US 2011 O2O1562A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0201562 A1 Lintner et al. (43) Pub. Date: Aug. 18, 2011 (54) FORMULATIONS AND METHOD FOR Publication Classification TREATING BALDNESS (51) Int. Cl. A638/06 (2006.01) (75) Inventors: Karl Lintner, Paris (FR); Claire A6IP 7/4 (2006.01) Maschamberlin, Chevreuse (FR) (52) U.S. Cl. ....................................................... S14/20.7 (57) ABSTRACT (73) Assignee: SEDERMA, Le Perray-en-Yvelines cedex (FR) The present invention includes 1) a novel formulation for the treatment of hair loss comprising oleanolic acid (a 5C-reduc tase inhibitor), apigenin (a vasodilator), and biotinyl-GHK (a (21) Appl. No.: 13/092,328 cell metabolism stimulant), 2) a novel additive for the treat ment of hair loss comprising oleanolic acid, apigenin, bioti (22) Filed: Apr. 22, 2011 nyl-GHK and a delivery agent, 3) a personal care, cosmetic, and/or dermopharmaceutical composition comprising olean olic acid, apigenin, biotinyl-GHK, and at least one additional Related U.S. Application Data ingredient, and 4) a method for treating hair loss comprising (63) Continuation of application No. 1 1/097.666, filed on the administration of oleanolic acid, apigenin, and biotinyl Apr. 1, 2005, now abandoned. GHK. US 2011/02O1562 A1 Aug. 18, 2011 FORMULATIONS AND METHOD FOR turn reduce levels of dihydrotestosterone and thereby slow, TREATING BALDNESS prevent, or even reverse hair loss, particularly in men. The present invention includes formulations and methods for CROSS-REFERENCE TO RELATED addressing this issue. The present invention comprises olean APPLICATIONS olic acid, apigenin, biotinyl-GHK as active ingredients. In a 0001. This application is a continuation of U.S. applica preferred embodiment, one, two or all three of these active tion Ser. No. 1 1/097,666, filed on Apr. 1, 2005, the disclosure ingredients are provided in a single formulation. Most pref of which is incorporated herein by reference. erably, in one embodiment, the present invention comprises a single formulation including oleanolic acid, apigenin, bioti BACKGROUND OF THE INVENTION nyl-GHK as active ingredients. In another embodiment, any 0002 Each hair is formed at the level of a dermal papilla, one of the aforementioned formulations may also include at which yields a hair bulb then a hair proper, through the cell least one additional ingredient and/or delivery agent. Thus, in division of keratinocytes. Obeying an internal clock, each a particularly preferred embodiment, a formulation in accor papilla, located at the base of the hair follicle, receives a dance with the present invention includes oleanolic acid, growth message necessary to trigger the cycle of natural apigenin, biotinyl-GHK as active ingredients and at least one renewal of the hair. additional ingredient and/or delivery agent. In addition or in 0003. The hair cycle consists of three phases. The first the alternative to the additional ingredients, the formulations phase, or growth phase, is known as anagen and lasts, on may include additional active ingredients. average, between three and four years. The second phase 0008. In another embodiment, the present invention pro consists of discontinuation of growth over a period of two to vides an additive for use in cosmetic and/or dermopharma three weeks. This phase is called catagen. The last phase, ceutical formulations. The additive comprises (comprising called telogen, is the phase when hair falls out. This phase oleanolic acid, biotinyl-GHK, apigenin and at least one deliv occurs fairly slowly, over the course of three to four months, ery agent. as the bulbar Zone of hair follicle regresses and the hair shaft 0009. The delivery agent is generally selected and pro detaches and is expulsed towards the Surface of the skin. vided in an amount which is sufficient to solubilize, disburse, 0004 Hair cells are formed by the interaction between the Suspend, chelate, preserve, stabilize, structure, adjust the pH dermis and the epidermis. An epidermal message stimulates of or protect from microbial attack the formulation compris the fibroblasts to organize and forward a signal to kerati ing oleanolic acid, biotinyl-GHK and apigenin. These addi nocytes which induces formation of an epidermal plate which tives can then be used in formulating personal care products, in turn invaginates in the dermis to form a primary bud. The cosmetics, and dermopharmaceuticals particularly those use primary bud emits messages which stabilize the Surrounding ful for reducing hair loss. In another embodiment, the additive fibroblasts to form the future dermal papilla. The bud gradu consists essentially of oleanolic acid, biotinyl-GHK and api ally differentiates into a hair follicle under the influence of genin and at least one delivery agent. messages sent by the dermal papilla. 0010. In a further embodiment, the present invention pro 0005. As in many systems in the human body, the chemi vides a personal care, cosmetic and/or dermopharmaceutical cal pathways and precise roles involved in the growth of hair product comprising oleanolic acid, biotinyl-GHK, apigenin are not fully known. However, it is known that hair growth is and at least one additional ingredient. Said personal care, facilitated through the physical interaction between the der cosmetic, and/or dermopharmaceutical composition may be mis and epidermis within the dermal papilla wherein kerati in the form of a lotion, a shampoo, a conditioner, a hairspray, nocytes and fibroblasts are condensed. The dermal papilla is a gel, a hair styling product, a hair holding product, a Sun a Zone that is particularly rich in collagens and glycosami screen, a Sunblock, a Soap, a cream, an emulsion, a dispersion, noglycans which maintain the close contact between the two a solution, a milk, a suspension, a cleanser, a wash, a scalp cell populations and promote the chemical communication treatment lotion, and/or a spray. necessary for hair shaft growth. Collagen IV and laminin 5 are 0011. The present invention further includes methods of important proteoglycans as they constitute the basement treating hair loss in a subject in need of Such a treatment membrane, the attachment Zone for the epidermis and dermis, comprising the steps of administering to at least one first and, in the case of hairs, between the root sheath and the portion of the scalp of said subject an effective amount of dermis. oleanolic acid, an effective amount of apigenin, and an effec 0006 Various forms of hair loss exist in both men and tive amount of biotinyl-GHK. These active agents may be women and the present invention can be used to treat this hair administered individually or in any possible combination. loss. The most common type of hair loss is androgenetic This administration could be in the form of a cosmetic or alopecia, or male pattern baldness. This condition affects dermopharmaceutical composition. millions of people, roughly forty million in the United States 0012. The present invention aims to slow, stop, or even alone. Male pattern baldness is generally caused by the trans reverse hair loss. Without wishing to be bound by any par formation of testosterone into dihydrotestosterone which ticular theory of operation, this can be accomplished by one shrinks the size of hair follicles and the blood vessels that or more of: 1) reducing production of dihydrotestosterone by Support them, eventually causing some of the follicles to shut inhibiting 5C.-reductase, 2) increasing blood flow to the der down or even die. The transformation of testosterone into mis and thus to the hair follicles, and/or 3) ensuring better dihydrotestosterone is caused by the hormone, 5C-reductase. rooting of the hair in the skin. It is also known that deficiencies in vitamin H (biotin) can result in fine alopecic hair. DETAILED DESCRIPTION SUMMARY OF THE INVENTION 0013 The use of oleanolic acid in the present invention 0007. Without wishing to be bound by any particular was selected for its ability to inhibit 5C-reductase. The use of theory of operation, reducing levels of 5C.-reductase will in apigenin in the present invention was selected for its vasodi US 2011/02O1562 A1 Aug. 18, 2011 lative properties. The use of biotinyl-GHK in the present acid, Asiatic acid, eriantic acid, taraxerol. Stereoisomers of invention was selected for its ability to improve hair adhesion oleanolic acid, such as epi-Oleanolic acid, an also be used. by increasing the quality and duration of the anagen phase Additionally glucoside or ester derivatives of oleanolic acid through improving the skin matrix and improving metabolic may be used. activity. Furthermore, enhancing anchorage of the hair sheath 0021 Biotinyl-GHK is a chemical with the general struc and dermis and increasing the length of the anagen phase ture: should result from the use of biotinyl-GHK thereby delaying the onset of the telogen phase. Thus, the use of these three active ingredients can provide results which are not obtain e O O able by the use of only two of them. H N Nulls N 0014. It has been discovered that oleanolic acid is 4. 2. N OH endowed with a strong inhibitory action on the enzyme, O N H O O 5C-reductase, and thus constitutes an important component for the treatment of hair loss. It has been discovered that oleanolic acid may thus be advantageously used in the treat ment of hair loss, since oleanolic acid inhibits the transfor NH2 mation of testosterone into dihydrotestosterone. 00.15 Apigenin is known to be an effective vasodilator. It Biotinyl-GHK is also known by the names biotinyl tripeptide has been discovered however, that its use on the scalp dilates and Biotinyl glycyl-hystidyl-lysine. Biotinyl-GHK can be the blood vessels in the dermis which allows for a greater flow formed by binding the peptide Glycyl-Hystidyl-Lysine and of blood to the hair follicles, promoting healthy hair growth.