Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1995-05-09
2002-11-19
Moezie, Minna (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06482826
ABSTRACT:
A healthy, thick and uniform hair growth on the scalp is generally considered an important aesthetic aspect of the human body. The loss of hair or any imperfection in the quality of the hair is consequently often experienced a very undesirable feature of one's physical appearance.
The fact that a majority of the male population is genetically predisposed to lose progressively its hair and the knowledge that current modes of treatment are very few, with a low number of individuals effectively responding to the treatment, more than amply illustrate the scope and magnitude of the problems involved and the need for additional therapies effective in reversing, arresting or retarding loss of hair and improving the quality of hair.
It has now been found that ketoconazole can effectively reverse, arrest or retard the loss of hair as experienced in alopecia and further, that ketoconazole does have a beneficial effect on the quality of hair.
The present invention is concerned with a method of treating individuals suffering from alopecia, said method comprising administering to said individuals the compound ketoconazole or a pharmaceutically acceptable acid addition salt thereof, in an amount effective in reversing, arresting or retarding said alopecia. Further, the present invention also is concerned with a method of treating individuals having an inferior quality of hair, said method comprising administering to said individuals the compound ketoconazole or a pharmaceutically acceptable acid addition salt thereof, in an amount effective in ameliorating the quality of hair.
Ketoconazole as mentioned hereinabove is the generic name of the compound (±)-cis-1-acetyl-4-[
4-[[2
-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine, which may be represented by the formula.
The compound ketoconazole used in the method of the present invention is a known antifungal agent and its preparation as well as its pharmacological properties are described in U.S. Pat. No. 4,335,125.
The compound ketoconazole can be used as such or in a pharmaceutically acceptable acid addition salt form, the latter being conveniently obtained by treating the base form with an appropriate acid. Appropriate acids comprise, for example, inorganic acids such as hydrohalic acids, e.g. hydrochloric or hydrobromic acid; sulfuric acid; nitric acid; phosphoric acid and the like; or organic acids, such as, for example, acetic, propanoic, hydroxyacetic, 2-hydroxypropanoic, 2-oxopropanoic, ethanedioic, propanedioic, butanedioic, (Z)-2-butenedioic, (E)-2-butenedioic, 2-hydroxybutanedioic, 2,3-dihydroxybutanedioic, 2-hydroxy- 1,2,3-propanetricarboxylic, methanesulfonic, ethanesulfonic, benzenesulfonic, 4-methylbenzenesulfonic, cyclohexanesulfamic, 2-hydroxybenzoic, 4-amino-2-hydroxybenzoic and the like acids. The term acid addition salt form as used hereinabove also comprises the solvates which the compound ketoconazole and its acid addition salts are able to form. Examples of such solvates are e.g. the hydrates, alcoholates and the like.
The term alopecia as used herein is meant to comprise the loss of hair from the scalp but also from the beard in humans. More in particular, the term alopecia relates to androgenetic alopecia or male pattern alopecia (baldness) which is characterized by the progressive, diffuse, symmetrical loss of hair from the scalp, typically starts at the frontal end of the scalp and gradually spreads to the vertex, ultimately leaving only a sparse peripheral band of hair covering the temples and occiput.
Since alopecia is a condition which at present can hardly be treated at all, the present finding that ketoconazole may effectively be employed in treating individuals suffering from alopecia, more in particular individuals with early androgenetic alopecia, is surprising. In this regard the term effectively means that treatment with ketoconazole results in the reversal, the arrest or the retardation of loss of hair and in the improvement of the quality of hair, in particular of the thickness of hair as can be gauged by measuring the calibre of the hairs. The term early androgenetic alopecia means male pattern baldness classified as type I, II, III, IV or V on the Hamilton scale.
The term quality of hair as used herein relates to desirable physical properties of hair such as strength, thickness, density, uniformity and sensibility of hair. Inferior strength may manifest itself, for example, by splitting or by breaking. The thickness of a hair most commonly is expressed by its diameter or calibre. Density is meant to define the number of hairs per unit area, whereas uniformity relates to the constancy or gradual change of said density in contiguous areas of the scalp. Sensibility of hair refers to the presence of tactile sense in hair.
The compound ketoconazole and its acid addition salts used in the methods of the present invention are most preferably applied to the affected areas of the scalp or beard in the form of appropriate compositions, in particular compositions usually employed for the topical administration of drugs or cosmetic compositions. Said compositions contain the active ingredient ketoconazole, preferably in a 0.1 to 5% concentration (weight by volume), and any known dermatologically acceptable carrier and may take a wide variety of forms such as, for example, liquid forms, e.g. solutions, or suspensions in aqueous or oily mediums; or semi-liquid formulations, e.g. creams, hydrogels, gels, pastes, ointments, salves, tinctures and the like.
Other such compositions are preparations of the cosmetic type, such as toilet waters, packs, lotions, skin milks or milky lotions and shampoos. Said preparations contain, besides the active ingredient ketoconazole, components usually employed in such preparations. Examples of such components are oils, fats, waxes, surfactants, humectants, penetration enhancing agents, thickening agents, lipid absorbents, anti-oxidants, viscosity stabilizers, chelating agents, buffers, preservatives, perfumes, dyestuffs, lower alkanols, and the like. If desired, further active ingredients may be incorporated in the compositions, e.g. antiinflammatory agents, antibacterials, antifungals, disinfectants, vitamins, sunscreens, antibiotics or anti-dandruff agents. Interesting compositions for use in the methods according to the present invention are lotions and shampoos, typically containing from 0.2 to 2.5%, in particular 2% ketoconazole.
The lotions mentioned hereinabove are novel and have been especially developed for use in the methods of the present invention. Typically such lotions comprise 0.2 to 2.5%, in particular about 2% (w/v) of the active ingredient ketoconazole; propylene carbonate in an amount of from 20 to 40%, in particular from 20 to 30%, more in particular about 25% (w/v); ethanol in an amount of from 25 to 55% in particular from 25 to 35%, more in particular about 28% (w/v); optionally any other components as defined hereinabove and usually employed in similar compositions; the remainder of the lotion being water.
Particular instances of the aforementioned preparations are those which comprise a cyclodextrin or a derivative thereof. Said cyclodextrin or derivative thereof defines the topically acceptable unsubstituted and substituted cyclodextrins known in the art, in particular &agr;-, &bgr;- or &ggr;-cyclodextrins and the derivatives thereof, such as ethers, polyethers, mixed ethers.
To prepare said cyclodextrin based formulations, ketoconazole is added to a solution of the cyclodextrin in water, preferably under vigorous stirring, and then adding the remainder of the ingredients. In the final compositions the amount of cyclodextrin is about 2 to 40%, in particular about 2.5 to 25%, more in particular about 5 to 20%.
Other particular compositions for use in the methods of the present invention are those wherein the active ingredient ketoconazole is formulated in liposome-containing compositions. Different types of liposomes may be employed such as coarse (multilayer) liposomes or un
Hui San
Janssen Pharmaceutica N.v.
Moezie Minna
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