# US 2013/0156724 A1 · Use of poloxaminesines as inducers of the osteogenic differentiation of mesenchymal cells

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- Number: US 2013/0156724 A1
- Document ID: US20130156724A1
- Status: Published application
- Kind: A1
- Application number: 13/704,986
- Filed: 2011-05-12
- Published: 2013-06-20
- Earliest claimed: 2010-05-18
- Assignees: Universidade De Santiago De Compostela
- Inventors: Carmen Alvarez Lorenzo; Ana Rey Rico; Teresa Silva Rivera; José Couceiro Follente; Angel Concheiro Nine
- Web page: https://patentgrep.com/patent/US20130156724A1

## CPC

- A61K 31/785: Polymers containing nitrogen
- A61K 31/133: having hydroxy groups, e.g. sphingosine
- A61P 19/00: Drugs for skeletal disorders
- C12N 5/0654: {Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth}
- C12N 2500/46: Amines, e.g. putrescine
- C12N 2506/1353: from bone marrow mesenchymal stem cells (BM-MSC)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The invention describes for first time the activity of poloxamines as inducers in the differentiation of mesenchymal or progenitor cells. In particular, the invention demonstrates that poloxamines have an osteogenic ability. The invention relates to the use of one or more poloxamines or a pharmaceutical composition comprising same for the preparation of a drug for treting patients with bone defects in general. The invention also relates to a method for inducing the differentiation of mesenchymal or progenitor cells into osteoblasts by bringing said cells into contact with a sterilised aqueous dispersion or solution of one or more poloxamines.

## Claims

### Claim at position 1

1-29. (canceled)

### Claim at position 2

30-36. (canceled)

### Claim 37

A method for inducing differentiation of mesenchymal or stem cells comprising administration to a patient in that need thereof a therapeutically effective amount of one or more poloxamines.

### Claim 38 (depends on 37)

A method according to claim 37, for inducing differentiation of mesenchymal or stem cells into osteoblasts.

### Claim 39

A method for treatment of bone defects, the method comprising administering a therapeutically effective amount of one or more poloxamines to a patient in the need of said treatment.

### Claim 40 (depends on 39)

A method for treatment of bone defects according to claim 39, wherein the bone defects are generated by comminutes fractures.

### Claim 41 (depends on 39)

A method for treatment of bone defects according to claim 39, wherein the bone defects are generated by fractures associated to osteopenia.

### Claim 42 (depends on 39)

A method for treatment of bone defects according to claim 39, wherein the bone defects are generated by pseudarthrosis.

### Claim 43 (depends on 39)

A method for treatment of bone defects according to claim 39, wherein the bone defects are generated by loss of bone stock.

### Claim 44

A pharmaceutically acceptable composition consisting of one or more poloxamines and one or more excipients.

### Claim 45 (depends on 44)

A pharmaceutically acceptable composition according to claim 44, in the form of solution or aqueous dispersion.

### Claim 46 (depends on 44)

A pharmaceutically acceptable composition according to claim 44, wherein a total concentration of poloxamines is between 2% and 30%.

### Claim 47 (depends on 44)

A pharmaceutically acceptable composition according to claim 44, wherein a total concentration of poloxamines is between 10% and 20%.

### Claim 48 (depends on 44)

A process for preparing a pharmaceutically acceptable composition as defined in claim 44, the process comprising:
a) mixing one or more poloxamines in an aqueous media at a pH between 6.5 and 7.5 and at a temperature between 0° C. and 37° C. to form a mixture; and
b) sterilizing the mixture.

### Claim 49

A method in vitro for inducing differentiation of mesenchymal or stem cells, except human embryonic stem cells, into osteoblasts, the method comprising contacting a) a sterilized solution or aqueous dispersion of one or more poloxamines, with b) mesenchymal or stem cells, except human embryonic stem cells, which are in a culture medium.

### Claim 50

A method for inducing differentiation of mesenchymal or stem cells, comprising contacting mesenchymal or stem cells with one or more poloxamines.

### Claim 51 (depends on 50)

A method according to claim 50, for inducing differentiation of mesenchymal or stem cells into osteoblasts.

### Claim 52

A method for treating at least one of the following conditions (i) to (iv): (i) bone defects generated by comminutes fractures, (ii) fractures associated to osteopenia, (iii) pseudarthrosis, and (iv) loss of bone stock, the method comprising administering to a patient in need of treatment a therapeutically effective amount of one or more poloxamines.

### Claim 53 (depends on 52)

A method according to claim 52, wherein said administering comprises parenteral administration.

### Claim 54 (depends on 53)

A method according to claim 53, wherein said parenteral administration comprises injection in a specific zone where the patient suffers at least one of the conditions (i) to (iv).

### Claim 55 (depends on 54)

A method according to claim 54, wherein said one or more poloxamines are administered in a pharmaceutical composition, wherein injection of the pharmaceutical composition to the patient forms a gel at a body temperature of the patient, and wherein said gel produces an extended therapeutic effect in treating at least one of the conditions (i) to (iv).

### Claim 56 (depends on 52)

A method according to claim 52, wherein said one or more poloxamines is administered in the form of a solution or aqueous dispersion.

### Claim 57 (depends on 52)

A method according to claim 52, wherein said one or more poloxamines is administered together with one or more excipients.
