|||||||||||| US005514672A United States Patent (19) 11 Patent Number: 5,514,672 Bazzano 45) Date of Patent: May 7, 1996 (54) USE OFRETINOIDS AND COMPOSITIONS 4,322,438 3/1982 Peck ................................. 424/70 UX CONTAINING SAME FOR HAR GROWTH 4,333,924 6/1982 Bowler et al. ... 424/70 UX 4,985,464 1/1991 Happle et al. .......................... 54/880 76) Inventor: Gail S. Bazzano, 4506 Avron Blvd., FOREIGN PATENT DOCUMENTS Metairie, La. 70006 158799 9/1954 Australia ........................ 424/70 UX 553262 12/1956 Belgium .................. ... 424/70 UX 21 Appl. No.: 283,649 024967 3/1987 European Pat. Off. T. 424/70 22 Filed: Dec. 13, 1988 2758485 5/1980 Germany ................. ... 424/70 906000 9/1962 United Kingdom. ... 424/70 1466062 3/1977 United Kingdom. ... 424/70 Related U.S. Application Data 1487543 5/1977 United Kingdom..................... 424/70 63) Continuation-in-part of Ser. No. 136,525, Dec. 22, 1987, OTHER PUBLICATIONS abandoned, which is a continuation of Ser. No. 463,146, Feb. 2, 1983, abandoned, which is a continuation-in-part of Ser. No. 235,169, Feb. 17, 1981, abandoned, Ser. No. Conn, Current Therapy, 1981, p. 662. 318,607, Nov. 9, 1981, abandoned, Ser. No. 386,730, Jun.9, Conn, Current Therapy, 1984, pp. 599 to 603. 1982, abandoned, and Ser. No. 414,854, Sep. 3, 1992, 9007/80, Jan. 1980, Japan laid open publication (translated abandoned. claims). (51) Int. Cl. ... A61K7/06 73137/76, Jun. 1976, Japan laid open publication (translated (52) U.S. Cl. ......................... 514/168; 424/70.1; 514/725; claim and summary). 514/880; 514/881; 514/946 Saitoh, M. et al. "Rate of Hair Growth' Chapter XIV, pp. 58 Field of Search ..................................... 514/725, 880, 183-201. 514/881, 168,946; 8/94.14 Pinkus, H. "Alternations of the Hair Follicle in Hair Dis eases,” pp. 237-243 in Hair Research Orafanos et al. (ed.) 56 References Cited Springer-Verlang 1981. U.S. PATENT DOCUMENTS Primary Examiner-Shelley A. Dodson Attorney, Agent, or Firm-Panitch Schwarze Jacobs & 2,268,736 11/1942 Buxton et al. .......................... 54/168 Nadel 2,276,531 3/1942 Wechsler et al. ... 514/168 2,310,479 2/1943 Vollmer ................................... 514/946 57) ABSTRACT 2,865,859 12/1958 Lubowe ..... 54/847 3,382,248 5/1968 Anthony et al. ... 424/70 Increase in the rate of hair growth, stimulation of hair 3,461.461 8/1969 Anthony et al. ... 424/70 follicles to produce new hair growth, prolongation of the 3,464,987 9/1969 Ursprung ....... ... 424/70 anagen phase of the hair cycle, and conversion of vellus hair 3,711,606 1/1973 Herschler ................................ 514/946 to growth as terminal hair, and treatment of allopecias due to 3,729,568 4/1973 Kligman. 3,882,244 5/1975 Lee ................................... 424/70 UX organic dysfunction of the hair follicle is attained in mam 3,973,016 8/1976 Morrison ................................... 424/70 malian skins by either oral administration or by topical 3,991,203 11/1976 Rajadhydaksha 514/946 application to the skin, hair and/or hair follicles of the 4,034,114 7/1977 Yu et al. ................................. 514/168 mammal of effective amounts of a retinoid, particularly 4,139,619 12/1979 Chielsey. 514/725 U X retinoic acid. The retinoid may be administered or applied 4,170,229 10/1979 Olson ..... ... 424/70 UX alone or with other adjunctive compounds including vita 4,201,235 5/1980 Cianatta .................................. 514/168 mins, such as Vitamin D, hormones, antiandrogens and/or 4,220,772 9/1980 Muller et al. ............................. 424/70 vasodilators. 4,247,547 1/1981 Marks ............ 424/70 UX 4,287,338 9/1981 McCall ...................................... 424/70 4,304,787 12/1981 Gander et al. .................... 424/70 UX 36 Claims, No Drawings 5,514,672 1 2 USE OF RETNODS AND COMPOSTIONS finally falls out, and normally lasting about three to four CONTAINING SAME FOR HAR GROWTH months. Normally 80 to 95 percent of the follicles are in the anagen phase, less than 1 percent being in the catagen phase, CROSS-REFERENCE TO RELATED APPLICATIONS and the rest being in the telogen phase. Whereas the telogen This application is a continuation-in-part of application 5 phase hair is uniform in diameter with a slightly bulbous, Ser. No. 136,525, filed Dec. 22, 1987, now abandoned which non-pigmented root, the anagen phase hair has a large in turn is a continuation of Ser. No. 463,146, filed Feb. 2, colored bulb at its root. 1983, now abandoned, which in turn is a continuation-in Alopecia results when the pilar cycle is disturbed, result part of applications Ser. No. 235,169, filed Feb. 17, 1981; ing in excessive hair loss. The most frequent phenomenon is O a shortening of the hair growth phase due to cessation of cell Ser. No. 318,607, filed Nov. 9, 1981; Ser. No. 386,730, filed proliferation. This results in an early onset of the catagen Jun. 9, 1982; and Ser. No. 414,854, filed Sep. 3, 1982, all phase, and consequently a large number of hairs in the now abandoned. This application is also related to my telogen phase during which the follicles are detached from co-pending application Ser. No. 283,646, filed concurrently the dermal papillae, and the hairs fall out. This shortening of herewith, entitled "Combinations of Retinoids and Minoxi the growth or anagen phase of the pilar cycle may have dil-Type Compounds For Hair Growth'. 15 different origins, among which are very diverse pathological origins such as febrile conditions, mental stresses, hormonal FIELD OF INVENTION problems (such as androgenetic alopecia due to male hor mones) and secondary effects of drugs. Alopecia may also be This invention generally relates to hair growth and, more due to age and to a slowing down of mitotic activity. This particularly, it relates to compositions and methods for 20 dysfunction of the biological mechanism of hair growth increasing the rate of and stimulating hair growth on mam leading to allopecia may be regarded as a disease. While malian skins, prolonging the anagen phase of the hair cycle, there are other causes of allopecia such as greasy or oily scalp and converting vellus hair to growth as terminal hair. due to seborrhea and the dandruff accompanying it, the present invention is not directed to treating these extraneous BACKGROUND OF THE INVENTION 25 causes of alopecia, but rather to treating the organic dys A normal characteristic of hair growth in mammals, function of the hair follicle. including humans, is that in most cases, the rate of hair German Patent No. 2758484 discloses certain chemical growth and the length of its growth cycle are reduced with preparations for treatment of scalp to prevent baldness. age. Those phenomena are common to all mammals with These preparations contain bile compounds as the active 30 ingredients and also include pro Vitamin A or tretinoin. The rare exceptions, and they must be differentiated from true active ingredient is a product obtained from gall or a male pattern alopecia, which is caused by target organ derivative thereof such as chenodeoxycholic acid, urodoxy sensitivity to androgens. cholic acid and their salts or derivatives. Several factors may influence the rate of hair growth. Another patentis Olsen U.S. Pat. No. 4,140,229 citing the These factors include race, sex, age, geography, season of 35 use of Vitamin A-containing crystal clear, transparent, aque the year, nutrition and hormones. See Myers, R. J. and ous, sprayable emulsions for reducing itching and flaking of Hamilton, J. B. "Regeneration and rate of growth of hairs in common dandruff and seborrhea. As stated in its abstract, in man' Ann. N.Y. Acad. Sci. 53:562-568 (1951); Hamilton, J. some instances, the use of such emulsions reduced excessive B. "Age, sex and genetic factors in the relation of hair falling hair. It does not purport to stimulate hair growth. It growth in man: A comparison of Caucasian and Japanese 40 simply teaches a method of conditioning hair and scalp to populations' The Biology of Hair Growth (Ed. Montagna, effect relief from dandruff symptoms. The only pertinent W. and Ellis, R. A.), Academic Press Inc., New York, pp. example in Olson is discussed under Case History No. 3 of 400 433 (1958); Yano, S. "Rate of hair growth” Hifu to Example IV wherein the "Spray-on-Brush-in-Solution” con Hinyo 4:546-552 (1936); Maeda, I. "Study on the cuticula tained Vitamin A palmitate and seven other ingredients. All of hair: (III) Relation between the cuticula and rate of the 45 that is disclosed is that "the daily loss of head hair was growth of human hair' Jyuzenkai-Zasski, 43:1298–1304 reduced to approximately 10 to 20." (1938); Trotter, M. "The resistance of hair to certain sup Knight British patent specification No. 1,466,062 dis posed growth stimulants' Arch. Dermatol. and Syphilol. closes a cosmetic composition containing tocopherol and 7:93-98 (1923); Pinkus, F. “Zur Kenntnis der Lebensdauer retinoic acid as a cosmetic preparation which can be used on der menschlichen terminal haare' Z. Morphol. und Anthro 50 the skin or as a hair cleaning or hair dressing agent. This pol. 24:256-269 (1924); Ono, M. "Studies on the hair multi-purpose cosmetic composition allegedly prevents age growth of beard and scalphair (1st report) Influencing factor spots, and is claimed to be good for clearing the scalp of in the rhythms of hair growth' J. Physiol. Soc. Japan dandruff. It appears that, during clearing of the scalp of 25:254-261 (1963). dandruff with this composition, the scalp can become Various preparations have heretofore been proposed for 55 healthier, hair loss is reduced, and hair growth can recom the treatment of male pattern baldness.