WO2013181487A2 - Procédé de traitement - Google Patents

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Publication number
WO2013181487A2
WO2013181487A2 PCT/US2013/043519 US2013043519W WO2013181487A2 WO 2013181487 A2 WO2013181487 A2 WO 2013181487A2 US 2013043519 W US2013043519 W US 2013043519W WO 2013181487 A2 WO2013181487 A2 WO 2013181487A2
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aga
disease
association
study
parkinson
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PCT/US2013/043519
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WO2013181487A3 (fr
Inventor
Hans Hofland
Vincent Eugene MOOSER
Kijoung Song
Dawn Marie WATERWORTH
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Stiefel Laboratories, Inc.
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Publication of WO2013181487A3 publication Critical patent/WO2013181487A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4986—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with sulfur as the only hetero atom
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • the invention relates to methods for treating alopecia, e.g. androgenic alopecia, with an HDAC4 inhibitor, or a pharmaceutically acceptable salt or composition thereof.
  • the invention further relates to methods of treating alopecia, e.g. androgenic alopecia with an HDAC4 inhibitor, or a pharmaceutically acceptable salt or composition thereof, in combination with one or more of finasteride, minoxidil, dutasteride, spironolactone, latanoprost, or oral contraceptives.
  • Methods are provided for treating alopecia in a mammal in need thereof comprising administering an HDAC (histone deacetylase) inhibitor, or a pharmaceutically acceptable salt or composition thereof.
  • HDAC histone deacetylase
  • the HDAC inhibitor is a class Ila HDAC inhibitor.
  • the HDAC inhibitor is an HDAC4 inhibitor.
  • the HDAC4 inhibitor is a selective HDAC4 inhibitor.
  • Histone deacetylases are involved in the deacetylation of histones, transcription factors, and other proteins in eukaryotic cells. HDAC inhibitors cause hyperacetylation of histones, opening chromatin and leading to gene transcription and leading to cell-growth arrest, differentiation, and apoptosis.
  • HDACsa Histone deacetylases
  • Class I, II, and IV HDACs are zinc-dependent enzymes, whereas class III HDACs (SIRTT -SIRT7) are structurally unrelated.
  • Class I HDACs HDAC1 , 2, 3, and 8 are usually present in the nucleus, while the class II HDACs exhibit shuttling.
  • Class II HDACs are subdivided into class Ila (HDAC4, 5, 7, and 9) and lib (HDAC6 and 10).
  • Class Ila enzymes have an N-terminal extension of about 5-600 residues whereas the class lib enzymes contain two catalytic domains.
  • Class IV comprises only HDAC11, which exhibits sequence similarity to the class I enzymes.
  • the HDAC inhibitors used in the methods herein have a wide variety of structures.
  • the HDAC inhibitors, e.g., the HDAC4 inhibitor is one or more of a hydroxamic acid based HDAC inhibiror, e.g. vorinostat (SAHA), belinostat, or
  • Panobinostat or is a nonhydroxamic acid-based HDAC inhibitor such as the 2- aminophenylamides MS-27510 or MGCD-01031 1 or the dithiol FK22812.
  • the HDAC inhibitors are 5-(trifluoroacetyl)- thiophene-2-carboxamides, which are potent and selective class II HDAC inhibitors.
  • the HDAC inhibitor is selected from the table below:
  • treatment means any manner in which one or more symptoms associated with the disorder are beneficially altered. Accordingly, the term includes healing or amelioration of a symptom or side effect of the disorder or a decrease in the rate of advancement of the disorder.
  • pharmaceutically acceptable salts may comprise acid addition salts derived from a nitrogen on a substituent in the compound of formula (I).
  • Representative salts include the following salts: acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, monopotassium maleate, mucate, napsylate, nitrate, N- methylglucamine, ox
  • Such a unit may contain, for example, 0.5 mg to lg, preferably lmg to 800mg, of a compound of the formula (I) depending on the condition being treated, the route of administration and the age, weight and condition of the patient.
  • Preferred unit dosage formulations are those containing a daily dose or sub-dose, as herein above recited, or an appropriate fraction thereof, of an active ingredient.
  • such pharmaceutical formulations may be prepared by any of the methods well known in the pharmacy art.
  • compositions may be adapted for administration by any appropriate route, for example by the oral (including buccal or sublingual), rectal, nasal, topical (including buccal, sublingual or transdermal), vaginal or parenteral (including subcutaneous, intramuscular, intravenous or intradermal) route.
  • Such formulations may be prepared by any method known in the art of pharmacy, for example by bringing into association the active ingredient with the carrier(s) or excipient(s).
  • compositions adapted for oral administration may be presented as discrete units such as capsules or tablets; powders or granules; solutions or suspensions in aqueous or non-aqueous liquids; edible foams or whips; or oil-in-water liquid emulsions or water- in-oil liquid emulsions.
  • the active drug component can be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like.
  • an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like.
  • Powders are prepared by comminuting the compound to a suitable fine size and mixing with a similarly comminuted
  • Capsules are made by preparing a powder mixture as described above, and filling formed gelatin sheaths. Glidants and lubricants such as colloidal silica, talc, magnesium stearate, calcium stearate or solid polyethylene glycol can be added to the powder mixture before the filling operation. A disintegrating or solubilizing agent such as agar-agar, calcium carbonate or sodium carbonate can also be added to improve the availability of the medicament when the capsule is ingested.
  • Glidants and lubricants such as colloidal silica, talc, magnesium stearate, calcium stearate or solid polyethylene glycol can be added to the powder mixture before the filling operation.
  • a disintegrating or solubilizing agent such as agar-agar, calcium carbonate or sodium carbonate can also be added to improve the availability of the medicament when the capsule is ingested.
  • suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes and the like.
  • Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like.
  • Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum and the like.
  • Tablets are formulated, for example, by preparing a powder mixture, granulating or slugging, adding a lubricant and disintegrant and pressing into tablets.
  • a powder mixture is prepared by mixing the compound, suitably comminuted, with a diluent or base as described above, and optionally, with a binder such as carboxymethylcellulose, an aliginate, gelatin, or polyvinyl pyrrolidone, a solution retardant such as paraffin, a resorption accelerator such as a quaternary salt and/or an absorption agent such as bentonite, kaolin or dicalcium phosphate.
  • a binder such as carboxymethylcellulose, an aliginate, gelatin, or polyvinyl pyrrolidone
  • a solution retardant such as paraffin
  • a resorption accelerator such as a quaternary salt
  • an absorption agent such as bentonite, kaolin or dicalcium phosphate.
  • the powder mixture can be granulated by wetting with a binder such as syrup, starch paste, acadia mucilage or solutions of cellulosic or polymeric materials and forcing through a screen.
  • a binder such as syrup, starch paste, acadia mucilage or solutions of cellulosic or polymeric materials and forcing through a screen.
  • the powder mixture can be run through the tablet machine and the result is imperfectly formed slugs broken into granules.
  • the granules can be lubricated to prevent sticking to the tablet forming dies by means of the addition of stearic acid, a stearate salt, talc or mineral oil.
  • the lubricated mixture is then compressed into tablets.
  • the compounds of the present invention can also be combined with a free flowing inert carrier and compressed into tablets directly without going through the granulating or slugging steps.
  • a clear or opaque protective coating consisting of a sealing coat of shellac, a coating of sugar or polymeric material and a polish coating of wax can be provided.
  • Dyestuffs can be added to these coatings to distinguish different unit dosages.
  • Oral fluids such as solution, syrups and elixirs can be prepared in dosage unit form so that a given quantity contains a predetermined amount of the compound.
  • Syrups can be prepared by dissolving the compound in a suitably flavored aqueous solution, while elixirs are prepared through the use of a non-toxic alcoholic vehicle.
  • Suspensions can be formulated by dispersing the compound in a non-toxic vehicle.
  • Solubilizers and emulsifiers such as ethoxylated isostearyl alcohols and polyoxy ethylene sorbitol ethers, preservatives, flavor additives such as peppermint oil or natural sweeteners or saccharin or other artificial sweeteners, and the like can also be added.
  • dosage unit formulations for oral administration can be any suitable dosage unit formulations for oral administration.
  • the formulation can also be prepared to prolong or sustain the release as for example by coating or embedding particulate material in polymers, wax or the like.
  • Dosage unit forms can also be in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine or phosphatidylcholines.
  • Pharmaceutical formulations adapted for transdermal administration may be presented as discrete patches intended to remain in intimate contact with the epidermis of the recipient for a prolonged period of time. For example, the active ingredient may be delivered from the patch by iontophoresis as generally described in Pharmaceutical Research, 3(6), 318 (1986).
  • compositions adapted for topical administration may be formulated as ointments, creams, suspensions, lotions, powders, solutions, pastes, gels, sprays, aerosols or oils.
  • compositions adapted for topical administration in the mouth include lozenges, pastilles and mouth washes.
  • compositions adapted for rectal administration may be presented as suppositories or as enemas.
  • Pharmaceutical formulations adapted for nasal administration wherein the carrier is a solid include a coarse powder having a particle size for example in the range 20 to 500 microns which is administered in the manner in which snuff is taken, i.e., by rapid inhalation through the nasal passage from a container of the powder held close up to the nose.
  • Suitable formulations wherein the carrier is a liquid, for administration as a nasal spray or as nasal drops, include aqueous or oil solutions of the active ingredient.
  • Fine particle dusts or mists which may be generated by means of various types of metered, dose pressurised aerosols, nebulizers or insufflators.
  • compositions adapted for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations.
  • compositions adapted for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.
  • the formulations may be presented in unit-dose or multi-dose containers, for example sealed ampules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use.
  • Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets.
  • formulations may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavouring agents.
  • a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate thereof will depend upon a number of factors including, for example, the age and weight of the animal, the precise condition requiring treatment and its severity, the nature of the formulation, and the route of administration, and will ultimately be at the discretion of the attendant physician or veterinarian.
  • GWA genome-wide association
  • AGA is the most common form of hair loss in humans, affecting 80% of men by age 80[5]. Its etiologic factors are androgen dependency and genetic predisposition[5]. While largely a cosmetic condition, the mechanisms influencing its etiology may also impact upon important medical conditions such as coronary heart disease, metabolic syndrome, and prostate cancer[6,7].
  • Prostate cancer is the most frequently diagnosed cancer and ranks second as a cancer killer among men in the United States[8]. Androgens play a key role in stimulation of normal prostate growth and are essential in prostate cancer initiation and progression[9].
  • the main genetic determinant of AGA is the androgen receptor ( ⁇ 4i?)[3,4] and prostate cancer susceptibility loci identified through recent GWA studies overlap with androgen receptor binding sites[10,l 1] demonstrating a shared etiologic factor in these two conditions.
  • the current analysis comprised 3,891 cases and 8,915 controls of European ancestry from seven independent studies: Bonn, CoLaus, TwinsUK, Nijmegen Biomedical, 23andMe, Icelandic, and an Australian population based twin study (Table 1). Briefly, we used an extreme discordant case-control design to contrast individuals with early-onset AGA to older individuals without alopecia as assessed by questionnaire, clinical visit or photographs evaluated by a dermatologist, where available. Genome -wide genotyping, using standard platforms, and imputation using the CEU panel of Phase II HapMap were performed. After the quality control criteria were applied, 2,391 ,230 SNPs remained for genotype-phenotype association analysis.
  • FOXA2 forkhead box A2
  • FOXA2 the transcription factor encoded by FOXA2 in mouse, interacts with AR, especially through DNA binding domain, to regulate gene expression[19]. It is expressed in prostate tissue and plays a pivotal role in neuroendocrine prostate tumors, a form of metastatic prostate tumors, by inducing development from androgen-dependent tumors to androgen-independent tumors [20-22]. Its expression was associated with the invasive phenotype in the primary prostate cancer[22]. Furthermore, the association of metastatic prostate cancer and AGA through AR polymorphisms was previously described in a well- defined case-control study[14].
  • HDAC4 and HDAC9 two independent signals arose from HDACs (HDAC4 and HDAC9) which act as transcriptional corepressors by deacetylating nucleosomal histones[23].
  • HDAC4 plays a critical role in inhibition of AR transactivation[24,25] and its accumulation coincides with loss of androgen sensitivity in prostate cancer[26].
  • HDAC9 and HDAC4 share conserved residues and their tissue specific expression pattern overlaps [27].
  • ZNF652 which has been shown to be involved in transcriptional repression effect of HDACs[28] was identified to be a prostate cancer susceptibility locus[29].
  • HDAC4 and HDAC9 might influence pathogenesis of AGA through dysregulation of the androgen pathway, highlighting a shared etiologic factor in this condition and prostate cancer.
  • TARDBP TAR DNA binding protein
  • PEX14 peroxisomal biogenesis factor 14
  • MASP2 mannan-binding lectin serine peptidase 2
  • SRM spermidine synthase
  • SETBPI again demonstrated expression in hair, skin, and scalp (detection p values are 2.64 x 10-3, ⁇ 1.00 x 10-3, and ⁇ 1.00 x 10-3 respectively, Table S3), but not blood.
  • Regional association plots for seven loci associated with AGA are shown in Figure 1. All these loci were associated with AGA in random-effect results except the locus on chromosome 18 (Table S4). While any of the above susceptibility loci may impart a small risk, examining the combined effect of these loci in individuals harboring more than one risk allele may improve the ability to identify individuals at high risk of AGA.
  • AR locus is the most important genetic factor contributing to AGA
  • Parkinson's disease is the second most common neurodegenerative disorder with a prevalence of one percent in individuals that are over 60 years old[40]. Despite the often- reported higher prevalence of Parkinson's disease in men, as compared to women[40], there are no previous reports investigating the relationship between AGA and Parkinson's disease. This novel association between Parkinson's disease and early-onset AGA indicated that there could be a shared genetic or environmental cause for both conditions
  • the 17q21 .31 locus harbors an inversion polymorphism that has previously been described to be under negative selection pressure and has been demonstrated to be associated with decreased fertility in women[43jj.
  • We found a genome-wide significant SNP for early-onset AGA, whose risk allele (rsl 800547 [A], p
  • the genotyping platforms, imputation methods and genome wide association methods used in participant studies are provided in Table S 1.
  • Extensive quality control thresholds were applied to include common SNPs (minor allele frequency > 1%) with a high call rate (> 95%) for genotyped SNPs, and imputed SNPs with high quality metrics (variance ratio > 0.3 for MACH and proper info statistic > 0.4 for IMPUTE)[54,55].
  • SNPs demonstrating deviation from Hardy Weinberg Equilibrium p > 10-6) were excluded.
  • the test statistics for each cohort at each SNP were corrected for their respective genomic inflation factors to avoid inflation of results due to population stratification.
  • RNA extracted from human hair follicles, skin from temple, scalp, and whole blood were used for array-based gene expression analysis.
  • the differential expression of genes in these tissues was determined by the average signal of identical probes and detection p values (which is significant, if a gene is reliably expressed). Further details are provided in Text SI .
  • genotype risk score analysis the association between a genotype risk score based on the weighted number of susceptibility al leles and AGA status was determined.
  • the resultant genotypi c risk score was divi ded into quartiles and the risk of AGA for each quarti le was tested in an additional set of subjects in 23andMe study, which were not included in the original meta-analysis, using the lowest risk quartile as the reference group.
  • the genotype data is complete without missing values based on phasing and imputation.
  • the trend for risk across the quartiles was tested using the non- parametric trend test[60].
  • Cremers RG, Aben KK, Vermeulen SH, den Heijer M, van Oort IM, et al. (2010) Androgenic alopecia is not useful as an indicator of men at high risk of prostate cancer. Eur J Cancer 46: 3294-3299.
  • HDAC4 histone deacetylase 4
  • deacetylase 9 gene encodes multiple protein isoforms. J Biol Chem 278: 16059- 16072.
  • Parkinsonism Relat Disord 10 51-52.
  • Integrator a biomformatics tool to explore human genetic associations reported in published genome-wide association studies. Eur J Hum Genet.
  • TwinsUK The TwinsUK cohort is a population-based sample of Britons, unselected for any disease or trait, which is representative of the UK singleton populationj 4].
  • Nijmegen Biomedical Study The details of this study were reported previously [6]. Briefly, this is a population-based survey conducted by the Department of Epidemiology and Biostaiistics and the Department of Clinical Chemistry of the Radboud University Nijmegen Medical Center (RUNMC), in which 9,371 individuals participated from a total of 22,500 age and sex stratified, randomly selected inhabitants of Nijmegen. Individuals in the Nijmegen Biomedical Study were invited to participate in a study on gene- environment interactions in multifactorial diseases, such as cancer. All participants are of self-reported European descent. In a second phase of this project, participants completed an additional questionnaire and matched their hair pattern at 20 years, 40 years and present age to a Hamilton grading schema[7]. Affected individuals were those reporting Hamilton grade I V-VII by age 40 and controls were those with Hamilton grade I at age 50 years or older, or Hamilton grade II-III at age 60 years or older. A total of 73 cases and 132 controls were included in the current analyses.
  • the THISEAS study is a case- control study for coronary arter disease. As part of the study, hair status was assessed in male individuals by trained scientists. The pattern of AGA was determined using the Hamilton and Norwood classification. The controls were those with no hair loss or those with Hamilton grade II at the age of 50 years or older. Participants with Hamilton grade III or higher, age of onset ⁇ 50 years were defined as cases. 297 controls and 219 cases were included in the analyses of the current study.
  • RNA from human hair follicles, skin from temple, scalp and whole blood was extracted (RNeasy Micro Kit, Qiagen, Hilden, Germany). Quality and quantity of the RNA was analyzed on a NanoDrop ND-1000 spectrophotometer (Peqlab Biotechnologie, Eriangen, Germany). For quality reasons, each RNA sample was additionally checked for degradation via gel electrophoresis in a BioAnalyzer 2100 (Agilent Technologies,
  • RNA 6000 nano lab chips following manufacturer's instructions.
  • Array-based gene expression analysis of individual tissue samples was performed on Illumina's human HT-12v3 Expression BeadChips using standard protocols (Illumina, San Diego, USA).
  • 50ng of total RNA was reverse transcribed into cRNA and biotin-UTP labelled using the Illumina TotalPrep 96-RNA Amplification Kit (Ambion/ Applied Biosystems, Darmstadt, Germany). Labelled cRNA was hybridized on Illumina HT-12v3 Expression BeadChips.
  • the obtained fluorescence expression data were background subtracted and quantile normalized using GenomeStudio software (Illumina, San Diego, USA).
  • Supplementar Table3 lists all genes shown in Figure 1 that neighbour the SNP achieving the most significant p- value at the respective identified risk loci for AGA.
  • the average signal (AVG-signal) of identical probes and the detection p- values (which is significant, if a gene is reliably expressed) are shown for each transcript tested. If the expression of a respective gene was detected by more than one Iliumina probe, the probe with the best expression values based on all samples tested is presented. The same applies, if several probes detected different transcript variants of a respective gene. Non-present fluorescence intensity after background subtraction was marked as "-" and defined as not expressed in the corresponding tissue.
  • SNPs indicates the LD with the lead SNP as red (0.8 : r : 1), orange (0.6 : r ⁇ 0.8), green
  • Figure 3 Qiiantile-qiiantile plot of Meta- Analytic Results after removing SNPs of AGA locus on chromosome 20 and SNPs of AR locus on chromosome X. (Genomic Control was applied to each individual cohort prior to meta-analysis and the overall results).
  • Figure 4 S3. Forest Plots of the Lead SNP from Genome-Wide Significant Loci,
  • S.iSSisS SS is r 3 ⁇ 4yi :? 3 ⁇ 4ii i S.3 ⁇ 4> t a i ;.s.3 ⁇ 4S: : .i,.JS;i. : : SS t wifiiiSiiSS A 3 ⁇ 4.

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Abstract

L'invention concerne des procédés pour traiter l'alopécie, par exemple l'alopécie androgénique, avec un inhibiteur de HDAC4, ou un sel pharmaceutiquement acceptable ou une composition de celui-ci.
PCT/US2013/043519 2012-05-31 2013-05-31 Procédé de traitement WO2013181487A2 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3062797A4 (fr) * 2014-05-23 2016-11-23 Triple Hair Inc Compositions permettant de réduire la chute des cheveux et/ou d'augmenter la repousse des cheveux
WO2019010535A1 (fr) * 2017-07-12 2019-01-17 Samson Clinical Pty Ltd Stimulation de la pousse des cheveux et traitement de la chute de cheveux ou de l'alopécie excessive
US11116770B2 (en) 2014-10-29 2021-09-14 Samson Clinical Pty Ltd Detection and treatment of excessive hair shedding
US11696883B2 (en) 2014-05-23 2023-07-11 Triple Hair Inc. Compositions for reducing hair loss and/or increasing hair regrowth

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5962523A (en) * 1996-10-25 1999-10-05 Discovery Laboratories, Inc. Methods of using butyric acid derivatives to protect against hair loss
US20100286278A1 (en) * 2004-03-26 2010-11-11 Dsm Ip Assets B.V. Composition comprising an HDAC inhibitor in combination with a retinoid

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5962523A (en) * 1996-10-25 1999-10-05 Discovery Laboratories, Inc. Methods of using butyric acid derivatives to protect against hair loss
US20100286278A1 (en) * 2004-03-26 2010-11-11 Dsm Ip Assets B.V. Composition comprising an HDAC inhibitor in combination with a retinoid

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DOKMANOVIC ET AL.: 'Histone Deacetylase Inhibitors: Overview and Perspectives.' MOL CANCER RES, [Online] vol. 5, no. 10, 2007, pages 981 - 989 Retrieved from the Internet: <URL:http://mcr.aacrjoumals.org/contenUS/10/981.full.pdf+html> [retrieved on 2013-10-28] *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3062797A4 (fr) * 2014-05-23 2016-11-23 Triple Hair Inc Compositions permettant de réduire la chute des cheveux et/ou d'augmenter la repousse des cheveux
US10470992B2 (en) 2014-05-23 2019-11-12 Triple Hair Inc. Compositions for reducing hair loss and/or increasing hair regrowth
US11696883B2 (en) 2014-05-23 2023-07-11 Triple Hair Inc. Compositions for reducing hair loss and/or increasing hair regrowth
US11116770B2 (en) 2014-10-29 2021-09-14 Samson Clinical Pty Ltd Detection and treatment of excessive hair shedding
WO2019010535A1 (fr) * 2017-07-12 2019-01-17 Samson Clinical Pty Ltd Stimulation de la pousse des cheveux et traitement de la chute de cheveux ou de l'alopécie excessive
AU2018250398B2 (en) * 2017-07-12 2019-02-28 Samson Clinical Pty Ltd Promoting hair growth and treatment of hair loss or excessive hair shedding
CN111065396A (zh) * 2017-07-12 2020-04-24 萨姆森临床私人有限公司 促进毛发生长和治疗毛发缺损或过度毛发脱落

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