WO1990006743A1

WO1990006743A1 - Method for restoring hair growth

Info

Publication number: WO1990006743A1
Application number: PCT/US1989/005790
Authority: WO
Inventors: Edward M. Alderman
Original assignee: Genetics Institute, Inc.
Priority date: 1988-12-21
Filing date: 1989-12-21
Publication date: 1990-06-28

Abstract

The use of M-CSF in the preparation of pharmaceutical compositions having hair growth promoting activity is disclosed.

Description

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METHOD FOR RESTORING HAIR GROWTH Hair loss, or alopecia, is a condition of various causes that may be hereditary, congenital or acquired. Certainly the form with which we are most familiar is hereditary alopecia, or male pattern baldness.

Recently, a great deal of attention has focused on the reported effects of minoxidil in treating male pattern baldness. See US Patent No. 4,596,812. I have surprisingly found that macrophage colony stimulating factor (M-CSF) may also have a positive effect in stimulating hair growth and restoring hair growth to dormant follicles, and thus may be used in the treatment of alopecia.

Summary of the Invention

My invention provides a method for promoting and restoring hair growth in a mammal, preferably human, in need of same. The method comprises administering to said mammal an effective amount of M-CSF to promote or restore hair growth in admixture with a pharmaceutically acceptable carrier. My invention is based at least in part on results unexpectedly obtained in experiments testing the effects of M-CSF on mice. In those experiments, I consistently observed that each mouse, about thirty in all, developed hair growth around the site of injection within about a week.

M-CSF and variants thereof have been obtained from natural sources and by recombinant DNA techniques. See, for example, Wong, et al., Science 235;1504-08 (1987), US Patent 4,868,119, WO87/06954, EP 0 261 592, WO88/03173, EP 0 276 551, US Patent 4,847,201, EP 0 249 477, GB 2 016 777, WO89/03881, US Patent 4,847,325, -WO88/08003 and WO86/04587. It is contemplated that M-CSF or biologically active variants thereof, including but not limited to those set forth in the publications just cited, and including PEGylated M-CSF, may be employed in the method of this invention, as long as the protein exhibits its characteristic biological activity of promoting hair growth and are encoded by DNAs capable of hybridizing, especially under stringent conditions, to DNAs for the naturally occurring form, as shown in Figure 2 of Wong, supra. Also included, of course, are naturally occurring isotypes or allelic variations in the proteins or in their coding sequences, as occur in different members of a species. Accordingly, by "M-CSF" I mean any of the above unless a specific form is designated.

It is contemplated that the preferred M-CSF employed will be human M-CSF free from association with other contaminating proteins. Such M-CSF preferably will have a specific activity of at least about 400,000 Dilution Units per milligram (DU/mg) in the Wong Mouse Bone Marrow Assay described in Wong et at. Science 235;1504-08 (1987).

For the purposes of my invention, an effective dose of M-CSF for stimulating or promoting hair growth is in the range of about 0.1 micrograms per dose to about 50 milligrams per dose. Within that range the precise amount of M-CSF used and the concentration of M-CSF in a pharmaceutical composition for use in accordance with this invention will depend on the mode of administration and hence on the choice of formulation. For instance, amounts in the lower portion of the range would typically be more appropriate for parenteral injections, whether intravenous, intramuscular or subcutaneous or intradermal, and thus for pharmaceutical compositions appropriate for such routes of administration. Because significantly higher dosages may be necessary for topical administration relative to injection, amounts in the higher portion of the range would typically be more appropriate for topical administration and for pharmaceutical compositions appropriate for those routes of administration. The precise amount and concentration of M-CSF used may also be varied by the attending physician or pharmacist in view of such factors that modify the action of drugs, for example, the method of administration, time of administration, the condition, age, sex, body weight and diet of the patient and the potential interaction with concurrent therapies. The M-CSF should be administered in a dose insufficient to cause a systemic toxic reaction, but sufficient to elicit a hair growing effect.

In one embodiment, this invention provides a method for stimulating hair growth which comprises parenteral, preferably intradermal or subcutaneous, administration to the patient of a pharmacuetical composition containing a treatment effective amount of an M-CSF protein in admixture with a pharmaceutically acceptable vehicle. Contemplated effective amounts of M-CSF for such administration range from about 0.1 micrograms per dose to about 500 micrograms per dose. Intradermal or subcutaneous injections of between about 0.1 and 50 micrograms per dose may be especially useful. For intradermal administration the volume injected is preferably kept at or below 50 icroliters per injection. The formulation should be non-toxic and non-allergenic. Such treatment may be repeated as necessary in the view of the attending physician or health care professional.

A presently preferred method for administration of M-CSF for -the purposes of this invention is intradermal or subcutaneous administration. For such administration, a typical formulation would comprise an M-CSF protein, a pharmaceutically acceptable polyoxyethylenic non-ionic surfactant such as a polysorbate or a poloxamer, glycine, sucrose and a pharmaceutically acceptable buffer such as sodium citrate, to bring the pH of the solution to about 6. Typically, M-CSF can be in a concentration of about 0.1 to about 20 milligrams per milliliter. An exemplary formulation is: M-CSF 0.5-5.0 mg/ml surfactant 0.0025-1% glycine 0.25-0.75 M sucrose 0.5-3% sodium citrate 0-50 mM

A preferred polysorbate is polysorbate 80, at a concentration of about 0.005% V/V, and a preferred poloxamer is poloxamer 338, at a concentration of about 0.05% V/V. Adjustments for tonicity of the final solution may be desirable.

In another embodiment, this invention provides a method for stimulating hair growth which comprises topical administration of a pharmaceutical composition containing a treatment effective amount of an M-CSF protein in admixture with a pharmaceutically acceptable topical vehicle directly to the region in which stimulated or restored hair growth is desired. Contemplated effective amounts of M-CSF for such administration range from about 0.01 milligram per dose to about 50 milligrams per dose, preferably from about 0.5 milligrams per dose to about 25 milligrams per dose. Useful concentrations may include those for injectable formulations. The formulation should be non-toxic and non-allergenic. Topical treatment may be repeated as necessary in the view of the attending physician or health care professional.

Topical administration may comprise administration with in a solution with dimethyl sulfoxide (DMSO) or some other such pharmaceutically acceptable carrier for medicated applications. Suitable vehicles are well known in the art and may comprise liquid solutions, ointments, creams, foams and gels. A general discussion of medicated applications is found in Remington's Pharmaceutical Sciences. pp. 1567-1584 (17 ed. , 1985). The components may vary widely as long as the pH of the composition is appropriate for topical application and not deleterious to the stability of the active ingredient.

An exemplary liquid solution preparation for topical application is 50 mM Hepes, pH 7.5, and 125 mM NaCl. To this preparation, M-CSF in an amount between about 0.1 micrograms and about 10 micrograms is added to make a total volume of 200 ml. The composition is applied to the skin surface desired such that the M- CSF is present in an amount sufficient to elicit a hair growing effect.

Exemplary ointment preparations for topical application include Hydrophilic Petrolatum USP (by weight, 3% cholesterol, 3% stearyl alcohol 80% white wax and 86% white petrolatum) and Hydrophilic Ointment USP (by weight, 0.025% methylparaben, 0.015% propylparaben, 1% sodium lauryl sulfate, 12% propylene glycol, 25% stearyl alcohol, 25% white petrolatum and 37% sterile purified water) .

An exemplary gel preparation is, by weight, about 75% sterile purified water, 3% propyleneglycol, 1% methylcellulose and 1% preservative.

Claims

(PI claim:

1. The use of M-CSF for the preparation of a pharmaceutical composition having hair growth promoting activity.

2. The use of claim 1 wherein the pharmaceutical composition is suitable for subcutaneous administration.

3. The use of claim 1 wherein the pharmaceutical composition is suitable for topical administration.

4. The use of claim 1 wherein the pharmaceutical composition is suitable for intradermal administration.

5. A pharmaceutical composition comprising M-CSF and a pharmaceutically acceptable vehicle suitable for topical administration.

6. A composition of claim 4 in which the vehicle is a liquid, cream, ointment or gel.