# US 2014/0193356 A1 · Compositions Comprising Citrate And Applications Thereof

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- Number: US 2014/0193356 A1
- Document ID: US20140193356A1
- Status: Published application
- Kind: A1
- Application number: 14/146,272
- Filed: 2014-01-02
- Published: 2014-07-10
- Earliest claimed: 2013-01-04
- Assignees: Board of Regents, The University of Texas System
- Applicants: The Board of Regents, The University of Texas System
- Inventors: Jian Yang
- Web page: https://patentgrep.com/patent/US20140193356A1

## CPC

- A61K 31/785: Polymers containing nitrogen
- A61K 31/765: Polymers containing oxygen
- A61K 33/42: Phosphorus; Compounds thereof
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C08G 63/12: derived from polycarboxylic acids and polyhydroxy compounds
- C08G 63/914: {derived from polycarboxylic acids and polyhydroxy compounds}
- C08G 81/00: Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers (involving only carbon-to-carbon unsaturated bond reactions C08F299/00 {; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42})
- C08L 67/04: Polyesters derived from hydroxycarboxylic acids, e.g. lactones (C08L67/06 takes precedence)
- C12N 5/0669: {Bone marrow stromal cells; Whole bone marrow (isolated stem cells from bone marrow C12N5/0647, C12N5/0663)}
- C08L 2203/02: for biomedical use
- C08L 2205/025: containing two or more polymers of the same hierarchy C08L, and differing only in parameters such as density, comonomer content, molecular weight, structure
- C12N 2500/30: Organic components
- C12N 2500/34: Sugars
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2533/18: Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells
- 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
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

In one aspect, methods of promoting bone growth are described herein. In some embodiments, a method of promoting bone growth described herein comprises promoting cell differentiation or phenotype progression in a population of bone cells by providing a citrate-presenting composition to the population of bone cells. In some embodiments, the citrate-presenting composition is provided to the bone cells at a first stage of cell development selected to obtain a first cell differentiation or phenotype progression. Additionally, in some cases, a second citrate-presenting composition is further provided to the bone cells at a second stage of cell development selected to obtain a second cell differentiation or phenotype progression.

## Claims

### Claim 1

A method of promoting bone growth comprising:
providing a citrate-presenting composition to a population of bone cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the citrate-presenting composition promotes cell differentiation and/or phenotype progression in the population of bone cells.

### Claim 3 (depends on 2)

The method of claim 2, wherein the citrate-presenting composition is provided to the bone cells at a first stage of cell development selected to obtain a first cell differentiation or phenotype progression.

### Claim 4 (depends on 3)

The method of claim 3, wherein a second citrate-presenting composition is further provided to the bone cells at a second stage of cell development selected to obtain a second cell differentiation or phenotype progression.

### Claim 5 (depends on 2)

The method of claim 2, wherein the citrate-presenting composition promotes osteoblast phenotype progression in the population of bone cells.

### Claim 6 (depends on 1)

The method of claim 1, wherein the bone cells comprise bone stem cells.

### Claim 7 (depends on 1)

The method of claim 1, wherein the bone cells are in vitro.

### Claim 8 (depends on 1)

The method of claim 1, wherein the citrate-presenting composition comprises citric acid or aqueous citrate.

### Claim 9 (depends on 1)

The method of claim 1, wherein the citrate-presenting composition comprises a polymer or oligomer comprising a citrate moiety.

### Claim 10 (depends on 9)

The method of claim 9 further comprising releasing citrate from the polymer or oligomer by degrading the polymer or oligomer.

### Claim 11 (depends on 10)

The method of claim 10, wherein degrading the polymer or oligomer comprises hydrolyzing an ester bond of the polymer or oligomer.

### Claim 12 (depends on 9)

The method of claim 9, wherein the citrate-presenting composition comprises a polymer or oligomer having the structure of Formula (I):
wherein
R1 is —H, —OC(O)NH, or ;
represents an additional chain of repeating units having the structure of Formula (I); and
m, n, and p are 8; and
q is 6.

### Claim 13 (depends on 9)

The method of claim 9, wherein the citrate-presenting composition comprises a polymer or oligomer having the structure of Formula (II):
wherein
R2 is —H or ;
represents an additional chain of repeating units having the structure of Formula (II); and
m, n, and p are 8.

### Claim 14 (depends on 9)

The method of claim 9, wherein the citrate-presenting composition comprises:
a first polymer or oligomer having the structure of Formula (I):
wherein
R1 is —H, —OC(O)NH , or ;
represents an additional chain of repeating units having the structure of Formula (I); and
m, n, and p are 8; and
q is 6; and
a second polymer or oligomer having the structure of Formula (II):
wherein
R2 is —H or ;
represents an additional chain of repeating units having the structure of Formula (II); and
m, n, and p are 8,
wherein the first polymer or oligomer is blended with the second polymer or oligomer.

### Claim 15 (depends on 9)

The method of claim 9 further comprising providing a biological factor to the bone cells.

### Claim 16 (depends on 15)

The method of claim 15, wherein the biological factor comprises BMP-2.

### Claim 17

A composition comprising:
a first polymer or oligomer having the structure of Formula (I):
wherein
R1 is —H, —OC(O)NH, or ;
represents an additional chain of repeating units having the structure of Formula (I); and
m, n, and p are 8; and
q is 6; and
a second polymer or oligomer having the structure of Formula (II):
wherein
R2 is —H or ;
represents an additional chain of repeating units having the structure of Formula (II); and
m, n, and p are 8,
wherein the first polymer or oligomer is blended with the second polymer or oligomer.

### Claim 18 (depends on 17)

The composition of claim 17, wherein the first polymer or oligomer and the second polymer or oligomer are cross linked with one another to form a polymer network.

### Claim 19 (depends on 18)

The composition of claim 18 further comprising a particulate material dispersed in the polymer network.

### Claim 20 (depends on 19)

The composition of claim 19, wherein the particulate material comprises one or more of hydroxyapatite, tricalcium phosphate, biphasic calcium phosphate, bioglass, ceramic, magnesium powder, magnesium alloy, and decellularized bone tissue particles.
