Epidermal growth factor (EGF) produced by an excretory recombinant approach was tested for its efficacy in treating various skin wounds. In a randomized double blind controlled study, local cream samples prepared with human EGF at a final concentration of as low as 0.02% (g/g) in topically suitable carrier were found to have an enhancing effect on the recovery of diabetes foot ulcers. This promotional effect is statistically significant and has resulted in a reduced mean healing time of over 3 weeks when compared with that of control. Both the 0.02% (g/g) and 0.04% (g/g) human EGF supplemented samples in comparison with control showed a trend of stimulatory effect when a recovery of 50% of an ulcer was considered. The EGF samples were also shown to be highly effective in promoting treatments of wounds resulting from bedsores and surgeries.

FIELD OF THE INVENTION

This invention relates to methods and compositions for treating skin wounds using epidermal growth factor (EGF).

BACKGROUND OF THE INVENTION

The ability of EGF to accelerate the metabolism of epithelial cells and its stimulatory effect on the healing of wounds such as skin and gastric ulcers, burns and corneal injuries suggested its potential application to the treatment of diabetes foot ulcer. However, while EGF has been shown to promote healing of corneal and burn wounds at a concentration of 10 .mu.g/ml, EGF failed to promote epithelization in wounds of patients suffering from venous stasis ulcers at the same concentration.

Diabetic foot ulcer is a major complication of diabetes mellitus. People with diabetes mellitus may have a five to fifteen times higher risk of non-traumatic amputation compared with non-diabetes. Between 1996-1998 diabetic patients accounted for 47% of all the lower limb amputations performed in a local Hong Kong hospital. In general, although some patients can be healed with traditional methods, diabetic foot ulcers can be difficult to heal in some patients and frequently lead to amputation if complicated by infection and gangrene. Several new treatment modalities such as an oxygen chamber, platelet derived growth factor (PDGF), and various local dressings have reported various degree of success. The efficacy of such methods may be relatively low, with some of such methods requiring at least 6 months for healing.

Besides diabetic foot ulcer, bedsores and large/deep surgical wounds may be difficult to heal even under medication, probably resulting from the large areas involved. If these wounds are not treated in time, they will deteriorate and subsequently may become incurable and life threatening. Therefore, an effective medical treatment may not only help the patients recover from these skin complications, but may also lead them to a better quality of life, reduced medical care or expense, or even a prolonged life span. Unfortunately, current treatment methods may not be able to provide a relatively effective method to such large-area wounds.

OBJECT OF THE INVENTION

Therefore, it is an object of this invention to resolve at least one or more of the problem as set forth in the prior art. As a minimum, it is an object of this invention to provide the public with a useful choice.

SUMMARY THE INVENTION

Accordingly, this invention provides, in the broad sense, a method and the corresponding composition for treating skin wounds using EGF as the active ingredient.

In one aspect of this invention, a method for treating skin wounds is provided, which comprises the step of topically administering a composition to the skin wounds, said composition including a topically effective amount of epidermal growth factor (EGF) and a topical acceptable carrier.

Another aspect of this invention provides a composition for treating skin wounds including a topically effective amount of epidermal growth factor (EGF) and a topical acceptable carrier.

DETAIL DESCRIPTION OF PREFERRED EMBODIMENTS

This invention is now described by ways of example (see Original Patent) with reference to the figures in the following sections (see Original Patent).

This invention relates to the application of a composition containing at least 0.02% (g/g) EGF and a topically acceptable carrier to the skin wound of a patient which resulted in unexpected positive healing effects. At the very least, the time required for 50% healing, in which the area of the shin wound is reduced by 50%, is substantially reduced compared with existing methods. The study of this invention found that using a composition containing 0.02% (g/g) or 0.04% (g/g) of EGF may reduce the time required to achieve 50% healing by 2-4 weeks. In the case of treating burns, it was found that even 0.001% (g) of EGF may be effective in accelerating wound healing.

Although using 0.02% (g/g) EGF in the composition of this invention was found to be effective in achieving 50% healing, it was also found that it may fail to achieve totally healing in some cases. On the other hand, when EGF is used in an amount of 0.04% (g/g), totally healing was observed in some patients after 4 weeks of treatment, and all of the patients were totally healed after 12 weeks. It was also found that when EGF is used in an amount of 0.03% (g/g), the results are almost indistinguishable from those using 0.04% (g/g) of EGF. Further details will be described in the following examples.

In one embodiment of this invention, the patient may first be with the composition containing 0.02% (g/g) EGF to achieve 50% healing, and then treated with the composition containing 0.04% (g/g) EGF to achieve total healing. Although this may be more economical than using 0.04% (g/g) EGF alone as less amount of EGF may be required, the complication may be less preferred in some cases.

Naturally, human EGF (hEGF) is preferred to be used in the method and composition of this invention when treating human. The structure of hEGF is well documented and can at least be found in "Epidermal Growth Factor and Transforming Growth Factor alpha (by King et al in: Physiology, Biochemistry, and Molecular Biology of the Skin, L. A. Goldsmith, ed.) 2nd edition, Vol. 1, pp. 329-350. Oxford University Press, N.Y.) and Proceedings of the 10th Americal Peptide Symposium by Han et al. (in: Peptides, Chemistry and Biology, (G. R. Marshall, ed.), pp 581-583. Escom, Leiden). However, if such are used to treat other mammals, it may be preferable to use EGF endogenous to the mammals, being treated.

The following may be the requirements on the topical acceptable carrier used in the invention: 1. non-toxic; and 2. the EGF will remain stable and bio-available when applied directly to the skin wound.

The EGF can be dissolved in a liquid, dispersed or emulsified in a medium in a conventional manner to form a liquid preparation or is mixed with a semi-solid (gel) or solid carrier to form a paste, powder, ointment, cream, lotion or the like for easy application to the skin. The choice of the final form may be decided in terms of convenience.

Although further description of the carrier may not be necessary to one skilled in the art, some suitable carriers will now be listed. These may include topically acceptable liquids, creams, oils, lotions, ointments, gels, or solids, such a conventional cosmetic night creams, foundation creams, suntan lotions, sunscreens, hand lotions, make-up and make-up bases, masks and the like. The compositions can contain other optional suitable ingredients estrogen Vitamin A, C and E, alpha-hydroxy of alpha-keto acids such as pyruvic, lactic or glycolic acids, lanolin, vaseline, aloe vera, methyl or propyl paraben, pigments and the like. Suitable topically acceptable carriers include water, petroleum jelly (vaseline), petrolatum, mineral oil, vegetable oil, animal oil, organic and inorganic waxes, such as microcrystalline, paraffin and ozocerite wax, natural polymers, such as xanthanes, gelatin, cellulose, collagen, starch, or gum arabic, synthetic polymers, such as discussed below, alcohols, polyols, and the like. Preferably, the carrier is a water miscible carrier composition that is substantially miscible in water. Such water miscible topical cosmetically acceptable carrier composition can include those made with one or more appropriate ingredients set forth above but can also include sustained or delayed release carrier, including water containing, water dispersable or water soluble compositions, such as liposomes, microsponges, microspheres or microcapsules, aqueous base ointments, water-in-oil or oil-in-water emulsions, gels or the like.
 

1. A method for treating a diabetic foot ulcer or bedsore wound comprising the steps of: performing debridement to the skin wound; and topically applying a composition to the skin wound, wherein said composition comprises a topically acceptable carrier and at least 0.03% by weight of epidermal growth factor (EGF) wherein said EGF is effective at treating the wound.
 

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