# US 10,945,993 B2 · Methods of recruiting SDF-producing macrophages

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- Number: US 10,945,993 B2
- Document ID: US10945993B2
- Status: Granted
- Kind: B2
- Application number: 14/787,164
- Filed: 2014-04-29
- Published: 2016-04-21
- Granted: 2021-03-16
- Earliest claimed: 2013-04-29
- Assignees: MedRegen, LLC
- Applicants: MedRegen, LLC
- Inventors: Zhaoli Sun; George Melville Williams; Qing Lin
- Web page: https://patentgrep.com/patent/US10945993B2

## CPC

- A61K 31/395: having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61K 31/4427: containing further heterocyclic ring systems
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 38/13: Cyclosporins
- A61K 38/18: Growth factors; Growth regulators
- A61K 38/193: {Colony stimulating factors [CSF]}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- 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 relates to the field of wound healing. More specifically, the present invention provides methods and compositions useful for improved wound healing via autologous stem cell mobilization. In one embodiment, a method for improving wound healing in a patient comprises administering to the patient a therapeutically effective amount of a stem cell mobilizer and a low dose of an immunosuppressive agent.

## Claims

### Claim 1

A method of recruitment of SDF-producing macrophages comprising administering to a human patient who is diabetic or has a burn injury and is in need of external wound treatment a therapeutically effective amount of a stem cell mobilizer and a low dose of Tacrolimus, and the low dose is in a range of about 0.004 mg/kg to about 0.008 mg/kg, and
wherein the stem cell mobilizer and the Tacrolimus are administered simultaneously to the patient about once every two days, wherein, after the administration, the patient's external wound healing is improved as compared to prior to the administration,
wherein the patient is diabetic or has a burn injury, and
wherein administration of the Tacrolimus and the stem cell mobilizer promotes granulation tissue formation, tissue regeneration and re-epithelialization of the wound, and
wherein administration of the Tacrolimus and the stem cell mobilizer recruits SDF-producing macrophages.

### Claim 2 (depends on 1)

The method of claim 1, wherein the stem cell mobilizer is selected from the group consisting of AMD3100, AMD3465, TG-0054, BKT140, G-CSF, GM-CSF, SDF-1, and SCF.

### Claim 3 (depends on 1)

The method of claim 1, wherein the stem cell mobilizer is a CXCR4 antagonist.

### Claim 4 (depends on 3)

The method of claim 3, wherein the stem cell mobilizer is AMD3100.

### Claim 5

A method of recruitment of SDF-producing macrophages comprising administering to a human patient who is diabetic or has a burn injury and is in need of external wound treatment a therapeutically effective amount of AMD3100 and a low dose of Tacrolimus,
wherein the low dose is in a range of about 0.004 mg/kg to about 0.008 mg/kg, and
wherein the AMD3100 and the Tacrolimus are administered simultaneously to the patient about once every two days, wherein, after the administration, the patient's external wound healing is improved as compared to prior to the administration,
wherein the patient is diabetic or has a burn injury, and
wherein administration of the Tacrolimus and the AMD3100 promotes granulation tissue formation, tissue regeneration and re-epithelialization of the wound, and
wherein administration of the Tacrolimus and the AMD3100 recruits SDF-producing macrophages.

### Claim 6

A method of recruitment of SDF-producing macrophages comprising administering to a human patient who is diabetic or has a burn injury and is in need of external wound treatment and is in need of external wound treatment a therapeutically effective amount of an agent that mobilizes CD34+ and/or CD133+ stem cells and a low dose of Tacrolimus, and the low dose is in a range of about 0.004 mg/kg to about 0.008 mg/kg, and
wherein the agent that mobilizes CD34+ and/or CD133+ stem cells and the Tacrolimus are administered simultaneously to the patient about once every two days, wherein, after administration, the patient's external wound healing is improved as compared to prior to the administration,
wherein the patient is diabetic or has a burn injury, and
wherein administration of the Tacrolimus and the agent that mobilizes CD34+ and/or CD133+ stem cells promotes granulation tissue formation, tissue regeneration and re-epithelialization of the wound, and
wherein administration of the Tacrolimus and the agent that mobilizes CD34+ and/or CD133+ stem cells recruits SDF-producing macrophages.

### Claim 7 (depends on 6)

The method of claim 6, wherein the agent that mobilizes CD34+ and/or CD133+ stem cells is AMD3100.

### Claim 8

A method of recruitment of SDF-producing macrophages comprising administering to a human patient who is diabetic or has a burn injury and is in need of external wound treatment and is in need of external wound treatment a low dose of Tacrolimus in an amount sufficient to mobilize stem cells to the peripheral blood of the recipient and a second agent to mobilize stem cells to the peripheral blood,
wherein the low dose of Tacrolimus is in a range of about 0.004 mg/kg to about 0.008 mg/kg, and
wherein the Tacrolimus and the second agent are administered to the patient simultaneously about once every two days, wherein, after administration, the patient's external wound healing is improved as compared to prior to the administration,
wherein the patient is diabetic or suffers from a burn injury, and
wherein administration of the Tacrolimus and the second agent promotes granulation tissue formation, tissue regeneration and re-epithelialization of the wound, and
wherein administration of the Tacrolimus and the second agent recruits SDF-producing macrophages.

### Claim 9 (depends on 8)

The method of claim 8, wherein the stem cell mobilizer is selected from the group consisting of AMD3100, AMD3465, TG-0054, BKT140, G-CSF, GM-CSF, SDF-1, and SCF.

### Claim 10 (depends on 8)

The method of claim 8, wherein the stem cell mobilizer is a CXCR4 antagonist.

### Claim 11 (depends on 8)

The method of claim 8, wherein the stem cell mobilizer is AMD3100.

### Claim 12

A method of recruitment of SDF-producing macrophages comprising administering a low dose of Tacrolimus to a human patient who is diabetic or has a burn injury and is in need of external wound treatment in an amount sufficient to mobilize CD34+ and/or CD133+ stem cells to the peripheral blood,
wherein the low dose is in a range of about 0.004 mg/kg to about 0.008 mg/kg, and
administering a stem cell mobilizer,
wherein the Tacrolimus and the stem cell mobilizer are administered to the patient simultaneously about once every two days, wherein, after administration, the patient's external wound healing is improved as compared to prior to the administration,
wherein the patient is diabetic or has a burn injury, and
wherein administration of the Tacrolimus and the stem cell mobilizer promotes granulation tissue formation, tissue regeneration and re-epithelialization of the wound, and
wherein administration of the Tacrolimus and the stem cell mobilizer recruits SDF-producing macrophages.
