CN115969729A - Clathrate compound of acetyl dipeptide-1 cetyl ester and preparation method thereof - Google Patents
Clathrate compound of acetyl dipeptide-1 cetyl ester and preparation method thereof Download PDFInfo
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- CN115969729A CN115969729A CN202310109628.4A CN202310109628A CN115969729A CN 115969729 A CN115969729 A CN 115969729A CN 202310109628 A CN202310109628 A CN 202310109628A CN 115969729 A CN115969729 A CN 115969729A
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- cyclodextrin
- cetyl ester
- acetyl dipeptide
- dipeptide
- acetyl
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- 229940014843 acetyl dipeptide-1 cetyl ester Drugs 0.000 title claims abstract description 72
- 108010074988 acetyltyrosyl-arginine cetyl ester Proteins 0.000 title claims abstract description 72
- JFHZXDZUXGBFAQ-KYJUHHDHSA-N hexadecyl (2s)-2-[[(2s)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](NC(C)=O)CC1=CC=C(O)C=C1 JFHZXDZUXGBFAQ-KYJUHHDHSA-N 0.000 title claims abstract description 72
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 150000001875 compounds Chemical class 0.000 title abstract description 21
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 63
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000003756 stirring Methods 0.000 claims abstract description 21
- 239000008367 deionised water Substances 0.000 claims abstract description 19
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 19
- 238000001816 cooling Methods 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 7
- 239000001116 FEMA 4028 Substances 0.000 claims description 14
- 229960004853 betadex Drugs 0.000 claims description 14
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 claims description 11
- 229940043377 alpha-cyclodextrin Drugs 0.000 claims description 11
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 9
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 8
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 6
- 239000002537 cosmetic Substances 0.000 claims description 5
- PCWPQSDFNIFUPO-VDQKLNDWSA-N (1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31S,33R,35R,36R,37S,38R,39S,40R,41S,42R,43S,44R,45S,46R,47S,48R,49S)-37,39,41,43,45,47,49-heptakis(2-hydroxyethoxy)-5,10,15,20,25,30,35-heptakis(hydroxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,38,40,42,44,46,48-heptol Chemical compound OCCO[C@H]1[C@H](O)[C@@H]2O[C@H]3O[C@H](CO)[C@@H](O[C@H]4O[C@H](CO)[C@@H](O[C@H]5O[C@H](CO)[C@@H](O[C@H]6O[C@H](CO)[C@@H](O[C@H]7O[C@H](CO)[C@@H](O[C@H]8O[C@H](CO)[C@@H](O[C@H]1O[C@@H]2CO)[C@@H](O)[C@@H]8OCCO)[C@@H](O)[C@@H]7OCCO)[C@@H](O)[C@@H]6OCCO)[C@@H](O)[C@@H]5OCCO)[C@@H](O)[C@@H]4OCCO)[C@@H](O)[C@@H]3OCCO PCWPQSDFNIFUPO-VDQKLNDWSA-N 0.000 claims description 4
- 238000001694 spray drying Methods 0.000 claims description 4
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- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims description 3
- 229940080345 gamma-cyclodextrin Drugs 0.000 claims description 3
- YZOUYRAONFXZSI-SBHWVFSVSA-N (1S,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31S,33R,35R,36R,37S,38R,39S,40R,41S,42R,43S,44R,45S,46R,47S,48R,49S)-5,10,15,20,25,30,35-heptakis(hydroxymethyl)-37,39,40,41,42,43,44,45,46,47,48,49-dodecamethoxy-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,38-diol Chemical compound O([C@@H]([C@H]([C@@H]1OC)OC)O[C@H]2[C@@H](O)[C@@H]([C@@H](O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3O)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O3)O[C@@H]2CO)OC)[C@H](CO)[C@H]1O[C@@H]1[C@@H](OC)[C@H](OC)[C@H]3[C@@H](CO)O1 YZOUYRAONFXZSI-SBHWVFSVSA-N 0.000 claims description 2
- QFSFPJHBIGWPMD-PBVGKYIBSA-N 104723-60-6 Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)O[C@H](OC[C@@H]2[C@H]3O[C@@H]4[C@H](O)[C@@H](O)[C@@H]([C@H](O4)CO)O[C@@H]4[C@H](O)[C@@H](O)[C@@H]([C@H](O4)CO)O[C@@H]4[C@H](O)[C@@H](O)[C@@H]([C@H](O4)CO)OC4[C@H](O)[C@@H](O)[C@@H]([C@H](O4)CO)O[C@@H]4[C@H](O)[C@@H](O)[C@@H]([C@H](O4)CO)O[C@@H]4[C@H](O)[C@@H](O)[C@@H]([C@H](O4)CO)O[C@H]([C@@H]([C@H]3O)O)O2)[C@H](O)[C@H]1O QFSFPJHBIGWPMD-PBVGKYIBSA-N 0.000 claims description 2
- 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 4
- 239000000463 material Substances 0.000 claims 1
- 239000002775 capsule Substances 0.000 abstract description 15
- 239000007787 solid Substances 0.000 abstract description 7
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- 238000002156 mixing Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- -1 cyclic oligosaccharides Chemical class 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 108010016626 Dipeptides Proteins 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- JXNRXNCCROJZFB-UHFFFAOYSA-N Tyrosyl-Arginine Chemical compound NC(N)=NCCCC(C(O)=O)NC(=O)C(N)CC1=CC=C(O)C=C1 JXNRXNCCROJZFB-UHFFFAOYSA-N 0.000 description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
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- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
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- 230000002087 whitening effect Effects 0.000 description 2
- GFLJSOROHICWQL-KBPBESRZSA-N (2s)-2-[[(2s)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)C)CC1=CC=C(O)C=C1 GFLJSOROHICWQL-KBPBESRZSA-N 0.000 description 1
- FLPJVCMIKUWSDR-UHFFFAOYSA-N 2-(4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1 FLPJVCMIKUWSDR-UHFFFAOYSA-N 0.000 description 1
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 1
- 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 description 1
- 108010025880 Cyclomaltodextrin glucanotransferase Proteins 0.000 description 1
- 102000009025 Endorphins Human genes 0.000 description 1
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- PXDJXZJSCPSGGI-UHFFFAOYSA-N hexadecanoic acid hexadecyl ester Natural products CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 1
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- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Abstract
The invention belongs to the technical field of biological medicines, and discloses an acetyl dipeptide-1 cetyl ester clathrate compound which contains acetyl dipeptide-1 cetyl ester and cyclodextrin or cyclodextrin derivatives. The invention also discloses a preparation method of the clathrate compound, which comprises the following steps: s1, respectively dissolving cyclodextrin or cyclodextrin derivatives and acetyl dipeptide-1 cetyl ester in deionized water; s2, adding the acetyl dipeptide-1 cetyl ester solution into the cyclodextrin or cyclodextrin derivative solution, uniformly stirring, cooling and drying. The molecular capsule clathrate compound provided by the invention has the advantages of few components, simple composition, capability of being dissolved by adding water, good stability, and capability of solving the problems of white solid precipitation and poor stability of the existing acetyl dipeptide-1 cetyl ester solution in use, and no need of adding a dispersing agent, an emulsifying agent and the like to increase the stability.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to an acetyl dipeptide-1 cetyl ester clathrate compound and a preparation method thereof.
Background
Researchers at Kyoto university, japan, in the 1980's, discovered a tyrosine-arginine dipeptide with analgesic activity that released endorphins and stabilized their degradation, and possibly had neurotransmitter properties that intervened in the sensory nerve level released by calcitonin gene-related peptide, inducing soothing effects on the skin. However, tyrosine arginine dipeptide does not penetrate the dermal layer and is therefore not suitable for use in cosmetics.
In order to solve the problem and improve the stability of the dipeptide, researchers develop a series of derivatives on the basis of the problem. Wherein acetyl dipeptide-1 cetyl palmitate (chemical name: N-acetyl-L-tyrosyl-L-arginine hexadecyl ester) is added with lipophilic 'acetyl' and 'cetyl ester' groups at two ends of the dipeptide respectively to enhance the transdermal absorption capability of the compound. It was reported that capsaicin was applied to the left and right nasolabial folds without using any skin care product, and that cosmetics containing acetyl dipeptide-1 cetyl ester had significantly lower burning and stinging values after one and two minutes of use, demonstrating a rapid and significant soothing effect in vivo. In 2006, companies disclosed that products with acetyl dipeptide-1 cetyl ester produced an increase in skin moisture of 39.5% more over four weeks than products without acetyl dipeptide-1 cetyl ester. In 2012, researchers reported that acetyl dipeptide-1 cetyl ester added to the skin had a certain whitening effect. In summary, the importance of acetyl dipeptide-1 cetyl ester in soothing, moisturizing and whitening is well known.
However, due to the structural characteristics of acetyl dipeptide-1 cetyl ester, not only is it less lipophilic, but it is also less hydrophilic. How to solve the solubility problem is less researched, and acetyl dipeptide-1 cetyl ester is prepared into a low-content solution mainly through an organic solvent and a solubilizer, and a preservative is added for preservation. However, the product still easily precipitates in the formula application, and is particularly not beneficial to the use in an essence system and a large amount of use, thereby limiting the application of the acetyl dipeptide.
The acetyl dipeptide-1 cetyl ester is taken as very promising soothing anti-allergic peptide, elastic peptide and healing peptide, and an essence system is a very important application scene, so the problem of the solubility of the acetyl dipeptide-1 cetyl ester is solved, and the acetyl dipeptide-1 cetyl ester has very important research significance and practical value.
Cyclodextrin is a generic name for cyclic oligosaccharides formed from 6 or more glucopyranose molecules, and is produced by the action of cyclodextrin glycosyltransferase on starch. The common cyclodextrins include alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin and delta-cyclodextrin, and the number of glucopyranose molecules constituting the cyclodextrins is 6,7,8,9. The beta-cyclodextrin has an external hydrophilic and internal hydrophobic hollow cylindrical structure, can form an inclusion compound with suitable indissolvable drug molecules, slowly controls the release of the drug, reduces the irritation of the drug and improves the bioavailability of the drug.
Disclosure of Invention
The invention aims to provide an inclusion compound formed by acetyl dipeptide-1 cetyl ester and cyclodextrin or cyclodextrin derivatives.
The invention also aims to provide a preparation method of the clathrate compound.
In order to achieve one of the purposes, the invention adopts the following technical scheme:
an inclusion compound of acetyl dipeptide-1 cetyl ester, which contains the acetyl dipeptide-1 cetyl ester and cyclodextrin or cyclodextrin derivatives, comprises the cyclodextrin or cyclodextrin derivatives and the acetyl dipeptide-1 cetyl ester embedded in the cavity of the cyclodextrin or cyclodextrin derivatives, and forms the inclusion compound by taking the cyclodextrin or cyclodextrin derivatives as a host molecule and taking the acetyl dipeptide-1 cetyl ester as a guest molecule.
Further, the weight ratio of the acetyl dipeptide-1 cetyl ester to the cyclodextrin or the cyclodextrin derivative is 1: (48 to 500).
Further, the ratio of the acetyl dipeptide-1 cetyl ester to the cyclodextrin or cyclodextrin derivative in parts by weight is 1.
The content of acetyl dipeptide-1 cetyl ester in the clathrate is less than or equal to 6wt%, preferably 0.2-2.5 wt%.
Further, the cyclodextrin is selected from at least one of alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin and delta-cyclodextrin; the cyclodextrin derivative is selected from at least one of hydroxypropyl-alpha-cyclodextrin, sulfobutyl-alpha-cyclodextrin, glucosyl-alpha-cyclodextrin, methyl-beta-cyclodextrin, hydroxyethyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, glucosyl-beta-cyclodextrin, 6-O-alpha-maltosyl-beta-cyclodextrin, hepta (2,3,6-tri-O-methyl) -beta-cyclodextrin, sulfobutyl ether-beta-cyclodextrin and sulfo-beta-cyclodextrin.
Further, the cyclodextrin is beta-cyclodextrin, and the cyclodextrin derivative is hydroxypropyl-alpha-cyclodextrin and/or hydroxypropyl-beta-cyclodextrin.
The preparation method of the clathrate compound of acetyl dipeptide-1 cetyl ester comprises the following steps:
s1, respectively dissolving cyclodextrin or cyclodextrin derivatives and acetyl dipeptide-1 cetyl ester in deionized water;
s2, adding the acetyl dipeptide-1 cetyl ester solution into the cyclodextrin or cyclodextrin derivative solution, uniformly stirring, cooling and drying.
Specifically, the steps are as follows:
adding cyclodextrin or cyclodextrin derivative into deionized water, heating, stirring, and dissolving to obtain cyclodextrin or cyclodextrin derivative water solution;
adding acetyl dipeptide-1 cetyl ester into deionized water, heating, stirring and dissolving uniformly to prepare an acetyl dipeptide-1 cetyl ester aqueous solution;
adding acetyl dipeptide-1 cetyl ester aqueous solution into cyclodextrin or cyclodextrin derivative solution, heating and stirring for about 6h, embedding uniformly, cooling, drying to obtain the cyclodextrin or cyclodextrin derivative molecular capsule clathrate of acetyl dipeptide-1 cetyl ester, and lyophilizing, spray drying or forced air drying to obtain white solid directly, and pulverizing to obtain uniform powder.
Further, the concentration of the cyclodextrin or cyclodextrin derivative solution is 9-50 wt%; the concentration of the acetyl dipeptide-1 cetyl ester solution is 2-17 wt%.
Further, the concentration of the cyclodextrin or cyclodextrin derivative solution is 25-45 wt%; the concentration of the acetyl dipeptide-1 cetyl ester solution is 2-5 wt%.
Further, the temperature of the embedding (step S2) is 45 to 100 ℃, preferably 65 to 90 ℃.
Further, the drying is freeze-drying, spray-drying or forced air drying.
A cosmetic preparation comprises clathrate of acetyl dipeptide-1 cetyl ester and acceptable adjuvants.
Suitable adjuvants present in cosmetic formulations are, for example, lubricants, emulsifiers and surfactants, thickeners/viscosity regulators/stabilizers, UV-photoprotective filters, antioxidants, hydrotropes, solids and fillers, film formers, pearlescent additives, deodorant and antiperspirant active ingredients, self-tanning agents, preservatives, conditioners, perfumes, dyes, bioactive ingredients, care additives, superfatting agents and other solvents.
The invention has the following beneficial effects:
1. the molecular capsule clathrate compound of the invention is composed of acetyl dipeptide-1 cetyl ester and cyclodextrin or cyclodextrin derivatives, has less components and simple composition, does not need to be preserved by a preservative like a commercially available acetyl dipeptide-1 cetyl ester solution, has higher safety, and does not need to be added with other components such as water-soluble polymers, pH regulators, bacteriostats and the like.
2. The preparation process is simple, and the solvent medium is deionized water, so that the preparation method is green and environment-friendly.
3. The molecular capsule inclusion compound of the present invention is in the form of solid or powder, unlike liquid capsules, and can be added in an amount increased to the maximum extent because no solvent is present.
4. The molecular capsule clathrate compound is convenient to use, can be dissolved by adding water, has good stability, solves the problems of white solid precipitation and poor stability of the existing acetyl dipeptide-1 cetyl ester solution in use, and does not need to add a dispersing agent, an emulsifying agent and the like to increase the stability.
Drawings
FIGS. 1, 2 and 3 are photographs of the stability test of example 6.
Detailed Description
The present invention will be further described with reference to the following specific examples.
Example 1
The inclusion compound was prepared according to the following steps:
preparation of an aqueous hydroxypropyl- β -cyclodextrin solution (phase a): weighing 36g of hydroxypropyl-beta-cyclodextrin and 50g of deionized water, heating, stirring and dissolving uniformly;
preparation of an aqueous solution of acetyl dipeptide-1 cetyl ester (phase B): weighing 0.4g of acetyl dipeptide-1 cetyl ester and 16g of deionized water, heating, stirring and dissolving uniformly;
mixing AB phase: adding the phase B into the phase A at 90 ℃, stirring for 6 hours, and uniformly embedding;
after cooling, the solution was lyophilized to obtain 36.50g of acetyl dipeptide-1 cetyl esters molecular capsule clathrate, the content of which was 1.10%.
Example 2
The inclusion compound was prepared according to the following steps:
preparation of an aqueous hydroxyethyl- β -cyclodextrin solution (phase a): weighing 36g of hydroxyethyl-beta-cyclodextrin and 100g of deionized water, heating, stirring and dissolving uniformly;
preparation of an aqueous solution of acetyl dipeptide-1 cetyl ester (phase B): weighing 0.4g of acetyl dipeptide-1 cetyl ester and 8g of deionized water, heating, stirring and dissolving uniformly;
mixing AB phase: adding the phase B into the phase A at 65 ℃, stirring for 6 hours, and uniformly embedding;
after cooling, the solution was lyophilized to give 36.46g of acetyl dipeptide-1 cetyl esters molecular capsule clathrate, which was 1.10%.
Example 3
The inclusion compound was prepared according to the following steps:
preparation of aqueous solution of glucosyl- β -cyclodextrin (phase a): weighing 36g of glucosyl-beta-cyclodextrin and 72g of deionized water, heating, stirring and dissolving uniformly;
preparation of an aqueous solution of acetyl dipeptide-1 cetyl ester (phase B): weighing 0.072g acetyl dipeptide-1 cetyl ester and 2g deionized water, heating, stirring and dissolving uniformly;
mixing AB phase: adding the phase B into the phase A at 70 ℃, stirring for 6 hours, and uniformly embedding;
after cooling, 36.13g of acetyl dipeptide-1 cetyl ester molecular capsule clathrate is obtained by air-blast drying, and the content is 0.20%.
Example 4
The inclusion compound was prepared according to the following steps:
preparation of an aqueous hydroxypropyl- α -cyclodextrin solution (phase a): weighing 36g of hydroxypropyl-alpha-cyclodextrin and 80g of deionized water, heating, stirring and dissolving uniformly;
preparation of an aqueous solution of acetyl dipeptide-1 cetyl ester (phase B): weighing 0.75g of acetyl dipeptide-1 cetyl ester and 25g of deionized water, heating, stirring and dissolving uniformly;
mixing AB phase: adding the phase B into the phase A at 90 ℃, stirring for 6 hours, and uniformly embedding;
after cooling, 36.80g of acetyl dipeptide-1 cetyl ester molecular capsule clathrate, the content of which is 2.04 percent, is obtained by spray drying.
Example 5
The inclusion compound was prepared according to the following steps:
preparation of aqueous beta-cyclodextrin solution (phase a): weighing 36g of beta-cyclodextrin and 72g of deionized water, heating, stirring and dissolving uniformly;
preparation of an aqueous solution of acetyl dipeptide-1 cetyl ester (phase B): weighing 0.072g acetyl dipeptide-1 cetyl ester and 2g deionized water, heating, stirring and dissolving uniformly;
mixing AB phase: adding the phase B into the phase A at 80 ℃, stirring for 6h, and embedding uniformly;
after cooling, freeze-drying to obtain 36.04g of acetyl dipeptide-1 cetyl ester molecular capsule clathrate, the content of which is 0.20%.
Example 6
Stability test
Preparing a molecular capsule solution: 3g of acetyl dipeptide-1 cetyl ester molecular capsule of example 1 was weighed, and 97g of deionized water was used to prepare a 3wt% molecular capsule solution (acetyl dipeptide-1 cetyl ester content: 0.03 wt%), and the solution was sampled into a sample bottle, and the bottle was refrigerated (5 ℃ C.), cooled at room temperature (25 ℃ C.), and heated (45 ℃ C.), and after one week, the three sample solutions were clear and transparent, and no precipitation occurred, as shown in FIG. 1.
Adding 0.03g of acetyl dipeptide-1 cetyl lipid powder into 99.97g of deionized water to prepare a 0.03wt% aqueous solution, wherein the acetyl dipeptide-1 cetyl lipid cannot be completely dissolved; ultrasonic sonication at 45 ℃ for 30 hours, as shown in FIG. 2, a white solid remained.
1g of a commercially available acetyl dipeptide-1 cetyl ester solution (composed of 0.3wt% of acetyl dipeptide-1 cetyl ester, 40wt% of pentanediol, 40wt% of RH, 1wt% of p-hydroxyacetophenone, and 48.7wt% of water) was added to 9g of deionized water, and the mixture was stirred uniformly to prepare a 0.03wt% solution, which was formulated so that a large amount of white foam was generated, as shown in FIG. 3; after one week, a large amount of acetyl dipeptide-1 cetyl ester was observed to precipitate at the bottom of the container.
The acetyl dipeptide-1 cetyl ester solid capsule embedded by the cyclodextrin or the cyclodextrin derivative is directly dissolved by water, and has obvious advantages: the water is added for rapid dissolution, the solution is clear and transparent, has no foam, does not need to add preservatives, organic solvents and solubilizers, is more green and environment-friendly, is more beneficial to product compatibility, and has obvious advantages in the essence.
The above description is only an embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.
Claims (10)
1. An inclusion complex of acetyl dipeptide-1 cetyl ester, comprising acetyl dipeptide-1 cetyl ester and a cyclodextrin or a cyclodextrin derivative.
2. The clathrate of acetyl dipeptide-1 cetyl ester, according to claim 1, wherein the ratio in parts by weight of acetyl dipeptide-1 cetyl ester and cyclodextrin or cyclodextrin derivative is 1: (48 to 500).
3. The clathrate of acetyl dipeptide-1 cetyl ester according to claim 2, wherein the ratio in parts by weight of acetyl dipeptide-1 cetyl ester and cyclodextrin or cyclodextrin derivative is 1.
4. The inclusion complex of acetyl dipeptide-1 cetyl ester according to any of claims 1 to 3, wherein the cyclodextrin is selected from at least one of a-cyclodextrin, β -cyclodextrin, γ -cyclodextrin, δ -cyclodextrin; the cyclodextrin derivative is selected from at least one of hydroxypropyl-alpha-cyclodextrin, sulfobutyl-alpha-cyclodextrin, glucosyl-alpha-cyclodextrin, methyl-beta-cyclodextrin, hydroxyethyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, glucosyl-beta-cyclodextrin, 6-O-alpha-maltosyl-beta-cyclodextrin, hepta (2,3,6-tri-O-methyl) -beta-cyclodextrin, sulfobutyl ether-beta-cyclodextrin and sulfo-beta-cyclodextrin.
5. The inclusion complex of acetyl dipeptide-1 cetyl ester according to claim 4, wherein the cyclodextrin is β -cyclodextrin and the cyclodextrin derivative is hydroxypropyl-a-cyclodextrin and/or hydroxypropyl- β -cyclodextrin.
6. A process for the preparation of a clathrate of acetyl dipeptide-1 cetyl ester as claimed in any of claims 1 to 5, comprising the steps of:
s1, respectively dissolving cyclodextrin or cyclodextrin derivatives and acetyl dipeptide-1 cetyl ester in deionized water;
s2, adding the acetyl dipeptide-1 cetyl ester solution into the cyclodextrin or cyclodextrin derivative solution, uniformly stirring, cooling and drying.
7. The method of claim 6, wherein the concentration of the cyclodextrin or cyclodextrin derivative solution is 9 to 50wt%; the concentration of the acetyl dipeptide-1 cetyl ester solution is 2-17 wt%.
8. The method according to claim 7, wherein the concentration of the cyclodextrin or cyclodextrin derivative solution is 25 to 45wt%; the concentration of the acetyl dipeptide-1 cetyl ester solution is 2-5 wt%.
9. The method according to claim 6, wherein step S2 is carried out at 45 to 100 ℃; the drying is freeze-drying, spray drying or forced air drying.
10. A cosmetic preparation comprising the clathrate of acetyl dipeptide-1 cetyl ester according to any of claims 1 to 5 and acceptable auxiliary materials.
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