CN114432460A - Fisetin inclusion compound and preparation method thereof - Google Patents
Fisetin inclusion compound and preparation method thereof Download PDFInfo
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- CN114432460A CN114432460A CN202210309274.3A CN202210309274A CN114432460A CN 114432460 A CN114432460 A CN 114432460A CN 202210309274 A CN202210309274 A CN 202210309274A CN 114432460 A CN114432460 A CN 114432460A
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- fisetin
- beta
- hydroxypropyl
- cyclodextrin
- inclusion compound
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- XHEFDIBZLJXQHF-UHFFFAOYSA-N fisetin Chemical compound C=1C(O)=CC=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 XHEFDIBZLJXQHF-UHFFFAOYSA-N 0.000 title claims abstract description 234
- 235000011990 fisetin Nutrition 0.000 title claims abstract description 116
- 150000001875 compounds Chemical class 0.000 title claims abstract description 58
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 85
- 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 abstract description 81
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 239000000243 solution Substances 0.000 claims abstract description 25
- 238000003756 stirring Methods 0.000 claims abstract description 22
- 238000007789 sealing Methods 0.000 claims abstract description 13
- 238000004108 freeze drying Methods 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 239000008367 deionised water Substances 0.000 claims abstract description 8
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 8
- 239000000706 filtrate Substances 0.000 claims abstract description 8
- 238000001914 filtration Methods 0.000 claims abstract description 8
- 239000011259 mixed solution Substances 0.000 claims abstract description 8
- 238000002390 rotary evaporation Methods 0.000 claims abstract description 8
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 2
- 238000005538 encapsulation Methods 0.000 abstract description 15
- 229920000858 Cyclodextrin Polymers 0.000 abstract description 13
- 238000007710 freezing Methods 0.000 abstract description 6
- 230000008014 freezing Effects 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 4
- 238000011084 recovery Methods 0.000 abstract description 3
- 239000001116 FEMA 4028 Substances 0.000 abstract description 2
- 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 abstract description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 abstract description 2
- 229960004853 betadex Drugs 0.000 abstract description 2
- 239000000523 sample Substances 0.000 description 20
- 238000000691 measurement method Methods 0.000 description 12
- 238000005303 weighing Methods 0.000 description 11
- 238000001514 detection method Methods 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 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 description 10
- 229940079593 drug Drugs 0.000 description 9
- 239000000843 powder Substances 0.000 description 6
- 241001411320 Eriogonum inflatum Species 0.000 description 5
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 5
- 239000012520 frozen sample Substances 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- -1 cyclic oligosaccharide compound Chemical class 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241001122767 Theaceae Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005961 cardioprotection Effects 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 235000014571 nuts Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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Abstract
The invention discloses a preparation method of a fisetin hydroxypropyl-beta-cyclodextrin inclusion compound, which comprises the following steps: dissolving hydroxypropyl-beta-cyclodextrin in deionized water, dissolving fisetin in ethanol, slowly dripping fisetin solution into hydroxypropyl-beta-cyclodextrin solution, sealing, transferring into a water bath, stirring in a dark place, removing organic solvent by rotary evaporation of the uniformly stirred mixed solution, filtering, pre-freezing the residual filtrate, and freeze-drying to obtain fisetin/hydroxypropyl-beta-cyclodextrin inclusion compound. The fisetin/hydroxypropyl-beta-cyclodextrin inclusion compound prepared by the invention can solve the problems of fast volatility, poor light stability, poor water solubility and the like of fisetin, and simultaneously improves the encapsulation rate and the recovery rate of fisetin and the application value of fisetin. The hydroxypropyl-beta-cyclodextrin which is good in water solubility and low in price is used as a wall material of the inclusion compound, and compared with the traditional beta-cyclodextrin, the hydroxypropyl-beta-cyclodextrin inclusion compound has better water solubility; the preparation process is simple, convenient and quick.
Description
Technical Field
The invention relates to the field of medicinal preparations, in particular to a fisetin inclusion compound and a preparation method thereof.
Background
Fisetin (Fisetin) with the molecular formula C15H10O6The chemical name is 3,3 ', 4', 7-tetrahydroxyflavone, which is yellow crystalline powder, is easily soluble in methanol, ethanol, acetic acid and acetone, and is hardly soluble in water, diethyl ether, dichloromethane, trichloromethane, cyclohexane and normal hexane. Is a naturally occurring low molecular weight polyphenolic compound that is found in a wide variety of vegetables, fruits, nuts and tea leaves. The flavonoid natural compound has abundant biological properties including cardioprotection, neuroprotection, antiallergic, antioxidant, anti-inflammatory, anticancer and the like, is a very good health promoter choice together with wide food sources and no toxicity, and therefore has wide scientific interest. Fisetin is a poorly soluble drug, which is almost insoluble in water and has low solubility in organic solvents. This property limits its application in the food and medical fields. Therefore, the solubility of the fisetin is improved, and the problems of fisetin can be effectively improved.
The cyclodextrin is a cyclic oligosaccharide compound which is obtained by enzymatic cyclization of starch and is formed by connecting 6-12 glucose molecules, the cyclodextrin is used as a main body, and hydrophobic drug molecules or functional groups with proper size and shape can be used as guest molecules to be embedded into a cylindrical cavity of the cyclodextrin to form a monomolecular inclusion compound, so that the cyclodextrin is also called as 'molecular microcapsule' or 'super microcapsule'. Cyclodextrins are less stable to acids, but are more acid resistant than starches and non-cyclic small molecule sugars, are quite stable to alkali, heat and mechanical action, and are good natural or synthetic inclusion materials. Animal and human body research shows that the cyclodextrin has the functions of biocompatibility, no immune reaction, low toxicity and raised medicine stability. The application finds a cyclodextrin inclusion technology suitable for fisetin to improve the solubility of fisetin, improve the encapsulation rate and the recovery rate of fisetin and improve the application value of fisetin. The application value of fisetin is improved.
Disclosure of Invention
The invention provides a preparation method of a fisetin hydroxypropyl-beta-cyclodextrin inclusion compound, which aims to solve the problems in the background technology.
The above purpose is realized by the following technical scheme:
a preparation method of a fisetin hydroxypropyl-beta-cyclodextrin inclusion compound comprises the following steps: dissolving hydroxypropyl-beta-cyclodextrin in deionized water to obtain a hydroxypropyl-beta-cyclodextrin aqueous solution; dissolving fisetin in ethanol to obtain fisetin ethanol solution; slowly dripping the fisetin ethanol solution into the hydroxypropyl-beta-cyclodextrin aqueous solution, sealing, transferring into a water bath, stirring in the dark, performing rotary evaporation on the uniformly stirred mixed solution to remove the organic solvent, filtering, retaining the filtrate, and performing freeze drying to obtain the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound.
In the preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound, the molar ratio of fisetin to hydroxypropyl-beta-cyclodextrin is 1: 1-1: 3.
In the preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound, the stirring reaction time in a water bath is 1-12 h.
In the preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound, the water bath temperature in the water bath kettle is 15-35 ℃.
In the preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound, the stirring speed is 200-600 r/min.
In the preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound, the dripping speed of fisetin ethanol solution to hydroxypropyl-beta-cyclodextrin water solution is 1.0-2.0 ml/min.
In the preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound, the freeze drying time of the inclusion compound is 6-24 hours.
The preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound has the following advantages:
(1) the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound prepared by the invention can solve the problems of fast volatility, poor light stability, poor water solubility and the like of fisetin; because the cyclodextrin is a nontoxic and harmless microcapsule wall material with good biocompatibility, the cyclodextrin is used for inclusion of a volatile and easily-oxidized compound, so that the effects of slow release and antioxidation can be achieved, the solubility and the stability of the volatile compound can be increased, the volatility and the irritation of the volatile compound are reduced, the volatile compound is powdered, the chemical components of the compound are basically the same before and after inclusion, and the lasting time of the compound is prolonged after the cyclodextrin inclusion;
(2) the hydroxypropyl-beta-cyclodextrin provided by the invention has a cavity with inner hydrophobicity and outer hydrophilicity, and the hydroxypropyl-beta-cyclodextrin which is good in water solubility and low in price is used as a wall material of the inclusion compound, so that the hydroxypropyl-beta-cyclodextrin has better water solubility compared with the traditional beta-cyclodextrin;
(3) the preparation process is simple, convenient and quick.
(4) The invention provides a cyclodextrin inclusion technology suitable for fisetin to improve the solubility of fisetin, improve the encapsulation rate and the recovery rate of fisetin and improve the application value of fisetin.
Drawings
FIG. 1 is an XRD pattern of fisetin;
FIG. 2 is an XRD pattern of hydroxypropyl-beta-cyclodextrin;
FIG. 3 is an XRD pattern of fisetin hydroxypropyl-beta-cyclodextrin inclusion compound;
FIG. 4 is a DSC chart of fisetin bulk drug, HP-beta-CD, inclusion compound;
FIG. 5 is a TG spectrum in which (A) is fisetin drug substance, (B) is HP-beta-CD, and (C) is clathrate;
FIG. 6 is an infrared spectrum diagram, in which (A) is fisetin bulk drug, (B) is HP-beta-CD, and (C) is inclusion compound.
Detailed Description
The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of the invention.
Example 1
Preparing a fisetin hydroxypropyl-beta-cyclodextrin solution with a molar ratio of 1: accurately weighing 154.15mg of dried hydroxypropyl-beta-cyclodextrin into a beaker, adding 30ml of deionized water, and stirring with a glass rod until the hydroxypropyl-beta-cyclodextrin is fully dissolved to obtain a hydroxypropyl-beta-cyclodextrin aqueous solution; accurately weighing 28.6mg of fisetin into a small beaker, adding 6ml of ethanol, stirring and ultrasonically treating to fully dissolve fisetin in the ethanol to obtain a fisetin ethanol solution; slowly dripping the fisetin ethanol solution into the prepared hydroxypropyl-beta-cyclodextrin aqueous solution at the speed of 2.0ml/min, adding a stirrer, plugging a bottle stopper, sealing by using a sealing film, wrapping by using tinfoil, putting into a constant-temperature magnetic stirrer, setting the temperature to be 30 ℃, the rotating speed to be 400r/min, stirring for 12 hours in a dark place, taking out the sample, performing rotary evaporation on the uniformly stirred mixed solution to remove an organic solvent, filtering, pre-freezing the filtrate, transferring the pre-frozen sample into a freeze dryer, and freeze-drying for 12 hours, wherein the sample is yellow, dried and fluffy powder, and the temperature of the sample in the freeze dryer is close to the room temperature; the sample was removed. The detection of the inclusion compounds of fisetin, hydroxypropyl-beta-cyclodextrin and fisetin hydroxypropyl-beta-cyclodextrin by XRD (figure 1, figure 2 and figure 3), DSC (figure 4), TG (figure 5) and FTIR (figure 6) respectively proves that fisetin is completely included in hydroxypropyl-beta-cyclodextrin. Solubility detection shows that compared with fisetin bulk drugs, the solubility of the prepared inclusion compound is remarkably improved, and fisetin hydroxypropyl-beta-cyclodextrin inclusion compound can also improve fisetin stability.
1.1 encapsulation efficiency determination
Weighing and calculating the yield of the inclusion compound, and finally determining the encapsulation rate of the inclusion compound by measuring the content of the inclusion compound through ultraviolet. The yield (mass of the inclusion compound/total charge amount) × 100%, and the encapsulation rate (%) (number of moles of fisetin in the inclusion compound/number of moles of fisetin initially charged) × 100%
Inclusion effect: the clathrate yield was determined to be 74.14% and the encapsulation efficiency was 73.57%.
1.2 solubility determination
Fisetin and 1g of each of the fisetin inclusion compounds prepared in this example were weighed out, placed in 10ml, 20ml, 50ml, 100ml and 1000ml volumetric flasks at 25 ℃ and 2 ℃ respectively, purified water was added to the scale, shaken vigorously for 30 seconds every 5 minutes, and the dissolution within 30 minutes was observed. If no particles are visible to the naked eye, it can be considered as complete dissolution.
The results of the experiments are shown in the following table:
solubility experiments show that after the fisetin is included, the water solubility is increased by more than 20 times.
Example 2
Preparing a fisetin hydroxypropyl-beta-cyclodextrin solution with a molar ratio of 1: 2: accurately weighing 154.15mg of dried hydroxypropyl-beta-cyclodextrin into a beaker, adding 30ml of deionized water, and stirring with a glass rod until the hydroxypropyl-beta-cyclodextrin is fully dissolved to obtain a hydroxypropyl-beta-cyclodextrin aqueous solution; accurately weighing 14.3mg of fisetin into a small beaker, adding 5ml of ethanol, stirring and ultrasonically treating to fully dissolve fisetin in the ethanol to obtain a fisetin ethanol solution; slowly dripping the fisetin ethanol solution into the prepared hydroxypropyl-beta-cyclodextrin aqueous solution at the speed of 1.5ml/min, adding a stirrer, plugging a bottle stopper, sealing by using a sealing film, wrapping by using tinfoil, putting into a constant-temperature magnetic stirrer, setting the temperature to be 25 ℃, the rotating speed to be 350r/min, stirring for 6 hours in a dark place, taking out the sample, performing rotary evaporation on the uniformly stirred mixed solution to remove an organic solvent, filtering, pre-freezing the filtrate, transferring the pre-frozen sample into a freeze dryer, and freeze-drying for 24 hours, wherein the sample is yellow, dried and fluffy powder, and the temperature of the sample in the freeze dryer is close to the room temperature; taking out a sample; XRD, DSC, TG and FTIR detection prove that the fisetin is completely included in the hydroxypropyl-beta-cyclodextrin. Solubility detection shows that compared with fisetin bulk drugs, the solubility of the prepared inclusion compound is remarkably improved, and fisetin hydroxypropyl-beta-cyclodextrin inclusion compound can also improve fisetin stability.
The yield measurement method, the encapsulation efficiency measurement method, and the solubility measurement method were the same as in example 1.
The inclusion compound yield was determined to be 80.57% and the encapsulation efficiency was 84.32%.
The results of the experiments are shown in the following table:
solubility experiments show that after the fisetin is included, the water solubility is increased by more than 20 times.
Example 3
Preparing a fisetin hydroxypropyl-beta-cyclodextrin solution with a molar ratio of 1: 3: accurately weighing 154.15mg of dried hydroxypropyl-beta-cyclodextrin into a beaker, adding 30ml of deionized water, and stirring with a glass rod until the hydroxypropyl-beta-cyclodextrin is fully dissolved to obtain a hydroxypropyl-beta-cyclodextrin aqueous solution; accurately weighing 9.54mg of fisetin into a small beaker, adding 5ml of ethanol, stirring and ultrasonically treating to fully dissolve fisetin in the ethanol to obtain a fisetin ethanol solution; slowly dripping the fisetin ethanol solution into the prepared hydroxypropyl-beta-cyclodextrin aqueous solution at the speed of 1.0ml/min, adding a stirrer, plugging a bottle stopper, sealing by using a sealing film, wrapping by using tinfoil, putting into a constant-temperature magnetic stirrer, setting the temperature to be 15 ℃, the rotating speed to be 200r/min, stirring for 1h in a dark place, taking out the sample, performing rotary evaporation on the uniformly stirred mixed solution to remove an organic solvent, filtering, pre-freezing the filtrate, transferring the pre-frozen sample into a freeze dryer, and freeze-drying for 12h, wherein the sample is yellow, dried and fluffy powder, and the temperature of the sample in the freeze dryer is close to the room temperature; the sample was removed. XRD, DSC, TG and FTIR detection prove that the fisetin is completely included in the hydroxypropyl-beta-cyclodextrin. Solubility detection shows that compared with fisetin bulk drugs, the solubility of the prepared inclusion compound is remarkably improved, and fisetin hydroxypropyl-beta-cyclodextrin inclusion compound can also improve fisetin stability.
The yield measurement method, the encapsulation efficiency measurement method, and the solubility measurement method were the same as in example 1.
The inclusion compound yield was determined to be 77.25% with an encapsulation efficiency of 74.66%.
The results of the experiments are shown in the following table:
solubility experiments show that after the fisetin is included, the water solubility is increased by more than 20 times.
Example 4
Preparing a fisetin hydroxypropyl-beta-cyclodextrin solution with a molar ratio of 1: 4: accurately weighing 154.15mg of dried hydroxypropyl-beta-cyclodextrin into a beaker, adding 30ml of deionized water, and stirring with a glass rod until the hydroxypropyl-beta-cyclodextrin is fully dissolved to obtain a hydroxypropyl-beta-cyclodextrin water solution; accurately weighing 7.155mg of fisetin into a small beaker, adding 5ml of ethanol, stirring and ultrasonically treating so that fisetin is fully dissolved in the ethanol to obtain a fisetin ethanol solution; slowly dripping the fisetin ethanol solution into the prepared hydroxypropyl-beta-cyclodextrin aqueous solution at the speed of 1.0ml/min, adding a stirrer, plugging a bottle stopper, sealing by using a sealing film, wrapping by using tinfoil, putting into a constant-temperature magnetic stirrer, setting the temperature to be 15 ℃, the rotating speed to be 200r/min, stirring for 1h in a dark place, taking out the sample, performing rotary evaporation on the uniformly stirred mixed solution to remove an organic solvent, filtering, pre-freezing the filtrate, transferring the pre-frozen sample into a freeze dryer, and freeze-drying for 12h, wherein the sample is yellow, dried and fluffy powder, and the temperature of the sample in the freeze dryer is close to the room temperature; the sample was removed. XRD, DSC, TG and FTIR detection prove that the fisetin is completely included in the hydroxypropyl-beta-cyclodextrin. Solubility detection shows that compared with fisetin bulk drugs, the solubility of the prepared inclusion compound is remarkably improved, and fisetin hydroxypropyl-beta-cyclodextrin inclusion compound can also improve fisetin stability.
The yield measurement method, the encapsulation efficiency measurement method, and the solubility measurement method were the same as in example 1.
The inclusion compound yield was determined to be 73.31% and the encapsulation efficiency was 44.53%.
The results of the experiments are shown in the following table:
solubility experiments show that after the fisetin is included, the water solubility is increased by more than 20 times.
Example 5
Preparing a fisetin hydroxypropyl-beta-cyclodextrin solution with a molar ratio of 1: 5: accurately weighing 154.15mg of dried hydroxypropyl-beta-cyclodextrin into a beaker, adding 30ml of deionized water, and stirring with a glass rod until the hydroxypropyl-beta-cyclodextrin is fully dissolved to obtain a hydroxypropyl-beta-cyclodextrin aqueous solution; accurately weighing 5.724mg of fisetin into a small beaker, adding 5ml of ethanol, stirring and ultrasonically treating to ensure that fisetin is fully dissolved in the ethanol to obtain a fisetin ethanol solution; slowly dripping the fisetin ethanol solution into the prepared hydroxypropyl-beta-cyclodextrin aqueous solution at the speed of 1.0ml/min, adding a stirrer, plugging a bottle stopper, sealing by using a sealing film, wrapping by using tinfoil, putting into a constant-temperature magnetic stirrer, setting the temperature to be 15 ℃, the rotating speed to be 200r/min, stirring for 1h in a dark place, taking out the sample, performing rotary evaporation on the uniformly stirred mixed solution to remove an organic solvent, filtering, pre-freezing the filtrate, transferring the pre-frozen sample into a freeze dryer, and freeze-drying for 12h, wherein the sample is yellow, dried and fluffy powder, and the temperature of the sample in the freeze dryer is close to the room temperature; the sample was removed. XRD, DSC, TG and FTIR detection prove that the fisetin is completely included in the hydroxypropyl-beta-cyclodextrin. Solubility detection shows that compared with fisetin bulk drugs, the solubility of the prepared inclusion compound is remarkably improved, and fisetin hydroxypropyl-beta-cyclodextrin inclusion compound can also improve fisetin stability.
The yield measurement method, the encapsulation efficiency measurement method, and the solubility measurement method were the same as in example 1.
The inclusion compound yield was determined to be 72.23% with an encapsulation efficiency of 41.72%.
The results of the experiments are shown in the following table:
solubility experiments show that after the fisetin is included, the water solubility is increased by more than 20 times.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (7)
1. A preparation method of a fisetin hydroxypropyl-beta-cyclodextrin inclusion compound is characterized by comprising the following steps: dissolving hydroxypropyl-beta-cyclodextrin in deionized water to obtain a hydroxypropyl-beta-cyclodextrin aqueous solution; dissolving fisetin in ethanol to obtain fisetin ethanol solution; slowly dripping the fisetin ethanol solution into the hydroxypropyl-beta-cyclodextrin aqueous solution, sealing, transferring into a water bath, stirring in the dark, performing rotary evaporation on the uniformly stirred mixed solution to remove the organic solvent, filtering, keeping the filtrate, and performing freeze drying to obtain the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound.
2. The method for preparing the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound according to claim 1, wherein the molar ratio of fisetin to hydroxypropyl-beta-cyclodextrin is 1:1 to 1: 3.
3. The preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound according to claim 1, wherein the stirring reaction time in a water bath is 1-12 hours.
4. The preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound according to claim 1, wherein the temperature of the water bath in the water bath kettle is 15-35 ℃.
5. The preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound according to claim 1, wherein the stirring speed is 200-600 r/min.
6. The method for preparing the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound according to claim 1, wherein the dropping speed of the fisetin ethanol solution to the hydroxypropyl-beta-cyclodextrin aqueous solution is 1.0 to 2.0 ml/min.
7. The preparation method of the fisetin hydroxypropyl-beta-cyclodextrin inclusion compound according to claim 1, wherein the freeze-drying time of the inclusion compound is 6-24 hours.
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| Title |
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| NORATIQAH MOHTAR: "Design and development of dry powder sulfobutylether-b-cyclodextrin complex for pulmonary delivery of fisetin" * |
| 李燕华等: "漆黄素与-β-环糊精衍生物的包合行为及性能研究" * |
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