# US 6,720,340 B1 · Nicotine receptor agonists in stem cell and progenitor cell recruitment

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- Number: US 6,720,340 B1
- Document ID: US6720340B1
- Status: Granted
- Kind: B1
- Application number: 09/627,643
- Filed: 2000-07-28
- Granted: 2004-04-13
- Earliest claimed: 1999-07-28
- Assignees: The Board of Trustees of the Leland Stanford, Jr. Unversity
- Inventors: John Cooke; Frances Lauri Johnson; Anjali Pathak; James Jang; Phillip Tsao; Christopher Heeschen
- Web page: https://patentgrep.com/patent/US6720340B1

## CPC

- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/465: Nicotine; Derivatives thereof
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/08: Vasodilators for multiple indications
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 31/12: Antivirals
- A61P 31/18: for HIV
- A61P 37/04: Immunostimulants
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

## Abstract

The present invention features methods for recruitment of bone marrow-derived stem cells (e.g., endothelial cell precursors, hematopoietic stem cells) by administration of nicotine or other nicotine receptor agonist. The methods of the invention can be used in, for example, treatment of conditions amenable to treatment by recruitment of bone marrow-derived stem cells (e.g., neutropenia).

## Claims

### Claim 1

A method of mobilizing a progenitor cell in a mammal, the method comprising administering to a mammal a nicotine receptor agonist in an amount effective to stimulate mobilization of a progenitor cell from bone marrow of the mammal to a site of deficiency or injury in the mammal, wherein the nicotine receptor agonist is nicotine, a nicotine salt, a nicotine derivative, a nicotine metabolite, or a derivative of a nicotine metabolite.

### Claim 2 (depends on 1)

The method of claim 1, wherein the nicotine receptor agonist is nicotine.

### Claim 3 (depends on 1)

The method of claim 1, wherein said administering is at a local site.

### Claim 4 (depends on 1)

The method of claim 1, wherein said administering is intramuscular.

### Claim 5 (depends on 1)

The method of claim 1, wherein said administering is intravascular.

### Claim 6 (depends on 1)

The method of claim 1, wherein the progenitor cell is of mesenchymal or hematopoietic lineage.

### Claim 7 (depends on 1)

The method of claim 1, wherein the agonist is effective to stimulate incorporation of circulating progenitor cells into the site.

### Claim 8 (depends on 1)

The method of claim 1, wherein the agonist is selected from cotinine, norcotinine, nicotine N-oxide, cotinine N-oxide, 3-hydroxycotinine, and 5-hydroxycotinine.

### Claim 9

A method of treating a condition amenable to treatment by recruitment of bone marrow-derived progenitor cells, the method comprising:
administering to a mammal a nicotine receptor agonist in an amount effective to stimulate mobilization of a progenitor cell from bone marrow of the mammal to a site of deficiency or injury in the mammal, wherein the nicotine receptor agonist is nicotine, a nicotine salt, a nicotine derivative, a nicotine metabolite, or a derivative of a nicotine metabolite.

### Claim 10 (depends on 9)

The method of claim 9, wherein the nicotine receptor agonist is nicotine.

### Claim 11 (depends on 9)

The method of claim 9, wherein said administering is at a local site.

### Claim 12 (depends on 9)

The method of claim 9, wherein said administering is intramuscular.

### Claim 13 (depends on 9)

The method of claim 9, wherein said administering is intravascular.

### Claim 14 (depends on 9)

The method of claim 9, wherein the progenitor cell is of mesenchymal or hematopoietic lineage.

### Claim 15 (depends on 9)

The method of claim 9, wherein the agonist is effective to stimulate incorporation of circulating progenitor cells into the site.

### Claim 16 (depends on 9)

The method of claim 9, wherein the agonist is selected from cotinine, norcotinine, nicotine N-oxide, cotinine N-oxide, 3-hydroxycotinine, and 5-hydroxycotinine.