CA2158041C

CA2158041C - Topical composition for inhibiting hair growth

Info

Publication number: CA2158041C
Application number: CA002158041A
Authority: CA
Inventors: Brian Alfred Boxall; Geoffrey Wilfred Amery; Gurpreet S. Ahluwalia
Original assignee: Gillette Co LLC
Current assignee: Gillette Co LLC
Priority date: 1993-03-19
Filing date: 1993-05-27
Publication date: 2001-04-03
Anticipated expiration: 2013-05-27
Also published as: WO1994021217A1; NO309752B1; NZ253858A; AU4524393A; AU3931093A; EP0689416A1; ATE172871T1; ES2125339T3; KR100294576B1; UA35611C2; RO117413B1; NO953580D0; PL310679A1; JPH08507785A; KR960700681A; DE69321974D1; CA2158041A1; WO1994021216A1; OA10183A; JP3659968B2

Abstract

The present invention embraces a topical composition for inhibiting mammalian hair growth, particularly human beard hair growth (including hirsutism), comprising a water-soluble, hair-growth-inhibiting agent dispersed in an oil-in-water emulsion in the form of a lotion or cream. The invention also embraces a method of inhibiting mammalian hair growth by applying an effective amount of the above composition to the skin. The invention further embraces a topical composition for delivering a pharmacological agent to the skin.

Description

_ W094~2~17 PCT~S93/05068 TOPICAL COMPOSITION FOR T~UTRTTING HAIR GROWTH
Bach4~ d of the Invention This invention relates to a new topical composition for inhibiting mam~ n hair growth. It also relates to a method of inhibiting hair growth by spplying a topical compcsition according to this invention to the skin.
In U.S. 4,720,489 it i8 disclosed that the topical application of a compo~ition ising an ornithine der~ho~ylase (nODCn) inhibitor will inhibit hair growth, including beard hair growth. A particularly advantageous ODC inhibitor for use in this application i~ 2-(difluoromethyl)-2,5-diaminopent~oic acid, also identified as ~-(difluoromethyl)ornithine ("DFMO"). Thi~ patent demon~trates the effectiveness of ODC inhibitors for inhibiting hair growth by measuring change~ in flank organ hair mass in adult male hamsters treated with ethanol solutions of such c~ _-~.ds. The patent also generally proposes the poRsible incor-poration of ODC inhibitors in cosmetic formulations such as skin lotions and cream~, bl~t the effectiveness of such proposed formulations and thei- stab_lity and aesthetic attribute~ are unknown. Since DFMO i~ a highly W094/21217 2 ¦ S ~ ~ ~ PCT~S93/05068 .

ionic material, it would tend to destabilize emulsion systems and would be difficult to formulate in such systems, particuIarly at higher dosage levels necessary to achieve maximum efficacy.
In U.S. 5,095,007, U.S. 5S096,911, and U.S. 5,132,293, additional hair growth inhibitors are diQclosed which are completely unrelated to the aforementioned ODC inhibitors.
H~.~eve , each of these patents disclo~es a water-ethanol vehicle for delivering the active cG~o~Ld. The vehicle comprises 68% water, 16%
ethanol, 5% ~ ~ylene glycol, 5% dipropylene glycol, 4% benzyl alcohol, and 2% ~ylene carbonate. This vehicle is not aeRthetically pleasing or easy to use since it i8 very runny and feels wet and tacky. Moreover, the efficacy of the active material in this vehicle may not be optimum even though the vehicle contains two known penetration ~nh~ncers, namely benzyl alcohol and propylene c~-hon~te.
It is an object of the present invention to provide a topical composition for inhibiting hair growth wh~ch i~ stable, highly efficacious and aesthetically pleasing.
SummarY of the Invention The pre3ent invention embraces a topical composition for inhibiting mammalian hair growth, particularly human beard hair growth (including hirsutism), comprising a water-~oluble, hair-growth-inhibiting agent dispersed in an oil-in-water emulsion in the form of a lotion or cream. The invention also embrace~ a method of inhibiting ~9m~ n hair growth by applying an effective -smount of the above compo~ition to the skin. The invention further ~braces a topical composition for ~ W09412~17 21~ 8 0 41 PCT~S93/OS068 delivering a water-soluble, pharmacological agent to the skin.
Detailed De~criPtion of the Invention The hair growth inhibiting agent which is utilized in the composition and method of the present invention may be any water-soluble, hair-growth-inhibiting agent, particularly any highly ionic, water-soluble, hair-growth-inhibiting agent. Such active agent~ may be selected from any of the classes of agent~
described in the aforementioned U.S. patents, namely U.S. 4,720,489, U.S. 5,095,007, U.S.
5,096,911, and ~.S. 5,132,293, provided such agent~ are water soluble. In a preferred embodiment, the hair growth inhibiting agent i~

2-(difluoromethyl)-2,5-diaminopentanoic acid, which is also identified as ~-(difluoromethyl)ornithine, hereinafter abbreviated "DFMOn.
The topical composition of the present invention r~ _ ise~ about 1 to 20 parts by weight, preferably 5 to 15 parts, of the aforedescribed water-soluble, hair-growth-inhibiting agent, particularly DFMO, dispersed 25 in 99 to 80 parts by weight, preferably 95 to 85 parts, of a vehicle comprising an oil-in-water emulsion of the formula (the laQt two ingredients being optional):

WO94/21217 215 8 0 4 ~ PCT~S93/05068 In~redient Wt. Percent Ex. I Ex. ~I
Water 78 to 87 80.84* 85.53*
Glyceryl Stearate 1 2.8 to 4.8 4.24 2.97 PEG-100 Stearate 1 2.7 to 4.74.09 2.86 Cetearyl Alcohol 2 1.9 to 3.3-3.05 2.14 Ceteareth-20 2 1.6 to 2.72.50 1.75 Mineral Oil 1.7 to 2.72.22 2.22 Stearyl Alcohol 3 1.0 to 2.01.67 1.17 Dimethicone 4 0.3 to 1.00.56 0.56 -- --------------______________________ Citric Acid 5 0 to 0.5 - 0.25 Sodium Hydroxide 6 q. 8 . q. ~ . q. 8.
* 0.5% water withheld for subsequent pH
adjustment.5 1 Available a~ a blend, for example Cithrol GMS A/S ES0743 from Croda Chemicals Ltd.
(U.g.) .
2 Available a~ a blend, for example Co~mowax EM5483 from Croda Chemical~ Ttd. (~.R.).

3 Available a~ Lorol-18 from R~nk~l Chemicals Ltd.

4 A~ailable a~ Silicone Fluid 200 - 100 cp~
from Dow Cor~;ng Corporation (e.g., 360 Medical Fluid or Q7-9120 Fluid).
Other weak acids may be substituted, for example lactic, tartaric or phosphoric acids to ~erve a~ a pH buffer.
6 Quantity sufficient to ad~ust pH to about 3.5. Other strong ba~es, such a~ ROH, may be used or, in ~ome ca~es, strong acid~
such as HCl, where the pH needs to be lowered.
The active agent plus ~ehicle will total 100 parts by weight when finished. Minor amountR of other ingredients, such as dyes, fragrances, and biocidal agents or preser~ati~es may be incorporated in the vehicle as deemed ~ W094/2~17 21~ 8 ~ ~1 PCT~S93/05068 necessary or de~irable. It is preferred to add about 0.5 to 0.9 parts of ph~non;p, a biocidal agent available from Nipa Laboratories Ltd.
(U.R.), to the above formulation.
The following procedure is carried out to make the vehicle utilized in the topical composition of the present invention. The water and water soluble comrQ~ents, are charged to a mixing vessel, the pH is adjusted to about 3.5, and the solution is heated to about 70C. The oil soluble components, except for the biocidal agent, are melted together at about 70C., then run into the water phase with brisk stirring.
M;Y;ng ig cont;n~ for about twenty minutes, then water cooling is applied. The biocidal agent is added at 40-45C. and stirring is cont;n~e~ until the temperature rs~ch~s 25C. to yield a white, soft cream with a viscosity of about 8,000-12,000 cps. If it is desired to increase the viscosity of the resulting emul~ion, shear can be applied u~ing a conventional homogenizer, for example a Silverson ~4R homogenizer with a ~quare hole high shear screen. Normally, this step is not required since the viscosity of the emul~ion can increase during dissolution of the active agent.
The topical composition of the present invention is made by blen~;ng about 1 to 20 parts by weight, preferably 5 to 15 parts, of the hair-growth-inhibiting active agent, preferably DFM0, with correspon~i ngly 99 to 80 parts by weight, preferably 95 to 85 parts, of the vehicle prepared a~ described above, and adjusting the pH to about 3.5 with aqueous sodium hydroxide (10%) or hydrochloric acid (10%). Of course, the topical composition could also be fabricated by including the active agent W094/2~17 215 ~ 0 4 ~ PCT~S93/0~068 in the water pha~e during the aforedescribed vehicle preparation.
EXAMPhE
Two vehicles were prepared having the composition designated Ex. I and Ex. II in the above Table according to the aforedescribed procedure. The two vehicles contA~nsA 0.83 and 0.55 parts ph~n~n;p respectively. To four separate batches of each vehicle was then added with mixing sufficient DFM0 to produce topical compositions cont~n~ng 2.5, 5, 10 and 15% DFM0.
Thus, a total of eight topical compositions were prepared in all. Each c~rosition was tested for hair growth inhibition using a st~n~d ham~ter flank organ hair mass study as described in the prQviously identified four U.S. patents.
For comparison, a control composition cont~ n ~ ng vehicle only wa~ tested (I-V and II-V below), as well as a composition cont~;n;ng 10% DFM0 in the water-ethanol vehicle shown in Ex. I of U.S.

5,096,911 (W-E below). The results of th~se studies were as follows:
Com- % I~hibi- Co~- % Inhibi-position tion ~osition tion I-A (15% DFM0) 84.2 II-A (15% DFN0) 89.1 I-B (10% DFM0) 87.6 II-B (10% DFM0) 91.4 I-C (5% DFM0) 84.5 II-C (5% DFM0) 85.5 I-D (2.5% DFM0) 60.0 II-D (2.5% DFM0) 81.4 I-V (0% DFM0) - II-V (0% DFM0) W-E (10% DFM0) 68.3 W-E (10% DFM0) 72.6 As can be seen, each of the compos$tions of the invention, namely I-A
through I-D and II-A through II-D, were highly efficacious in inhibiting ~am~alian hair growth.
Similarly, beard hair growth inhibition is obtA~ne~ when such compositions are applied to the human face. Remarkably, the above data also ~ WO94/21217 215 8 0 ~1 PCT~S93/05068 demonstrate that the present compositions are 3uperior in efficacy to a water-ethanol composition which contains penetration e ~nh~ncerg. This suggests that the present composition achieves either ~nh~nced skin penetration of the active agent or increased residence time of the active agent at the treated site. Moreover, the compositions of the invention remain stable over an extended period of time and have aesthetically pleasing attributes.
The topical compositions of the present invention are applied to mammalian skin, particularly the human face, on a daily or twice daily basis to provide a level of active agent of about 10 to 2000 mic Oylo~.~ per square centimeter of skin. Obviously, the application dose may be varied to achieve a suitable level of effectiveness for each individual being treated.
It will be apparent that equivalent materials may be substituted for those specified in the aforement;o~e~ table of ingredient~
without departing from the spirit and scope of thi~ invention. For example, other water-soluble, pharmacological agents may be delivered to the skin by incG ~o-ating from about 1 to 20%
of such an agent in the previously described vehicle.

Claims

The claims defining the invention are as follows:

1. A topical composition for inhibiting mammalian hair growth which comprises about 1 to 20 parts by weight of a water-soluble, hair-growth-inhibiting active agent dispersed in about 99 to 80 parts by weight correspondingly of a vehicle comprising an oil-in-water emulsion of the following components in parts by weight:
Water 78 to 87 Glyceryl Stearate 2.8 to 4.8 PEG-100 Stearate 2.7 to 4.7 Cetearyl Alcohol 1.9 to 3.3 Ceteareth-20 1.6 to 2.7 Mineral Oil 1.7 to 2.7 Stearyl Alcohol 1.0 to 2.0 Dimethicone 0.3 to 1.0

2. The composition of claim 1, comprising 5 to 15 parts by weight of said active agent dispersed in 95 to 85 parts by weight correspondingly of said vehicle.

3. The composition of claim 2, wherein said vehicle comprises an oil-in-water emulsion of the following components in parts by weight:
Water 80.84 Glyceryl Stearate 4.24 PEG-100 Stearate 4.09 Cetearyl Alcohol 3.05 Ceteareth-20 2.50 Mineral Oil 2.22 Stearyl Alcohol 1.67 Dimethicone 0.56

4. The composition of claim 2, wherein said vehicle comprises an oil-in-water emulsion of the following components in parts by weight:
Water 85.53 Glyceryl Stearate 2.97 PEG-100 Stearate 2.86 Cetearyl Alcohol 2.14 Ceteareth-20 1.75 Mineral Oil 2.22 Stearyl Alcohol 1.17 Dimethicone 0.56 Citric Acid 0.25

5. The composition of claim 1, 2, 3 or 4, wherein said active agent is 2-(difluoromethyl)-2,5-diaminopentanoic acid.

6. The composition of any one of the preceding claims, adjusted to a pH of about 3.5 and optionally comprising a pH
buffer.

7. A method of inhibiting mammalian hair growth which comprises applying to the skin of a mammal an effective amount of a topical composition according to any one of claims 1 to 4 or 6.

8, The method of claim 7, wherein the active agent in said topical composition is 2-(difluoromethyl)-2,5-diaminopentanoic acid.

9. The method of claim 8, wherein said topical composition is applied daily or twice daily at a level sufficient to provide about 10 to about 2000 micrograms of active agent per square centimeter of skin.

10. The method of claim 8, wherein said topical composition is applied to human skin.

11. A topical composition for delivering a water-soluble, pharmacological agent to the skin which comprises about 1 to 20 parts by weight of said water-soluble, pharmacological agent dispersed in about 99 to 80 parts by weight correspondingly of a vehicle comprising an oil-in-water emulsion of the following components in parts by weight:
Water 78 to 87 Glyceryl Stearate 2.8 to 4.8 PEG-100 Stearate 2.7 to 4.7 Cetearyl Alcohol 1.9 to 3.3 Ceteareth-20 1.6 to 2.7 Mineral Oil 1.7 to 2.7 Stearyl Alcohol 1.0 to 2.0 Dimethicone 0.3 to 1.0