# US 11,077,051 B2 · Shear-thinning therapeutic composition, and related methods

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- Number: US 11,077,051 B2
- Document ID: US11077051B2
- Status: Granted
- Kind: B2
- Application number: 16/333,627
- Filed: 2017-09-15
- Published: 2019-07-18
- Granted: 2021-08-03
- Earliest claimed: 2016-09-15
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Inventors: Xiaochu Ding; Jin Gao; Yadong Wang
- Web page: https://patentgrep.com/patent/US11077051B2

## CPC

- 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 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 31/727: Heparin; Heparan
- A61K 38/1825: {Fibroblast growth factor [FGF]}
- A61K 47/02: Inorganic compounds
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61L 27/10: Ceramics or glasses
- A61L 27/20: Polysaccharides
- A61L 27/446: {with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46}
- A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 27/52: Hydrogels or hydrocolloids
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- C08J 3/075: Macromolecular gels
- A61L 2300/414: Growth factors
- A61L 2400/06: Flowable or injectable implant compositions
- A61L 2430/34: for soft tissue reconstruction
- C08J 2305/10: Heparin; 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)
- 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)
- C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29)

## Abstract

A shear-thinning therapeutic composition is provided along with methods of making and using the therapeutic composition.

## Claims

### Claim 1

A shear-thinning therapeutic composition, comprising:
silicate platelets;
a gelling agent non-covalently linking the platelets to form a shear-thinning composition; and
a therapeutic agent that binds non-covalently to the gelling agent and that is complexed non-covalently with the gelling agent wherein the gelling agent is a sulfated or sulfamated polymer, polysaccharide, or glycosaminoglycan.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the sulfated glycosaminoglycan is heparin, heparan sulfate, or a member of the heparin interactome.

### Claim 3 (depends on 1)

The composition of claim 1, wherein:
the ratio of therapeutic agent to the sulfated or sulfamated polymer, polysaccharide, or glycosaminoglycan ranges from 1:16000 to 1:1 by weight, from 1:8000 to 1:3 by weight, or from 1:1520 up to 1:3 by weight; or
the ratio of the sulfated or sulfamated polymer, polysaccharide, or glycosaminoglycan and/or to the gelling agent ranges to the silicate platelets ranges from 1:10 to 1:1 by weight, or from 1:10 to 1:2 by weight.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the therapeutic agent is a growth factor.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the silicate platelets comprise hydrous sodium lithium magnesium silicate platelets.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the therapeutic agent is an oligopeptide, a polypeptide or a protein.

### Claim 7 (depends on 4)

The composition of claim 4, wherein the growth factor is Fibroblast Growth Factor 2 (FGF-2).

### Claim 8 (depends on 1)

The composition of claim 1, wherein the concentration of the silicate platelets ranges from 10 mg/mL to 80 mg/mL (1% to 8%), or from 15 mg/mL to 50 mg/mL (1.5% to 5.0%).

### Claim 9

A method of making a composition for delivery of a therapeutic agent, comprising:
mixing a gelling agent with a therapeutic agent that is a binding partner of the gelling agent to produce a complex of the gelling agent and the therapeutic agent; and
mixing the complex of the gelling agent and the therapeutic agent with silicate platelets to produce a shear-thinning hydrogel
wherein the gelling agent non-covalently links the platelets and is a sulfated or sulfamated polymer, polysaccharide, or glycosaminoglycan; and
wherein the therapeutic agent binds non-covalently to the gelling agent and is complexed non-covalently with the gelling agent.

### Claim 10 (depends on 9)

The method of claim 9, wherein the sulfated or sulfamated polymer, polysaccharide, or glycosaminoglycan is heparin, heparan sulfate, or a member of the heparin interactome.

### Claim 11 (depends on 9)

The method of claim 9, wherein the silicate platelets comprise hydrous sodium lithium magnesium silicate platelets.

### Claim 12 (depends on 9)

The method of claim 9, wherein the therapeutic agent is an oligopeptide, a polypeptide or a protein.

### Claim 13 (depends on 9)

The method of claim 9, wherein the therapeutic agent is a growth factor.

### Claim 14 (depends on 13)

The method of claim 13, wherein the growth factor is Fibroblast Growth Factor 2 (FGF-2).

### Claim 15 (depends on 9)

The method of claim 9, wherein:
the ratio of therapeutic agent to the gelling agent ranges from 1:16000 to 1:1 by weight, from 1:8000 to 1:3 by weight, or from 1:1520 up to 1:3 by weight;
the ratio of the gelling agent to the silicate platelets ranges from 1:10 to 1:1 by weight, or from 1:10 to 1:2 by weight; or
the concentration of the silicate platelets ranges from 10 mg/mL to 80 mg/mL (1% to 8%), or from 15 mg/mL to 35 mg/mL (1.5% to 5.0%).

### Claim 16 (depends on 9)

The method of claim 9, wherein:
the ratio of therapeutic agent or to the sulfated or sulfamated polymer ranges from 1:16000 to 1:1 by weight, from 1:8000 to 1:3 by weight, or from 1:1520 up to 1:3 by weight; or
the ratio of the gelling agent, or the sulfated or sulfamated polymer to the silicate platelets ranges from 1:10 to 1:1 by weight, or from 1:10 to 1:2 by weight.

### Claim 17 (depends on 9)

The method of claim 9, wherein the concentration of the silicate platelets ranges from 10 mg/mL to 80 mg/mL (1% to 8%), or from 15 mg/mL to 50 mg/mL (1.5% to 5.0%).

### Claim 18 (depends on 9)

The method of claim 9, wherein the shear-thinning therapeutic hydrogel is administered parenterally at a location in a patient of an injury or defect, to promote tissue growth, differentiation, and/or repair of the injury or defect.

### Claim 19 (depends on 1)

A method of inducing angiogenesis in a patient, comprising administering to a patient an amount of the composition of claim 1 effective to induce angiogenesis in a patient, wherein the therapeutic agent is an angiogenic agent.

### Claim 20 (depends on 1)

A method of filling a soft tissue in a patient, comprising injecting or implanting in a patient the composition of claim 1.