CN104098622A - Beta-arbutin crystal IV material and preparation method, composition and use - Google Patents
Beta-arbutin crystal IV material and preparation method, composition and use Download PDFInfo
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- CN104098622A CN104098622A CN201310121628.2A CN201310121628A CN104098622A CN 104098622 A CN104098622 A CN 104098622A CN 201310121628 A CN201310121628 A CN 201310121628A CN 104098622 A CN104098622 A CN 104098622A
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- arbutin
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- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 title claims abstract description 147
- 239000013078 crystal Substances 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- 239000000203 mixture Substances 0.000 title claims abstract description 28
- 239000000463 material Substances 0.000 title abstract description 11
- 239000007787 solid Substances 0.000 claims abstract description 49
- 229960000271 arbutin Drugs 0.000 claims abstract description 37
- 239000003814 drug Substances 0.000 claims description 32
- 230000015572 biosynthetic process Effects 0.000 claims description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 230000003203 everyday effect Effects 0.000 claims description 14
- 239000003826 tablet Substances 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 12
- 239000000470 constituent Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- 239000000839 emulsion Substances 0.000 claims description 7
- 238000004458 analytical method Methods 0.000 claims description 6
- 239000006072 paste Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 5
- 230000000845 anti-microbial effect Effects 0.000 claims description 5
- 230000001741 anti-phlogistic effect Effects 0.000 claims description 5
- 230000002354 daily effect Effects 0.000 claims description 5
- 239000003405 delayed action preparation Substances 0.000 claims description 5
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000002474 experimental method Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 238000001965 diffuse reflectance infrared spectroscopy Methods 0.000 claims description 2
- 238000002329 infrared spectrum Methods 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims description 2
- 230000003595 spectral effect Effects 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 1
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 abstract description 28
- 239000002537 cosmetic Substances 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 6
- 239000004480 active ingredient Substances 0.000 abstract description 3
- -1 beta-arbutin compound Chemical class 0.000 abstract description 2
- 239000011343 solid material Substances 0.000 abstract 2
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- 229940124599 anti-inflammatory drug Drugs 0.000 abstract 1
- 229930182478 glucoside Natural products 0.000 abstract 1
- 238000000034 method Methods 0.000 description 18
- BJRNKVDFDLYUGJ-ZIQFBCGOSA-N alpha-Arbutin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-ZIQFBCGOSA-N 0.000 description 10
- 229940033280 alpha-arbutin Drugs 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 7
- 239000002994 raw material Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 241000208340 Araliaceae Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 3
- 235000003140 Panax quinquefolius Nutrition 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 235000008434 ginseng Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000007916 tablet composition Substances 0.000 description 3
- UAOKXEHOENRFMP-UHFFFAOYSA-N (2,3,4,5-tetraacetyloxy-6-oxohexyl) acetate Chemical compound CC(=O)OCC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C=O UAOKXEHOENRFMP-UHFFFAOYSA-N 0.000 description 2
- RFWGABANNQMHMZ-UHFFFAOYSA-N 8-acetoxy-7-acetyl-6,7,7a,8-tetrahydro-5H-benzo[g][1,3]dioxolo[4',5':4,5]benzo[1,2,3-de]quinoline Natural products CC=C1C(CC(=O)OCCC=2C=C(O)C(O)=CC=2)C(C(=O)OC)=COC1OC1OC(CO)C(O)C(O)C1O RFWGABANNQMHMZ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- HKVGJQVJNQRJPO-UHFFFAOYSA-N Demethyloleuropein Natural products O1C=C(C(O)=O)C(CC(=O)OCCC=2C=C(O)C(O)=CC=2)C(=CC)C1OC1OC(CO)C(O)C(O)C1O HKVGJQVJNQRJPO-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004367 Lipase Substances 0.000 description 2
- 102000004882 Lipase Human genes 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- 208000003351 Melanosis Diseases 0.000 description 2
- RFWGABANNQMHMZ-HYYSZPHDSA-N Oleuropein Chemical compound O([C@@H]1OC=C([C@H](C1=CC)CC(=O)OCCC=1C=C(O)C(O)=CC=1)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RFWGABANNQMHMZ-HYYSZPHDSA-N 0.000 description 2
- 240000004534 Scutellaria baicalensis Species 0.000 description 2
- 235000017089 Scutellaria baicalensis Nutrition 0.000 description 2
- 240000000851 Vaccinium corymbosum Species 0.000 description 2
- 235000003095 Vaccinium corymbosum Nutrition 0.000 description 2
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 235000021014 blueberries Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 239000008271 cosmetic emulsion Substances 0.000 description 2
- 239000007854 depigmenting agent Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 210000001822 immobilized cell Anatomy 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229940040461 lipase Drugs 0.000 description 2
- 235000019421 lipase Nutrition 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- RFWGABANNQMHMZ-CARRXEGNSA-N oleuropein Natural products COC(=O)C1=CO[C@@H](O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)C(=CC)[C@H]1CC(=O)OCCc3ccc(O)c(O)c3 RFWGABANNQMHMZ-CARRXEGNSA-N 0.000 description 2
- 235000011576 oleuropein Nutrition 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000005464 sample preparation method Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000002087 whitening effect Effects 0.000 description 2
- 235000020985 whole grains Nutrition 0.000 description 2
- 241000228245 Aspergillus niger Species 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- AFSDNFLWKVMVRB-UHFFFAOYSA-N Ellagic acid Chemical compound OC1=C(O)C(OC2=O)=C3C4=C2C=C(O)C(O)=C4OC(=O)C3=C1 AFSDNFLWKVMVRB-UHFFFAOYSA-N 0.000 description 1
- ATJXMQHAMYVHRX-CPCISQLKSA-N Ellagic acid Natural products OC1=C(O)[C@H]2OC(=O)c3cc(O)c(O)c4OC(=O)C(=C1)[C@H]2c34 ATJXMQHAMYVHRX-CPCISQLKSA-N 0.000 description 1
- 229920002079 Ellagic acid Polymers 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 102000019280 Pancreatic lipases Human genes 0.000 description 1
- 108050006759 Pancreatic lipases Proteins 0.000 description 1
- 241000589636 Xanthomonas campestris Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000008300 cosmetic paste Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960002852 ellagic acid Drugs 0.000 description 1
- 235000004132 ellagic acid Nutrition 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- BECNKUVYBNETOM-UHFFFAOYSA-N ethyl n-(4-hydroxyphenyl)carbamate Chemical compound CCOC(=O)NC1=CC=C(O)C=C1 BECNKUVYBNETOM-UHFFFAOYSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229940029988 ginseng preparation Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- FAARLWTXUUQFSN-UHFFFAOYSA-N methylellagic acid Natural products O1C(=O)C2=CC(O)=C(O)C3=C2C2=C1C(OC)=C(O)C=C2C(=O)O3 FAARLWTXUUQFSN-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 235000012459 muffins Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940116369 pancreatic lipase Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a beta-arbutin crystal IV (with a chemical name of 4-hydroxy phenyl-beta-D-pyrans glucoside hydrate and an english name of Arbutin hydrate), a preparation method, a composition and use. Specifically, the present invention discloses a solid state beta-arbutin compound in a crystal IV solid material state, a preparation method of a crystal IV solid material sample, as well as use of the beta-arbutin crystal IV material as an active ingredient in preparation of antibacterial anti-inflammatory drugs and cosmetics. The (H2O) 2.5 beta-arbutin crystal IV molecular structure formula is shown in the specification.
Description
Technical field
The present invention relates to find the brilliant IV type of the one solid matter stastus format that β-arbutin exists under solid state; Relate to the preparation method who has invented brilliant IV type sample; Relate to and invented the pharmaceutical composition or the makeup that contain the brilliant IV type of β-arbutin and contain the mixing crystal formation of the brilliant IV type of arbitrary proportion; The invention still further relates to β-arbutin crystal-form substances as medicine or makeup effective constituent, in the application of preparing in antimicrobial antiphlogistic medicine and makeup.
Background technology
Brilliant IV type (chemical name: 4-hydroxyphenyl-β-D-glucopyranoside hydrate, English name: the Arbutin hydrate) molecular structural formula of β-arbutin is as follows:
(H
2O)
2.5
At Chinese patent CN1302599A(publication number) in recorded " make-up composition that contains N-ethoxycarbonyl-4-amino-phenol and arbutin or derivatives thereof and/or ellagic acid or derivatives thereof " [1] of the invention of III She Waliye DM method nurse, wherein relate to a kind of preparation method of arbutin make-up composition.
At Chinese patent CN1481233A(publication number) in recorded " comprising arbutin and the Polyglucosidase skin whitening composition as activeconstituents " [2] of Cotde Inc.'s invention, wherein relate to a kind of skin whitening composition that comprises arbutin.
At Chinese patent CN1228300A(publication number) in recorded " a kind of preparation method of freckle-removing pretty gel cosmetics " of Luo Xiuying, Liang Yuzhen invention
[3], wherein relate to a kind of preparation method of the freckle-removing pretty gel cosmetics that comprises arbutin.
At Chinese patent CN1208608A(publication number) in recorded " arbutin monoesters is as the application of depigmenting agent " of M Fei Lipei invention
[4], wherein relate in the composition of topical application and use arbutin monoesters as the depigmenting agents such as human body skin or SYNTHETIC OPTICAL WHITNER.
At Chinese patent CN1608693A(publication number) in recorded Ding Jiayi invention " a kind of ginseng that contains arbutin, Radix Panacis Quinquefolii and preparation method thereof "
[5], wherein relate to a kind of ginseng that contains arbutin, Radix Panacis Quinquefolii and preparation method thereof.
At Chinese patent CN1633980A(publication number) in recorded " makeup of the ginseng preparation that a kind of use contains arbutin " of Ding Jiayi invention
[6], wherein relate to the cosmetics of being made by the ginseng that contains arbutin.
At Chinese patent CN1635139A(publication number) in recorded " method of preparing alpha-arbutin through fermentation " [7] of Liu Chunqiao invention, wherein relate to the preparation method of alpha-arbutin.
At Chinese patent CN1724551A(publication number) in record Liao Chen state honor, imperial court's rosy clouds, execute little neoteric " a kind of preparation method of alpha-arbutin "
[8], wherein relating to a kind of preparation method of alpha-arbutin, final step recrystallization solvent adopts sherwood oil (60～90 ° of C): ethyl acetate=9～7:1.
At Chinese patent CN1727493A(publication number) in recorded " free cell or immobilized cell catalyze and synthesize the method for alpha-arbutin " of the inventions such as Zhang Peng, Zhang Shurong, Liu Chunqiao
[9], wherein relating to the preparation method who utilizes xanthomonas campestris CGMCC NO.1243 free cell or immobilized cell to catalyze and synthesize alpha-arbutin, final step recrystallization solvent adopts water.
At Chinese patent CN101247816A(publication number) in recorded " comprising arbutin; xitix; the molecular complex of Oleuropein and derivative thereof and the related application at field of medicaments thereof " [10] of the invention of M figure Dinon, wherein relate to one and comprise fruit glycosides, xitix, the molecular complex of Oleuropein or its derivative, and in the related application of field of medicaments.
At Chinese patent CN101732169A(publication number) in recorded " a kind of arbutin multi-functional skin moisturizer " of Wang Juan invention
[11], wherein relate to a kind of multifunctional skin-care fluid that comprises arbutin.
At Chinese patent CN101597631A(publication number) in recorded " a kind of method of producing A-arbutin that transforms with root arrhizus fermentation " of Liang Jingjuan, Pang Zongwen, the invention of Feng's ancient flag with yak's tail
[12], wherein relate to a kind of method of producing A-arbutin that transforms with root arrhizus fermentation.
At Chinese patent CN102040636A(publication number) in recorded " method for synthesizing beta-arbutin by adopting alpha-D-glucose pentaacetate " of Li Anliang, Yang Shuqin, Guo Xiuru invention
[13], wherein relating to the method that thereby synthetic key intermediate synthesizes β-arbutin taking alpha-D-glucose pentaacetate as raw material, final step recrystallization solvent adopts ethanol, water.
At Chinese patent CN102093442A(publication number) in recorded " separation purification method of arbutin in a kind of blueberry " of Zhao Yuhong, Wang Zhenyu, Wang Jinling invention
[14], wherein relating to a kind of method of the arbutin extracting in blueberry pomace being carried out to separation and purification, final step recrystallization solvent adopts water.
At Chinese patent CN102505031A(publication number) in " utilizing the method for the synthetic arbutin of hairy roots of scutellaria baicalensis Resorcinol " of having recorded Qi Xiangjun, Peng Feiyu, Qian Weidong, having executed spring sun-light invention
[15], wherein relate to a kind of method of utilizing the synthetic arbutin of hairy roots of scutellaria baicalensis Resorcinol.
At Chinese patent CN102329838A(publication number) in recorded " a kind of technique of producing alpha-arbutin by microbial transformation " of Du Gang, Yang Haiying invention
[16], wherein relate to a kind of method of producing alpha-arbutin that transforms with Aspergillus niger strain.
At Chinese patent CN102517361A(publication number) in recorded " method of catalytic synthesis of arbutin by using lipase " of Deng Li, Liu Chunqiao, Wang Fang, Tan Tianwei, Nie Kaili, Cao Xi invention
[17], wherein relate to the preparation method who utilizes free or immobilized porcine pancreatic lipase to catalyze and synthesize arbutin.
At Chinese patent CN102517362A(publication number) in recorded " a kind of method of utilizing lipase-catalyzed synthesis alpha-arbutin " of Wang Fang, Liu Chunqiao, Deng Li, Tan Tianwei, Nie Kaili, Cao Xi invention
[18], wherein relating to a kind of preparation method who utilizes free or immobilized candida sp.lipase to catalyze and synthesize alpha-arbutin, final step recrystallization solvent adopts water.
At Chinese patent CN102697672A(publication number) in recorded strong, Chen Yanling invention of summer " arbutin multiple emulsion and preparation method thereof "
[19], wherein relate to a kind of arbutin multiple emulsion, the described carrier loaded arbutin active ingredient that has.
In periodical " Journal of Molecular Structure ", record the article " Arbutin:Isolation, X-ray structure and computional studies " that the people such as Jacek E.Nycz deliver abroad
[20], wherein relate to the β-arbutin crystal formation that contains 0.5 water molecules.
The present invention has found a kind of β-arbutin brilliant IV type solid matter state and the preparation method that contain 1 molecular crystal water different from above-mentioned patent or literature research Reporting.
Research purpose of the present invention is to start with from the crystal formation solid matter existence research of β-arbutin, by crystal formation triage techniques, crystal formation evaluated biological activity technology, in the active ingredient raw materials aspect of D&C, find, find that crystal formation solid matter exists kind and status flag, crystal-form substances is combined with biologically effective Journal of Sex Research, for the advantage medicinal crystal-form solid matter of finding, finding, exploitation has the β-arbutin of optimal clinical curative effect provides basic science data; Meanwhile, also for providing scientific basis from β-arbutin solid pharmaceutical raw material basis application country or international intellecture property invention patent protection.
Summary of the invention
One of the object of the invention: the brilliant IV type solid matter existence of β-arbutin and describing mode are provided.
Two of the object of the invention: the preparation method that the brilliant IV type of β-arbutin solid matter sample is provided.
Three of the object of the invention: the solid pharmaceutical and the composition thereof that are to provide the mixing crystal formation that contains the brilliant IV type sterling of β-arbutin or contain the brilliant IV type of arbitrary proportion.
Four of the object of the invention: provide and use the pharmaceutical composition of the brilliant IV type of β-arbutin solid matter as active constituents of medicine, its, dosage was within the scope of 10～500mg every day; Provide and use the makeup of β-arbutin crystal formation solid matter as effective constituent, its every daily dosage is within the scope of 100～1000mg.
Five of the object of the invention: provide and use the brilliant IV type solid matter of β-arbutin to manufacture out for clinical tablet, capsule, pill, injection, slowly-releasing or controlled release preparation medicine as active constituents of medicine raw material; Provide and use β-arbutin crystal formation solid matter to be solid, suspension, emulsion or paste as the makeup of effective constituent.
Six of the object of the invention: provide the brilliant IV type of β-arbutin material to bring into play the effective therapeutic action of medicine because crystal-form substances improves Plasma Concentration in organism in treatment lysis.
Seven of the object of the invention: provide and use the brilliant IV type solid matter of β-arbutin as active raw materials, in the application of preparing in antimicrobial antiphlogistic medicine and makeup.
The invention provides the brilliant IV type solid matter form of β-arbutin compound under solid state, the preparation method of brilliant IV type sample; The medicine that the different crystal forms material of discovery use β-arbutin is developed as active fraction preparation and composition thereof are for the preparation of the application in antimicrobial antiphlogistic medicine and makeup.
Technical characterictic
1. the brilliant IV type solid sample morphological specificity of β-arbutin:
The brilliant IV type of 1.1 β that the present invention relates to-arbutin solid matter, is characterized in that, be hydrate, and between β-arbutin molecule and water molecules, ratio is 1:2.5, when using powder x-ray diffraction analysis to adopt CuK
αwhen radiation experiments condition, show as diffraction peak position: 2-Theta value (°) or d value (
) and diffraction peak relative intensity: the solid matter (table 1, Fig. 1) when peak height value (Height%) or peak area value (Area%) have following characteristic peaks:
The powder x-ray diffraction peak value of the brilliant IV type of table 1 β-arbutin solid sample
。
The brilliant IV type of 1.2 β that the present invention relates to-arbutin solid matter, it is characterized in that, use infrared spectra while analyzing 3364,3286,3038,2939,2891,2716,2241,2163,1609,1511,1461,1444,1400,1382,1309,1285,1268,1223,1216,1121,1099,1079,1071,1057,1046,1013,924,898,829,804,779,716,706,664cm
-1there is diffuse reflectance infrared spectroscopy peak in place, the permissible variation at its mid-infrared spectral behavior peak is ± 2cm
-1(Fig. 2).
The brilliant IV type of 1.3 β that the present invention relates to-arbutin solid matter, it is characterized in that, while using thermogravimetric technical Analysis, show as in temperature rise rate is the TG collection of illustrative plates of 10 ° of C of per minute and have the weightless steps of 1 water constituent at 125 ° of C temperature places, weightless ratio is 14% ± 1%(Fig. 3).
2. the preparation method characteristic of the brilliant IV type of β-arbutin sample:
The preparation method of the brilliant IV type of the β-arbutin sample the present invention relates to, it is characterized in that, use tetrahydrofuran solvent, at ° C temperature of 50 ° of C～80, reflux is dissolved β-arbutin sample completely, and goes down to desolventize the brilliant IV type of the β-arbutin solid matter of acquisition through envrionment temperature 4 ° of C～80 ° C, ambient relative humidity 10%～75%, normal pressure or vacuum experiment conditions.
3. the crystal formation composition of β-arbutin, dosage and pharmaceutical preparations composition feature:
3.1 β-arbutin mixing crystal formation the solid matters that the present invention relates to, is characterized in that, the brilliant IV type of the β-arbutin composition that contains arbitrary proportion.
3.2 pharmaceutical composition the present invention relates to or makeup, is characterized in that, contain the brilliant IV type of β-arbutin, or contain β-arbutin mixed crystal solid matter and pharmaceutically acceptable carrier.
3.3 pharmaceutical compositions that the present invention relates to, β-arbutin every day dosage within the scope of 10～500mg.
3.4 makeup that the present invention relates to, the every daily dosage of β-arbutin is within the scope of 100～1000mg.
3.5 pharmaceutical compositions that the present invention relates to, is characterized in that, described pharmaceutical composition is various tablets, capsule, pill, injection, sustained release preparation, controlled release preparation.
3.6 makeup that the present invention relates to, is characterized in that, described makeup are solid, suspension, emulsion or paste.
The 3.7 brilliant IV type of the β-arbutin mixed crystal compositions that the present invention relates to the brilliant IV type of β-arbutin or contain arbitrary proportion are in the application of preparing in antimicrobial antiphlogistic medicine and makeup.
Brief description of the drawings
The x-ray diffractogram of powder of the brilliant IV type of Fig. 1 β-arbutin solid sample
The infrared absorpting light spectra of the brilliant IV type of Fig. 2 β-arbutin sample
The thermal multigraph of the brilliant IV type of Fig. 3 β-arbutin sample
Embodiment
For better explanation technical scheme of the present invention, spy provides following examples, but the present invention is not limited to this.
Embodiment 1
The brilliant IV type sample preparation methods 1 of β-arbutin:
60 ° of C reflux of β-arbutin bulk drug of 100mg are dissolved in 100ml tetrahydrofuran (THF), filtered while hot obtains settled solution, room temperature hold over night, sample obtains β-arbutin solid matter of 87mg through drying under reduced pressure, the sample obtaining is carried out to powder x-ray diffraction analysis, its diffracting spectrum is consistent with Fig. 1, shows that gained sample is the brilliant IV type of β-arbutin solid matter.
The brilliant IV type sample preparation methods 2 of β-arbutin:
80 ° of C reflux of β-arbutin bulk drug of 200mg are dissolved in 150ml tetrahydrofuran (THF), filtered while hot obtains settled solution, room temperature hold over night, sample obtains β-arbutin solid matter of 181mg through drying under reduced pressure, the sample obtaining is carried out to powder x-ray diffraction analysis, its diffracting spectrum is consistent with Fig. 1, shows that gained sample is the brilliant IV type of β-arbutin solid matter.
Embodiment 2
The preparation method 1(tablet of combined pharmaceutical formulation):
A kind of preparation method of medicinal composition tablet, the mixed crystal solid matter that it is characterized in that using the brilliant IV type sterling of β-arbutin or contain the brilliant IV type of arbitrary proportion as the bulk drug of medicinal composition, use several vehicle as the adjunct ingredient of preparing medicinal composition tablet, proportioning is made the tablet samples of every content of dispersion at 10～300mg according to a certain percentage, and table 2 provides tablet formulation ratio:
The preparation formula of table 2 β-arbutin composite medicine tablet
The method that brilliant β-arbutin IV type sterling or the mixed crystal bulk drug that contains the brilliant IV type of arbitrary proportion is prepared into tablet formulation is: several vehicle are mixed with bulk drug, add 1% sodium cellulose glycolate solution appropriate, make soft material, the granulation of sieving, wet grain is dried, and the whole grain that sieves, adds Magnesium Stearate and talcum powder to mix, compressing tablet, to obtain final product.
The preparation method 2(capsule of combined pharmaceutical formulation):
A kind of preparation method of medicinal composition capsule, the mixed crystal solid matter that it is characterized in that using the brilliant IV type sterling of β-arbutin or contain the brilliant IV type of arbitrary proportion as the bulk drug of medicinal composition, use several vehicle as the adjunct ingredient of preparing medicinal composition capsule, proportioning is made the capsule sample of every content of dispersion at 10～200mg according to a certain percentage, and table 3 provides capsule formula ratio:
Bulk drug and the accessory formula of the brilliant IV type of table 3 β-arbutin medicinal composition capsule preparations
The method that brilliant β-arbutin IV type sterling or the mixed crystal bulk drug that contains the brilliant IV type of arbitrary proportion is prepared into tablet formulation is: several vehicle are mixed with bulk drug, add 1% sodium cellulose glycolate solution appropriate, make wet grain and dry the whole grain that sieves, add Magnesium Stearate to mix, insert capsule and make; Or do not use granulation step, and directly β-arbutin bulk drug is mixed with several vehicle auxiliary materials, after sieving, directly incapsulate and make.
The preparation method 3(pulvis of makeup):
A kind of preparation method of makeup, the mixed crystal solid matter that it is characterized in that using the brilliant IV type sterling of β-arbutin or contain the brilliant IV type of arbitrary proportion as cosmetic material medicine, use several vehicle as the adjunct ingredient of preparing makeup, proportioning is made the pulvis of content at 100～500mg according to a certain percentage, and table 4 provides makeup wp formula ratio:
The brilliant IV type of table 4 β-arbutin makeup wp formula
Above-mentioned system component was pulverized to 200 mesh sieves, and after evenly mixing, compressing tablet mounted box is made muffin.
The preparation method 4(suspension of makeup):
A kind of preparation method of makeup, the mixed crystal solid matter that it is characterized in that using the brilliant IV type sterling of β-arbutin or contain the brilliant IV type of arbitrary proportion as cosmetic material medicine, use several vehicle as the adjunct ingredient of preparing makeup, proportioning is made the suspension of content at 100～500mg according to a certain percentage, and table 5 provides makeup suspension formula rate:
The brilliant IV type of table 5 β-arbutin makeup suspension formula
Above-mentioned system component was pulverized to 200 mesh sieves, added glycerine, water constituent, and through the ultrasonic suspension of evenly making, bottled and get final product.
Preparation method 5(emulsion or the paste of makeup):
A kind of preparation method of makeup, the mixed crystal solid matter that it is characterized in that using the brilliant IV type sterling of β-arbutin or contain the brilliant IV type of arbitrary proportion as cosmetic material medicine, use several vehicle as the adjunct ingredient of preparing makeup, proportioning is made emulsion or the paste of content at 100～500mg according to a certain percentage, and table 6 provides cosmetic emulsions or paste ingredient ratio:
The brilliant IV type cosmetic emulsions of table 6 β-arbutin or paste ingredient
Above-mentioned system component was pulverized to 200 mesh sieves, added appropriate glycerine, a little moisture, and through stirring sample blending, bottled and get final product.
Embodiment 3
The dosage 1(tablet of β-arbutin crystal formation medicinal composition):
The pharmaceutical composition that uses crystal formation β-arbutin sample to manufacture as active constituents of medicine, it is characterized in that using the activeconstituents of brilliant IV type β-arbutin as medicine, every day, dosage was 30mg, can be prepared into respectively 3 times/each 1 10mg conventional tablet every day, every day 2 times/each 1 15mg conventional tablet or every day 1 time/each 1 30mg tablet type.
The dosage 2(capsule of β-arbutin crystal formation medicinal composition):
The pharmaceutical composition that uses crystal formation β-arbutin sample to manufacture as active constituents of medicine, it is characterized in that using the activeconstituents of brilliant IV type β-arbutin as medicine, every day, dosage was 60mg, can be prepared into respectively 2 times/each 1 30mg capsule every day, every day 1 time/each 1 60mg capsule.
Need the problem of explanation: the β-arbutin crystal formation pharmaceutical composition the present invention relates to has perhaps multifactor impact on the dosage of effective constituent, for example: cause the difference of dosage every day for preventing different with the purposes for the treatment of; Ill character is different from ill severity and cause the different of dosage every day; The difference of Gender, age, body surface area, route of administration, administration number of times, therapeutic purpose are different and cause the difference of dosage every day; In addition, the absorption existing between crystal form samples and Plasma Concentration are not equal, and also causing the present invention is 0.01-300mg/kg body weight in suitable dose scope every day that uses β-arbutin crystal formation composition, is preferably 10-100mg/kg body weight.When use, should formulate different brilliant IV type β-arbutin effective constituent total dose schemes from treatment different situations demand according to actual prevention, and can be divided into repeatedly or single administration mode completes.
The using dosage of β-arbutin crystal formation makeup:
Use the makeup late frost of crystal formation β-arbutin sample as active fraction preparation exploitation, it is characterized in that using the activeconstituents of brilliant IV type β-arbutin as makeup, every daily dosage portion is 200mg, and used night.
Use the makeup foundation cream of crystal formation β-arbutin sample as active fraction preparation exploitation, it is characterized in that using the activeconstituents of brilliant IV type β-arbutin as makeup, every daily dosage portion is 100mg, and used morning.
Embodiment 4
The brilliant IV type of β-arbutin stability advantage:
Draw moistly in view of anhydrous type β-arbutin sample exists, therefore the brilliant IV type of β-arbutin hydrate solids material belongs to a kind of stable crystal form state of matter, difficultly turn brilliant phenomenon, there is the controlled advantage of crystal-form substances state as medicine and cosmetic material.
Reference
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Claims (12)
1. the brilliant IV type of β-arbutin solid matter, is characterized in that, be hydrate, and between β-arbutin molecule and water molecules, ratio is 1:2.5, when using powder x-ray diffraction analysis to adopt CuK
awhen radiation experiments condition, diffraction peak position 2-Theta value (°) or d value
diffraction peak relative intensity peak height value (Height%) or peak area value (Area%) have following expression:
。
2. the brilliant IV type of β according to claim 1-arbutin solid matter, it is characterized in that, use infrared spectra while analyzing 3364,3286,3038,2939,2891,2716,2241,2163,1609,1511,1461,1444,1400,1382,1309,1285,1268,1223,1216,1121,1099,1079,1071,1057,1046,1013,924,898,829,804,779,716,706,664cm
-1there is diffuse reflectance infrared spectroscopy peak in place, the permissible variation at its mid-infrared spectral behavior peak is ± 2cm
-1.
3. the brilliant IV type of β according to claim 1-arbutin solid matter, it is characterized in that, while using thermogravimetric technical Analysis, show as in temperature rise rate is the TG collection of illustrative plates of 10 ° of C of per minute and have the weightless steps of 1 water constituent at 125 ° of C temperature places, weightless ratio is 14% ± 1%.
4. the brilliant IV type solid matter preparation method of β-arbutin claimed in claim 1, it is characterized in that, use tetrahydrofuran solvent, at ° C temperature of 50 ° of C～80, reflux is dissolved β-arbutin sample completely, and through 4 ° of C～80 ° C of envrionment temperature, ambient relative humidity 10%～75%, hold over night, remove the brilliant IV type of the β-arbutin solid matter that solvent obtains.
5. a mixing crystal formation solid matter for β-arbutin, is characterized in that, the brilliant IV type of the β claimed in claim 1-arbutin composition that contains arbitrary proportion.
6. pharmaceutical composition or makeup, is characterized in that, contains the brilliant IV type sterling of β claimed in claim 1-arbutin and pharmaceutically acceptable carrier.
7. pharmaceutical composition or makeup, is characterized in that, contains β-arbutin mixing crystal formation solid matter and the pharmaceutically acceptable carrier described in claim 5.
8. according to the pharmaceutical composition of claim 6 or 7, it is characterized in that, β-arbutin every day dosage within the scope of 10～500mg.
9. according to the makeup of claim 6 or 7, it is characterized in that, the every daily dosage of β-arbutin is within the scope of 100～1000mg.
10. according to the pharmaceutical composition of claim 6 or 7, it is characterized in that, the formulation of described composition is tablet, capsule, pill, injection, sustained release preparation or controlled release preparation.
11. according to the makeup of claim 6 or 7, it is characterized in that, described makeup are solid, suspension, emulsion or paste.
The brilliant IV type composition of 12. β claimed in claim 1-arbutin and/or mixing crystal formation solid matter claimed in claim 5 are in the application of preparing in antimicrobial antiphlogistic medicine and makeup.
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| CN115894583A (en) * | 2023-02-17 | 2023-04-04 | 天津大学 | Arbutin solvent compound and crystallization preparation method thereof |
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