# US 8,784,850 B2 · Highly biocompatible dual thermogelling chitosan/glucosamine salt composition

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,784,850 B2
- Document ID: US8784850B2
- Status: Granted
- Kind: B2
- Application number: 13/908,299
- Filed: 2013-06-03
- Published: 2013-10-10
- Granted: 2014-07-22
- Earliest claimed: 2010-08-27
- Applicants: Oligo Médic Inc.
- Inventors: Abdellatif Chenite; Amine Selmani
- Web page: https://patentgrep.com/patent/US8784850B2

## CPC

- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels 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 31/722: Chitin, chitosan
- A61K 35/14: Blood; Artificial blood (perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42)
- A61K 35/16: Blood plasma; Blood serum (umbilical cord blood A61K35/51)
- A61K 35/32: Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- A61K 38/18: Growth factors; Growth regulators
- A61K 38/1875: {Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor}
- A61K 38/19: Cytokines; Lymphokines; Interferons
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61L 27/20: Polysaccharides
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61P 17/00: Drugs for dermatological disorders
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 25/00: Drugs for disorders of the nervous system
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61L 2300/10: containing or releasing inorganic materials
- A61L 2300/30: Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to a chitosan solution neutralized with amino-sugar carbonate buffering solution or amino-sugar phosphate buffering solution or phosphorylated aminosugar buffering solution. The resulting thermogelling chitosan composition is highly biocompatible, isotonic and has the ability to rapidly turn into gel upon heating to the body temperature. It provides a novel chitosan-based composition to suitable for drug delivery, cell delivery and repair or regeneration of tissues and organs as well as other clinical treatment.

## Claims

### Claim 1

A method of treating, repairing, regenerating, replacing or substituting a tissue or organ within a mammalian or human body comprising the step of administering a thermogelling composition comprising:
a) a chitosan solution; and
b) a buffering solution consisting of an amino-sugar carbonate solution, an amino-sugar phosphate solution or a phosphorylated amino-sugar solution;
wherein the composition, being liquid at a pH between 6.5 and 7.6, is biocompatible, isotonic and turns into gel when heated up to a temperature range between about 25° C. and about 60° C., and cooled down to a temperature range between about 8° C. and about 1° C.

### Claim 2 (depends on 1)

The method of claim 1, wherein said buffering solution is a glucosamine carbonate solution, a glucosamine phosphate solution or a glucosamine-6-phosphate solution.

### Claim 3 (depends on 1)

The method of claim 1, wherein the composition is injected then gelled in the mammalian or human body.

### Claim 4 (depends on 1)

The method of claim 1, wherein said composition is pregelled before being injected in mammalian or human body.

### Claim 5 (depends on 1)

The method of claim 1, wherein the tissue or organ comprises articular cartilage, fibrocartilage, meniscus, intervertebral discs, bone tissues, muscular tissues, nerve and spinal cord soft-tissues, skin or dermal tissues.

### Claim 6 (depends on 1)

The method of claim 1, wherein the composition is injected intrarticular to treat or improve body joint functions, or to repair cartilage defects.

### Claim 7 (depends on 1)

The method of claim 1, wherein said composition is prepared by:
a) dissolving chitosan in an acidic solution to obtain the aqueous solution of chitosan; and
b) admixing the buffering solution to said chitosan solution.

### Claim 8 (depends on 7)

The method of claim 7, wherein the chitosan is dissolved at a temperature between 15 and 22° C.

### Claim 9 (depends on 1)

The method of claim 1, wherein said composition is in liquid state having a pH between 6.7 and 7.2.

### Claim 10 (depends on 1)

The method of claim 1, wherein said composition forms a gel when heated up to 37° C.

### Claim 11 (depends on 1)

The method of claim 1, wherein the concentration of chitosan ranges from 0.1% to 5.0%.

### Claim 12 (depends on 2)

The method of claim 2, wherein the concentration of glucosamine carbonate, glucosamine phosphate or glucosamine-6-phosphate ranges from 0.002M to 0.100M.

### Claim 13 (depends on 1)

The method of claim 1, wherein the concentration of chitosan ranges from 1.0% to about 3.0%.

### Claim 14 (depends on 2)

The method of claim 2, wherein the ratio of chitosan to glucosamine carbonate, glucosamine phosphate or glucosamine-6-phosphate is between 1 and 3.

### Claim 15 (depends on 1)

The method of claim 1, wherein said chitosan has a degree of deacetylation (DDA) ranging between 70% and 100% and a molecular weight (Mw) ranging from 50 kDa to 1000 kDa.

### Claim 16 (depends on 1)

The method of claim 1, wherein said chitosan has a degree of deacetylation (DDA) of 80% to 99%, and a Mw of 200 kDa to 500 kDa.

### Claim 17 (depends on 1)

The method of claim 1, wherein the osmolarity of said composition is between 270 mOsmol/kg and 340 mOsmol/kg.

### Claim 18 (depends on 1)

The method of claim 1, further comprising at least one material or compound selected from the group consisting of cells, stem cells, peptides, growth factors, human blood, platelet-rich plasma, nucleotides, bone, bone-derived materials, calcium phosphates, calcium carbonates, bioglasses, ceramics, drugs and imaging agents.

### Claim 19 (depends on 18)

The method of claim 18, wherein said calcium phosphate particles are biphasic calcium phosphates, tetra-calcium phosphates, tri-calcium phosphates, hydroxyapatite, di-calcium phosphates, mono-calcium phosphates, amorphous calcium phosphates, octa-calcium phosphate, fluorinated calcium phosphate, strontied calcium phosphate, or a mixture thereof.