WO1990006100A1

WO1990006100A1 - Minoxidil and vasoconstrictor compositions for treating alopecia

Info

Publication number: WO1990006100A1
Application number: PCT/US1989/004775
Authority: WO
Inventors: Virginia C. Fiedler
Original assignee: The Upjohn Company
Priority date: 1988-12-02
Filing date: 1989-10-30
Publication date: 1990-06-14
Also published as: EP0451156A1; JPH04501851A; KR910700039A; AU4500889A

Abstract

An improved composition and method for the promotion of hair growth or treatment of alopecia where the composition comprises at least 2.5 percent of minoxidil and a vasoconstrictor in an effective amount wherein hair growth is increased over the application of minoxidil alone. The composition can be present in a topical formulation using suitable pharmaceutical carriers. The method comprises the topical administration of the minoxidil and vasoconstrictor in an effective amount to stimulate hair growth.

Description

MINOXIDIL AND VASOCONSTRICTOR COMPOSITIONS FOR TREATING ALOPECIA Background of the Invention

The present invention relates to an improved composition for treating alopecia, including alopecia areata which can effect young children. The improved composition is effective in the treatment of alopecia which is generally defined as a baldness resulting from common male pattern baldness or hair loss disorders which can occur in females and young children. In the latter two situation, while the disorder poses little threat to the individuals health, it can be emotionally devastating. Therefore it is desirable to develop new and improved methods for restoring hair growth.

The present invention comprises an application of minoxidil and vasoconstrictors which is herein demonstrated to have superior hair growth results over the application of minoxidil alone. Minoxidil and its analogs are well known in the treatment of hair loss. For example, minoxidil is available by prescription as ROGAINE^® a trademark of The Upjohn Company, Kalamazoo, Michigan. The prepara¬ tion of minoxidil topical compounds for application to the scalp are also disclosed in U.S. Patents 4,139,619 and 4,596,812.

Previously, the attempted use of a 2% solution of minoxidil and betamethasone cream (a vasoconstrictor) was reported by the inventor in Pediatric Dermatology, Vol. 4, No. 2, pages 136-158 (page 150) (1987) entitled "Special Symposium: Alopecia Areata Symposium". However, no effect was reported and the levels of minoxidil was low as compared to the improved treatment and composition of the present invention. Information Disclosure

Topical compositions of minoxidil for the treatment of hair growth, alopecia, are known as disclosed in U.S. Patents 4,139,619 and 4,596,812. Also, background information on various minoxidil compounds and analogs is disclosed in U.S. Patents 3,382,247, 3,461,461, 3,644,364 and 4,287,338. Also, the use of a 2% solution of minoxidil with betamethasone cream was reported in Pediatric Dermatology, Vol. 4, No. 2, pages 136-158 (page 150) (1987) entitled "Special Symposium: Alopecia Areata Symposium". Summary of the Invention

In one aspect the subject invention is an improved composition for the 'promotion of hair growth or treatment of alopecia comprising minoxidil in an amount of at least 2.5 percent and a vasoconstrictor in an effective amount wherein hair growth is increased over the use of minoxidil alone. A vasoconstrictor is a corticosteroid or a scopolamine, preferably betamethasone dipropionate. The amount of a vasoconstrictor is from about 0.01 to about 1.0 percent, preferably about 0.01 to about 0.10 percent, more preferably 0.05 percent.

The composition can additionally include a pharmaceutical carrier adapted for topical application.

In another aspect, the present invention is a method for treating or preventing alopecia comprising the topical administration to hair follicles of a composition comprising at least 2.5% minoxidil and a vasoconstrictor in an effective amount to treat or prevent alopecia. The topical administration can be preformed by applying the minoxidil and vasoconstrictor either separately or simultaneously as a single topical application. In the method the composition is routinely applied to the hair follicles, preferably twice daily or daily. Detailed Description of the Invention

The improved topical composition for the treatment of hair growth comprises minoxidil and a vasoconstrictor. The minoxidil portion is 6-amino-l,2-dihydro-hydroxy-2-imino-4-piperidinopyrimidine and analogs thereof. The preparation of these compounds are describ- ed in U.S. Patents 3,382,247, 3,461,461 and 3,644,364 and J.M. McCall, et al., Journal of Organic Chemistry, 40, 3304 (1975) all of which are hereby incorporated by reference. Related compounds are sulfoxypyrimidinium, -pyridinium, and -triazinium which are described in U.S. Patent 4,287,338 herein incorporated by reference. Herein- after, the term "minoxidil" means any of the various forms of 6- amino-1,2-dihydro-hydroxy-2-imino-4-piperidinopyrimidine, derivatives and analogs thereof.

Minoxidil is present in the composition in an amount of from about one to about five percent by weight ("percent"), preferably at least two and a half to about five percent. Best results can be achieved when the minoxidil is present in an amount of about five percent; however, when treating children lesser amounts of minoxidil is employed to avoid any adverse reactions. The vasoconstrictor portion of the composition provides enhanced action of the minoxidil and hair growth is significantly improved versus an application of only minoxidil.

Ideally, the vasoconstrictor is incorporated with minoxidil such that they can both be applied in a single application. Alternative¬ ly, the vasoconstrictor and minoxidil can be applied separately to the treatment area without departing from the improved benefit of this invention. Therefore, the term "composition" and amounts of either minoxidil and vasoconstrictor present therein are determined when both are present on the treatment area regardless of method of application.

Vasoconstrictors appropriate for applying or compounding with minoxidil comprise potent topical corticosteriods which can include a class of natural and synthetic compounds. Typically these steroids are hormones secreted by the adrenal cortex and are noted for their vasoconstrictive actions. One preferred vasoconstrictor is betameth¬ asone dipropionate. Other agents such as scopolamine which is a belladonna alkaloid and has vasoconstrictor activity can be used.

The vasoconstrictor is applied to the scalp or is present in the composition from about 0.01 to about 1.0 percent, preferably from about 0.01 to about 0.10 percent, more preferably 0.05 percent.

The improved minoxidil composition is characterized by the presence of a vasoconstrictor as described above. Typically, the improved composition is a formulation of minoxidil and the vasocon- stricter suitable for topical administration. The term "topical" means a composition of minoxidil and a composition of vasoconstrictor or both incorporated in a suitable pharmaceutical carrier which can be applied to the treatment site for local action.

Typical topical compositions include those pharmaceutical forms in which can be applied externally by direct contact with the surface to be treated. Conventional pharmaceutical forms for this purpose include ointments, waxes, lotions, pastes, jellies, sprays, aerosols, and the like in aqueous or nonaqueous formulations. The term "ointment" embraces formulations (including creams) having oleagin- ous, absorption, water-soluble and emulsion-type bases, e.g., petrolatum, lanolin, polyethylene glycols, as well as mixtures of these.

Preparation of minoxidil topical compositions are disclosed in U.S. Patents 4,139,619 and 4,596,812, both herein incorporated by reference. The preparation of topical compositions containing both minoxidil and a vasoconstrictor is the result of admixing the vaso¬ constrictor with the minoxidil topical composition. The improved composition can be applied to the area to be treated, such as the scalp in humans, by spraying, dabbing or swabbing. Other less specific methods can be employed provided the active ingredients, minoxidil and vasoconstrictor, are delivered to the region of the hair follicle. Preferably, the composition is periodically applied to the treatment area on a routine basis prior to, during and subsequent to hair growth. Generally, the routine treatment would be to apply the minoxidil and vasoconstrictor at least daily, preferably twice daily. In some situations where the alopecia areata is in remission treatment can be discontinued. Four patients with severe, treatment resistant alopecia areata were treated with one milliliter of a 2% topical minoxidil solution by applying it to their entire scalp. The patients also had their entire scalp treated with a 1 gram application of a vasoconstrictor, betamethasone dipropionate 0.05% cream. The vasoconstrictor in some treatments was applied 30 minutes before and in some cases 30 minutes after the minoxidil treatment. All four patients exhibited cosmeti- cally good hair growth and have maintained the regrowth with con¬ tinued treatment. This program demonstrated the improved results of combining a vasoconstrictor with minoxidil. In additional studies patients with alopecia areata are treated with 5% topical minoxidil solution and applications of betamethasone dipropionate 0.05% cream. The higher level of minoxidil and simul¬ taneous application of a vasoconstrictor will provide good hair growth.

Claims

1. A composition for the promotion of hair growth comprising:

(a) minoxidil in an amount of at least 2.5 percent; and

(b) a vasoconstrictor in an effective amount wherein hair growth is increased over the use of minoxidil alone.

2. The composition of claim 1 wherein said vasoconstrictor is a corticosteroid or a scopolamine.

3. The composition of claim 2 wherein said vasoconstrictor is betamethasone dipropionate.

4. The composition of claim 1 wherein the amount of a vasoconstric¬ tor is from about 0.01 to about 1.0 percent.

5. The composition of claim 4 wherein the amount of a vasoconstric¬ tor is from about 0.01 to about 0.10 percent.

6. The composition of claim 5 wherein the amount of a vasoconstric- tor is 0.05 percent.

7. The composition of claim 1 which includes a pharmaceutical carrier adapted for topical application.

8. Use of a topically administered composition comprising at least 2.5% minoxidil and a vasoconstrictor in an effective amount wherein hair growth is increased over the use of minoxidil alone for the promotion of hair growth.

9. The use of claim 8 wherein said vasoconstrictor is corticos¬ teroid or a scopolamine.

10. The use of claim 9 wherein said vasoconstrictor is betamethasone dipropionate.

11. The use of claim 8 wherein the amount of a vasoconstrictor is from about 1.0 to about 0.01 percent.

12. The use of claim 8 which includes a pharmaceutical carrier adapted for topical application.

13. The use of claim 8 wherein said composition is routinely applied to an area of treatment.

14. The use of claim 13 wherein said composition is applied daily or twice daily.