Use of pharmaceutical composition containing epidermal growth factor (EGF) for diabetic foot amputation prevention

• US 20050107294A1
• Filed: 12/04/2002
• Published: 05/19/2005
• Est. Priority Date: 12/20/2001
• Status: Active Grant

• Current Assignee: Centro De Ingenieria Genetica Y Biotecnologia
• Original Assignee: Centro De Ingenieria Genetica Y Biotecnologia
• Inventors: Guillen Nieto, Gerardo E., Canan-Haden Frias, Leonardo, Sotolongo Pena, Jorge, Geronimo Perez, Haydee, Valdes Perez, Calixto, Acosta, Jorge Berlanga, Constantin, Ingrid Rojas, Perez, Neobalis Franco, Fernandez Montequin, Jose I, Milian, Hector Santana, Corvea, Larissa Chacon, Martinez, Luis Herrera
• Granted Patent: US 7,465,704 B2
• Time in Patent Office: Days
• US Class Current: 514/9.600
• CPC Class Codes: A61K 38/1808 Epidermal growth factor [EGF] urogastrone
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The invention relates to the use of Epidermal Growth Factor (EGF) in a preferably-injectable pharmaceutical composition which is administered by means of infiltration into and around chronic cutaneous ischaemic lesions in order to prevent diabetic foot amputation. Said composition can be administered to recently-created surgical surfaces damaged by the effect of acute reperfusion with oxygenated blood following prolonged ischaemia, thereby preventing further surgical procedures and favouring the preservation of the extremity. The aforementioned composition can be used to improve (i) the cell microenvironment, thereby increasing the reparative and defensive capacity and viability of the is tissues and (ii) the cicatrisation of cutaneous ischaemic lesions, thereby stimulating cell proliferation. The invention is suitable for use in human, veterinary and experimental medicine, specifically in vascular angiology and surgery, dermatology, burn treatment and reconstructive surgery and geriatric medicine. Said composition can be used for recalcitrant ulcers which are associated with lesions in the macro and/or microvasculature, patients with inadequate lymphatic and/or venous return and ulcers or other lesions which are difficult to cicatrise and/or heal.

Claims

1. Use of Epidermal Growth Factor (EGF) for preparing a pharmaceutical composition for the treatment of an ischemic lesion or a reperfusion lesion in a diabetic patient by local infiltration in tissue comprising the edges and bottom of the lesion.

2. Use of Epidermal Growth Factor according to claim 1, wherein said ischemic lesion or reperfusion lesion is in lower limb such as foot, lower leg or upper leg, or both.

3. Use of Epidermal Growth Factor according to claim 1, wherein said treatment renders amputation or further re-amputation unnecessary.

4. Use of Epidermal Growth Factor according to claim 1, wherein said EGF is human EGF.

5. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition is a liquid composition or a dry or lyophilized composition for reconstitution before use with water or an aqueous buffer.

6. Use of Epidermal Growth Factor according to claim 5, wherein said EGF-containing pharmaceutical composition is an aqueous optionally buffered liquid composition or a dry or lyophilized composition for reconstitution with water or an aqueous buffer.

7. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition contains EGF from 10 to 1000 micrograms of EGF per milliliter.

8. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition also contains from 10 micrograms to 500 milligrams of at least one member of the group consisting of Fibronectin, O-Raffinose, Levane, and Polyethyleneimine (PEI).

9. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition also contains from 20 to 1000 micrograms per milliliter of at least one natural isoflavonoid.

10. Use of Epidermal Growth Factor according to claim 9, wherein said natural isoflavonoid is Rutine.

11. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition also contains from 5 to 40 milligrams per milliliter of lidocaine.

12. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition also contains from 0.05 to 20 milligrams per milliliter of adenosine triphosphate (ATP) or a salt thereof.

13. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition also contains from 1 to 100 milligrams per milliliter of guanosine triphosphate (GTP) or a salt thereof.

14. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition also contains from 1 to 130 milligrams per milliliter mg/ml of nicotinamide.

15. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition also contains 1 to 100 nanograms per milliliter of L-Arginine.

16. Use of Epidermal Growth Factor according to claim 1, wherein said EGF-containing pharmaceutical composition also contains from 1 to 10 micrograms per milliliter of a heparin salt.

17. Use of Epidermal Growth Factor according to claim 1, wherein said treatment by local infiltration is carried out once per day, once every other day, once every three days, two or three times per week.

18. Use of Epidermal Growth Factor according to claim 1, wherein said treatment by local infiltration is carried out three or more times, preferably from 4 to 20 times.

19. Use of Epidermal Growth Factor according to claim 1, wherein said treatment by local infiltration is carried out each time at three or more spots, preferably at from 4 to 20 spots, distributed along the circumference of the lesion.

20. A pharmaceutical composition for the treatment of an ischemic lesion or a reperfusion lesion in a diabetic patient by local infiltration in tissue at the edges and bottom of the lesion, which is a liquid or lyophilized composition containing from 10 to 1000 micrograms of EGF per milliliter in combination with at least one member of the group consisting of Fibronectin, O-Rafinose, Levane, Polyethyleneimine, and isoflavonoid such as Rutine, lidocaine, adenosine triphosphate, or a salt thereof, guanosine triphosphate or a salt thereof, nicotinamide, L-arginine, and a heparin salt.