an oral contraceptive, a GnRH agonist, an antiprogestogen, or a selective progesterone receptor modulator. ### Claim 17 (depends on 16) The method of claim 16, wherein said composition comprises a chemical ablation agent. ### Claim 18 (depends on 17) The method of claim 17, wherein said chemical ablation agent is a salt. ### Claim 19 (depends on 17) The method of claim 17, wherein said chemical ablation agent is selected from an enzyme, an acid, a base and an oxidizing agent. ### Claim 20 (depends on 1) The method of claim 1, wherein said composition comprises one or more uterine fibroid treatment agents. ### Claim 21 (depends on 1) The method of claim 1, wherein said composition is a solid dosage form having a largest dimension between 1 mm and 20 mm. ### Claim 22 (depends on 1) The method of claim 1, wherein said composition is delivered through a delivery channel into said fibroid, wherein the delivery channel is in a needle, syringe, cannula, catheter or jet injector. ### Claim 23 (depends on 1) The method of claim 1, wherein said composition is encapsulated. ### Claim 24 (depends on 1) The method of claim 1, wherein said composition is a powder. ### Claim 25 (depends on 24) The method of claim 24, wherein said powder is introduced into said fibroid by jet injection. ### Claim 26 (depends on 1) The method of claim 1, wherein the composition further comprises a viscosity adjusting agent is present in an amount effective to provide a viscosity ranging from 10,000 centipoise to 50,000 centipoise. ### Claim 27 (depends on 1) The method of claim 1, wherein said composition is a fluid formulation that is crosslinked in vivo. ### Claim 28 (depends on 1) The method of claim 1, wherein said composition comprises an alginate polymer. ### Claim 29 (depends on 1) The method of claim 1, wherein said composition comprises gelatin. ### Claim 30 (depends on 1) The method of claim 1, wherein the composition provides sustained release of an amount of said collagenase sufficient to treat said uterine fibroids. ### Claim 31 (depends on 1) The method of claim 1, wherein 100 μL of said composition is injected or inserted into 1 cm3 uterine fibroid tissue. ### Claim 32 A method for the treatment of uterine fibroids in a patient, comprising administering into the uterine fibroid a composition comprising an amount of collagenase from Clostridium histolyticum sufficient to cleave disordered collagen fibrils of types I, III and V in said uterine fibroids, wherein said amount is 0.25-2.0 mg/mL collagenase from Clostridium histolyticum, and wherein said administering is by injecting or inserting said composition into the uterine fibroid tissue. ### Claim 33 (depends on 32) The method of claim 32, wherein said composition comprises 0.25 mg/mL collagenase from Clostridium histolyticum. ### Claim 34 (depends on 32) The method of claim 32, wherein said composition comprises 0.5 mg/mL collagenase from Clostridium histolyticum. ### Claim 35 (depends on 32) The method of claim 32, wherein said composition comprises 1.0 mg/mL collagenase from Clostridium histolyticum. ### Claim 36 (depends on 32) The method of claim 32, wherein said composition comprises 2.0 mg/mL collagenase from Clostridium histolyticum.