CN116327737B - Preparation method of resveratrol microcapsule based on metal-organic framework - Google Patents
Preparation method of resveratrol microcapsule based on metal-organic framework Download PDFInfo
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- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 title claims abstract description 259
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 title claims abstract description 259
- 235000021283 resveratrol Nutrition 0.000 title claims abstract description 259
- 229940016667 resveratrol Drugs 0.000 title claims abstract description 259
- 239000012621 metal-organic framework Substances 0.000 title claims abstract description 228
- 238000002360 preparation method Methods 0.000 title claims abstract description 55
- 239000003094 microcapsule Substances 0.000 title claims abstract description 49
- 239000000843 powder Substances 0.000 claims abstract description 80
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 164
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 144
- 239000000243 solution Substances 0.000 claims description 93
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 66
- 238000006243 chemical reaction Methods 0.000 claims description 48
- 229920000858 Cyclodextrin Polymers 0.000 claims description 39
- 238000010438 heat treatment Methods 0.000 claims description 39
- 229940080345 gamma-cyclodextrin Drugs 0.000 claims description 36
- 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 33
- 239000004094 surface-active agent Substances 0.000 claims description 25
- 238000004140 cleaning Methods 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 17
- 229920002538 Polyethylene Glycol 20000 Polymers 0.000 claims description 16
- 238000001816 cooling Methods 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 13
- 230000036571 hydration Effects 0.000 claims description 13
- 238000006703 hydration reaction Methods 0.000 claims description 13
- 239000011259 mixed solution Substances 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 8
- 238000001291 vacuum drying Methods 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 abstract description 10
- 238000007254 oxidation reaction Methods 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 9
- 230000008569 process Effects 0.000 abstract description 2
- 238000001179 sorption measurement Methods 0.000 description 58
- 235000019441 ethanol Nutrition 0.000 description 48
- 239000002245 particle Substances 0.000 description 46
- 239000000126 substance Substances 0.000 description 42
- 238000002835 absorbance Methods 0.000 description 29
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 15
- 239000013078 crystal Substances 0.000 description 14
- 239000012086 standard solution Substances 0.000 description 14
- 239000013119 CD-MOF Substances 0.000 description 10
- 239000003963 antioxidant agent Substances 0.000 description 9
- 230000003078 antioxidant effect Effects 0.000 description 9
- 235000006708 antioxidants Nutrition 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 9
- 235000012754 curcumin Nutrition 0.000 description 8
- 229940109262 curcumin Drugs 0.000 description 8
- 239000004148 curcumin Substances 0.000 description 8
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000004729 solvothermal method Methods 0.000 description 8
- 238000009826 distribution Methods 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000007760 free radical scavenging Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000002159 nanocrystal Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000005303 weighing Methods 0.000 description 7
- 238000000502 dialysis Methods 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000002292 Radical scavenging effect Effects 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 5
- 238000000691 measurement method Methods 0.000 description 5
- 239000011148 porous material Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 238000003556 assay Methods 0.000 description 3
- MGJZITXUQXWAKY-UHFFFAOYSA-N diphenyl-(2,4,6-trinitrophenyl)iminoazanium Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1N=[N+](C=1C=CC=CC=1)C1=CC=CC=C1 MGJZITXUQXWAKY-UHFFFAOYSA-N 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000003760 magnetic stirring Methods 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 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 3
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000218231 Moraceae Species 0.000 description 1
- 235000008708 Morus alba Nutrition 0.000 description 1
- 241001648835 Polygonum cuspidatum Species 0.000 description 1
- 235000018167 Reynoutria japonica Nutrition 0.000 description 1
- 241001170744 Veratrum nigrum Species 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- -1 flavonoid polyphenol compound Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 235000020939 nutritional additive Nutrition 0.000 description 1
- 239000013384 organic framework Substances 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5089—Processes
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of resveratrol metal organic framework microcapsules, which comprises the following steps: preparing a metal organic framework reaction liquid, preparing a metal organic framework, preparing metal organic framework powder, preparing resveratrol metal organic framework microcapsules and preparing resveratrol metal organic framework microcapsule powder. The resveratrol metal organic framework microcapsule prepared by adsorbing the resveratrol by using the metal organic framework has the advantages of uniform size, simple process, high stability, strong oxidation resistance and slow release effect.
Description
Technical Field
The invention belongs to the technical field of microcapsule preparation, and particularly relates to a preparation method of resveratrol microcapsule based on a metal organic framework.
Background
Resveratrol is a natural non-flavonoid polyphenol compound, and exists in medicinal materials such as veratrum nigrum, polygonum cuspidatum and the like, and also exists in foods such as grapes, mulberries and the like. Resveratrol exists in two forms, namely a trans isomer and a cis isomer, and the trans isomer has stronger biological activity but is easy to be converted into the cis isomer under the irradiation of ultraviolet light. Resveratrol has many biological activities such as anti-inflammatory, antioxidant, anti-free radical, anti-cardiovascular disease, anti-tumor and the like, but has the property of poor water solubility and easy decomposition of visible light, and the wide metabolism in vivo severely limits the exertion of the biological activity. In recent years, a nano-delivery system attracts attention of researchers due to its good biocompatibility, targeting property and sustained release property. The resveratrol nano-delivery system is hopeful to make up for the deficiency of physical properties of resveratrol, improve the bioavailability, fully exert the bioactivity of the resveratrol, improve the application value and be applied to medicines, foods and nutritional additives.
Metal Organic Frameworks (MOFs) are a new class of porous crystalline materials formed by self-assembly of metal ions or ion clusters and organic ligands, which have attracted considerable attention in industry and academia as a new class of functional molecular materials. The MOF material has the advantages of rich topological structure and designability; the size is controllable, and the aperture is adjustable; the specific surface area is large, and the adsorption and embedding are easy; easy functionalization, etc. However, the common MOF material has higher cost and complicated preparation process, and the transition metal is used as a complex, so that the application of the MOF material in foods and medicines is limited. The hydroxyl structure of cyclodextrin is a good hydrogen bond donor, and is also a coordination site combined with metal ions, and a huge hydrophobic cavity is added, so that the cyclodextrin becomes an important member in a supermolecular system. Cyclodextrin in alkaline solution, C 2 -OH and C 3 OH is easy to remove proton, can self-assemble with metal ions to form a mononuclear or polynuclear complex, namely, cyclodextrin metal-organic frameworks (CD-MOFs) are increasingly focused on research along with the proposal of a green chemical concept and the discovery of excellent adsorption and embedding controlled release characteristics of MOF materials in foods and medicines. Therefore, the adsorption of resveratrol by using CD-MOF is an effective way for improving the stability and prolonging the storage period.
Disclosure of Invention
This section is intended to outline some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section as well as in the description summary and in the title of the application, to avoid obscuring the purpose of this section, the description summary and the title of the invention, which should not be used to limit the scope of the invention.
The present invention has been made in view of the above and/or problems occurring in the prior art.
Therefore, the invention aims to overcome the defects in the prior art and provide a preparation method of resveratrol metal organic framework microcapsules.
In order to solve the technical problems, the invention provides the following technical scheme: a preparation method of resveratrol metal organic framework microcapsules, which comprises the following steps,
preparing a metal organic framework reaction solution: dissolving gamma-cyclodextrin powder and potassium hydroxide powder in water according to a certain proportion, refrigerating and hydrating;
preparing a metal organic framework: adding methanol with a certain proportion into the reaction liquid, heating for a certain time, quickly adding a surfactant with a certain concentration after finishing, and cooling at room temperature;
Preparing metal organic framework powder: centrifuging the prepared metal-organic framework, cleaning with methanol, and freeze-drying;
preparing resveratrol metal organic framework microcapsules: the resveratrol powder and the metal organic framework powder are redistributed in ethanol solution according to a certain proportion, and heated and stirred for a certain time.
Preparing resveratrol metal organic framework microcapsule powder: centrifuging the ethanol mixed solution of resveratrol and the metal organic framework, washing the precipitate with the ethanol solution for three times, and then carrying out vacuum drying.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the metal organic framework reaction solution, the total concentration of the gamma-cyclodextrin powder and the potassium hydroxide is 21.8-98.1 mg/mL.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the reaction solution for preparing the metal-organic framework, the molar ratio of the gamma-cyclodextrin to the potassium hydroxide is 9-6: 1.
as a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the metal-organic framework, the volume ratio of the added methanol to the reaction solution is 5-8: 10.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the metal-organic framework, the heating time is 40-70 min.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the metal-organic framework, the heating temperature is 40-70 ℃.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the metal-organic framework, the surfactant is one of PEG200, PEG2000, PEG10000 and PEG 20000.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the metal-organic framework, the concentration of the surfactant is 6-10 mg/mL.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the resveratrol metal organic framework microcapsule, the stirring time is 3-7 hours.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the resveratrol metal organic framework microcapsule, the heating temperature is 40-70 ℃.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the resveratrol metal organic framework microcapsule, the concentration of the resveratrol is 1-5 mg/mL.
As a preferable scheme of the preparation method of the resveratrol metal organic framework microcapsule, the preparation method comprises the following steps: in the preparation of the resveratrol metal-organic framework microcapsule, the mass ratio of resveratrol to the metal-organic framework is 0.7-1.1: 1.
the invention has the beneficial effects that:
the invention prepares the gamma-cyclodextrin metal organic framework with uniform size and three-dimensional structure by utilizing a solvothermal synthesis method, has simple process and is suitable for industrial production. The gamma-cyclodextrin metal organic framework can be used for effectively adsorbing the resveratrol in the metal organic framework, so that the retention rate of the resveratrol in different mediums is prolonged, the antioxidation characteristic of the resveratrol is enhanced, the stability of the resveratrol under ultraviolet irradiation is improved, and meanwhile, the resveratrol metal organic framework microcapsule has the effect of slowly releasing the resveratrol.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the description of the embodiments will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art. Wherein:
FIG. 1 is a scanning electron microscope image of a resveratrol metal-organic framework curcumin microcapsule in example 1 of the present invention;
FIG. 2 is a graph showing the particle size of the metal organic framework of example 2 of the present invention at various total concentrations of gamma cyclodextrin powder and potassium hydroxide;
FIG. 3 is a graph showing the particle size of the metal organic framework of example 3 of the present invention at different molar ratios of gamma-cyclodextrin to potassium hydroxide;
FIG. 4 shows the particle size of the metal-organic framework of example 4 according to the present invention at different volume ratios of methanol to reaction solution;
FIG. 5 is a graph showing the particle size of the metal-organic framework of example 5 according to the present invention at different heating times;
FIG. 6 is a graph showing the particle size of the metal-organic framework of example 6 according to the present invention at different heating temperatures;
FIG. 7 is a graph showing the particle size of the metal organic framework of example 7 according to the present invention for different surfactant types;
FIG. 8 is a graph showing the particle size of the metal organic framework of example 8 of the present invention at various surfactant concentrations;
FIG. 9 shows the adsorption rate of resveratrol in a metal organic framework at various stirring times in example 9 of the present invention;
FIG. 10 shows the adsorption rate of resveratrol in metal organic frameworks at different stirring temperatures in example 10 of the present invention;
FIG. 11 shows the adsorption rate of resveratrol in metal organic frameworks at different concentrations in example 11 of the present invention;
FIG. 12 shows the adsorption rate of resveratrol in the metal organic framework under different ratios of resveratrol to metal organic framework in example 12 of the present invention;
FIG. 13 shows the adsorption rate of resveratrol in comparative example 1 and example 1 according to the present invention;
FIG. 14 shows the stability of resveratrol in comparative example 1 and example 13 according to the present invention;
FIG. 15 shows the cumulative release of resveratrol from different vehicles in comparative example 1 and example 13 according to the present invention;
FIG. 16 is the radical scavenging ability of resveratrol in comparative example 1 and example 13 according to the present invention;
FIG. 17 shows the anti-UV oxidative stability of resveratrol in comparative example 1 and example 13 according to the present invention;
FIG. 18 shows the stability of resveratrol in comparative example 2 and example 13 according to the present invention;
FIG. 19 is a graph showing the cumulative release of resveratrol from different vehicles according to comparative example 2 and example 13 of the present invention;
FIG. 20 is the radical scavenging ability of resveratrol in comparative example 2 and example 13 according to the present invention;
figure 21 is the uv oxidation stability of resveratrol in comparative example 2 and example 13 of the present invention.
Detailed Description
In order that the above-recited objects, features and advantages of the present invention will become more apparent, a more particular description of the invention will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways other than those described herein, and persons skilled in the art will readily appreciate that the present invention is not limited to the specific embodiments disclosed below.
Further, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic can be included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at 60 ℃ for 60min, rapidly adding surfactant PEG20000 with concentration of 8mg/mL after the completion of the heating, and cooling at room temperature;
3. Preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use;
4. preparing resveratrol metal organic framework microcapsules:
resveratrol powder and metal organic framework powder were mixed in a ratio of 1:1 in the ethanol solution to make the resveratrol concentration be 4mg/mL, and heating and stirring for 6h at 60 ℃;
5. preparing resveratrol metal organic framework microcapsule powder:
centrifuging ethanol mixed solution of resveratrol and metal organic framework, cleaning precipitate with ethanol solution for three times, and vacuum drying at 45deg.C overnight.
And (3) observing the prepared resveratrol metal organic framework microcapsule by a scanning electron microscope to obtain the figure 1. As can be taken from fig. 1, the resveratrol metal organic framework microcapsules prepared in this example exhibit uniformly dispersed cubes.
Example 2
Kinetic capture of MOFs of a particular size depends on the adjustment of chemical equilibrium at the preparation stage. Because these chemical balances determine whether MOFs grow steadily to bulk phases or are rapidly trapped to form nanocrystals. In solvothermal methods, the operating conditions and formulations greatly affect the chemical equilibrium and directly affect the unique characteristics of MOFs, including crystal size distribution, crystallinity, and crystal morphology. The chemical equilibrium in the preparation process of the metal-organic framework has an influence on the performance of the finished product, and the influence of different concentrations of the reaction solution on the particle size of the metal-organic framework is explored in the embodiment.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in molar ratio in water to obtain sample reaction solutions with different concentrations (21.8 mg/mL, 43.6mg/mL, 65.4mg/mL and 98.1 mg/mL), and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at 60 ℃ for 60min, rapidly adding surfactant PEG20000 with concentration of 8mg/mL after the completion of the heating, and cooling at room temperature;
3. preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use; the particle size of the resulting emulsion was measured at 25 ℃ using a laser particle sizer and the data obtained is recorded in fig. 2.
As can be seen from fig. 2, as the concentration of the reaction solution increases, the particle diameter of the metal-organic framework tends to decrease first and then increase, and when the concentration of the reaction solution is 43.6mg/mL, the particle diameter of the prepared metal-organic framework is smallest, so that 43.6mg/mL is preferable as the concentration of the reaction solution.
Example 3
Kinetic capture of MOFs of a particular size depends on the adjustment of chemical equilibrium at the preparation stage. Because these chemical balances determine whether MOFs grow steadily to bulk phases or are rapidly trapped to form nanocrystals. In solvothermal methods, the operating conditions and formulations greatly affect the chemical equilibrium and directly affect the unique characteristics of MOFs, including crystal size distribution, crystallinity, and crystal morphology. The chemical equilibrium in the preparation process of the metal-organic framework has an influence on the performance of the finished product, and the influence of different molar ratios of gamma-cyclodextrin and potassium hydroxide on the particle size of the metal-organic framework is explored in the embodiment.
1. Preparing a metal organic framework reaction solution:
dissolving gamma-cyclodextrin powder and potassium hydroxide powder in water according to different molar ratios (9:1, 8:1, 7:1 and 6:1) to ensure that the sample concentration reaches 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at 60 ℃ for 60min, rapidly adding surfactant PEG20000 with concentration of 8mg/mL after the completion of the heating, and cooling at room temperature;
3. preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use; the particle size of the resulting emulsion was measured at 25 ℃ using a laser particle sizer and the data obtained is recorded in fig. 3.
As can be seen from fig. 3, as the molar ratio of γ -cyclodextrin to potassium hydroxide increases, the particle size of the metal-organic framework tends to decrease and then increase, when the molar ratio of γ -cyclodextrin to potassium hydroxide is 8:1, the metal-organic framework prepared has the smallest particle size, and the molar ratio of gamma-cyclodextrin to potassium hydroxide is preferably 8 in terms of both the combination cost and the particle size: 1 as the optimal reaction molar ratio.
Example 4
Kinetic capture of MOFs of a particular size depends on the adjustment of chemical equilibrium at the preparation stage. Because these chemical balances determine whether MOFs grow steadily to bulk phases or are rapidly trapped to form nanocrystals. In solvothermal methods, the operating conditions and formulations greatly affect the chemical equilibrium and directly affect the unique characteristics of MOFs, including crystal size distribution, crystallinity, and crystal morphology. The chemical balance in the preparation process of the metal-organic framework has an influence on the performance of the finished product, and the embodiment explores the influence of different volume ratios of methanol to reaction liquid on the particle size of the metal-organic framework.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding different volumes of methanol (reaction liquid: methanol=10:8, 10:7, 10:6, 10:5, v/v) into the reaction liquid, heating at 60 ℃ for 60min, rapidly adding surfactant PEG20000 with concentration of 8mg/mL after the completion, and cooling at room temperature;
3. preparing metal organic framework powder:
Centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use; the particle size of the resulting emulsion was measured at 25 ℃ using a laser particle sizer and the data obtained is recorded in fig. 4.
As can be taken from fig. 4, as the volume of methanol added increases, the particle size of the metal-organic framework tends to decrease and then increase, and when the reaction liquid: methanol=10: 6, the metal-organic framework prepared has the smallest particle size, and the reaction liquid is preferable in terms of both the combination cost and the particle size: methanol=10: 6 as the optimal volume ratio of methanol to reaction solution.
Example 5
Kinetic capture of MOFs of a particular size depends on the adjustment of chemical equilibrium at the preparation stage. Because these chemical balances determine whether MOFs grow steadily to bulk phases or are rapidly trapped to form nanocrystals. In solvothermal methods, the operating conditions and formulations greatly affect the chemical equilibrium and directly affect the unique characteristics of MOFs, including crystal size distribution, crystallinity, and crystal morphology. The chemical equilibrium in the preparation process of the metal-organic framework has an influence on the performance of the finished product, and the influence of different heating time on the particle size of the metal-organic framework is explored in the embodiment.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at 60 ℃ for a certain time (40 min, 50min, 60min and 70 min), rapidly adding surfactant PEG20000 with concentration of 8mg/mL after the completion, and cooling at room temperature;
3. preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use; the particle size of the resulting emulsion was measured at 25 ℃ using a laser particle sizer and the data obtained is recorded in fig. 5.
As can be seen from fig. 5, as the heating time increases, the particle size of the metal-organic framework tends to decrease first and then increase, and when the heating time is 60min, the particle size of the prepared metal-organic framework is smallest, and 60min is preferable as the optimal heating time in terms of both the combination cost and the particle size.
Example 6
Kinetic capture of MOFs of a particular size depends on the adjustment of chemical equilibrium at the preparation stage. Because these chemical balances determine whether MOFs grow steadily to bulk phases or are rapidly trapped to form nanocrystals. In solvothermal methods, the operating conditions and formulations greatly affect the chemical equilibrium and directly affect the unique characteristics of MOFs, including crystal size distribution, crystallinity, and crystal morphology. The chemical equilibrium in the preparation process of the metal-organic framework has an influence on the performance of the finished product, and the influence of different heating temperatures on the particle size of the metal-organic framework is explored in the embodiment.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at different temperature conditions (40 ℃, 50 ℃, 60 ℃ and 70 ℃) for 60min, rapidly adding surfactant PEG20000 with concentration of 8mg/mL after finishing, and cooling at room temperature;
3. preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use; the particle size of the resulting emulsion was measured at 25 ℃ using a laser particle sizer and the data obtained is recorded in fig. 6.
As can be seen from fig. 6, as the heating temperature increases, the particle size of the metal-organic framework tends to decrease and then increase, and when the heating temperature is 60 ℃, the particle size of the prepared metal-organic framework is smallest, and 60 ℃ is preferable as the optimal heating temperature in terms of both the combination cost and the particle size.
Example 7
Kinetic capture of MOFs of a particular size depends on the adjustment of chemical equilibrium at the preparation stage. Because these chemical balances determine whether MOFs grow steadily to bulk phases or are rapidly trapped to form nanocrystals. In solvothermal methods, the operating conditions and formulations greatly affect the chemical equilibrium and directly affect the unique characteristics of MOFs, including crystal size distribution, crystallinity, and crystal morphology. The chemical equilibrium in the preparation process of the metal-organic framework has an influence on the performance of the finished product, and the influence of different surfactant types on the particle size of the metal-organic framework is explored in the embodiment.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at 60deg.C for 60min, rapidly adding surfactant (PEG 200, PEG2000, PEG10000 and PEG 20000) with concentration of 8mg/mL after finishing, and cooling at room temperature;
3. preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use; the particle size of the resulting emulsion was measured at 25 ℃ using a laser particle sizer and the data obtained is recorded in fig. 7.
As can be taken from fig. 7, when PEG20000 is selected as the surfactant, the particle size of the prepared metal-organic framework is smallest, and thus PEG20000 is preferable as the surfactant.
Example 8
Kinetic capture of MOFs of a particular size depends on the adjustment of chemical equilibrium at the preparation stage. Because these chemical balances determine whether MOFs grow steadily to bulk phases or are rapidly trapped to form nanocrystals. In solvothermal methods, the operating conditions and formulations greatly affect the chemical equilibrium and directly affect the unique characteristics of MOFs, including crystal size distribution, crystallinity, and crystal morphology. The chemical equilibrium in the preparation process of the metal-organic framework has an influence on the performance of the finished product, and the influence of different concentrations of the surfactant on the particle size of the metal-organic framework is explored in the embodiment.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
methanol (reaction solution: methanol=10:6, v/v) was added to the reaction solution and heated at 60 ℃ for 60min, and after the completion, surfactants PEG20000 of different concentrations (6 mg/mL, 7mg/mL, 8mg/mL, 9mg/mL and 10 mg/mL) were rapidly added and cooled at room temperature;
3. preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use; the particle size of the resulting emulsion was measured at 25 ℃ using a laser particle sizer and the data obtained is recorded in fig. 8.
As can be seen from fig. 8, as the concentration of the surfactant increases, the particle size of the metal-organic framework tends to decrease and then increase, and when the concentration of the surfactant is 8mg/mL, the particle size of the prepared metal-organic framework is smallest, and from the viewpoints of the combination cost and the particle size, 8mg/mL is preferable as the optimum surfactant concentration.
Example 9
The cyclodextrin metal organic framework is used as a porous material, has larger specific surface area and has great potential in the aspects of active ingredient adsorption and embedding. However, during adsorption of the active ingredient on the metal-organic framework, the operating conditions and the concentration of the active ingredient greatly influence the adsorption rate. This example discusses the effect of agitation time on resveratrol adsorption rate.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at 60 ℃ for 60min, rapidly adding surfactant PEG20000 with concentration of 8mg/mL after the completion of the heating, and cooling at room temperature;
3. preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use;
4. preparing resveratrol metal organic framework microcapsules:
resveratrol powder and metal organic framework powder were mixed in a ratio of 1:1 in ethanol solution to obtain resveratrol concentration of 4mg/mL, and heating and stirring at 60deg.C for different times (4 h, 5h, 6h and 7 h);
5. preparing resveratrol metal organic framework microcapsule powder:
centrifuging ethanol mixed solution of resveratrol and metal organic framework, cleaning precipitate with ethanol solution for three times, and vacuum drying at 45deg.C overnight. The prepared resveratrol metal organic framework microcapsule powder is subjected to resveratrol adsorption rate measurement, and the measurement method comprises the following steps of:
(1) Drawing resveratrol standard curve
Accurately weighing 1mg of resveratrol standard substance, dissolving the resveratrol standard substance in an absolute ethanol solution, and fixing the volume to 10mL to obtain resveratrol standard liquid with the mass concentration of 0.1 mg/mL. Accurately sucking 1, 2, 3, 4 and 5mL of curcumin standard solution respectively, adding the standard solution into a 10mL volumetric flask, then using absolute ethyl alcohol to fix the volume, and measuring the absorbance value at 306 nm. Respectively taking resveratrol concentration and absorbance value as the abscissa and ordinate to obtain a standard curve: y= 71.02x-0.1236, r 2 =0.99; wherein y is the absorbance value, x is the resveratrol mass concentration (mg/mL);
(2) Determination of resveratrol adsorption Rate
The absorbance of the supernatant after centrifugation in 5 above was measured at 306nm using a spectrophotometer, and the content of unadsorbed free resveratrol was calculated from the standard curve.
The adsorption rate of resveratrol = (total resveratrol content-free resveratrol content)/total resveratrol content is 100%, and the obtained data is recorded in fig. 9.
As can be seen from fig. 9, the adsorption rate of resveratrol gradually increased with the increase of the stirring time, and the adsorption rate of resveratrol reached the maximum value when the stirring time was 6 hours. Further increase of the stirring time does not increase the adsorption rate of resveratrol, and 6h is preferable as the optimal stirring time in view of the adsorption rate.
Example 10
The cyclodextrin metal organic framework is used as a porous material, has larger specific surface area and has great potential in the aspects of active ingredient adsorption and embedding. However, during adsorption of the active ingredient on the metal-organic framework, the operating conditions and the concentration of the active ingredient greatly influence the adsorption rate. This example discusses the effect of stirring temperature on resveratrol adsorption rate.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at 60 ℃ for 60min, rapidly adding surfactant PEG20000 with concentration of 8mg/mL after the completion of the heating, and cooling at room temperature;
3. preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use;
4. preparing resveratrol metal organic framework microcapsules:
resveratrol powder and metal organic framework powder were mixed in a ratio of 1:1 in an ethanol solution to a resveratrol concentration of 4mg/mL, and heating and stirring at different heating temperatures (40 ℃, 50 ℃, 60 ℃ and 70 ℃) for 6 hours;
5. Preparing resveratrol metal organic framework microcapsule powder:
centrifuging ethanol mixed solution of resveratrol and metal organic framework, cleaning precipitate with ethanol solution for three times, and vacuum drying at 45deg.C overnight. The prepared resveratrol metal organic framework microcapsule powder is subjected to resveratrol adsorption rate measurement, and the measurement method comprises the following steps of:
(1) Drawing resveratrol standard curve
Accurately weighing 1mg of resveratrol standard substance, dissolving the resveratrol standard substance in an absolute ethanol solution, and fixing the volume to 10mL to obtain resveratrol standard liquid with the mass concentration of 0.1 mg/mL. Accurately sucking 1, 2, 3, 4 and 5mL of curcumin standard solution respectively, adding the standard solution into a 10mL volumetric flask, then using absolute ethyl alcohol to fix the volume, and measuring the absorbance value at 306 nm. Respectively taking resveratrol concentration and absorbance value as the abscissa and ordinate to obtain a standard curve: y=71.02x-0.1236，R 2 =0.99; wherein y is the absorbance value, and x is the resveratrol mass concentration (mg/mL).
(2) Determination of resveratrol adsorption Rate
The absorbance of the supernatant after centrifugation in 5 above was measured at 306nm using a spectrophotometer, and the content of unadsorbed free resveratrol was calculated from the standard curve.
The adsorption rate of resveratrol = (total resveratrol content-free resveratrol content)/total resveratrol content is 100%, and the obtained data is recorded in fig. 10.
As can be seen from fig. 10, the adsorption rate of resveratrol gradually increases with an increase in the stirring temperature, and reaches the maximum value when the stirring temperature is 60 ℃. Further improvement of the stirring temperature does not increase the adsorption rate of resveratrol, but 60 ℃ is preferable as the optimal stirring temperature in view of the adsorption rate.
Example 11
The cyclodextrin metal organic framework is used as a porous material, has larger specific surface area and has great potential in the aspects of active ingredient adsorption and embedding. However, during adsorption of the active ingredient on the metal-organic framework, the operating conditions and the concentration of the active ingredient greatly influence the adsorption rate. This example discusses the effect of resveratrol concentration on its adsorption rate.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at 60 ℃ for 60min, rapidly adding surfactant PEG20000 with concentration of 8mg/mL after the completion of the heating, and cooling at room temperature;
3. Preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use;
4. preparing resveratrol metal organic framework microcapsules:
resveratrol powder and metal organic framework powder were mixed in a ratio of 1:1 in ethanol solution while adjusting the dissolution concentrations of the different resveratrol (1 mg/mL, 2mg/mL, 3mg/mL, 4mg/mL and 5 mg/mL), and heating and stirring at 60 ℃ for 6h.
5. Preparing resveratrol metal organic framework microcapsule powder:
centrifuging ethanol mixed solution of resveratrol and metal organic framework, cleaning precipitate with ethanol solution for three times, and vacuum drying at 45deg.C overnight. The prepared resveratrol metal organic framework microcapsule powder is subjected to resveratrol adsorption rate measurement, and the measurement method comprises the following steps of:
(1) Drawing resveratrol standard curve
Accurately weighing 1mg of resveratrol standard substance, dissolving the resveratrol standard substance in an absolute ethanol solution, and fixing the volume to 10mL to obtain resveratrol standard liquid with the mass concentration of 0.1 mg/mL. Accurately sucking 1, 2, 3, 4 and 5mL of curcumin standard solution respectively, adding the standard solution into a 10mL volumetric flask, then using absolute ethyl alcohol to fix the volume, and measuring the absorbance value at 306 nm. Respectively taking resveratrol concentration and absorbance value as the abscissa and ordinate to obtain a standard curve: y= 71.02x-0.1236, r 2 =0.99; wherein y is the absorbance value, and x is the resveratrol mass concentration (mg/mL).
(2) Determination of resveratrol adsorption Rate
The absorbance of the supernatant after centrifugation in 5 above was measured at 306nm using a spectrophotometer, and the content of unadsorbed free resveratrol was calculated from the standard curve.
The adsorption rate of resveratrol = (total resveratrol content-free resveratrol content)/total resveratrol content is 100%, and the obtained data is recorded in fig. 11.
As can be seen from fig. 11, the adsorption rate of resveratrol gradually increased as the dissolution concentration of resveratrol increased, and the adsorption rate of resveratrol reached the maximum value when the dissolution concentration was 4 mg/mL. Further improvement of the dissolution concentration does not increase the absorption rate of resveratrol, but preferably 4mg/mL is the optimal dissolution concentration in terms of both the combination cost and the absorption rate.
Example 12
The cyclodextrin metal organic framework is used as a porous material, has larger specific surface area and has great potential in the aspects of active ingredient adsorption and embedding. However, during adsorption of the active ingredient on the metal-organic framework, the operating conditions and the concentration of the active ingredient greatly influence the adsorption rate. This example discusses the effect of different mass ratios of resveratrol and metal organic frameworks on their adsorption rates.
1. Preparing a metal organic framework reaction solution:
taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
2. preparing a metal organic framework:
adding methanol (reaction solution: methanol=10:6, v/v) into the reaction solution, heating at 60 ℃ for 60min, rapidly adding surfactant PEG20000 with concentration of 8mg/mL after the completion of the heating, and cooling at room temperature;
3. preparing metal organic framework powder:
centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use;
4. preparing resveratrol metal organic framework microcapsules:
resveratrol powder and metal organic framework powder were redistributed in ethanol solution in different ratios (0.7:1, 0.8:1, 0.9:1, 1:1 and 1.1:1, w/w) while adjusting the dissolution concentration of resveratrol to 4mg/mL, and heated and stirred at 60 ℃ for 6h.
5. Preparing resveratrol metal organic framework microcapsule powder:
centrifuging ethanol mixed solution of resveratrol and metal organic framework, cleaning precipitate with ethanol solution for three times, and vacuum drying at 45deg.C overnight. The prepared resveratrol metal organic framework microcapsule powder is subjected to resveratrol adsorption rate measurement, and the measurement method comprises the following steps of:
(1) Drawing resveratrol standard curve
Accurately weighing 1mg of resveratrol standard substance, dissolving the resveratrol standard substance in an absolute ethanol solution, and fixing the volume to 10mL to obtain resveratrol standard liquid with the mass concentration of 0.1 mg/mL. Accurately sucking 1, 2, 3, 4 and 5mL of curcumin standard solution respectively, adding the standard solution into a 10mL volumetric flask, then using absolute ethyl alcohol to fix the volume, and measuring the absorbance value at 306 nm. Respectively taking resveratrol concentration and absorbance value as the abscissa and ordinate to obtain a standard curve: y= 71.02x-0.1236, r 2 =0.99; wherein y is the absorbance value, and x is the resveratrol mass concentration (mg/mL).
(2) Determination of resveratrol adsorption Rate
The absorbance of the supernatant after centrifugation in 5 above was measured at 306nm using a spectrophotometer, and the content of unadsorbed free resveratrol was calculated from the standard curve.
The adsorption rate of resveratrol = (total resveratrol content-free resveratrol content)/total resveratrol content is 100%, and the obtained data is recorded in fig. 12.
As can be seen from fig. 12, as the ratio of resveratrol to metal organic framework increases, the adsorption rate of resveratrol gradually increases, and when the mass ratio of resveratrol to metal organic framework is 1: in 1, the adsorption rate of resveratrol reaches the maximum value. Further improving the mass ratio of the resveratrol and the metal organic framework does not increase the adsorption rate of the resveratrol, and considering the combination cost and the adsorption rate, the ratio of the resveratrol to the metal organic framework is preferably 1:1 is the optimal mass ratio.
Example 13
This example is a measurement of the properties of the finished product obtained in example 1, including stability, amount of released, ability to scavenge free radicals, and stability to ultraviolet oxidation, as follows:
(1) Drawing resveratrol standard curve
Accurately weighing 1mg resveratrol standard substance, dissolving in absolute ethanol solution, and fixing volume to 10mL to obtain resveratrol with mass concentration of 0.1mg/mLStandard solution. Accurately sucking 1, 2, 3, 4 and 5mL of curcumin standard solution respectively, adding the standard solution into a 10mL volumetric flask, then using absolute ethyl alcohol to fix the volume, and measuring the absorbance value at 306 nm. Respectively taking resveratrol concentration and absorbance value as the abscissa and ordinate to obtain a standard curve: y= 71.02x-0.1236, r 2 =0.99; wherein y is the absorbance value, and x is the resveratrol mass concentration (mg/mL).
(2) Resveratrol stability assay
The metal organic skeleton loaded with 4mg of resveratrol was dissolved in ethanol, and then diluted with water or ethanol to a final concentration of 14 μm of resveratrol, and left in the dark. And (3) measuring the stable state of resveratrol in the aqueous solution and the ethanol solution by using a visible spectrophotometer within different time intervals of 0-12 h. And records the data in fig. 14.
As can be seen from fig. 14, resveratrol has better stability in the metal organic framework. (3) Cumulative release in different media
The metallo-organic framework loaded with 4mg of resveratrol was dispersed in 10mL of release medium and then placed in a dialysis bag (dialysis bag cut-off molecular weight, 10 kDa), 150mL of different medium (HCl solution ph=1.2, phosphate buffer ph=6.8, where the treatment time ph=1.2 was 6 h) was added around to simulate different physiological pH conditions, 20% ethanol was added to the simulated medium for a more uniform release of resveratrol in the medium, and magnetic stirring was performed at 37 ℃. At predetermined time points (0-24 h) the amount of resveratrol released in the three different media was determined by uv-vis spectrum at 306 nm. The data is recorded in fig. 15.
From fig. 15, it can be seen that the resveratrol loaded metal organic frameworks can be released slowly under the low pH environment with the same maximum release amount, and have the ability of slow release.
(4) Free radical scavenging ability
An amount of resveratrol-metal organic framework powder was dissolved in 2mL of ethanol to prepare ethanol solutions containing different concentrations of resveratrol. The resveratrol-metal organic framework ethanol dispersions of varying concentrations were then added to 2mL of ethanol DPPH solution (0.2 mM). The solution was then thoroughly mixed and left to stand in the dark at room temperature for 30min. The absorbance was recorded at 517nm with ethanol as a blank. The data is recorded in fig. 16.
As can be seen from fig. 16, the antioxidant capacity of resveratrol is strong in the metal organic framework.
(5) Stability against ultraviolet oxidation
To examine the antioxidant stability of the resveratrol loaded metal organic frameworks, DPPH radical scavenging activity was measured on the resveratrol loaded metal organic frameworks after 30min of irradiation with a 20W uv lamp. The data are recorded in fig. 17, and it can be seen from fig. 17 that resveratrol has strong anti-ultraviolet oxidation stability in the metal organic framework.
Control 1 (adsorption of resveratrol in gamma-cyclodextrin)
1. Preparing resveratrol ethanol solution:
a certain amount of resveratrol powder is dissolved in ethanol solution to make the concentration of resveratrol powder 8mg/mL.
2. Preparing a gamma-cyclodextrin solution:
an amount of gamma-cyclodextrin was dissolved in an aqueous solution to a concentration of 8mg/mL.
3. The solutions prepared in 1 and 2 were combined in 1:1, and heated and stirred at 60 ℃ for 6 hours. After completion, the mixed solution was centrifuged, and the precipitate was washed three times with ethanol solution and dried overnight under vacuum at 45 ℃ for use. The prepared resveratrol-gamma cyclodextrin microcapsule powder is subjected to measurement of adsorption rate, stability, release amount, free radical scavenging capacity and ultraviolet oxidation resistance stability, and the measurement method comprises the following steps:
(1) Drawing resveratrol standard curve
Accurately weighing 1mg of resveratrol standard substance, dissolving the resveratrol standard substance in an absolute ethanol solution, and fixing the volume to 10mL to obtain resveratrol standard liquid with the mass concentration of 0.1 mg/mL. Accurately sucking 1, 2, 3, 4 and 5mL of curcumin standard solution respectively, adding the standard solution into a 10mL volumetric flask, then using absolute ethyl alcohol to fix the volume, and measuring the absorbance value at 306 nm. Respectively take resveratrol concentration and absorbance value as horizontal and vertical sitting positionsLabeling, and obtaining a standard curve: y= 71.02x-0.1236, r 2 =0.99; wherein y is the absorbance value, and x is the resveratrol mass concentration (mg/mL).
(2) Determination of resveratrol adsorption Rate
The absorbance of the supernatant after centrifugation in 3 above was measured at 306nm using a spectrophotometer, and the content of unadsorbed free resveratrol was calculated from a standard curve. The adsorption rate of resveratrol = (total resveratrol content-free resveratrol content)/total resveratrol content is 100%, and the obtained data is recorded in fig. 13.
As can be seen from fig. 13, the adsorption rate of resveratrol in gamma cyclodextrin is significantly lower than in the metal organic framework.
(3) Resveratrol stability assay
Gamma cyclodextrin loaded with 4mg of resveratrol was dissolved in ethanol, then diluted with water or ethanol to a final concentration of 14 μm of resveratrol and placed in the dark. And (3) measuring the stable state of resveratrol in the aqueous solution and the ethanol solution by using a visible spectrophotometer within different time intervals of 0-12 h. And records the data in fig. 14.
As can be seen from fig. 14, the stability of resveratrol in gamma cyclodextrin is significantly lower than in the metal organic framework.
(4) Cumulative release in different media
The gamma cyclodextrin loaded with 4mg of resveratrol was dispersed in 10mL of release medium and then placed in a dialysis bag (dialysis bag cut-off molecular weight, 10 kDa), 150mL of different medium (HCl solution ph=1.2, phosphate buffer ph=6.8, where the treatment time ph=1.2 was 6 h) was added around to simulate different physiological pH conditions, 20% ethanol was added to the simulated medium for a more uniform release of resveratrol in the medium, and magnetic stirring was performed at 37 ℃. The amount of resveratrol released in two different media was measured at 306nm by uv-vis spectrum at predetermined time points (0-24 h) and the data recorded in figure 15.
From fig. 15, it can be seen that the resveratrol loaded metal organic frameworks are able to release more slowly under low pH conditions with the same maximum release, with the ability to release slowly, mainly due to the formation of their dense structure, thus limiting the media diffusion capacity of resveratrol. In the case of digestion through the digestive tract after use by a human body, for example, the metal-organic framework can be used as an effective delivery vehicle for the slow release of resveratrol, exhibiting a slower release rate in an acidic environment such as that in the case of the use.
(5) Free radical scavenging ability
An amount of resveratrol-gamma-cyclodextrin powder was dissolved in 2mL of ethanol to prepare ethanol solutions containing different concentrations of resveratrol. The resveratrol-gamma-cyclodextrin ethanol dispersions of different concentrations were then added to 2mL of ethanol DPPH solution (0.2 mM). The solution was then thoroughly mixed and left to stand in the dark at room temperature for 30min. The absorbance was recorded at 517nm with ethanol as a blank, and the data was recorded in fig. 16.
As can be seen from fig. 16, the antioxidant capacity of resveratrol can be maintained, or even enhanced, by encapsulation in a metal organic framework. This is probably because the metal-organic framework has a smaller volume and a large specific surface area, and thus increases the chance of contact of resveratrol with free radicals, thereby improving the activity thereof.
(6) Stability against ultraviolet oxidation
To examine the antioxidant stability of resveratrol-loaded gamma-cyclodextrin, DPPH radical scavenging activity on resveratrol-loaded gamma-cyclodextrin powder after 30min irradiation with a 20W uv lamp was measured and the data is recorded in fig. 17.
Resveratrol is easily decomposed by light, especially by ultraviolet rays, so that the biological activity and bioavailability of resveratrol are reduced. After ultraviolet irradiation, the free radical scavenging activity of resveratrol is obviously reduced, and as can be seen from figure 17, resveratrol is encapsulated in a metal organic framework, so that the oxidation resistance stability of resveratrol is obviously improved.
Control 2 (pure resveratrol powder)
The stability, the release amount, the free radical scavenging capacity and the ultraviolet oxidation resistance stability of the pure resveratrol powder are measured, and the measuring method comprises the following steps:
(1) Drawing resveratrol standard curve
Accurately weighing 1mg of resveratrol standard substance, dissolving the resveratrol standard substance in an absolute ethanol solution, and fixing the volume to 10mL to obtain resveratrol standard liquid with the mass concentration of 0.1 mg/mL. Accurately sucking 1, 2, 3, 4 and 5mL of curcumin standard solution respectively, adding the standard solution into a 10mL volumetric flask, then using absolute ethyl alcohol to fix the volume, and measuring the absorbance value at 306 nm. Respectively taking resveratrol concentration and absorbance value as the abscissa and ordinate to obtain a standard curve: y= 71.02x-0.1236, r 2 =0.99; wherein y is the absorbance value, and x is the resveratrol mass concentration (mg/mL).
(2) Resveratrol stability assay
4mg of resveratrol was dissolved in ethanol, then diluted with water or ethanol to a final concentration of 14 μm and placed in the dark. And (3) measuring the stable state of resveratrol in the aqueous solution and the ethanol solution by using a visible spectrophotometer within different time intervals of 0-12 h. And records the data in fig. 18.
As can be seen from fig. 18, the stability of pure resveratrol is significantly lower than in the metal organic framework.
(3) Cumulative release in different media
4mg of resveratrol was dispersed in 10mL of release medium and then placed in a dialysis bag (dialysis bag cut-off, 10 kDa), 150mL of different medium (HCl solution ph=1.2, phosphate buffer ph=6.8) was added around to simulate different physiological pH conditions, 20% ethanol was added to the simulated medium in order to allow a more uniform release of resveratrol in the medium, and magnetic stirring was performed at 37 ℃. The amount of resveratrol released in two different media was measured at 306nm by uv-vis spectrum at predetermined time points (0-24 h) and the data recorded in figure 19.
From fig. 19, it can be seen that the release rate of pure resveratrol is high, the resveratrol is released rapidly within 10 hours, and the metal organic framework loaded with resveratrol has the capacity of slow release, which shows that the metal organic framework can be used as an effective delivery carrier for the slow release of resveratrol.
(5) Free radical scavenging ability
An amount of resveratrol powder was dissolved in 2mL of ethanol to prepare ethanol solutions containing different concentrations of resveratrol. The resveratrol ethanol dispersions of different concentrations were then added to 2mL of ethanol DPPH solution (0.2 mM). The solution was then thoroughly mixed and left to stand in the dark at room temperature for 30min. The absorbance was recorded at 517nm with ethanol as a blank, and the data was recorded in fig. 20.
As can be seen from fig. 20, the antioxidant capacity of pure resveratrol is slightly lower than that of resveratrol encapsulated in the metal organic framework. This is probably because the metal-organic framework has a smaller volume and a large specific surface area, and thus increases the chance of contact of resveratrol with free radicals, thereby improving the activity thereof.
(6) Stability against ultraviolet oxidation
To examine the antioxidant stability of resveratrol, DPPH radical scavenging activity of resveratrol after irradiation with a 20W uv lamp for 30min was measured, and the data are recorded in fig. 21.
Resveratrol is easily decomposed by light, especially by ultraviolet rays, so that the biological activity and bioavailability of resveratrol are reduced. After ultraviolet irradiation, the free radical scavenging activity of resveratrol is significantly reduced, and as can be seen from fig. 21, the antioxidant capacity of pure resveratrol is rapidly reduced after irradiation, and the resveratrol encapsulated in the metal organic framework maintains the antioxidant stability of the resveratrol.
The cyclodextrin metal organic framework is used as a porous material, has larger specific surface area and has great potential in the aspects of active ingredient adsorption and embedding. However, during adsorption of the active ingredient on the metal-organic framework, the operating conditions and the concentration of the active ingredient greatly influence the adsorption rate. This example discusses the effect of different mass ratios of resveratrol and metal organic frameworks on their adsorption rates.
It should be noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the present invention may be modified or substituted without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered in the scope of the claims of the present invention.
Claims (1)
1. A preparation method of resveratrol microcapsule based on a metal organic framework is characterized by comprising the following steps: the method comprises the following steps:
preparing a metal organic framework reaction solution: taking gamma-cyclodextrin powder and potassium hydroxide powder according to a ratio of 8:1 in a molar ratio of 43.6mg/mL, and refrigerating for hydration;
preparing a metal organic framework: adding methanol into the reaction solution, heating at 60 ℃ for 60min, rapidly adding surfactant PEG20000 with the concentration of 8mg/mL after finishing, and cooling at room temperature;
preparing metal organic framework powder: centrifuging the prepared metal organic framework, cleaning with methanol, and drying under vacuum at 45deg.C overnight for use;
preparing resveratrol metal organic framework microcapsules: resveratrol powder and metal organic framework powder were mixed in a ratio of 1:1 in the ethanol solution to make the resveratrol concentration be 4mg/mL, and heating and stirring for 6h at 60 ℃;
Preparing resveratrol metal organic framework microcapsule powder: centrifuging ethanol mixed solution of resveratrol and metal organic framework, cleaning precipitate with ethanol solution for three times, and vacuum drying at 45deg.C overnight;
wherein, the volume ratio of the reaction liquid to the methanol is 10:6.
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