CN105073092A - Combination of alkylamidothiazoles and cyclodextrins - Google Patents
Combination of alkylamidothiazoles and cyclodextrins Download PDFInfo
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- CN105073092A CN105073092A CN201480013608.6A CN201480013608A CN105073092A CN 105073092 A CN105073092 A CN 105073092A CN 201480013608 A CN201480013608 A CN 201480013608A CN 105073092 A CN105073092 A CN 105073092A
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
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- A61K8/738—Cyclodextrins
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- A—HUMAN NECESSITIES
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- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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Abstract
The invention relates to active ingredient combinations consisting of alkylamidothiazoles and one or more cyclodextrins.
Description
Technical field
The present invention relates to the active ingredient combinations be made up of N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) isobutyramide and one or more cyclodextrin.The present invention and then the beauty treatment related to certain this type of active ingredient combinations of content and dermatological preparation, and it is for the purposes of blast human skin.
Background technology
Melanocyte is responsible for the pigmentation of skin, described melanocyte in epidermis orlop (basal layer), basal cell other as depending on the isolated ground of skin type or with frequency appearance more or less, the cell of formation pigment and existing.
Melanocyte contains the melanosome as characteristic cell device, forms melanin wherein.In addition, when being stimulated by ultraviolet radiation, melanin is defined with strengthening.Melanin is finally transferred to horny layer (horn cell) by the living cells layer (keratinocyte) of epidermis, and causes obvious brown to memnonious skin color more or less.
Melanin is formed as the end-product of oxidizing process, in described oxidizing process, tyrosine under the assistance of tryrosinase by multiple converted for being converted into rubescent brown-black element under brown to memnonious eumelanin (DHICA (dihydroxy indole carboxylic acid)-melanin and DHI (dihydroxy indole)-melanin) or the participation at sulfur-containing compound.DHICA-melanin and DHI-melanin are produced by common intermediate DOPA quinone and dopachrome.Dopachrome is partly converted into indole-5,6-quinones-carboxylic acid or indole-5,6-quinone in the presence of other enzymes, thus, produces described two kinds of eumelanins.
Pheomelanins is generated by intermediate product DOPA quinone and cysteinyl-DOPA in addition.The expression of melanin synthesis enzyme is controlled by idiosyncratic transcription factor (microphthalmia associated transcription factor, MITF).Except the enzymatic processes of described B16 cell, in melanosome, other protein are also important for B16 cell.So-called p-protein seems to have important function at this, and wherein, exact function is still not clear.
Except the process of B16 cell in above-described melanocyte, during cutaneous pigmentation melanosome transfer, its residual in epidermis and decompose and also have melanic decomposition all significant.Can confirm, PAR-2-receptor is important (people such as M.Seiberg, 2000, J.Cell.Sci., 113:3093-101) for melanosome from melanocyte is transferred to keratinocyte.
In addition, the size and dimension of melanosome affects its light scatter properties and therefore cutaneous color appearance.Therefore, for the situation of Black African, find great self-existent spherical melanosome, and for white situation, the found out that less melanosome occurred with group.
The problem that skin pigment is excessively calm has many reasons, and be the concomitant symptom of many biological processes, such as ultraviolet radiation (such as sunburn, freckle), genetic predisposition, skin Wound healing or healing time abnormal pigmentation (after inflammation hyperpigmentation) or skin aging time abnormal pigmentation (such as senile plaque).
After inflammatory reaction, the pigmentary system of skin reacts, and is attended by the reaction that part resists mutually.This both can cause hyperpigmentation after inflammation, also can cause hypopigmentation.After inflammation, albinism often occurs with specific reaction, lupus erythematosus and psoriasis.The differential responses form of pigmentary system after inflammatory phenomena of human skin is completely understood not yet.
After inflammation, the problem of hyperpigmentation often comes across more dark skin type.Especially, be known for the problem of pseudofolliculitis barbae male coloured race, this problem with or cause the less desirable abnormal pigmentation in beauty treatment aspect.Hyperpigmentation after the form (producing in Asia women face and breast cervical region especially) of chloasma and the various forms of anomalous pigmentation of skin also belong to inflammation.In addition, black eye are also regarded as hyperpigmentation after a kind of inflammation of form, and wherein, potential inflammation occurs in subclinical mode usually.
In many cases, after this inflammation, abnormal pigmentation is strengthened by the effect of sunlight (ultraviolet), but the inflammation (sunburn) that ultraviolet can not be caused to cause.
Effective ingredient and the preparation of opposing cutaneous pigmentation are known.Be the ingredients based on hydroquinone substantially in practical application, this ingredients just demonstrates its effect in several weeks after application on the one hand, and on the other hand, it is worrying for toxicity reason that this ingredients crosses application for a long time.The people such as AlbertKligman have developed so-called " Triformula (three-in-one prescription) ", it shows as the combination (A.Kligman of 0.1% retinoic acid, 5.0% hydroquinone, 0.1% dexamethasone, 1975, Arch.Dermatol., 111:40-48).But described formula has dispute owing to may cause irreversible change in dermal pigmentary system.
In addition, use removes seed-skin method (chemistry with " peeling/Exfoliating Scrub (Peeling) " of mechanics), but remove seed-skin method and be usually attended by inflammatory reaction, and even can cause more serious pigmentation (but not the pigmentation reduced) due to hyperpigmentation after the inflammation that occurs subsequently.The feature of all these common methods (it is also for the treatment of hyperpigmentation after inflammation) is serious side effect.
In addition known various other, the material described with bright skin effect.What will list especially at this is, hexadecene-1,16-dicarboxylic acids, kojic acid and derivant thereof, arbutin, ascorbic acid and derivant, flavonoid, ellagic acid and derivant thereof, tranamic acid and different resorcinol derivatives, such as Lucin, 4-n-hexyl resorcinol and 4-(1-phenethyl) benzene-1,3-glycol.
J.M.Ready delivers in document (Bioorganic & MedicinalChemistryLetter17 (2007) 6871) at one and describes the thiazole that is particularly the substituted inhibitory action for Mushroom Tyrosinase.
In the patent application (WO2009099195) of Shiseido company, describe the thiazole amine be substituted for bright skin or hydrogenation thiazole amine.
Material described in above prior art shows medium effectiveness.
Black eye may produce as the result of pigmentation disorder equally, wherein, black eye also corresponding to general pressure, such as not enough sleep or merely manifested by the overtired of eyes.For younger people, after the nighttime sleep of abundance, symptom disappears again, but after long period of time, situation can transfer to chronic and become for the people related to and perplex very much.Manifest for this skin and also lack enough promising active substance and process probability.
Summary of the invention
The object of following invention is to remedy for defective prior art provides.
Another object of the present invention is to, provide the active component containing this type of material, active ingredient combinations and preparation, it discharges active component especially well from preparation.
This object is resolved by the active ingredient combinations be made up of one or more alkylamidoalkyl thiazoles and one or more cyclodextrin.
Favourable implementation of the present invention is also beauty treatment aspect with certain content this kind of active ingredient combinations and dermatological preparation, and it is for the purposes of blast human skin.
Cyclodextrin (cyclic linear starch (Cycloamylosen), ring-type glucosan (Cycloglucane)) is known in beauty treatment and in the middle of pharmacopedics.These materials are through being often used as " molecular capsule ", that is the protectiveness inclusion enclave to sensitive molecule.Do not relate to proper capsule (kernel/inclusion enclave) at this, and relate to the clathrate with nonpolar organic compound.This complex usually has better water solublity or makes described material stabilisation.
Relate to the glucose unit of 6,7,8 or more α-Isosorbide-5-Nitrae-connection at this, wherein, the feature of hexamethylene amylose (alpha-cyclodextrin) is following structure:
The feature of cycloheptaamylose (beta-schardinger dextrin-) is following structure:
The feature of the pungent amylose of ring (gamma-cyclodextrin) is following structure:
The feature of ring amylose in the ninth of the ten Heavenly Stems (Cycloenneaamylose) (δ-cyclodextrin) is following structure:
In the meaning of this patent, adopt polarity and nonpolar the cyclodextrin replaced.For this reason preferably including but not limited to methyl-, ethyl-and hydroxypropyl-cyclodextrin.
Advantageously, preparation according to the present invention contains one or more cyclodextrin, wherein, this cyclodextrin be 0.1 to 10.0 % by weight, preferably 0.5 to 5.0 % by weight, particularly preferably 1.0 to 3.0 % by weight.
Particularly advantageously according to preparation of the present invention or purposes, it is characterized in that, said preparation have based on described total formulation weight amount 0.000001 to 10 % by weight, particularly 0.0001 to 3 % by weight, particularly 0.001 to 1 % by weight one or more alkylamidoalkyl thiazoles.
In the sense of the present invention, favourable alkylamidoalkyl thiazole is the material of following general formula:
Wherein, R
1, R
2, X, Y can be different, part identical or identical, and can to represent independently of one another:
R
1=-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24thiazolinyl-(straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
8-cycloalkyl-alkyl hydroxy ,-C
1-C
24alkyl hydroxy (straight chain and side chain) ,-C
1-C
24-alkylamine (straight chain and side chain) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-alkylaryl-alkyl-hydroxyl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain) ,-C
1-C
24-alkyl-O-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-alkyl-morpholinyl ,-C
1-C
24-alkyl-piperidinyl ,-C
1-C
24-alkyl-piperazinyl ,-C
1-C
24-alkyl-piperazinyl-N-alkyl,
R
2=H ,-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
24-hydroxy alkyl (straight chain and side chain) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain),
X=-H ,-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl, C
1-C
24-aryl is (optionally by-OH ,-F ,-Cl ,-Br ,-I ,-O ,-Me ,-NH
2,-CN single or repeatedly replace) ,-C
1-C
24-heteroaryl is (optionally by-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN single or repeatedly replace) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain) ,-aryl are (optionally by-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN single or repeatedly replace) ,-phenyl ,-2,4-dihydroxy phenyls ,-2,3-dihydroxy phenyls ,-2,4-Dimethoxyphenyls ,-2,3-Dimethoxyphenyls,
Y=H ,-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
24-aryl ,-C
1-C
24-heteroaryl ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain) ,-aryl ,-phenyl ,-2,4-dihydroxy phenyl ,-2,3-dihydroxy phenyls ,-2,4-Dimethoxyphenyls ,-2,3-Dimethoxyphenyl ,-COO-alkyl ,-COO-thiazolinyl ,-COO-cycloalkyl ,-COO-aryl ,-COO-heteroaryl
And X, Y can also optionally=condensed ring aromatics,
Wherein X, Y can with form fragrance each other or the homoatomic ring of aliphatic series or heteroaryl ring system, it has n ring member nitrogen atoms at the most, and wherein digital n can get the value of 5-8, and each loop systems subsequently can by n-1 alkyl group, oh group, carboxylic group, amino group, nitrile functionality, sulfur-bearing substituent group, ester group and/or ether group replace at the most.
The alkylamidoalkyl thiazole addressed both can exist as free alkali and also can exist as salt: such as, as fluoride, bromide, iodide, sulfate, carbonate, Ascorbate, acetate or phosphate.Particularly as haloid, as such as chloride and bromide.
In addition, favourable implementation of the present invention is beauty treatment and dermatological preparation, and it is with one or more aforesaid alkylamidoalkyl thiazoles of certain effective content.
In addition, according to the present invention, the purposes of aforesaid alkyl amide thiazole be for the treatment of and/or prevent the pigmentation of unexpected skin.
At this, process and/or prevent undesired cutaneous pigmentation can be not only in beauty treatment category, and can be in pharmacy category.
In this respect, pharmacy (or Dermatology) process be mainly understood to for be affected skin situation, in contrast, process and/or prevent undesired cutaneous pigmentation to relate generally to healthy skin in beauty treatment.
Advantageously, X is selected from the group of the phenyl be substituted, and wherein, substituent group (Z) can be selected from-H ,-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN, acetyl group and can be identical or different.
Particularly advantageously, X is selected from the group of the phenyl group replaced with one or more oh group, and wherein, substituent group (Z) can be selected from-H ,-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN, acetyl group, and following formula is preferred, wherein, Y, R
1, R
2the characteristic defined above can be had.
Particularly advantageously those compounds, wherein:
Y＝H
R
1=-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl, C
1-C
8-cycloalkyl-alkyl hydroxy ,-C
1-C
24alkyl hydroxy (straight chain and side chain) ,-C
1-C
24alkylamine (straight chain and side chain) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-alkyl-aryl-alkyl-hydroxyl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain) ,-C
1-C
24-alkyl-O-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24alkyl-morpholinyl ,-C
1-C
24alkyl-piperidinyl ,-C
1-C
24alkyl-piperazinyl ,-C
1-C
24alkyl-piperazinyl-N-alkyl,
R
2=H ,-C
1-C
24-alkyl (straight chain and side chain),
Z=-H ,-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN, acetyl group.
Particularly preferably be those compounds, wherein:
Y＝H
R
1=-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
8-cycloalkyl-alkyl hydroxy ,-C
1-C
24alkyl hydroxy (straight chain and side chain) ,-C
1-C
24alkylamine (straight chain and side chain) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-alkyl-aryl-alkyl-hydroxyl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain) ,-C
1-C
24-alkyl-O-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24alkyl-morpholinyl ,-C
1-C
24alkyl-piperidinyl ,-C
1-C
24alkyl-piperazinyl ,-C
1-C
24alkyl-piperazinyl-N-alkyl,
R
2＝H。
According to the preferred following compound of the present invention:
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) pivaloyl amine
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) isobutyramide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) butyramide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) heptamide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-6-hydroxyl hexanamide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-3-hydroxypropanamide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-2-methoxyl acetamide
3-amino-N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) propionic acid amide.
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) acetamide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-4-(methylol) cyclohexanecarbonyl amine
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) cyclohexanecarbonyl amine, and
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-2-(4-(methylol) phenyl) acetamide.
Surprisingly, can show, the according to the present invention alkylamidoalkyl thiazole combined with cyclodextrin according to the present invention has the release of improvement.
Detailed description of the invention
The method explanation of release experiment
This external model for assessment of active component from the release in the middle of cosmetic base.Detect for this bioavailability, Beiersdorf limited company uses the Franz pond (Franz-zelle) through revising.
Consisting of of measurement device: donor chamber (detecting medium (product) to be positioned at wherein), receptor cavity (receptor fluid is positioned at wherein).Two chambeies are separated by permeable membrane.Relate at this commercial filtration film be made up of NC Nitroncellulose, it is with the aperture (MiliporeVSWP04700) of 0.025 μm.In order to carry out the kinetic determination discharged, sample from receptor cavity with fixed time interval.The amount of the active component in the middle of from product diffusion to receptor fluid is determined with common analytical method.
Release: [percentage ratio of the detected components used]
Meansigma methods/receptor the phase of triplicate: the ethanol of 25%
The composition rule of the exemplary alkylamidoalkyl thiazole selected:
2-bromo-2 ', 4 '-bi-methoxy ketonic oxygen base-1-Phenylethanone.:
Mitchell,David；Doecke,ChristopherW.；Hay,Lynne.；Koenig,ThomasM.；Wirth,DavidD.TetrahedronLetters,1995
60g (369mmol) 2,4-dihydroxyacetophenone in 900ml oxolane and the solution of 186ml triethylamine are cooled to 0 DEG C, and slowly instill the 93ml chlorine formic acid methyl ester in 400ml oxolane.Form white precipitate.After at room temperature stirring three hours, reaction terminates (DC (thin layer chromatography) contrast).Sucking-off precipitates and cleans with sufficient oxolane.Filtrate rotary evaporation is dry, insert in ethyl acetate, with 1NHCl and the washing of (saturated) NaCl solution, and through dried over mgso, filtered by magnesium sulfate, and concentrated ethyl acetate on the rotary evaporator.Obtain 2, the 4-bi-methoxy ketonic oxygen base-1-Phenylethanone .s of 105g.
1HNMR(DMSO-D
6):8.05(d,1H),7.38(d,1H),7.36(s,1H),3.86(d,6H)。Product without the need to using with purifying further.In 3 hours, in 2, the 4-pairs-methoxycarbonyl oxygen base-acetophenone solution of the 105g in chloroform (1000ml), drip 63g (392mmol) bromine in 450ml chloroform.After this, reaction is at room temperature stirred 15 minutes, rotary evaporation of solvent.In ethyl acetate/n-hexane, stir residue, sucking filtration goes out generated precipitation.From ethyl acetate/n-hexane, recrystallization obtains the 2-bromo-2 ' of 100g, 4 '-bi-methoxy ketonic oxygen base-1-Phenylethanone..
1hNMR (DMSO-D
6): 8.11 (d, 1H), 7.42 (m, 2H), 4.87 (s, 2H), 3.87 (s, 3H), 3.85 (s, 3H) ppm; Fusing point 73-74 DEG C.
n-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) pivaloyl amine
The thiourea of 126g (1.66mmol) is first joined in the middle of toluene (1000ml), and instills the pivaloyl chloride of 100g (829mmol).Reaction solution boiled under reflux 3 hours, wherein generates two phases.Decant goes out the phase on top and cools.The colorless needles that sucking filtration goes out to be settled out and with spicule described in cyclohexane, and dry in a vacuum.Output: 64g.
1HNMR(DMSO-D
6):10.27(s,1H),9.74(s,1H),9.40(s,1H),1.19(s,9H)ppm。
The 2-bromo-2 ' of 107.7g (310mmol), the N-pivaloyl thiourea of 4 '-bi-methoxy ketonic oxygen base-1-Phenylethanone. and 49.7g (13.6mmol) and the NaHCO of 39.2g (466mmol)
3seethe with excitement under reflux in 1.2 liters of ethanol 0.5 hour.This reaction solution is cooled and mixes in 250ml water with the NaOH of 50.6g (1.27mol).At room temperature stir after 30 minutes, reaction solution to be inserted in 300ml water and to neutralize with 2NHCl.The precipitation generated is then through filtration and by ethanol/water recrystallization.Obtain the thiazole of 80g.
1hNMR (DMSO-D
6): 11.77 (bs, 1H), 11.02 (bs, 1H), 9.47 (bs, 2H), 7.65 (d, 1H), 7.39 (s, 1H), 6.30 (s, 1H), 6.28 (d, 1H), 1.27 (s, 9H) ppm; Fusing point 257-259 DEG C.
n-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) isobutyramide
114g (1.5mol) thiourea is first joined in the middle of toluene (800ml), and instills the isobutyryl chloride of 80g (0.75mol).Reaction solution seethes with excitement 3 hours under reflux, wherein generates two phases.Decant goes out the phase on top and cools.The colorless needles that sucking filtration goes out to be settled out and clean described spicule with toluene, and dry in a vacuum.Output: 62g.
1HNMR(DMSO-D
6):11.03(bs,1H),9.66(bs,1H),9.35(bs,1H),2.72(m,1H),1.03(d,6H)ppm.。
The 2-bromo-2 ' of 89g (260mmol), the N-isobutyryl thiourea of 4 '-bi-methoxy ketonic oxygen base-1-Phenylethanone. and 37.5g (260mmol) and the NaHCO of 32g (380mmol)
3seethe with excitement under reflux in 1000ml ethanol 0.5 hour.This reaction solution is cooled and mixes in 250ml water with the NaOH of 41g (0.93mol).At room temperature stir after 30 minutes, reaction solution to be inserted in 300ml water and to be adjusted to pH=3 with 2NHCl.The precipitation generated is then through filtration and by ethanol/water recrystallization.Obtain the thiazole of 56g.
1hNMR (DMSO-D
6): 12.16 (bs, 1H), 10.88 (bs, 1H), 9.47 (bs, 1H), 7.65 (m, 1H), 7.41 (s, 1H), 6.32 (m, 2H), 2.75 (m, 1H), 1.14 (d, 6H) ppm; Fusing point 243-245 DEG C.
n-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) butyramide
143g (1.88mol) thiourea is first joined in the middle of toluene (1000ml), and instills the n-butyryl chloride of 100g (0.93mol).Reaction solution seethes with excitement 3 hours under reflux, wherein generates two phases.Decant goes out the phase on top and cools.Micro-yellow needles that sucking filtration goes out to be settled out and clean described spicule with toluene, and dry in a vacuum.Output: 88g.
1hNMR (DMSO-D
6): 11.03 (bs, 1H), 9.65 (bs, 1H), 9.33 (bs, 1H), 2.33 (t, 2H), 1.53 (m, 2H), 0.86 (t, 3H) ppm; Fusing point 115-188 DEG C.
The 2-bromo-2 ' of 92g (265mmol), the N-isobutyryl thiourea of 4 '-bi-methoxy ketonic oxygen base-1-Phenylethanone. and 38.75g (265mmol) and the NaHCO of 34g (397mmol)
3seethe with excitement 0.5 hour in 900ml ethanol under reflux.This reaction solution is cooled and mixes in 300ml water with the NaOH of 37g (0.93mol).After at room temperature stirring 30 minutes, receive reaction solution with 300ml water and neutralize with 2NHCl.Then the precipitation generated is filtered across and by ethanol/water recrystallization.Obtain the thiazole of 67g.
1hNMR (DMSO-D
6): 12.18 (bs, 1H), 10.89 (bs, 1H), 9.48 (bs, 1H), 7.65 (1 aromatics H), 7.40 (s, 1H), 6.31 (2 aromatics H), 2.43 (t, 2H), 1.64 (m, 2H), 0.91 (t, 3H) ppm; Fusing point 227-229 DEG C.
n-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) acetamide
The 2-bromo-2 ' of 4.71g (13.6mmol), the N-isobutyryl thiourea of 4 '-bi-methoxy ketonic oxygen base-1-Phenylethanone. and 1.61g (13.6mmol) and the NaHCO of 1.72g (20.4mmol)
3seethe with excitement 0.5 hour in 45ml ethanol under reflux.This reaction solution is cooled and mixes in 20ml water with the NaOH of 2.0g (50mmol).After stirring 20 minutes at 0 DEG C, receive reaction solution with 30ml water and the HCl neutralization concentrated with half.Then the precipitation generated is filtered across and by ethanol/water recrystallization.Obtain the product of 2.73g.
1hNMR (DMSO-D
6): 12.20 (b, 1H), 10.85 (s, 1H), 9.46 (s, 1H), 7.64 (m, 1H), 7.38 (s, 1H), 6.28 (m, 2H), 2.15 (s, 3H), ppm; Fusing point 264-264 DEG C.
n-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-4-(hydroxymethyl)) cyclohexanecarbonyl amine
Analogously carry out with document.
BANYU (universal) Pharmaceutical Co.EP2072519A1,2009
Productive rate: 96%.
1HNMR(DMSO-D
6):12.03(bs,1H),3.85,3.82(2×d,2H),2.50,2.47(2×m,1H),2.00(s,3H),0.95-1.90(m,9H),ppm；
95g (0.47mol) 4-ethoxyl methyl cyclohexanecarboxylic acid is placed in the middle of thionyl chloride (350ml), reflux 2 hours.After removing excessive thionyl chloride in a vacuum, residue is inserted in the middle of 1l toluene, and add 71g (0.94mol) thiourea.This reaction solution boils under reflux and boils 3 hours, and then heat filtering.After making mother solution cooling, sucking filtration goes out generated white crystals, with toluene rinse, and dry in a vacuum.Output: 59g.
1HNMR(DMSO-D
6):11.03,10.97(2×s,1H),9.64(bs,1H),9.35(bs,1H),3.82(2×d,2H),2.61,2.42(2×m,1H),2.00(s,3H),1.60(m,8H),1.35,0.94(2×m,1H)ppm；
The 2-bromo-2 ' of 79g (228mmol), N-(the 4-acetyl methoxycyclohexyl carbonyl) thiourea of 4 '-bi-methoxy ketonic oxygen base-1-Phenylethanone. and 59g (228mmol) and the NaHCO of 29g (340mmol)
3seethe with excitement 0.5 hour in ethanol (1000ml) under reflux.This reaction solution is cooled and mixes in 300ml water with the NaOH of 73g (1.8mol).After at room temperature stirring 30 minutes, reaction solution inserted 300ml water and be adjusted to pH=3 with 2NHCl.Then the precipitation generated is filtered across and by ethanol/water recrystallization.Obtain the thiazole of 47g.
1hNMR (DMSO-D
6): 12.15,12.10 (2 × s, 1H), 10.96 (2 × s, 1H), 9.47 (br, 2H), 7.64 (d, 1H), 7.39 (s, 1H), 6.29 (m, 2H), 4.40 (br, 1H), 3.32,3.23 (2 × d, 2H), 2.65,2.44 (2 × m, 1H), 1.90 (m, 1H), 1.78 (m, 2H), 1.50 (m, 5H), 0.94 (m, 1H) ppm; Fusing point: 152 DEG C-160 DEG C.
n-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-cyclohexanecarbonyl amine
The thiourea of 52g (0.68mol) first to be joined in the middle of toluene (500ml) and to instill 50g (0.34mol) cyclohexanecarbonyl chloride.This reaction solution seethes with excitement 3 hours under reflux, wherein generates biphase.Decant goes out the phase on top and cools.The crystal that sucking filtration goes out to be settled out and with toluene cleaning, and in methanol recrystallization.Output: 35g.
1HNMR(DMSO-D
6):10.98(bs,1H),9.65(bs,1H),9.32(bs,1H),2.49(t,1H),1.75(m,4H),1.61(m,1H),1.18(m,5H),ppm；
The 2-bromo-2 ' of 92g (265mmol), the N-cyclohexanoyl thiourea of 4 '-bi-methoxy ketonic oxygen base-1-Phenylethanone. and 49.4g (265mmol) and the NaHCO of 34g (397mmol)
3seethe with excitement 0.5 hour in ethanol (900ml) under reflux.This reaction solution is cooled and mixes in 300ml water with 37g (930mmol) NaOH.At room temperature stir after 30 minutes, reaction solution to be inserted in 300ml water and is neutralized with 2NHCl.Remove ethanol as far as possible in a rotary evaporator.Then the precipitation generated is filtered across and by ethanol/water recrystallization.Obtain the thiazole of 70g.1HNMR (DMSO-D
6): 12.14 (bs, 1H), 11.00 (bs, 1H), 9.48 (bs, 1H), 7.64 (1arom, H), 7.39 (s, 1H), 6.30 (2arom, H), 2.49 (m, 1H), 1.84 (m, 2H), 1.76 (m, 2H), 1.65 (m, 1H), 1.42 (m, 2H), 1.25 (m, 3H), ppm; Fusing point 262-266 DEG C.
n-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-2-(4-(methylol) phenyl) acetamide
Analogously carry out with document.
BANYU Pharmaceutical Co.EP2072519A1,2009
Productive rate: 76%.
1HNMR(DMSO-D
6):12.31(bs,1H),7.26(m,4H),5.05(s,2H),3.57(s,2H),2.05(s,3H),ppm；
3.7g (18mmol) 4-acetoxy-methyl phenylacetic acid is placed in the middle of thionyl chloride (40ml), reflux 2 hours.After removing excessive thionyl chloride in a vacuum, residue is inserted in 70ml toluene, and add 2.7g (36mmol) thiourea.This reaction solution boils under reflux and boils 3 hours, and then removes solvent in a vacuum.Purify on silica gel by means of the cyclohexane/ethyl acetate of column chromatography by 1:1.Output: 2.7g.
1HNMR(DMSO-D
6):11.29(bs,1H),9.55(bs,1H),9.40(bs,1H),7.30(m,4H),5.04(s,2H),3.71(s,2H),2.05(s,3H),ppm；
The 2-bromo-2 ' of 3.5g (10mmol), N-[2-(the 4-acetoxy-methyl phenyl) acetyl group] thiourea of 4 '-bi-methoxy ketonic oxygen base-1-Phenylethanone. and 2.7g (10mmol) and the NaHCO of 1.3g (15mmol)
3seethe with excitement 0.5 hour in ethanol (50ml) under reflux.This reaction solution is cooled and mixes in 20ml water with 4.0g (0.1mol) NaOH.Stir after 2 hours at 60 DEG C, reaction solution to be inserted in 100ml water and is adjusted to pH=3 with 2NHCl.Then the precipitation generated is filtered across and by ethanol/water recrystallization.Obtain the thiazole of 1.3g.
1hNMR (DMSO-D
6): 12.44 (s, 1H), 10.80 (s, 1H), 9.48 (s, 1H), 7.66 (d, 1H), 7.41 (s, 1H), 7.29 (m, 4H), 6.32 (m, 2H), 5.13 (t, 1H), 4.47 (d, 2H), 3.77 (s, 2H) ppm; Fusing point 254-256 DEG C.
Particularly favourable, these preparations contain 0.000001 to 10 % by weight of gross weight based on said preparation, particularly 0.0001 to 3 % by weight, more especially 0.001 to 1 % by weight one or more according to alkylamidoalkyl thiazole used in the present invention.
Can exist in different forms according to beauty treatment aspect of the present invention and dermatological preparation.Thus it can be such as solution, anhydrous formulation, Emulsion or microemulsion (water-in-oil type W/O or oil-in-water type O/W), multiple Emulsion (such as W/O/W W/O/W type Emulsion), gel, solid bar, ointment or aerosol.
Feasible equally in the sense of the present invention and advantageously, be added to in the aqueous systems of cleaning skin and hair or surfactant formulations according to material used in the present invention and/or its derivant.
Can containing, for example the usual cosmetic additive used in this preparation according to beauty treatment of the present invention and dermatological preparation, the such as composition (as alcohols, polyhydric alcohol, polymer, foam stabiliser, electrolyte, organic solvent or silicone derivative) of antiseptic, antibacterial, spice, froth breaking material, dyestuff, the pigment with pigmentation, thickening agent, surfactant, emulsifying agent, softening, moistening and/or moisturizing materials, lipid, oils, wax class or other common beauty treatments or dermatological formulation.
Fat advantageously can be selected from the group of following substances mutually:
-mineral oil, mineral wax
-oils (as capric acid or sad triglyceride), and then also have natural oil (as such as Oleum Ricini)
The fat-body of-lipid, wax class and other natural and synthesis, the ester of the alcohol (such as with isopropyl alcohol, propylene glycol or glycerol) of preferred fatty acid and low carbon number, or the alkanoic acid of fatty alcohol and low carbon number or the ester with fatty acid
-alkyl esters
-silicone oil (as polydimethylsiloxane, diethyl polysiloxanes, diphenylpolysiloxane and their mixed form).
The oil phase of Emulsion, oleogel or aqueous dispersion or oil dispersion is advantageously selected from the group of following esters in the sense of the present invention: its alkane carboxylic acid being 3 to 30 C atoms by saturated and/or undersaturated, side chain and/or non-branched, chain length and saturated and/or undersaturated, side chain with non-branched, the group of ester that alcohol that chain length is 3 to 30 C atoms is formed; And by the group of aromatic carboxylic acids and saturated and/or that the alcohol with the chain length of 3 to 30 carbon atoms that is undersaturated, side chain and/or non-branched is formed ester.This kind of esters is preferably selected from following group: isopropyl myristate, isopropyl palmitate, isopropyl stearate, acid isopropyl, n-butyl stearate, the just own ester of lauric acid, oleic acid ester in the positive last of the ten Heavenly stems, Ethylhexyl stearate, stearic acid ester in the different ninth of the ten Heavenly Stems, isononyl isononanoate, Palmic acid 2-Octyl Nitrite, lauric acid 2-Octyl Nitrite, stearic acid 2-hexyl ester in the last of the ten Heavenly stems, Palmic acid 2-octyl group lauryl, Cetiol, oleyl erucate, oleic acid mustard ester, the synthesis of erucic acid mustard ester and these esters, semisynthetic and natural mixture (such as Jojoba oil).
According to the present invention particularly advantageously, adopt Emulsion form according to active ingredient combinations of the present invention, the ester that one or more parts of its monoglyceride and/or diglyceride of containing satisfied fatty acid and citric acid neutralize as emulsifying agent, particularly stearic acid citric acid glyceride, its with
the trade name of 372P is obtained by Sasol company.
According to the aqueous phase of preparation of the present invention optionally advantageously (always singly or in combination) containing wetting agent (as such as propylene glycol, pantothenylol or hyaluronic acid), and particularly one or more thickening agents, it is advantageously selected from following group: silicon dioxide, aluminium silicate, hypromellose, particularly advantageously polyacrylate (as such as 980 type carbomers), above-mentioned substance is respectively alone or in combination.
Particularly use the mixture of aforementioned solvents.When alcoholic solvent, another kind of component can be water.
Emulsion according to the present invention is favourable and containing such as addressed lipid, oils, wax class and other fat-body and water and the such as usual emulsifying agent used for such formula.
Usually under the existence of thickening agent, low carbon number alcohol is comprised according to gel of the present invention, such as ethanol, propylene glycol and water or the oil addressed above, this thickening agent is preferably silicon dioxide or aluminium silicate when oiliness alcogel, is preferably polyacrylate when aqueous alcoholic gel or alcogel.
As for according to of the present invention, the carminative of the preparation that can be sprayed by aerosol can is usually the propellant of known volatile, liquefaction, and such as Hydrocarbon (propane, butane, iso-butane), it uses individually or with being mixed with each other.Compressed air is used also to be favourable.
Advantageously containing in addition according to preparation of the present invention can at the material of UVB region absorption ultraviolet radiation; wherein the total content of ray filtering material is the gross weight of said preparation: such as 0.1 % by weight to 30 % by weight; preferably 0.5 to 10 % by weight; particularly 1.0 to 6.0 % by weight, the whole locality protection hair of ultraviolet radiation and the cosmetic formulation of skin can be provided in.It can also be used as the sunscreen of hair and skin.
In addition, can advantageously containing for antiseptical added substance according to preparation of the present invention, wherein the total amount of antiseptic is such as 0.001 to 30 % by weight of the gross weight based on said preparation, preferably 0.05 to 10 % by weight, be in particular 0.1 to 5.0 % by weight, to provide beauty treatment aspect preparation.
Following embodiment should illustrate the present invention, and does not cause restriction to it.The consumption of all explanations, share and percentage ratio share, as long as no separately adding explanation, are all based on the weight of said preparation, total amount or gross weight.
| 1 | 2 | |
| INCI title | % by weight | % by weight |
| Stearic acid citric acid glyceride | 1.5 | 1.5 |
| Cetearyl alcohol | 1 | 1 |
| Octyldodecanol | 1 | 1 |
| Myristyl alcohol myristinate | 1.5 | 1.5 |
| Cyclomethicone | 2 | 2 |
| Glycerol | 5 | 5 |
| Butanediol | 15 | 15 |
| PASELLI EASYGEL | 2 | 2 |
| W630 | 0.1 | 0.1 |
| HP-β-CD | - | 1.0 |
| Ethylhexyl methoxy cinnamate+BHT | 6 | 6 |
| PAROSOL 1789 | 1 | 1 |
| BP-3 | 2 | 2 |
| Methylisothiazolinone | 0.09 | 0.09 |
| Phenoxyethanol | 0.5 | 0.5 |
| Denatured ethyl alcohol | 3 | 3 |
| Water+EDTA trisodium | 1 | 1 |
| Carbomer | 0.4 | 0.4 |
| Sodium polyacrylate | 0.2 | 0.2 |
| Sodium hydroxide | 0.15 | 0.15 |
| Spice | 0.3 | 0.3 |
| Water | 56.26 | 55.26 |
Film method:
Lecithin is weighed dividually in three round flasks, and then with a small amount of dissolve with ethanol.This solvent is then removed on the rotary evaporator at the temperature improved a little (40 DEG C), thus lecithin leaves thin film on glass inner wall.Final solvent residues is removed by means of compressed air rinsing.The active ingredient solution of alkylamidoalkyl thiazole is distributed on flask equally, and shaking flasks, until film dissolves (but at least shaking 15 minutes) completely.Have employed two different methods that homogenize: carry out 5 minutes or carry out lasting 20 minutes ultrasonic at middle-grade use Ultraturrax.
[1] prepare by sol-gel process.Such as prepare with alkoxy silane; Picture is exemplarily described in EP1104287B1.
[2] exemplarily its preparation is described at US6932984B1.
Claims (15)
1. the active ingredient combinations be made up of one or more alkylamidoalkyl thiazoles and one or more cyclodextrin.
2. active ingredient combinations according to claim 1, is characterized in that, to select from one or more materials of following group as cyclodextrin:
Alpha-cyclodextrin,
Beta-schardinger dextrin-,
Gamma-cyclodextrin,
δ-cyclodextrin,
Methyl flamprop, ethyl cyclodextrin and hydroxypropyl cyclodextrin.
3. active ingredient combinations according to claim 1 and 2, is characterized in that, alkylamidoalkyl thiazole described in one or more is the material of following general formula:
Wherein, R
1, R
2, X, Y can be different, part identical or identical, and can to represent independently of one another:
R
1=-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24thiazolinyl-(straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
8-cycloalkyl-alkyl hydroxy ,-C
1-C
24alkyl hydroxy (straight chain and side chain) ,-C
1-C
24-alkylamine (straight chain and side chain) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-alkylaryl-alkyl-hydroxyl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain) ,-C
1-C
24-alkyl-O-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-alkyl-morpholinyl ,-C
1-C
24alkyl-piperidinyl ,-C
1-C
24alkyl-piperazinyl ,-C
1-C
24alkyl-piperazinyl-N-alkyl,
R
2=H ,-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
24-hydroxy alkyl (straight chain and side chain) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain),
X=-H ,-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
24-aryl is (optionally by-OH ,-F ,-Cl ,-Br ,-I ,-O ,-Me ,-NH
2,-CN single or repeatedly replace) ,-C
1-C
24-heteroaryl is (optionally by-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN single or repeatedly replace) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain) ,-aryl are (optionally by-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN single or repeatedly replace) ,-phenyl ,-2,4-dihydroxy phenyls ,-2,3-dihydroxy phenyls ,-2,4-Dimethoxyphenyls ,-2,3-Dimethoxyphenyls,
Y=H ,-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
24-aryl ,-C
1-C
24-heteroaryl ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain) ,-aryl ,-phenyl ,-2,4-dihydroxy phenyl ,-2,3-dihydroxy phenyls ,-2,4-Dimethoxyphenyls ,-2,3-Dimethoxyphenyl ,-COO-alkyl ,-COO-thiazolinyl ,-COO-cycloalkyl ,-COO-aryl ,-COO-heteroaryl
And X, Y can also optionally=condensed ring aromatics,
Wherein X, Y can with form fragrance each other or the homoatomic ring of aliphatic series or heteroaryl ring system, it has n ring member nitrogen atoms at the most, and wherein digital n can get the value of 5-8, and each loop systems subsequently can by n-1 alkyl group, oh group, carboxylic group, amino group, nitrile functionality, sulfur-bearing substituent group, ester group and/or ether group replace at the most
Wherein, one or more alkylamidoalkyl thiazoles described can exist as free alkali and as the salt that beauty treatment aspect and dermatological can use.
4. active ingredient combinations according to claim 3, is characterized in that, X is selected from the group of the phenyl group be substituted, and Y, R
1and R
2characteristic claimed in claim 3 can be had.
5. active ingredient combinations according to claim 3, is characterized in that, X is selected from the group of the phenyl group be substituted, and is particularly selected from the group of the material with following structure:
Wherein, substituent group (Z) can be selected from-H ,-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN, acetyl group and can be identical or different, and Y, R
1and R
2characteristic claimed in claim 3 can be had.
6. the active ingredient combinations according to any one of aforementioned claim, is characterized in that, one or more alkylamidoalkyl thiazoles described have following structure:
Wherein, substituent group (Z) can be selected from-H ,-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN, and Y, R
1and R
2characteristic claimed in claim 3 can be had.
7. the active ingredient combinations according to any one of aforementioned claim, is characterized in that, one or more alkylamidoalkyl thiazoles described have following structure:
X＝
Y＝H
R
1=-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
8-cycloalkyl-alkyl hydroxy ,-C
1-C
24alkyl hydroxy (straight chain and side chain) ,-C
1-C
24alkylamine (straight chain and side chain) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-alkylaryl-alkyl-hydroxyl (straight chain and side chain) ,-C
1-C
24miscellaneous alkyl aryl (straight chain and side chain) ,-C
1-C
24-alkyl-O-C1-C24-alkyl (straight chain and side chain) ,-C
1-C
24alkyl-morpholinyl ,-C
1-C
24alkyl-piperidinyl ,-C
1-C
24alkyl-piperazinyl ,-C
1-C
24alkyl-piperazinyl-N-alkyl,
R
2=H ,-C
1-C
24-alkyl (straight chain and side chain),
Z=-H ,-OH ,-F ,-Cl ,-Br ,-I ,-OMe ,-NH
2,-CN, acetyl group.
8. the active ingredient combinations according to any one of aforementioned claim, is characterized in that, one or more alkylamidoalkyl thiazoles described have following structure:
X＝
Y＝H
R
1=-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24-thiazolinyl (straight chain and side chain) ,-C
1-C
8-cycloalkyl ,-C
1-C
8-cycloalkyl-alkyl hydroxy ,-C
1-C
24alkyl hydroxy (straight chain and side chain) ,-C
1-C
24alkylamine (straight chain and side chain) ,-C
1-C
24-alkylaryl (straight chain and side chain) ,-C
1-C
24-alkylaryl-alkyl-hydroxyl (straight chain and side chain) ,-C
1-C
24-miscellaneous alkyl aryl (straight chain and side chain) ,-C
1-C
24-alkyl-O-C
1-C
24-alkyl (straight chain and side chain) ,-C
1-C
24alkyl-morpholinyl ,-C
1-C
24alkyl-piperidinyl ,-C
1-C
24alkyl-piperazinyl ,-C
1-C
24alkyl-piperazinyl-N-alkyl,
R
2＝H。
9. the active ingredient combinations according to any one of aforementioned claim, is characterized in that, one or more alkylamidoalkyl thiazoles described have following structure:
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) pivaloyl amine
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) isobutyramide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) butyramide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) heptamide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-6-hydroxyl hexanamide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-3-hydroxypropanamide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-2-methoxyl acetamide
3-amino-N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) propionic acid amide.
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) acetamide
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-4-(methylol) cyclohexanecarbonyl amine
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl) cyclohexanecarbonyl amine
And
N-(4-(2,4-dihydroxy phenyl) thiazol-2-yl)-2-(4-(methylol) phenyl) acetamide.
10. the active ingredient combinations according to any one of aforementioned claim, is characterized in that, one or more alkylamidoalkyl thiazoles described can exist as halogenide, carbonate, Ascorbate, sulfate, acetate and/or phosphate.
11. 1 kinds of beauty treatments or dermatological preparation, its have certain content, active ingredient combinations according to any one of aforementioned claim.
12. preparations according to claim 11, it is characterized in that, described preparation contain based on described total formulation weight amount 0.000001 to 10 % by weight, particularly 0.0001 to 3 % by weight, more especially 0.001 to 1 % by weight one or more alkylamidoalkyl thiazoles.
13. preparations according to claim 11, is characterized in that, the total amount of one or more cyclodextrin is based on described total formulation weight amount 0.00001 to 10 % by weight, preferably 0.001 to 5 % by weight, particularly 0.005 to 3 % by weight.
The non-therapeutic beautifying use for blast human skin of 14. preparations according to any one of aforementioned claim or active ingredient combinations.
15. active ingredient combinations according to any one of aforementioned claim and preparation, its being used for the treatment of property blast human skin.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102013204110.1 | 2013-03-11 | ||
| DE102013204110.1A DE102013204110A1 (en) | 2013-03-11 | 2013-03-11 | Active ingredient combinations of alkylamidothiazoles and one or more cyclodextrins |
| PCT/EP2014/052614 WO2014139741A1 (en) | 2013-03-11 | 2014-02-11 | Combinations of alkylamidothiazoles and cyclodextrins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105073092A true CN105073092A (en) | 2015-11-18 |
Family
ID=50489056
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480013608.6A Pending CN105073092A (en) | 2013-03-11 | 2014-02-11 | Combination of alkylamidothiazoles and cyclodextrins |
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| Country | Link |
|---|---|
| EP (1) | EP2968104A1 (en) |
| CN (1) | CN105073092A (en) |
| DE (1) | DE102013204110A1 (en) |
| WO (1) | WO2014139741A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105828798A (en) * | 2013-12-19 | 2016-08-03 | 拜尔斯道夫股份有限公司 | Use of alkylamidothiazoles in cosmetic or dermatological preparations for the prevention and treatment of sensitive skin |
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| DE102013204088A1 (en) * | 2013-03-11 | 2014-09-11 | Beiersdorf Ag | Active ingredient combinations of alkylamidothiazoles and one or more cosmetically or dermatologically relevant fragrances |
| DE102017201050A1 (en) * | 2017-01-24 | 2018-07-26 | Beiersdorf Ag | Active substance combinations of trans-4-t-butylcyclohexanol and one or more alkylamidothiazoles and cosmetic or dermatological preparations containing these active substance combinations |
| DE202018004125U1 (en) | 2018-09-05 | 2018-10-11 | Beiersdorf Ag | Alkylamidothiazoles in polypropylene-containing packaging |
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| CN101953755A (en) * | 2005-07-29 | 2011-01-26 | 株式会社资生堂 | The tension force of hair and toughness improving agent and hair-dressing cosmetics |
| US20130039870A1 (en) * | 2010-03-23 | 2013-02-14 | Beiersdorf Ag | Cosmetic Or Dermatological Preparations With A Content Of One Or More Thiazole Derivates |
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| JPS61109705A (en) * | 1984-11-01 | 1986-05-28 | Sansho Seiyaku Kk | Whitening cosmetics |
| WO2000009652A2 (en) | 1998-08-13 | 2000-02-24 | Sol-Gel Technologies Ltd. | Method for the preparation of oxide microcapsules loaded with functional molecules and the products obtained thereof |
| GB2356386A (en) | 1999-11-17 | 2001-05-23 | Tagra Biotechnologies Ltd | Microencapsulation |
| JPWO2008038692A1 (en) | 2006-09-28 | 2010-01-28 | 萬有製薬株式会社 | Diaryl ketimine derivatives |
| RU2434634C1 (en) | 2008-02-08 | 2011-11-27 | Шисейдо Компани Лтд. | Bleaching agent and composition for skin for external application |
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2013
- 2013-03-11 DE DE102013204110.1A patent/DE102013204110A1/en not_active Withdrawn
-
2014
- 2014-02-11 EP EP14717675.4A patent/EP2968104A1/en not_active Withdrawn
- 2014-02-11 WO PCT/EP2014/052614 patent/WO2014139741A1/en active Application Filing
- 2014-02-11 CN CN201480013608.6A patent/CN105073092A/en active Pending
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| EP1941863A2 (en) * | 2002-07-25 | 2008-07-09 | Lion Corporation | External preparation composition |
| CN101953755A (en) * | 2005-07-29 | 2011-01-26 | 株式会社资生堂 | The tension force of hair and toughness improving agent and hair-dressing cosmetics |
| US20130039870A1 (en) * | 2010-03-23 | 2013-02-14 | Beiersdorf Ag | Cosmetic Or Dermatological Preparations With A Content Of One Or More Thiazole Derivates |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105828798A (en) * | 2013-12-19 | 2016-08-03 | 拜尔斯道夫股份有限公司 | Use of alkylamidothiazoles in cosmetic or dermatological preparations for the prevention and treatment of sensitive skin |
Also Published As
| Publication number | Publication date |
|---|---|
| DE102013204110A1 (en) | 2014-09-25 |
| EP2968104A1 (en) | 2016-01-20 |
| WO2014139741A1 (en) | 2014-09-18 |
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Application publication date: 20151118 |