WO2010128755A2 - Composition pour la prévention ou le traitement de la chute des cheveux contenant du thréonate comme principe actif - Google Patents

Composition pour la prévention ou le traitement de la chute des cheveux contenant du thréonate comme principe actif Download PDF

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WO2010128755A2
WO2010128755A2 PCT/KR2010/001555 KR2010001555W WO2010128755A2 WO 2010128755 A2 WO2010128755 A2 WO 2010128755A2 KR 2010001555 W KR2010001555 W KR 2010001555W WO 2010128755 A2 WO2010128755 A2 WO 2010128755A2
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threonate
hair
hair loss
composition
dht
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PCT/KR2010/001555
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English (en)
Korean (ko)
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WO2010128755A3 (fr
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성영관
김문규
김정철
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(주)트리코진
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia

Definitions

  • the present invention relates to a composition for preventing or treating hair loss using L-threonate as an active ingredient.
  • AGA Androgenetic alopecia
  • AA alopecia areata
  • AA alopecia associated with chemotherapy or radiation therapy
  • hair is usually divided into two types, "breed hair” and "soft hair".
  • a bald hair is a long hair that grows from the hair follicles that are thick, colored, and deeply developed in the dermis.
  • Cilia are typically thin, colorless hairs that grow from smaller hair follicles located on the surface of the dermis. As hair loss progresses, the hairs change into the form of soft hair and the hair follicles shrink correspondingly.
  • hair loss Another factor of hair loss is the change in hair growth cycle. Hair typically grows through three cycles: growth phase (active hair growth), retrogression (transitional) and rest period (stoppage of hair loss before new growth). Usually, about 88% of the hair on the scalp is in the growing phase, only about 1% is in the degenerative phase and the rest is in the resting phase. As hair loss progresses, a sharply high rate of hair belongs to the resting period, and accordingly, the proportion of hair belonging to an active growth phase is lower.
  • hair follicle size and density are both significantly reduced in relation to alopecia.
  • bald humans aged 30 to 90 years have been reported to have only about 306 hair follicles on average. This is about 33% less than the average of about 460 hair follicles in the non-bald head of the same age range. The above factors combine to create baldness.
  • the effects of a commercially available product as a hair growth or hair loss preventing agent on the hair include hair growth phase induction effect, hair growth phase extension effect, 5 ⁇ -reductase inhibitory effect, blood circulation promoting effect, bactericidal effect, anti-dandruff effect, moisturizing effect, antioxidant effect, etc.
  • hair growth phase induction effect hair growth phase extension effect
  • 5 ⁇ -reductase inhibitory effect blood circulation promoting effect
  • bactericidal effect bactericidal effect
  • anti-dandruff effect moisturizing effect
  • antioxidant effect etc.
  • the effect of preventing hair loss and promoting hair growth in such a conventional formulation is not sufficient. This is because the causes of hair loss are very complicated and variously entangled, while these preparations focus on only one or two types of hair loss or hair growth phenomena to improve them. That is, to date, preparations focusing on various and complicated hair growth mechanisms are rare.
  • Japanese Patent Application Laid-Open No. 2000-169326 discloses a blood flow promoter containing at least one or more selected from benzoic acid, alkali metal salts of benzoic acid, benzaldehyde, cuminaldehyde, mirtenal and hydroxy citronellal as an active ingredient. It is starting. These blood stimulators improve the large intestinal sensation of local tissues due to peripheral blood flow and exert an excellent blood flow promoting effect. Therefore, it is compounded in oral compositions, medicines, cosmetics, hair growth agents, bath solvents, external preparations, periodontal disease, soot, hair loss. It is described that it can be used to improve shoulder stiffness, muscle pain and the like. However, only the blood flow promoting effects of hydroxy citronellal and the like are shown here, and in fact, the effect on the improvement of hair loss is not specifically demonstrated.
  • circulating androgens including dihydrotestosterone (DHT) enter hair follicles through dermal papillary capillaries and bind to androgen receptors present in dermal papilla cells to activate or inhibit the expression of target genes (Randall VA, Thornton MJ, Hamada). K, Messenger AG. Skin Pharmacol 1994; 7: 20-6).
  • DHT-regulated autosecretory and paracrine (peripheral) factors will be the center of masculine alopecia (Inui S, Fukuzato Y, Nakajima T, Yoshikawa K, Itami S. FASEB). J 2002; 16: 1967-9; Hibino T, Nishiyama T.
  • DKK-1 dickkopf 1
  • DHT-induced DKK-1 might be one of the important factors involved in male alopecia: 1) DKK-1 mRNA in dermal papilla cells was 3-6 after 50-100 nM DHT treatment.
  • DKK-1 protein was increased by DHT through ELISA method.
  • Cell death of epithelial cells is caused by DHT in cultured hair follicles, and neutralizing antibodies against DKK-1 reverse it again. 5) It was confirmed by the immunobloting method that DKK-1 was expressed higher in the bald area of male hair loss patients than the non-hair loss area.
  • DKK-1 is a potent and specific Wnt antagonist that binds to the low-density lipoprotein receptor related protein, a receptor required for canonical Wnt signaling involved in hair growth (Millar SE, Willert K, Salinas).
  • PC Roelink H, Nusse R, Barsh GS. Dev Biol 1999; 207: 133-49; Kishimoto J, Burgeson RE, Morgan BA.Genes Dev 2000; 14: 1181-5; Shimizu H, Morgan BA.J Invest Dermatol 2004 122: 239-45).
  • the present invention solves the above problems, and the object of the present invention as devised by the necessity of the above is to provide a composition for treating or preventing hair loss.
  • the present invention provides a composition for preventing or treating hair loss using threonate as an active ingredient.
  • the threonate (threonate) is preferably L-threonate, calcium L- threonate, sodium L- threonate, chromium L- threonate, and iron L- threonate More preferably, it is selected from the group consisting of, but is not limited thereto.
  • the hair loss of the present invention is preferably male hair loss, and is preferably caused by androgen, but is not limited thereto.
  • compositions of the present invention are designed for topical administration at the site of hair loss or at the desired site for hair growth. Specifically, administration of the compositions of the present invention is accomplished by any method that selectively delivers an effective amount of the composition (including delivery to hair follicles) to the desired skin site (hereinafter referred to as the "treatment site") to stimulate hair growth. Can be.
  • administration can be accomplished by topical administration directly to the treatment site or by injection (eg intradermal injection) to the treatment site, including the scalp.
  • effective amount herein is meant the amount of the composition identified above that is used to treat or prevent a disease associated with hair loss as discussed above and discussed herein.
  • composition of the present invention can be applied in an amount of 0.1 to 20 mg / kg body weight per day, preferably 1 to 10 mg / kg body weight divided into three times per day, in the case of oral preparations 1 to 1 per day
  • amount of 500 mg / kg body weight, preferably 10 to 100 mg / kg body weight, may be taken once to three times.
  • compositions of the present invention are formulated for intradermal injection at the site of treatment and further contain a vehicle suitable for such injection.
  • Suitable vehicles include, but are not limited to, saline, bacteriostatic saline and sterile water. Methods of making such compositions are well known in the art. For example, a metered amount of active compound is placed in a vial and the contents inside are sterilized and sealed. Subsequent vials containing sterile water for injection or a compound of the invention as a vehicle for forming a dispersion prior to administration are provided.
  • compositions of the present invention further contain a physiologically acceptable inert carrier or diluent to be suitable for topical administration of the composition to the skin.
  • physiologically acceptable inert carriers or diluents include water, physiological saline, bacteriostatic saline (saline containing 0.9 mg / ml benzyl alcohol), creams, lotions, gels and short chain alcohols and glycols of various forms (e.g. ethyl Alcohols and propylene glycol).
  • composition for topical administration contains a compound of the invention at a concentration of about 0.1% to about 20% based on the total weight of the composition.
  • compositions of the present invention suitable for topical administration further contain a penetration enhancer, surfactant or mixtures thereof.
  • a penetration enhancer for example, such compositions may contain from 0.5% to 10% (by weight) of one or more surfactants (also called emulsifiers).
  • the surfactant can be ionic or nonionic.
  • nonionic surfactants are nonylphenoxypolyethoxy ethanol (nonoxynol-9), polyoxyethylene oleyl ether (Brij-97), various polyoxyethylene ethers (Tritons), and ethylene oxide of various molecular weights. And block copolymers of propylene such as Pluronic F68.
  • suitable ionic surfactants include sodium lauryl sulfate and similar compounds.
  • Suitable permeation enhancers include dimethyl sulfoxide (DMSO), urea and substituted urea compounds.
  • DMSO dimethyl sulfoxide
  • urea urea
  • substituted urea compounds for liquid formulations for topical administration, the concentration of a penetration enhancer (eg, DMSO) can range from 30% to 80% of the composition.
  • composition of the present invention suitable for topical administration further containing a sunscreen, skin conditioner, skin protectant, emollient, moisturizer, hair conditioner or mixtures thereof.
  • Suitable sunscreens absorb, reflect or disperse radiation in the UV range wavelength of 290 to 400 nm, specific examples of which are benzophenone-3 (oxybenzone), benzophenone-4 (sulisobenzone), benzophenone-8 (di Oxybenzone), butyl methoxydibenzoylmethane (Avobenzone), DEA-methoxycinnamate (diethanolamine methoxycinnamate), ethyl dihydroxypropyl PABA (ethyl 4- [bis (hydroxypropyl)] aminobenzoate ), Ethylhexyldimethyl PABA (Padimate O), ethylhexyl methoxycinnamate (octyl methoxycinnamate), ethylhexyl salicylate (octyl salicylate), homosalate, menthyl anthranilate (Meradimate), octo Kylene, PABA (aminobenzoic acid),
  • Suitable skin conditioning agents improve the appearance of dry or damaged skin, reduce flake formation, restore flexibility, and generally improve the appearance of skin.
  • Representative examples include acetyl cysteine, N-acetyl dihydrosphingosine, acrylate / behenyl acrylate / dimethicone acrylate copolymer, adenosine, adenosine cyclic phosphate, adenosine phosphate, adenosine triphosphate, alanine, albumen, algae Extracts, allantoin and derivatives, aloe barbadensis extract, aluminum PCA, amyloglucosidase, arbutin, arginine, azulene, bromelain, buttermilk powder, butylene glycol, caffeine, calcium gluconate, capsaicin, carbocysteine , Carnosine, beta-carotene, casein, catalase, cephalin, ceramide, chamomile recutita
  • skin conditioning agents include lactoferrin, lanosterol, lauryl PCA, lecithin, linoleic acid, linolenic acid, lipase, lysine, lysozyme, malt extract, maltodextrin, melanin, methionine, mineral salts, niacin, niacinamide, oat amino acids , Oranol, palmitoyl hydrolyzed protein, pancreatin, papain, PEG, pepsin, phospholipid, phytosterol, placental enzyme, placental lipid, pyridoxal 5-phosphate, quercetin, resorcinol acetate, riboflavin, RNA, Saccharomyces supernatant extract, silk amino acid, sphingolipid, stearamidopropyl betaine, stearyl palmitate, tocopherol, tocopheryl acetate, tocopheryl lino
  • skin protectant herein is meant a compound that protects damaged or exposed skin from harmful or irritating external compounds. Suitable examples include algae extract, allantoin, aluminum hydroxide, aluminum sulfate, betaine, camellia sinensis leaf extract, cerebrose, dimethicone, glucuronolactone, glycerin, kaolin, lanolin, malt extract, mineral oil, petrolatum, potassium Gluconate and talc.
  • emollient herein is meant a cosmetic ingredient that can help to maintain a smooth, smooth and supple appearance of the skin. Emollients may provide these advantages primarily because of their ability to remain on the skin surface to act as a lubricant and reduce flake formation.
  • emollients suitable for embodiments of the invention include acetyl arginine, acetylated lanolin, algae extracts, apricot kernel oil PEG-6 esters, avocado oil PEG-11 esters, bis-PEG-4 dimethicone, butoxyethyl stearate , C18-C36 acid glycol ester, C12-C13 alkyl lactate, caprylyl glycol, cetyl ester, cetyl laurate, coconut oil PEG-10 ester, di-C12-C13 alkyl tartrate, diethyl sebacate, dihydro Cholesteryl butyrate, dimethiconol, dimyristyl tartrate, disteares-5 lauroyl glutamate, ethyl avocadodate, ethylhexyl myristate, glyceryl isostearate, glyceryl oleate, hexyldecyl stearate and Hexyl
  • suitable emollients include hydrogenated palm glycerides, hydrogenated soy glycerides, hydrogenated tallow glycerides, hydroxypropyl bisisostearamide MEA, isostearyl neopentanoate, isostearyl palmitate, isotri Decyl isononanoate, laureth-2 acetate, lauryl polyglyceryl-6 cetearyl glycol ether, methyl gluses-20 benzoate, mineral oil, myres-3 palmitate, octyldecanol, octyldodecanol , Odontella aurita oil, 2-oleamido-1,3 octadecanediol, palm glycerides, PEG avocado glycerides, PEG castor oil, PEG-22 / dodecyl glycol copolymers, PEG che ( shea) butter glycerides, phytol, raffinose, stea
  • Moisturizers are cosmetic ingredients that help to maintain moisture on the skin. Suitable examples include acetyl arginine, algae extract, aloe barbadensis leaf extract, betaine, 2,3-butanediol, chitosan lauroyl glycinate, diglyceres-7 malate, diglycerin, diglycol guanidine succinate, Erythritol, fructose, glucose, glycerin, honey, hydrogenated wheat protein / PEG-20 acetate copolymer, hydroxypropyltrimonium hyaluronate, inositol, lactitol, maltitol, maltose, mannitol, mannose, methoxy PEG , Myristamidobutyl guanidine acetate, polyglyceryl sorbitol, potassium PCA, propylene glycol, sodium PCA, sorbitol, sucrose and urea. Other humec
  • Hair conditioning agents are cosmetic ingredients used to provide specific effects on hair. It contains ingredients that improve the appearance and feel of hair, increase hair flexibility, facilitate styling, improve gloss or gloss, and improve the texture of hair damaged by chemicals or environmental influences. Suitable examples include acetylated lanolin, amodimethicone, behenamidopropyl ethyldimonium ethosulfate, behentrimonium chloride, Butyrospermum Parkii (She Butter) oil, caprylic acid / capric Acid glycerides, ceteareth-20, cetylpyridinium chloride, cocamidopropyl betaine, cocamidopropyl hydroxysulfine, cocodimonium hydroxypropyl hydrolyzed keratin, dicetyldimonium chloride, dimethyl laumine iso Stearates, Glyceryl Stearate SE, Guar Hydroxypropyltrimonium Chloride, Hydrolyzed Glycosaminoglycans,
  • the active compounds are formulated in the device for delivery to hair follicles by iontophoresis.
  • formulated compositions are typically in the form of liquids (ie, solutions) rather than creams or gels.
  • a device applied for such a transfer is a large bandage that includes a chamber and supplies current. The chamber is placed in contact with the skin and contains the formulation.
  • the active compound is formulated for delivery to hair follicles via ultrasound.
  • ultrasound and iontophoresis enhance the delivery of the active compound to hair follicles by destroying the stratum corneum and enhancing the transport of the active compound.
  • compositions of the present invention may be in the form of liquids, creams, suspensions, gels, emulsions, lotions or oils.
  • the invention in another aspect, relates to a method of stimulating hair growth in alopecia patients using the compositions of the invention described above.
  • the method comprises administering a topically or intradermal injection of an effective amount of the composition of the invention to alopecia skin area of an AGA, AA or secondary alopecia patient.
  • a method for preventing or restoring AGA comprising administering an effective amount of a composition of the invention to the scalp of a patient in need of arresting or restoring from AGA in a continuous or periodic manner via topical or intradermal injection The method is described.
  • the present invention provides a method comprising the steps of applying the composition of the present invention prepared for topical administration as described above directly onto the treatment site by rubbing onto the skin of the treatment site in the form of a lotion or gel or spraying onto the treatment site in liquid form. It may include. A sufficient amount of the composition is effective to promote the rate of hair growth or to prevent continued hair loss, and treatment can be repeated as often as the progress of hair growth is indicated.
  • the present invention reports that L-threonate inhibits DKK-1 expression by DHT in human dermal papilla cells.
  • DHT inhibits the growth of co-cultured keratinocytes, which is mainly due to DKK-1 (Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK, Kim JC). J Invest Dermatol 2008; 128: 262-9).
  • DKK-1 Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK, Kim JC).
  • FIG. 3, lanes 1 and 2 L-threonate inhibited DKK-1 expression by DHT (see Figures 1 and 2) to study whether L-threonate attenuates the growth inhibition of co-cultured keratinocytes by DHT.
  • L-threonate reversed the inhibition of keratinocyte growth by DHT (compare FIG. 3, lanes 2, 3, 4).
  • pGL3-DKK-1 plasmid expressing the luciferase reporter gene according to the degree of DKK-1 promoter activation was made, and reporter assay was performed using this.
  • DHT was treated to dermal papilla cells, increased luciferase activity was observed (FIG. 4, lane 1 and 2 compared).
  • L-threonate and DHT were simultaneously treated, increased luciferase activation by DHT in dermal papilla cells was significantly inhibited by L-threonate (compare FIG. 4, lanes 2, 3 and 4).
  • Figure 1 shows that D-KK-1 mRNA expression by DHT is inhibited by L-threonate.
  • Human dermal papilla cells were treated with 100 nM DHT and L-threonate (0.25 mM and 1 mM) for 6 hours and analyzed by RT-PCR.
  • Figure 2 shows that L-threonate inhibits DKK-1 protein production by DHT.
  • Human dermal papilla cells were treated with 100 nM DHT and L-threonate (0.25 mM and 1 mM) for 4 days, and then the DKK-1 concentration of the medium was measured by ELISA. Data are expressed as mean +/- standard deviation based on the results of three independent experiments.
  • Figure 3 shows that L-threonate attenuates the growth inhibition of hair root growth by DHT.
  • 100 nM DHT and L-threonate (0.25 mM and 1 mM) were treated for 4 days while co-cultured with dermal papilla cells and superficial myelinated cells. Data were performed three times for each condition and expressed as mean +/- standard deviation based on the results of three independent experiments.
  • Figure 4 shows that the activation of the DKK-1 promoter by DHT is inhibited by L-threonate.
  • Human dermal papilla cells were treated with 100 nM DHT and L-threonate (0.25 mM and 1 mM) and luciferase reporter activity was measured. Data are expressed as mean +/- standard deviation based on the results of three independent experiments.
  • Example 1 Culture of dermal papilla cells and hair root sheath keratinocytes
  • Biopsy tissue (4 mm) was obtained during hair transplantation in male hair loss patients. The research committee was approved by Kyungpook National University Hospital's Ethics Committee. Hair follicles were isolated by slightly modifying the previous method (Philpott MP, Sanders DA, Westgate GE, Kealey T. J Invest Dermatol 1994; 102: 857-61; Magerl M, Kauser S, Paus R, Tobin DJ.Exp Dermatol 2002 11: 381-5). In brief, the subcutaneous fat portion of the scalp, including the subfollicles, was separated from the epidermis and dermis, and the hair follicles were separated using tweezers under a microscope.
  • the dishes were transferred to a plate and incubated in DMEM with penicillin (100 U / ml), streptomycin (100 ug / ml) and 20% heat inactive serum at 95 ° C. in air, 5% CO 2 and 37 ° C. Leave it on for a week and then change the medium once every 3 days when the nipples were attached to the culture dish and cells began to stretch out. When the cells were grown, cells were collected using 0.25% trypsin / 10mM EDTA, and maintained at 10% DMEM in a ratio of 1: 3.
  • the hair follicles were separated from the hair follicle tissues, and in order to prevent contamination of other cells, the hair shafts and hair follicles of the hair were removed and cleaned, and then cultured in DMEM with 20% heat-inactive serum. After 3 days, the medium was changed to KGM with penicillin (100 U / ml), streptomycin (100 ug / ml) and amphotericin B (250 ng / ml). After that, it is maintained in KGM, and in this experiment, the experiment was performed using the cells that were passaged twice.
  • Example 2 Co-culture of dermal papilla cells and keratinocytes
  • the dermal papilla cells were cultured in serum-free medium with 3 ⁇ 10 4 cells in the compartment below the transwell dish. After 24 hours, keratinocytes (1.5 ⁇ 10 4 ) were incubated in cells on the permeable membrane coated with type I and III collagen. Both cells were co-cultured with MCDB 153 medium for 4 days and treated with DHT and L-threonate according to the conditions. After 3 hours in MTT solution (70ug / well), formazan was dissolved in DMSO and measured at 570nm,
  • ELISA was performed with a slight modification of the previous method (Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Shaughnessy J D. N Engl J Med 2003; 349: 2483-94). Briefly, 100 ⁇ l of goat-anti-human DKK-1 antibody at a concentration of 1 ⁇ g / ml was coated on a 96 well plate at 4 ° C. After 16 hours, 4% BSA was added and blocked for 1 hour, and then 100 ⁇ l of the condition medium was added and stored at room temperature for 2 hours.
  • Human genomic DNA was isolated from the dermal papilla cells of male baldness using the QIAamp DNA Mini kit.
  • pGL3-DKK-1 promoter plasmid preparation was made as previously mentioned (Ohnaka K, Taniguchi H, Kawate H, Nawata H, Takayanagi R. BBRC 2004; 318: 259-64). Briefly, the front 988 bp of the human DKK-1 promoter was PCR using 5′-CTCACGCGTCTGCCTAATCA-3 ⁇ (sense) (SEQ ID NO: 5) and 5′-AAGCTTTCAGAAGGACTCAAGAGGGA-3 ⁇ (antisense) (SEQ ID NO: 6) primers. Amplification was performed.
  • pGL3-Basic vector Promega
  • pGL3-DKK-1 a luciferase expression vector having no promoter
  • the human hair papilla cells (10 4 / well) were introduced with 450ng pGL3-DKK-1 and 50ng pRLCMV as a control using a microporator. After 24 hours, 100nM DHT and L-threonate were treated in serum-free medium. After 24 hours, firefly and renilla luciferase activities were measured using a dual luciferase assay kit.

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Abstract

La présente invention concerne une composition permettant de prévenir ou de traiter la chute des cheveux, contenant du L-thréonate comme principe actif.
PCT/KR2010/001555 2009-05-08 2010-03-12 Composition pour la prévention ou le traitement de la chute des cheveux contenant du thréonate comme principe actif WO2010128755A2 (fr)

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KR1020090040280A KR101113806B1 (ko) 2009-05-08 2009-05-08 트레오네이트를 유효성분으로 하는 탈모 예방 또는 치료용 조성물
KR10-2009-0040280 2009-05-08

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KR100650283B1 (ko) * 2000-06-14 2006-11-27 김정웅 항균성 한방 조성물, 그 제조방법 및 그 조성물이 함입된약포
JP7322140B6 (ja) 2018-05-02 2024-02-21 ジェイダブリュ ファーマシューティカル コーポレーション 新規なヘテロサイクル誘導体

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6150405A (en) * 1985-07-18 2000-11-21 Proctor; Peter H. Hair loss treatment with ascorbates
US20040033963A1 (en) * 2002-04-10 2004-02-19 Yu Ruey J. Urea composition
US20040242679A1 (en) * 2001-08-24 2004-12-02 Jariwalla Raxit J Methods and compositions for potentiating cancer chemotherapeutic agents
WO2006075854A1 (fr) * 2005-01-13 2006-07-20 Trichogene Inc. Composition comprenant des derives de la vitamine c qui permet de stimuler la croissance des cellules de la papille dermique et de promouvoir la croissance du follicule pileux

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6150405A (en) * 1985-07-18 2000-11-21 Proctor; Peter H. Hair loss treatment with ascorbates
US20040242679A1 (en) * 2001-08-24 2004-12-02 Jariwalla Raxit J Methods and compositions for potentiating cancer chemotherapeutic agents
US20040033963A1 (en) * 2002-04-10 2004-02-19 Yu Ruey J. Urea composition
WO2006075854A1 (fr) * 2005-01-13 2006-07-20 Trichogene Inc. Composition comprenant des derives de la vitamine c qui permet de stimuler la croissance des cellules de la papille dermique et de promouvoir la croissance du follicule pileux

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