Reduction of hair growth

Drug – bio-affecting and body treating compositions – Live hair or scalp treating compositions

Reexamination Certificate

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C424S650000, C424S401000, C424S078020, C424S646000, C514S456000, C514S368000, C514S880000

Reexamination Certificate

active

06299865

ABSTRACT:

BACKGROUND OF THE INVENTION
The invention relates to reducing hair growth in mammals, particularly for cosmetic purposes.
A main function of mammalian hair is to provide environmental protection. However, that function has largely been lost in humans, in whom hair is kept or removed from various parts of the body essentially for cosmetic reasons. For example, it is generally preferred to have hair on the scalp but not on the face.
Various procedures have been employed to remove unwanted hair, including shaving, electrolysis, depilatory creams or lotions, waxing, plucking, and therapeutic anti androgens. These conventional procedures generally have drawbacks associated with them. Shaving, for instance, can cause nicks and cuts, and can leave a perception of an increase in the rate of hair regrowth. Shaving also can leave an undesirable stubble. Electrolysis, on the other hand, can keep a treated area free of hair for prolonged periods of time, but can be expensive, painful, and sometimes leaves scarring. Depilatory creams, though very effective, typically are not recommended for frequent use due to their high irritancy potential. Waxing and plucking can cause pain, discomfort, and poor removal of short hair. Finally, antiandrogens—which have been used to treat female hirsutism—can have unwanted side effects.
It has previously been disclosed that the rate and character of hair growth can be altered by applying to the skin inhibitors of certain enzymes. These inhibitors include inhibitors of 5-alpha reductase, omithine decarboxylase, S-adenosylmethionine decarboxylase, gamma-glutamyl transpeptidase, and transglutaminase. See, for example, Breuer et al., U.S. Pat. No. 4,885,289; Shander, U.S. Pat. No. 4,720,489; Ahluwalia, U.S. Pat. No. 5,095,007; Ahluwalia et al., U.S. Pat. No. 5,096,911; and Shander et al., U.S. Pat. No. 5,132,293.
Alkaline phosphatase is a widely distributed zinc-metalloenzyme that is thought to make a contribution to the maintenance of cellular homeostasis. Although the precise function for alkaline phosphatase in the maintenance of cellular homeostasis remains unclear, numerous physiological activities have been suggested for this enzyme. Such activities include controlling the levels of inorganic phosphate, regulation of inorganic phosphate transport, acting as a calcium-binding protein and a calcium-magnesium ATPase, and functioning as a tyrosine-specific phosphoprotein phosphatase.
In addition to its enzymatic activity, alkaline phosphatase levels have been used as diagnostic markers in the clinical evaluation of numerous diseases. For instance, alkaline phosphatase is used as a nonspecific indicator for cancer to characterize bone resorption patterns in individuals susceptible to osteoporosis.
Four alkaline phosphatase genes have been cloned and sequenced. In addition, their chromosomal locations have been determined and the regulation of these genes has been studied. Human alkaline phosphatases are encoded by a gene family including four loci. At the end of the long chromosome 2, bands q34-q37, are clustered three tissue specific alkaline phosphatase genes: intestinal, placental, and germ cell. A tissue nonspecific alkaline phosphatase gene is located at the end of the short arm of chromosome 1, bands p36.1-p34. The amino acid sequence homology for the tissue-specific enzymes is 90-98%, whereas the gnonspecific form is only 50-60% homologous with any of the specific forms.
Human alkaline phosphatase display a unique characteristic not seen in alkaline phosphatase from lower species (prokaryotic)—uncompetitive inhibition by certain L-amino acids (Millan, Clinica Chimica Acta. 209:123-129, 1992). For example, tryptophan, phenylalanine and leucine inhibit the tissue-specific form of alkaline phosphatase in a stereoselective fashion in that only the L-form is active. L-homoarginine acts as an inhibitor of the tissue nonspecific form of alkaline phosphatase in several species.
Inhibitors of mast cell degranulation interfere with the release of histamine from mast cells. Examples of inhibitors of mast cell degranulation include mycophenolic acid, bromoryptine, and cromoglycate.
SUMMARY OF THE INVENTION
The invention features reducing unwanted mammalian (including human) hair growth ) —particularly androgen-stimulated hair growth—by applying to the skin a composition including an inhibitor of alkaline phosphatase other than cromoglycate (or salts thereof) in an amount effective to reduce hair growth. The unwanted hair growth which is reduced may be normal hair growth, or hair growth that results from an abnormal or diseased condition.
The invention also features reducing unwanted mammal hair growth by reducing the amount of alkaline phosphatase enzyme protein in hair follicle cells. This can be accomplished by the use of agents such as antisense-oligonucleotides that are designed to bind specifically the alkaline phosphatase messenger-RNA. The latter molecule is responsible for the synthesis of alkaline phosphatase enzyme in cells.
Other features and advantages of the invention may be apparent from the description of the preferred embodiments thereof, and from the claims.
DESCRIPTION OF PREFERRED EMBODIMENTS
The preferred composition includes at least one inhibitor of alkaline phosphatase in a cosmetically and/or dermatologically acceptable vehicle. The composition may be a solid, semi-solid, or liquid. The composition may be, for example, a cosmetic and dermatologic product in the form of an, for example, ointment, lotion, foam, cream, gel, or hydroalcoholic solution. The composition may also be in the form of a shaving preparation or an after shave. The vehicle itself can be inert or it can possess cosmetic, physiological and/or pharmaceutical benefits of its own.
Inhibitors of alkaline phosphatase include uncompetitive inhibitors such as tetramisole ([±]-2,3,5,6-tetrahydro-6-phenyl-imidazo[2,1-b]thiazole]) and competitive inhibitors such as sodium orthovanadate. Other inhibitors of alkaline phosphatase include levamisole (L[−]-2,3,5,6-tetrahydro-6-phenyl-imidazo[2,1-b]thiazole]), vanadium nitrate, and gallium nitrate.
The composition may include more than one inhibitor of alkaline phosphatase. In addition, the composition may include one or more other types of hair growth reducing agents, such as those described in U.S. Pat. No. 4,885,289; U.S. Pat. No. 4,720,489; U.S. Pat. No. 5,132,293; U.S. Pat. No. 5,096,911; U.S. Pat. No. 5,095,007; U.S. Pat. No. 5,143,925; U.S. Pat. No. 5,328,686; U.S. Pat. No. 5,440,090; U.S. Pat. No. 5,364,885; U.S. Pat. No. 5,411,991; U.S. Pat. No. 5,648,394; U.S. Pat. No. 5,468,476; U.S. Pat. No. 5,475,763; U.S. Pat. No. 5,455,608; U.S. Pat. No. 5,674,477; U.S. Pat. No. 5,728,736; U.S. Pat. No. 5,652,273; WO 94/27586; WO 94/27563; and WO 98/03149, all of which are incorporated herein by reference.
The concentration of the inhibitor of alkaline phosphatase in the composition may be varied over a wide range up to a saturated solution, preferably from 0.1% to 30% by weight or even more; the reduction of hair growth increases as the amount of inhibitor applied increases per unit area of skin. The maximum amount effectively applied is limited only by the rate at which the inhibitor penetrates the skin. The effective amounts may range, for example, from 10 to 3000 micrograms or more per square centimeter of skin.
Vehicles can be formulated with liquid or solid emollients, solvents, thickeners, humectants and/or powders. Emollients include stearyl alcohol, mink oil, cetyl alcohol, oleyl alcohol, isopropyl laurate, polyethylene glycol, olive oil, petroleum jelly, palmitic acid, oleic acid, and myristyl myristate. Solvents may include ethyl alcohol, isopropanol, acetone, diethylene glycol, ethylene glycol, dimethyl sulfoxide, and dimethyl formamide.
The composition also may include components that enhance the penetration of the inhibitors of alkaline phosphatase into the skin and/or to the site of action. Examples of penetration enhancers include urea, propan-2-ol, polyoxyethyl

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