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

• US 7,799,760 B2
• Filed: 08/22/2008
• Issued: 09/21/2010
• Est. Priority Date: 12/20/2001
• Status: Expired due to Term

• 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, Rojas Constantin, Ingrid, Sotolongo Pena, Jorge, Chacon Corvea, Larissa, Santana Milian, Hector, Valdes Perez, Calixto, Fernandez Montequin, Jose I., Herrera Martinez, Luis, Franco Perez, Neobalis, Berlanga Acosta, Jorge, Geronimo Perez, Haydee
• Primary Examiner(s): Allen; Marianne P
• Application Number:
  US12/197,001
• Publication Number:
  US 20080312139A1
• Time in Patent Office: 760 Days
• Field of Search: None
• US Class Current: 514/6.9
• 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 favoring 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 cicatrization 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 cicatrize and/or heal.

Claims

1. A method for treatment of an ischemic lesion or a reperfusion lesion in a diabetic patient, said method comprising perilesionally injecting said lesion with a therapeutically effective amount of a pharmaceutical composition comprising epidermal growth factor (EGF), wherein tissue survival is enhanced.

2. The method according to claim 1, wherein said ischemic lesion or reperfusion lesion is in a lower limb.

3. The method according to claim 1, wherein said ischemic lesion or reperfusion lesion is in a foot, lower leg or upper leg.

4. The method according to claim 1, wherein said EGF is human EGF.

5. The method 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. The method 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. The method according to claim 1, wherein said EGF-containing pharmaceutical composition contains EGF from 10 to 1000 micrograms of EGF per milliliter.

8. The method 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, Levan, and Polyethyleneimine (PEI).

9. The method 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. The method according to claim 9, wherein said natural isoflavonoid is Rutin.

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

12. The method 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. The method 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. The method according to claim 1, wherein said EGF-containing pharmaceutical composition also contains from 1 to 130 milligrams per milliliter mg/ml of nicotinamide.

15. The method according to claim 1, wherein said EGF-containing pharmaceutical composition also contains 1 to 100 nanograms per milliliter of L-Arginine.

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

17. The method according to claim 1, wherein said perilesional injection is carried out once per day, once every other day, once every three days, or two or three times per week.

18. The method according to claim 1, wherein said perilesional injection is carried out three or more times.

19. The method according to claim 1, wherein said perilesional injection is carried out 4 to 20 times.

20. A method according to claim 18, wherein said perilesional injection is carried out each time at three or more locations, and wherein said injections are distributed along the circumference of the lesion.

21. A method according to claim 19, wherein said perilesional injection is carried out each time at from four to twenty locations, and wherein said injections are distributed along the circumference of the lesion.