EP1159256A1 - Derives a base sphingoide et leurs utilisations - Google Patents

Derives a base sphingoide et leurs utilisations

Info

Publication number
EP1159256A1
EP1159256A1 EP00907673A EP00907673A EP1159256A1 EP 1159256 A1 EP1159256 A1 EP 1159256A1 EP 00907673 A EP00907673 A EP 00907673A EP 00907673 A EP00907673 A EP 00907673A EP 1159256 A1 EP1159256 A1 EP 1159256A1
Authority
EP
European Patent Office
Prior art keywords
acid
sphingoid base
sphingoid
base derivative
hydrophilic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00907673A
Other languages
German (de)
English (en)
Inventor
Hugo Streekstra
Pieter Gijsbert Weber
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cosmoferm BV
Original Assignee
Cosmoferm BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cosmoferm BV filed Critical Cosmoferm BV
Priority to EP00907673A priority Critical patent/EP1159256A1/fr
Publication of EP1159256A1 publication Critical patent/EP1159256A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/22Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
    • C07C215/24Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and acyclic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/68Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005Antimicrobial preparations

Definitions

  • the present invention relates to the field of topical application, especially topical application of sphingoid base derivatives.
  • Sphingoid bases like sphingosine are known to be potent effectors of skin cell differentiation and proliferation, by interfering with basic biochemical cell processes (Hannun, Y.A. and Bell, R.M. (1 989), Science 243, 500-507).
  • free sphingosine inhibits the activity of protein kinase C and thus plays a pivotal role in signal transduction and regulation of cell division (Hannun, Y.A. et al. (1 986), J. Biol. Chem. 261 , 1 2604-1 2609).
  • sphingoid bases such as antimicrobial activity
  • sphingoid bases may be included as an active ingredient in various cosmetic compositions.
  • sphingosine has been described for the treatment of various abnormalities and disorders concerning the skin, such as dry skin, xeroderma and psoriasis. Sphingosine can also protect the skin against various harmful or undesirable effects, such as the effects of UV light and skin ageing.
  • sphingoid bases have been included in topical compositions as an antiinflammatory agent or an antimicrobial agent (W098/49999).
  • a disadvantage of sphingoid bases is their scarce solubility in an aqueous environment. This phenomenon hampers the use of these compounds in aqueous formulations. For instance, to display an effective antimicrobial activity, it is important to have the sphingoid base solubilized in an aqueous formulation. Pegcription pf the inventipn
  • the present invention discloses derivatives of sphingoid bases which have a substantially increased solubility in water than their free base counterparts. As a consequence, these sphingoid base derivatives display a surprisingly improved efficacy when formulated in an aqueous composition.
  • the sphingoid base derivatives of the invention are salts of sphingoid bases.
  • the anion of a sphingoid base salt is derived from any suitable acid.
  • a suitable acid is defined as an acid which, upon mixing with a sphingoid base in a suitable solvent, produces a salt which has an increased solubility in an aqueous medium as compared to the solubility of the sphingoid base as such.
  • the acid is an acid which itself may have an efficacy in topical application.
  • the acid is a hydrophilic acid able to deliver the sphingoid base to the water phase of a cosmetic or pharmaceutical composition.
  • the acid is a hydrophilic organic acid such as an ⁇ -hydroxy alkanoic acid, a ?-hydroxy alkanoic acid, an ⁇ , ?-dihydroxy alkanoic acid, an alkanedioic acid or a mineral acid.
  • hydrophilic organic acids are lactic acid, glycolic acid, malic acid, pyruvic acid, succinic acid, fumaric acid, citric acid, ascorbic acid, gluconic acid and/or pyroglutamic acid (pyrrolidone carboxylic acid).
  • mineral acids are hydrochloric acid, nitric acid and/or phosphoric acid.
  • the acid is a lipophilic organic acid, such that the combination with a sphingoid base increases the efficacy of both the lipophilic acid as well as the sphingoid base.
  • the sphingoid base salts of the invention may be prepared as follows.
  • the sphingoid base is dissolved in a suitable organic solvent, whereupon at least one equivalent of a suitable acid is added.
  • a suitable organic solvent preferably is a solvent wherein the end product, i.e. the sphingoid base salt, is insoluble.
  • a suitable organic solvent for instance is ethanol or methyl isobutyl ketone.
  • a sphingoid base salt is used as a starting compound for the preparation of another sphingoid base salt. It is essential that the sphingoid base salts of the invention are prepared prior to their intended use, e.g. their inclusion in a topical composition. The inclusion of a free sphingoid base in a topical composition additionally containing anions from one or more of the acids as defined herein above will not result in an increased solubility and/or an increased efficacy.
  • the sphingoid base salts of the invention preferably are salts of the sphingoid bases sphingosine, sphinganine or phytosphingosine. More preferably, the sphingoid base salts are salts of phytosphingosine.
  • phytosphingosine is obtained via a microbial fermentation.
  • phytosphingosine is obtained from Pichia ciferrii-derived tetraacetyl-phytosphingosine (TAPS), by a suitable deacetylation reaction.
  • the deacetylation may be chemical, e.g. by base catalyzed hydrolysis with potassium hydroxide, or enzymatical.
  • the resulting phytosphingosine may be purified. Such a purification can occur by any method known to a person skilled in the art.
  • Yeast-derived phytosphingosine is human skin-identical, as it is reported to have the same stereochemical configuration as mammalian phytosphingosine, i.e. the D-D-erythro configuration.
  • the sphingoid base salts of the invention have a solubility in an aqueous environment which is considerably higher than the solubility of the free sphingoid base. It is further surprisingly shown by the present invention that sphingoid base salts have an increased efficacy as compared to the free sphingoid base, even in an environment where the free sphingoid base also is in a solubilised form.
  • the free sphingoid base may be in a solubilised form by the additional presence in the aqueous medium of an organic solvent and a surface active compound.
  • compositions comprising a sphingoid base derivative according to the invention are suitable for topical application, whereby topical application is understood to comprise cosmetic and/or dermatological application on the skin, on hair and on the epithelial linings of mouth, nose, eye, urogenital tract, and the like.
  • the sphingoid base derivatives of the present invention preferably are incorporated in a topical composition in a concentration which may range from 0.001 to 5 wt %, preferably from 0.005 to 5 wt %, more preferably from 0.01 to 2.5 wt %, most preferably from 0.02 to 1 wt %, especially preferably from 0.02 to 0.5 wt %.
  • Topical compositions including a sphingoid base derivative according to the invention are particularly suitable to apply to various topically occurring undesirable and/or abnormal conditions associated with inflammation and/or microbial activity.
  • topically occurring undesirable and/or abnormal conditions to which topical compositions comprising the sphingoid base derivatives of the invention are advantageously applied are eczema, psoriasis, atopic dermatitis, acne, dandruff, mouth and/or lip infections, mycoses, various other skin- infectious diseases or vaginal infections.
  • Topical compositions comprising said sphingoid base derivatives are further advantageously applied for wound-healing, e.g. in case of burns, and for normalisation of skin flora.
  • the sphingoid base derivatives of the invention additionally may function as a preservative in cosmetic and dermatological compositions, to decrease and/or substitute for existing chemical preservatives.
  • the precipitate was filtered off and the cake was replaced with 1 50 ml of ethanol (fast filtration and replacing, total of 2 minutes).
  • the precipitate was filtered off and the cake was replaced with 1 50 ml of ethanol (fast filtration and replacing, total of 3 minutes)
  • a glassy precipitate was obtained. At 45 °C a 1 ml sample was taken which started to crystallise upon scratching. This was used to seed the mixture during further cooling.
  • a 10 mg/ml stock solution of phytosphingosine (PS) was prepared in a solvent system, consisting of 1 volume fraction ethanol, 2 volume fractions Tween 20 and 17 volume fractions 50% glycerol in water.
  • the components of the solvent system were added to the phytosphingosine in this order, and the solution was shaken vigorously after each addition. When all solvents had been added, the mixture was heated to 40°C for 1 5 to 30 minutes. Dilutions from this stock solution (if necessary) were made in 5% ethanol in water. All solutions were prepared 24 hours prior to use, and kept at room temperature.
  • Example 6 the procedure described in Example 6 was slightly modified (all methods and conditions were identical unless specified otherwise).
  • the starved cells were more susceptible to the antifungal action of PS than were the energised cells.
  • 250 mg/l PS proved to be as effective in killing the starved cells as 500 mg/l.
  • the lag phase is presumably due to the presence of endogenous energy stores of the cells, and this again shows that PS is particularly effective towards the starved condition.
  • Staphylococcus aureus ATCC 14458 was prepared similarly to the procedure described in Example 6 (BHI medium (Difco), incubation at 37°C).
  • agar plates for the diffusion test 300 ml of BHI medium, with 1 % agar and 1 5 % glycerol added, was molten and cooled to 50°C. Then 6 ml of a sterile glucose solution (50% w/v) and 6 ml of the overnight culture of the micro-organism were added. Petri dishes were filled with 1 2.5 ml of this agar medium, and the medium was allowed to solidify.
  • test formulations were prepared as indicated in Figure 6, with a lipid phase of octyl dodecyl lactate. They contained 1 , 2 or 5 g/l PS.
  • a stainless steel ring (6 mm internal diameter) was put into an empty, sterile Petri dish. Inside this ring, 2 paper disks (6 mm diameter) were placed to cover the bottom, and 50 ⁇ of the test formulation was applied to the filter disks.
  • the rings were put on the surface of the agar plates containing the micro-organisms, the agar plates were stored at 5°C for the periods indicated in the Table to allow diffusion of the test solutions, after which the rings were removed. Subsequently, the agar plates were incubated at a temperature suitable for the growth of the micro-organisms (37°C).
  • phytosphingosine had an improved solubility in aqueous systems. This prompted us to compare their antimicrobial activity to that of PS itself.
  • the following derivatives were investigated: the glycolic acid, lactic acid and hydrochloric acid salts of phytosphingosine. Stock solutions of the phytosphingosine salts were prepared as described in Example 6 for phytosphingosine, and the same experimental conditions were used.
  • Staphylococcus aureus ATCC 14458 and Escherichia coli 421 were used: Staphylococcus aureus ATCC 14458 and Escherichia coli 421 . All incubations were performed at 37°C. Both bacteria were grown as described in Example 8, 50 ⁇ culture was harvested by centrifugation, washed with 1 ml sterile demineralised water, and resuspended in 0.5 ml sterile demineralised water.
  • a 10 mg/ml stock solution of PS was prepared as described previously. Dilutions from this stock solution (if necessary) were made in 5% ethanol in water. All solutions were prepared 24 hours prior to use, and kept at room temperature. The antibacterial effect of phytosphingosine against these two bacteria was investigated using the LIVE/DEAD ® Bac ⁇ ghtTM Bacterial Viability Kit L-701 2 (Molecular Probes Inc., Oregon, USA). This kit employs two different fluorescent stains, SYTO 9 stain and propidium iodide, to make distinction between living and dead cells, which can be observed using a fluorescence microscope with the appropriate filters.
  • the solutions of the dyes provided in the kit were mixed 1 : 1 just before use, and 1 .5 ⁇ of this fluorescent dye mixture was added to 0.5 ml bacterial suspension. Subsequently, 50 ⁇ of an appropriate dilution of the phytosphingosine stock solution were added, to obtain the final concentrations indicated in Figure 5. After mixing, these suspensions were incubated, and the fraction of living and dead cells were followed over time.
  • the microscopic examinations were performed using an Olympus BHB fluorescence microscope, with the following filter set: dichroic mirror blue (B), excitation filter IF490, emission filter O530 (living cells are green, dead cells are orange/yellow).
  • filter set dichroic mirror blue (B), excitation filter IF490, emission filter O530 (living cells are green, dead cells are orange/yellow).
  • the E. coli cells were also killed quite effectively, and in this organism the dead cells could be quantified readily (Figure 5). It appears that the cells are ⁇ o killed by PS in a dose-dependent manner, and that the bacteria are more sensitive to this compound than are the fungi.
  • Example 6 An overnight culture of the indicated test organisms was prepared as described in Example 6 and 8, and the samples were applied to the test plates as described in Example 8. The samples were prepared as the appropriate dilutions from stock solutions, prepared as described previously. The agar plates
  • the agar plates were incubated at a temperature suitable for the growth of the micro-organisms (37 °C). After the micro-organisms were fully grown in the non-inhibited areas of the agar plates, the degree of inhibition was measured as the zone of no growth

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Biophysics (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Molecular Biology (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne des dérivés à base sphingoïde qui sont des sels d'une base sphingoïde. Ces sels ont une solubilité sensiblement accrue dans un environnement aqueux et présentent une meilleure efficacité dans compositions à usage topique.
EP00907673A 1999-03-09 2000-03-09 Derives a base sphingoide et leurs utilisations Withdrawn EP1159256A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP00907673A EP1159256A1 (fr) 1999-03-09 2000-03-09 Derives a base sphingoide et leurs utilisations

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP99200700 1999-03-09
EP99200700 1999-03-09
PCT/EP2000/002191 WO2000053568A1 (fr) 1999-03-09 2000-03-09 Derives a base sphingoide et leurs utilisations
EP00907673A EP1159256A1 (fr) 1999-03-09 2000-03-09 Derives a base sphingoide et leurs utilisations

Publications (1)

Publication Number Publication Date
EP1159256A1 true EP1159256A1 (fr) 2001-12-05

Family

ID=8239966

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00907673A Withdrawn EP1159256A1 (fr) 1999-03-09 2000-03-09 Derives a base sphingoide et leurs utilisations

Country Status (6)

Country Link
EP (1) EP1159256A1 (fr)
JP (1) JP2002539110A (fr)
KR (1) KR20010108331A (fr)
CN (1) CN1360567A (fr)
BR (1) BR0009265A (fr)
WO (1) WO2000053568A1 (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002060405A1 (fr) * 2001-01-29 2002-08-08 Cosmoferm B.V. Composition dermatologique veterinaire contenant une base sphingoide et/ou un derive de base sphingoide
EP1287815A1 (fr) * 2001-08-31 2003-03-05 Cosmoferm B.V. Utilisation d'une base sphingoide pour inhiber l'activité de la céramidase
EP1291340B1 (fr) * 2001-09-05 2006-03-15 Charmzone Co., Ltd Dérivés de phytosphingosine avec une activité antitumorale
FR2836630B1 (fr) * 2002-03-01 2004-07-09 Lvmh Rech Utilisation cosmetique de la phytosphingosine comme agent amincissant et compositions cosmetiques contenant de la phytosphingosine
CA2482784A1 (fr) * 2002-05-02 2003-11-13 Ui-Chan Koh Composition permettant de traiter le cancer comprenant n,n-dimethylphytosphingosine
DE10255554A1 (de) 2002-11-28 2004-06-17 Goldschmidt Ag Emulgator-Wachs-Gele auf Wasserbasis
FR2855049B1 (fr) * 2003-05-19 2006-07-21 Oreal Composition comprenant un precurseur de ceramide a base 6-hydroxy-sphingenine et un activeur de la voie des 6-hydroxylases, utilisation pour renforcer la fonction barriere de la peau
FR2855048B1 (fr) * 2003-05-19 2006-07-21 Oreal Composition comprenant un precurseur de ceramide a base phytosphingosine et un activeur de la voie des 4-hydroxylases, utilisation pour renforcer la fonction barriere de la peau
KR101288776B1 (ko) 2011-12-07 2013-07-22 가톨릭대학교 산학협력단 신규한 피토스핑고신 유도체 및 이를 포함하는 염증성 피부질환과 피부과다각화증질환 예방 및 개선용 화장료 조성물
WO2017176246A1 (fr) * 2016-04-04 2017-10-12 Ocusoft, Inc. Compositions, trousses et procédés pour maintenir l'hygiène des paupières
WO2024201287A1 (fr) 2023-03-27 2024-10-03 Cataya Bio (Shanghai) Co. Production de sels de bases sphingoïdes

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1235162B (it) * 1988-12-02 1992-06-22 Fidia Farmaceutici Derivati di lisosfingolipidi
US5190876A (en) * 1988-12-27 1993-03-02 Emory University Method of modifying cellular differentiation and function and compositions therefor
WO1993020038A1 (fr) * 1992-04-03 1993-10-14 Gist-Brocades N.V. N-acylation selective d'amino-alcools
DE69419601T2 (de) * 1993-03-17 1999-12-02 Kao Corp., Tokio/Tokyo Aminderivate und sie enthaltende dermatologische zubereitungen
GB2323594A (en) * 1997-03-25 1998-09-30 Victor Martin 2-amino-alkanoic acid derivatives, 2-amino alcohols and diamines
BR9804872A (pt) * 1997-05-02 1999-08-24 Gist Brocades Bv Composi-{es antimicrobianas para uso tÄpico

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0053568A1 *

Also Published As

Publication number Publication date
CN1360567A (zh) 2002-07-24
KR20010108331A (ko) 2001-12-07
WO2000053568A1 (fr) 2000-09-14
JP2002539110A (ja) 2002-11-19
BR0009265A (pt) 2001-11-20

Similar Documents

Publication Publication Date Title
EP0749960B1 (fr) Procede de synthese de tensioactifs cationiques derives de la condensation d'acides gras avec des aminoacides dibasiques esterifies
KR100541271B1 (ko) 국소적 사용을 위한 항균조성물
JP3533218B2 (ja) 不飽和脂肪族ジカルボン酸
WO2000053568A1 (fr) Derives a base sphingoide et leurs utilisations
EP2283143B1 (fr) Procédé de production de sphingolipides par n-acylation de lysosphingolipids en utilisant une lipase fongique
EP0049858A2 (fr) Procédé pour la préparation de dérivés de la désoxy-1 nojirimycine N-substitués
DE60221126T2 (de) Verbessertes verfahren zum nachweis und zur identifizierung eines eine infektion verursachenden mikroorganismus
Sawer et al. The effect of cryptolepine on the morphology and survival of Escherichia coli, Candida albicans and Saccharomyces cerevisiae
JP2024532812A (ja) 毛髪処置のための組成物、製剤および方法
Lukáč et al. Synthesis and antimicrobial activity of a series of optically active quaternary ammonium salts derived from phenylalanine
CA1231046A (fr) Composition renfermant de l'imidazolidinyluree et des parabens
US3934029A (en) Certain aminimides used to control bacteria and fungi
EP3349744A1 (fr) Sulfolipides utilisés comme nouveaux inhibiteurs de la glutaminyl cyclase
EP1892236B9 (fr) Iodures d'éster d'acides gras de diméthylaminoéthanol dotés d'une activité bactériostatique, mycostatique, levurostatique et/ou microbicide pour une utilisation dans des formulations de nettoyage ou de purification
CN115227592B (zh) 抑菌剂组合物及其应用
CN114044803B (zh) 一种乙酰基六肽-1衍生物及其应用
CN107982256A (zh) 2-氨基咪唑衍生物在制备抑制细菌生物膜活性药物中的用途
JPH04187618A (ja) 皮膚外用剤
JP3262780B2 (ja) フィトスフィンゴシン水溶液、その製造方法及び使用方法
DE69810906T2 (de) Optisch aktive 2-amino-tetraline, verfahren zu ihrer herstellung und pharmazeutische zusammensetzungen die diese enthalten und die nützlich sind zur vorbeugung und behandlung von septischem schock
CN117567270B (zh) 一种醇胺-壬二酸超分子离子盐及其制备和应用
RU2259369C2 (ru) 5-арил-1-фенил-4-гетероил-3-гидрокси-3-пирролин-2-оны, проявляющие противомикробную активность
CN112889835B (zh) 新的食品防腐剂及其制备方法和应用
US20240082125A1 (en) Use of a short chain fatty acid as antidandruff agent
CN115089504A (zh) 新的化妆品组合物及其制备方法和应用

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20010922

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

17Q First examination report despatched

Effective date: 20021126

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

18W Application withdrawn

Effective date: 20021231