HAIR REMOVAL METHODS AND COMPOSITIONS

Abstract

Compositions and methods for selectively and permanently removing hair from the body. The compositions are formulated to be topically applied upon discrete areas of the body and contain an agent present in an amount sufficient to cause permanent alopecia about the area upon which the composition is applied. Exemplary of such agents include taxanes, such as docetaxel and paclitaxel, and busulfan and other agents known in the art to cause permanent chemotherapy-induced alopecia (CIA). The compositions and methods of applying the same are limited exclusively to transdermal application and operative to induce a localized CIA, and thus avoid systemic distribution of the CIA agent throughout the body. The compositions may further be deployed through known transdermal application mechanisms, such as transdermal patches and the like.

Claims

1. A method for removing hair from skin comprising: topically applying a composition upon an area of skin from which hair is sought to be removed, said composition containing an agent operative to effectuate chemotherapy-induced alopecia, said agent being present in an amount sufficient to effectuate chemotherapy-induced alopecia upon said area of skin upon which said composition is topically applied.

2. The method of claim 1 wherein said composition is applied in a single application.

3. The method of claim 2 wherein said composition is applied via a transdermal drug delivery system.

4. (canceled)

5. (canceled)

6. (canceled)

7. (canceled)

8. (canceled)

9. The method of claim 1 wherein said agent for effectuating said chemotherapy-induced alopecia is busulfan, said busulfan being applied in an amount ranging from 20 to 100,000 mg per square decimeter of skin to be treated.

10. The method of claim 9 wherein said agent for effectuating said chemotherapy-induced alopecia is busulfan, said busulfan being applied in an amount ranging from 20 to 10,000 mg per square decimeter of skin to be treated.

11. The method of claim 10 wherein said agent for effectuating said chemotherapy-induced alopecia is busulfan, said busulfan being applied in an amount ranging from 0.2 to 2,000 mg of busulfan per square decimeter of skin to be treated.

12. The method of claim 1 wherein said composition is applied from 1 to 3 times per day for up to 365 days.

13. (canceled)

14. (canceled)

15. The method of claim 1 wherein said agent operative to effectuate chemotherapy-induced alopecia is busulfan and is present in an amount ranging from 0.2 to 10 percent by weight of said composition.

16. The method of claim 13 wherein said agent operative to effectuate chemotherapy-induced alopecia is busulfan and is present in an amount ranging from 0.2 to 2 percent by weight of said composition.

17. (canceled)

Description

DETAILED DESCRIPTION

[0019] The detailed description set forth below is intended as a description of the presently preferred embodiment of the invention, and is not intended to represent the only form in which the present invention may be implemented or performed. The description sets forth the functions and sequences of steps for practicing the invention. It is to be understood, however, that the same or equivalent functions and sequences may be accomplished by different embodiments and that they are also intended to be encompassed within the scope of the invention.

[0020] The present invention is directed to compositions and methods for the permanent removal of hair by chemotherapy-induced alopecia (CIA). The compositions comprise an effective amount of an agent known to cause permanent non-scarring CIA that is formulated to be topically applied and transdermally delivered on selectively chosen, discrete areas of the body. In a preferred embodiment, discussed more fully below, the composition may be applied manually or through a conventional transdermal drug delivery mechanism, such as a transdermal patch and the like. In this regard, the compositions of the present invention, as well as the manner by which the same are applied, are specifically formulated for localized application on discrete areas of the body where hair removal is desired, and are specifically formulated and intended to be implied in a manner that does not involve any systemic distribution of the CIA agent. Rather, the objectives of the present invention are to provide a composition and a manner of applying the same that is exceedingly simple to administer and provide exceptionally effective, permanent hair loss on only those portions of the body as selectively chosen by the individual user.

[0021] Bearing such principles in mind, it is contemplated that the agent operative to induce the permanent non-scarring CIA effect may take any of those agents known in the art or later discovered that impart permanent CIA effects. Among the most well-known of such agents include anti-cancer chemotherapy agents, and in particular the class of chemotherapy agents known as taxanes and busulfan, which are well-understood an extensively utilized to treat cancer. In this regard, taxanes are drugs known as mitotic inhibitor and a type of antimicrotubule agent. Perhaps the most well-known of the taxanes are paclitaxel, whose chemical structure is shown below,

##STR00001##

[0022] and docetaxel, whose molecular structure is shown below.

##STR00002##

[0023] With regard to busulfan, it is a well-understood an extensively utilized to treat cancer. Busulfan is known is an alkylsulfonate, an alkylating agent that forms DNA-DNA intrastrand crosslinks between the DNA bases guanine and adenine and between guanine and guanine. Busulfan' s molecular structure is shown below,

##STR00003##

[0024] The medical use, mechanism of action and side effects associated with taxanes, and in particular paclitaxel and docetaxel referenced above, as well as busulfan, are extremely well-known in the art. Such agents are believed to be exceptionally effective in the practice of the present invention due to the ability of such compositions to cause CIA in virtually all types of individuals to which such compositions are administered. Moreover, such CIA agents are operative to remove all types of hair anywhere about the body. Accordingly, it is believed that when specifically applied to a discrete area to which permanent hair removal is desired, taxanes and busulfan represent a preferred agent for effectuating selective CIA.

[0025] In the case of taxanes, and in particular docetaxel, it is also well-known that such drug is a highly hydrophobic drug that needs solvents to enhance its solubility and enable its formulation. In order to produce the desired permanent CIA, it is contemplated that the docetaxel must be applied in amounts ranging from 20 to 100,000 mg/square decimeter of skin, and in a more refined embodiment applied in amounts from 200 to 10,000 mg/square decimeter of skin. In a most highly preferred embodiment, it is administered in an amount ranging from 200 to 2000 mgs of docetaxel per decimeter of skin to be treated. According to one preferred formulation, it is contemplated that docetaxel may be applied via a pharmaceutical composition wherein the docetaxel component will be present in the composition in an amount ranging from 0.2 to 10 percent by weight, and in a more highly preferred embodiment 0.2 to 2 percent by weight. The composition will also preferably be formed as a cream, lotion, ointment, gel, foam, wax, spray or other formulation for ease of topical application. Such compositions may be applied as a single, one-time application or, alternatively, may be applied according to a regimen ranging from 1-3 times per day for up to 365 days.

[0026] In the case of busulfan, it is contemplated that the busulfan must be applied in amounts ranging from 20 to 100000 mg/square decimeter of skin, and in a more refined embodiment applied in amounts from 20 to 10000 mg/square decimeter of skin and in, and in a most highly preferred embodiment, it is administered in an amount ranging from 2 to 2000 mgs of busulfan per decimeter of skin to be treated. According to one preferred formulation, it is contemplated that busulfan may be applied via a pharmaceutical composition comprising the ingredients below and their relative amount by weight: In a preferred embodiment, the busulfan component will be present in the composition in an amount ranging from 0.02 to 10 percent by weight, and in a more highly preferred embodiment 0.2 to 2 percent by weight. The composition will also preferably be formed as a cream, lotion, ointment, gel, foam, wax, spray or other formulation for ease of topical application. Such compositions may be applied as a single, one-time application or, alternatively, may be applied according to a regimen ranging from 1-3 times per day for up to 365 days.

[0027] The formulation and manufacture of the compositions disclosed herein would be readily understood and within the skill level of the ordinary artisan. Indeed, it is contemplated that formulation of pharmaceutically-stabile compositions for use in deploying taxane-based or busulfan CIA agents may take any of a variety of existing forms known in the art, exemplary of which include those disclosed in Published PCT Application No. PCT/US2005/019017, entitled A MIXTURE FOR TRANSDERMAL DELIVERY OF LOW AND HIGH MOLECULAR WEIGHT COMPOUNDS, filed in the name of Jordan, et al., published Mar. 28, 2007, the teachings of which are expressly incorporated herein by reference. Likewise exemplary of such teachings include those of U.S. Pat. No. 8,652,511 B2, entitled TRANSDERMAL

[0028] DELIVERY PATCH, issued to Cottrell, et al. on Feb. 18, 2014, the teachings of which are expressly incorporated by reference. With respect to such reference, there is disclosed composition suitable for use in the transdermal delivery of both paclitaxel and docetaxel, and are believed to be suitable for use in the practice of the present invention. Still further exemplary teachings include those of Published United States Patent Application No. US 2005/0095283 A1, entitled COMPOSITIONS AND METHODS FOR TOPICALLY TREATING DISEASES, filed in the name of Castor, et al., published May 5, 2005; PCT Application No. PCT/US 2006/042827, entitled MACROCYCLIC FORMULATIONS FOR TRANSMEMBRANE DRUG DELIVERY, filed in the name of Gyunik, et al., published May 18, 2007, the teachings of which are likewise incorporated herein by reference.

[0029] In addition to such exemplary teachings, it will be understood and well within the competency of one of ordinary skill to use any of a variety of ingredients and formulations operative to derive a topically-administered pharmaceutical composition that achieves the objective of the present invention. Along those lines, well-known ingredients such as citric acid, polyethylene glycol, propylene glycol, stearyl alcohol, cocoa butter, cotton seed oil, olive oil, white petrolatum, water, mineral oil, methyl paraben, propyl paraben and other base materials as are frequently utilized as inactive ingredients in the formulation of creams, gels, foams, ointments, soaps, shampoos, lotions and the like, and can be selectively chosen based upon the compatibility with a particular CIA agent. Such ingredients are also readily available and can be incorporated in a variety of amounts as may be desired to formulate a particular pharmaceutical composition having a desired potency and ability for a particular CIA agent to become evenly and readily distributed over a specific surface area of skin such that an effective amount of a given CIA agent is sufficiently contacted with a given surface of skin to which the removal of hair is desired. Exemplary of such prior art teachings include those of Published United States Published Patent Application US 2011/0269704 A1, entitled METHOD FOR DEVELOPING A LIQUID COMPOSITION TO BE APPLIED TO THE SKIN AS A FOAM AND A COMPOSITION THAT CAN BE APPLIED TOPICALLY, filed in the name of Seigfried, published Nov. 3, 2011, the teachings of which are expressly incorporated herein by reference.

[0030] In addition to being able to formulate pharmaceutical compositions operative to deliver therapeutically effective amounts of the CIA agent to the localized area for which hair removal is desired, it will further be understood, that, when desired, other methodologies and/or compounds may be used to enhance the rate of absorption of the CIA agent so as to cause the CIA agent to penetrate the skin in order to produce the desired CIA effect. Accordingly, such pharmaceutical compositions may deploy additional components which act as an absorption promoter to facilitate transport of the CIA agent in sufficient amounts across the skin to achieve the desired effect. Among the types of known technologies operative to determine such formulations include those disclosed in PCT Patent Application No. PCT/US/2004/023634, entitled PENETRATION ENHANCER COMBINATIONS FOR TRANSDERMAL DELIVERY, filed by Mitragotri, et al., on Feb. 3, 2005, the teachings of which are expressly incorporated by reference. In addition, it is contemplated that other techniques, such as lightly abrading the skin and/or applying an electrical current, ultrasound or other enhancing forces to the skin so as to facilitate the ability of a particular agent to penetrate into the skin in amounts sufficient to produce a permanent CIA about the desired localized area. The general principles associated with the application of electrical fields and/or ultrasound to enhance transdermal drug delivery are set forth in U.S. Pat. No. 6,041,253 A, entitled EFFECT OF ELECTRIC FIELD AND ULTRASOUND FOR TRANSDERMAL DRUG DELIVERY, issued to Kost, et al., Mar. 21, 2000 the teachings of which are expressly incorporated herein by reference.

[0031] As will be appreciated by those skilled in the art, however, it is contemplated that through further experimentation and clinical testing will likely produce data indicative of optimal dosages and application regimens. Accordingly, it is contemplated that further refinements in dosing and applications may vary over time.

[0032] Along those lines, it is contemplated that the compositions of the present invention will be effective to effectuate permanent hair loss. However, to the extent hair regrowth does occur, it is contemplated that the compositions and methods of applying the same according to the present invention may be repeated as necessary so as to effectuate long term, preferably permanent hair removal upon discrete surface areas of the skin.

[0033] As discussed above, numerous other agents operative to produce permanent CIA when topically applied in an effective amount to an area of skin where selective alopecia is desired are deemed to fall within the scope of the present invention. Accordingly, in addition to taxanes and busulfan, other agents such as disulfan, cyclophosphamide, thiotepa, melphalan, etoposide, carboplatin, cisplatin, ifosfamide, doxorubicin, dactinomycin, vincristine, and combinations thereof may be formulated in a transdermally-applied composition such that the CIA agent is present in an amount effective to effectuate permanent hair loss upon a selectively discrete area of a user's body. As per the discussion above, it is contemplated that the agent will be formulated as part of a transdermally-applied composition that is formulated to be manually applied to a selective area of skin or otherwise formulated to be deployed through a transdermal drug delivery system, such as patches and the like.

[0034] As per the taxane embodiments discussed above, it is contemplated that the compositions may be formulated to address the hydrophobic or hydrophilic nature of the agents in question, or formulated to promote the stability of the drug, enhance the ability of the drug to become absorbed through the skin and ultimately be delivered in potent amounts effective to produce the desired CIA effect while also avoiding any type of systemic distribution throughout the body or beyond the desired site of application. Such considerations would be well-known and understood by those skilled in the art, and readily addressed using known pharmaceutical formulation techniques that is well within the knowledge of those of ordinary skill. For example, in compositions that utilize ifosfamide, it will be understood that any composition will be formulated to address its chemical properties, such as its solubility in water and its stability under certain conditions, including those as published in Trissel, L. A. Handbook on Injectable Drugs, 9.sup.th ed. Bethesda, Md., American Society of Health-System Pharmacists' Product Development, 1996, p. 594, identifying the chemical and physical stability of ifosfamide at certain conditions and temperatures. Moreover, such composition will further necessarily take into account any activation typically required via microsomal liver enzymes to convert ifosfamide into its active metabolite in order to exert the desired cytotoxic effect. Again, such considerations are known within the art. Exemplary of such teachings include those of Published United States Patent Application No. US20140018435 A1, entitled TRANSDERMAL DELIVERY OF THERAPEUTIC AGENTS USING POLY(AMIDOAMINE) DENDRIMERS, published Jan. 16, 2014, the teachings of which are expressly incorporated by reference. Accordingly, it is believed to be readily understood by those skilled in the art that while the identification of a particular CIA agent for use in the present invention may be understood, it will further require taking into consideration the dosage amounts necessary to produce the desired CIA effect, developing a pharmaceutical composition operative to be topically applied and further operative to administer an effective amount of the CIA agent over a particular surface area of skin, and further enable the pharmaceutical composition to be stable, prevent to the highest degree possible any systemic distribution of the CIA agent, and further preferably formulate the product in such a way such that the CIA agent is absorbed through the skin in the safest and most efficient manner possible.

[0035] Additional modifications and improvements of the present invention may also be apparent to those of ordinary skill in the art. Thus, the particular combination of parts and steps described and illustrated herein is intended to represent only certain embodiments of the present invention, and is not intended to serve as limitations of alternative devices and methods within the spirit and scope of the invention.