CN108478550B - Medicine carrier based on alkyl glycoside lyotropic liquid crystal and preparation method and application thereof - Google Patents
Medicine carrier based on alkyl glycoside lyotropic liquid crystal and preparation method and application thereof Download PDFInfo
- Publication number
- CN108478550B CN108478550B CN201810236053.1A CN201810236053A CN108478550B CN 108478550 B CN108478550 B CN 108478550B CN 201810236053 A CN201810236053 A CN 201810236053A CN 108478550 B CN108478550 B CN 108478550B
- Authority
- CN
- China
- Prior art keywords
- drug
- curcumin
- liquid crystal
- chitosan
- carrier
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229930182470 glycoside Natural products 0.000 title claims abstract description 41
- -1 alkyl glycoside Chemical class 0.000 title claims abstract description 27
- 239000004976 Lyotropic liquid crystal Substances 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000003814 drug Substances 0.000 title claims description 67
- 229940079593 drug Drugs 0.000 title claims description 61
- 229920001661 Chitosan Polymers 0.000 claims abstract description 49
- 239000003937 drug carrier Substances 0.000 claims abstract description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000004973 liquid crystal related substance Substances 0.000 claims abstract description 39
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims abstract description 30
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims abstract description 30
- 229940093471 ethyl oleate Drugs 0.000 claims abstract description 30
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 26
- 239000004094 surface-active agent Substances 0.000 claims abstract description 25
- 150000002338 glycosides Chemical class 0.000 claims abstract description 15
- 238000002156 mixing Methods 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 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 claims description 144
- 235000012754 curcumin Nutrition 0.000 claims description 72
- 229940109262 curcumin Drugs 0.000 claims description 72
- 239000004148 curcumin Substances 0.000 claims description 72
- 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 claims description 72
- 238000003756 stirring Methods 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 11
- 238000005119 centrifugation Methods 0.000 claims description 3
- 230000006196 deacetylation Effects 0.000 claims description 3
- 238000003381 deacetylation reaction Methods 0.000 claims description 3
- 238000011068 loading method Methods 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 12
- 230000004043 responsiveness Effects 0.000 abstract description 7
- 239000010981 turquoise Substances 0.000 abstract description 2
- 230000001186 cumulative effect Effects 0.000 description 17
- 239000012071 phase Substances 0.000 description 16
- 238000005303 weighing Methods 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 229930182478 glucoside Natural products 0.000 description 9
- 150000008131 glucosides Chemical class 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 239000012154 double-distilled water Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 6
- 230000002535 lyotropic effect Effects 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000007423 decrease Effects 0.000 description 4
- 238000000235 small-angle X-ray scattering Methods 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 238000010587 phase diagram Methods 0.000 description 3
- 238000010008 shearing Methods 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 235000013824 polyphenols Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 240000002791 Brassica napus Species 0.000 description 1
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 244000163122 Curcuma domestica Species 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
- 206010040880 Skin irritation Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000005882 aldol condensation reaction Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- VEKIZRLWPXYFMW-UHFFFAOYSA-N hepta-1,6-diene-3,5-dione Chemical compound C=CC(=O)CC(=O)C=C VEKIZRLWPXYFMW-UHFFFAOYSA-N 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000011229 interlayer Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Images
Classifications
-
- 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
- A61K31/12—Ketones
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P37/02—Immunomodulators
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Inorganic Chemistry (AREA)
- Pain & Pain Management (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a drug carrier based on alkyl glycoside lyotropic liquid crystal and a preparation method and application thereof, wherein the drug carrier is prepared by mixing a surfactant, ethyl oleate and water to form lamellar liquid crystal, the mass percentage of the surfactant, the ethyl oleate and the water is 40-81: 5.7-21.4: 0-49.5, the surfactant is a mixture of dodecyl mixed glycoside and chitosan, the mass ratio of the dodecyl mixed glycoside to the chitosan is 9: 1-7: 3, and the drug carrier has a good slow release effect on turquoise and has pH responsiveness.
Description
Technical Field
The invention relates to a drug carrier based on alkyl glycoside lyotropic liquid crystal, a preparation method and application thereof.
Background
Curcumin is a herbal polyphenol compound extracted from the famous spice curcuma longa. Has pharmacological activity with various biological characteristics: antioxidant, anti-inflammatory, immunomodulating, antimicrobial, anticancer, etc. However, curcumin has low availability due to unstable pH, low solubility in water, high metabolism speed and the like under photo-thermal conditions, and the application of curcumin is limited. To overcome these disadvantages of curcumin, two methods are commonly used: firstly, curcumin is modified by chemical reaction, wherein the common method comprises 1. modification of benzene ring: phenolic hydroxyl groups are esterified or etherified, etc.; 2. modification of 1,6 heptadiene 3,5 dione connecting chain to modify double bonds existing in the structure, such as reduction of double bonds, modification of methylene, condensation of ketone groups and the like, but the method for chemical modification is complex in operation process and limits application; and secondly, a drug carrier is constructed to encapsulate the drug, and the encapsulation method not only can improve the solubility of the drug, but also can play a certain slow release role in the release of the drug, thereby protecting the drug from being eroded by a complex external environment. And also can keep the original structure of the drug from being damaged, in recent years, various encapsulation methods are widely used, including: lyotropic liquid crystals, microemulsions, liposomes, and the like.
The lyotropic liquid crystal is a transparent, thermodynamically stable and non-flowing system formed when the surfactant reaches a certain concentration, and is a microscopically long-range ordered and short-range disordered structure. Lyotropic liquid crystals can be classified into lamellar phase, cubic phase, and hexagonal phase according to their microstructures. The lamellar liquid crystal has a bilayer structure similar to a cell membrane, has a better application prospect as a drug carrier, can dissolve a compound which is easy to dissolve in water in a hydrophilic region of the lamellar liquid crystal, and can dissolve a compound which is hydrophobic in a hydrophobic region, so that the lyotropic liquid crystal can entrap both the hydrophobic drug and the hydrophilic drug, the solubility of the drug is increased, and the slow release of the drug is realized. It has received much attention due to its excellent drug loading and drug release properties.
The alkyl glycoside is a mixed product of hydroxyl of glucose subjected to aldol condensation and fatty alcohol subjected to chemical reaction under the condition of acid catalysis, and one molecule of water is removed. Has better biocompatibility, is easy to degrade, has low skin irritation and no dependence on temperature, and raw materials (such as starch and rapeseed) used for synthesis are natural renewable and are good biocompatible surfactants. The biocompatibility of the lyotropic liquid crystal serving as a drug carrier is generally considered, and a green low-toxicity drug carrier harmless to organisms is expected to be constructed, so that the selected amphiphilic molecules for constructing the lyotropic liquid crystal have the following characteristics: the alkyl glycoside is a raw material for well constructing a drug carrier, and is biodegradable, biocompatible, nontoxic and the like. However, so far, there are few reports on the construction of drug carriers using alkylglycosides.
Disclosure of Invention
In order to solve the defects of the prior art, the invention aims to provide a drug carrier based on alkyl glycoside lyotropic liquid crystal, which has a good slow release effect on turquoise and has pH responsiveness.
In order to achieve the purpose, the technical scheme of the invention is as follows:
the drug carrier based on the alkyl glycoside lyotropic liquid crystal is formed by mixing a surfactant, ethyl oleate and water in a ratio of 40-81: 5.7-21.4: 0-49.5 by mass, wherein the water is not 0, the surfactant is a mixture of dodecyl mixed glycoside and chitosan, and the mass ratio of the dodecyl mixed glycoside to the chitosan is 9: 1-7: 3.
According to the invention, firstly, dodecyl mixed glucoside is used as a surfactant, ethyl oleate and water are added to prepare the lamellar liquid crystal, however, when the lamellar liquid crystal is used for drug release of curcumin, the drug release rate of the lamellar liquid crystal obtained by only using dodecyl mixed glucoside as the surfactant is too fast, and the lamellar liquid crystal has no pH responsiveness. Therefore, the chitosan is added into the dodecyl mixed glucoside, the drug release rate of the curcumin is reduced, and the drug release of the curcumin has pH responsiveness.
The invention also aims to provide a preparation method of the drug carrier, which comprises the steps of uniformly mixing dodecyl mixed glucoside, chitosan, ethyl oleate and water at 60-70 ℃, and removing bubbles to obtain the drug carrier.
The invention also aims to provide application of the drug carrier in preparation of a carrier drug loaded with curcumin.
The fourth purpose of the invention is to provide a carrier drug, and the drug carrier loads curcumin.
The fifth purpose of the invention is to provide a preparation method of the carrier drug, which comprises the steps of adding curcumin into the drug carrier, stirring at 37 +/-0.5 ℃ until the curcumin is completely dissolved, removing bubbles, and standing for 6-8 days to obtain the carrier drug.
The invention has the beneficial effects that:
1. the invention adopts dodecyl mixed glucoside, ethyl oleate and water to prepare the lamellar liquid crystal, and the lamellar liquid crystal prepared on the surface after the chitosan is added has a good slow release effect on curcumin.
2. The drug carrier prepared by the invention has pH responsiveness to the release effect of curcumin.
3. The drug carrier prepared by the invention has response to the release amount of curcumin to temperature, and the cumulative release amount of curcumin is increased when the temperature is increased.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate embodiments of the application and, together with the description, serve to explain the application and are not intended to limit the application.
FIG. 1 is a three-phase diagram, where (a) is APG/EtOL/H2O system, (b) is APG/WCS (9:1)/EtOL/H2An O system;
FIG. 2 is BL0And BL1SAXS spectrum of;
FIG. 3 is BL0And BL1Temperature scan of (a);
FIG. 4 is BL0And BL1A graph of shear viscosity as a function of shear rate;
FIG. 5 is BL0And BL1The relationship between storage modulus loss modulus and complex viscosity and frequency;
FIG. 6 shows curcumin in ethanol solution, sample L0Sample L1The in vitro release profile of (1);
fig. 7 is an in vitro release profile of curcumin at different pH in different samples;
FIG. 8 shows curcumin at L at different temperatures1The in vitro release profile of (1);
fig. 9 is an in vitro release curve of curcumin in different samples, wherein a is a lyotropic lamellar liquid crystal sample constructed with different oil contents, and b is a lyotropic lamellar liquid crystal sample constructed with different water contents.
Detailed Description
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.
The dodecyl mixed glycoside is a mixture of dodecyl single glycoside and dodecyl polyglycoside, and can be abbreviated as C12Gn(n is a non-integer greater than 1) and is abbreviated herein as APG.
As described in the background art, there is no description in the prior art of constructing a drug carrier using alkyl glycoside, and in order to solve the above technical problems, the present application proposes a drug carrier based on alkyl glycoside lyotropic liquid crystal, and a preparation method and applications thereof.
The application provides a drug carrier based on an alkyl glycoside lyotropic liquid crystal, which is formed by mixing a surfactant, ethyl oleate and water in a layered manner, wherein the mass percentage of the surfactant, the ethyl oleate and the water is 40-81: 5.7-21.4: 0-49.5, the water is not 0, the surfactant is a mixture of dodecyl mixed glycoside and chitosan, and the mass ratio of the dodecyl mixed glycoside to the chitosan is 9: 1-7: 3.
In the application, firstly, dodecyl mixed glucoside is used as a surfactant, ethyl oleate and water are added to prepare the lamellar liquid crystal, however, when the lamellar liquid crystal is used for drug release of curcumin, the drug release rate of the lamellar liquid crystal obtained by only using dodecyl mixed glucoside as the surfactant is too high, and the lamellar liquid crystal does not have pH responsiveness. Therefore, the chitosan is added into the dodecyl mixed glucoside, the drug release rate of the curcumin is reduced, and the drug release of the curcumin has pH responsiveness.
Preferably, the mass ratio of the dodecyl mixed glycoside to the chitosan is 9: 1.
Preferably, the mass ratio of the surfactant, the ethyl oleate and the water is 63:7: 30.
Preferably, the chitosan is water-soluble chitosan, and the deacetylation degree is more than 85%. The size of the chitosan is 60 meshes.
Another embodiment of the application provides a preparation method of the drug carrier, which comprises the steps of placing dodecyl mixed glucoside, chitosan, ethyl oleate and water at 60-70 ℃, uniformly mixing, and removing bubbles to obtain the drug carrier.
Preferably, the bubbles are removed by centrifugation.
In a third embodiment of the application, the application of the drug carrier in preparing a carrier drug by loading curcumin is provided.
In a fourth embodiment of the present application, there is provided a carrier drug, the above drug carrier carrying curcumin.
Preferably, curcumin is 1 × 10 of the mass of the drug carrier-3％～2×10-3％。
The fifth embodiment of the application provides a preparation method of the carrier drug, which comprises the steps of adding curcumin into the drug carrier, stirring at 37 +/-0.5 ℃ until the curcumin is completely dissolved, removing bubbles, and standing for 6-8 days to obtain the carrier drug.
Preferably, the bubbles are removed by centrifugation.
Preferably, the method comprises the preparation method of the drug carrier.
In order to make the technical solutions of the present application more clearly understood by those skilled in the art, the technical solutions of the present application will be described in detail below with reference to specific embodiments.
Materials: dodecyl mixed glycoside (APG) is provided by daily chemical college of China, ethyl oleate, curcumin, ethanol, disodium hydrogen phosphate and sodium dihydrogen phosphate are purchased from chemical reagents of national medicine group, Inc., water-soluble chitosan (WCS, 60 mesh, deacetylation degree > 85%) is purchased from ocean bioengineering, Inc. of Kyohaibei, and all the medicines are not further treated before use, and water is secondary distilled water.
Drawing of photo
Accurately weighing the surfactant and a colorimetric tube according to the condition that the mass ratio of the surfactant (APG, APG: WCS is 9:1) to the oil phase is changed from 10:0 to 0:10, then sequentially adding the oil phase ethyl oleate into the colorimetric tube with the accurate ratio, uniformly stirring the sample in a water bath kettle at 60-70 ℃, dropwise adding secondary distilled water into the colorimetric tube, controlling the dropwise adding amount (2% interval increase) of the dropwise adding speed, uniformly stirring, centrifuging to remove bubbles, finally balancing in a water bath at 37 ℃, observing the phenomenon, and prolonging the balancing time of aggregates when the phase boundary is approached. The phase diagram obtained is shown in fig. 1.
The following examples were made to prepare samples according to the phase diagram.
Example 1
Weighing 1.26g of alkyl glycoside and 0.14g of ethyl oleate respectively, placing the alkyl glycoside and the ethyl oleate into a clean colorimetric tube, adding magnetons, then adding 0.6g of double distilled water, stirring by using a magnetic stirrer, controlling the water bath temperature to be 60-70 ℃, and uniformly mixing. Centrifuging by using a centrifuge to remove air bubbles in the sample, thereby obtaining a blank drug carrier containing chitosan, which is marked as BL0。
Example 2
Weighing 1.134g of alkyl glycoside, 0.126g of chitosan and 0.14g of ethyl oleate respectively, placing the alkyl glycoside, the chitosan and the ethyl oleate into a clean colorimetric tube, adding magnetons, adding 0.6g of double distilled water, stirring by using a magnetic stirrer, controlling the water bath temperature to be 60-70 ℃, and uniformly mixing. Centrifuging by using a centrifuge to remove air bubbles in the sample, thereby obtaining a blank drug carrier containing chitosan, which is marked as BL1。
Example 3
Weighing 1.26g of alkyl glycoside and 0.14g of ethyl oleate respectively, placing the alkyl glycoside and the ethyl oleate into a clean colorimetric tube, adding magnetons, then adding 0.6g of double distilled water, stirring by using a magnetic stirrer, controlling the water bath temperature to be 60-70 ℃, and uniformly mixing. Centrifuging with a centrifuge to remove air bubbles in the sample to obtain chitosan-containing blank drug carrier, weighing curcumin 3.4mg, adding into blank liquid crystal, stirring at constant temperature of 37 deg.C until the drug is completely dissolved, and centrifuging to remove air bubbles. The prepared sample is balanced for one week at room temperature to obtain a stable carrier drug sample, which is marked as L0。
Example 4
Weighing 1.134g of alkyl glycoside, 0.126g of chitosan and 0.14g of ethyl oleate respectively, placing the alkyl glycoside, the chitosan and the ethyl oleate into a clean colorimetric tube, adding magnetons, adding 0.6g of double distilled water, stirring by using a magnetic stirrer, controlling the water bath temperature to be 60-70 ℃, and uniformly mixing. Centrifuging with a centrifuge to remove air bubbles in the sample to obtain chitosan-containing blank drug carrier, weighing curcumin 3.4mg, adding into blank liquid crystal, stirring at constant temperature of 37 deg.C until the drug is completely dissolved, and centrifuging to remove air bubbles. The prepared sample is balanced for one week at room temperature to obtain a stable carrier drug sample, which is marked as L1。
Example 5
Weighing 1.008g of alkyl glycoside, 0.112g of chitosan and 0.28g of ethyl oleate respectively, placing the alkyl glycoside, the chitosan and the ethyl oleate into a clean colorimetric tube, adding magnetons, then adding 0.6g of double distilled water, stirring by using a magnetic stirrer, controlling the water bath temperature to be 60-70 ℃, and uniformly mixing. Centrifuging with a centrifuge to remove air bubbles in the sample to obtain chitosan-containing blank drug carrier, weighing curcumin 3.4mg, adding into blank liquid crystal, stirring at constant temperature of 37 deg.C until the drug is completely dissolved, and centrifuging to remove air bubbles. The prepared sample is balanced for one week at room temperature to obtain a stable carrier drug sample, which is marked as L2。
Example 6
Respectively weighing 0.882g of alkyl glycoside, 0.098g of chitosan and 0.42g of ethyl oleate, placing the mixture into a clean colorimetric tube, adding magnetons, adding 0.6g of double distilled water, stirring by using a magnetic stirrer, and controlling the water bath temperature to be 60 ℃Mixing at 70 deg.C. Centrifuging with a centrifuge to remove air bubbles in the sample to obtain chitosan-containing blank drug carrier, weighing curcumin 3.4mg, adding into blank liquid crystal, stirring at constant temperature of 37 deg.C until the drug is completely dissolved, and centrifuging to remove air bubbles. The prepared sample is balanced for one week at room temperature to obtain a stable carrier drug sample, which is marked as L3。
Example 7
Weighing 1.053g of alkyl glycoside, 0.117g of chitosan and 0.13g of ethyl oleate respectively, placing the alkyl glycoside, the chitosan and the ethyl oleate into a clean colorimetric tube, adding magnetons, then adding 0.7g of double distilled water, stirring by using a magnetic stirrer, controlling the water bath temperature to be 60-70 ℃, and uniformly mixing. Centrifuging with a centrifuge to remove air bubbles in the sample to obtain chitosan-containing blank drug carrier, weighing curcumin 3.4mg, adding into blank liquid crystal, stirring at constant temperature of 37 deg.C until the drug is completely dissolved, and centrifuging to remove air bubbles. The prepared sample is balanced for one week at room temperature to obtain a stable carrier drug sample, which is marked as L4。
Example 8
Respectively weighing 0.972g of alkyl glycoside, 0.108g of chitosan and 0.12g of ethyl oleate, placing the mixture into a clean colorimetric tube, adding magnetons, then adding 0.8g of double distilled water, stirring by using a magnetic stirrer, controlling the water bath temperature to be 60-70 ℃, and uniformly mixing. Centrifuging with a centrifuge to remove air bubbles in the sample to obtain chitosan-containing blank drug carrier, weighing curcumin 3.4mg, adding into blank liquid crystal, stirring at constant temperature of 37 deg.C until the drug is completely dissolved, and centrifuging to remove air bubbles. The prepared sample is balanced for one week at room temperature to obtain a stable carrier drug sample, which is marked as L5。
Compositions of samples prepared in examples 1 to 8 are shown in Table 1
TABLE 1 compositions of samples prepared in examples 1-8 are shown in Table 1
The samples prepared in examples 1-8 were characterized as follows:
small angle X-ray scatter (SAXS)
The light source of the small-angle X-ray scatterometer is a copper target, the excitation wavelength is 0.1542nm, the working voltage and the current of the small-angle X-ray scatterometer are respectively 40kV and 50mA, the distance from a sample to be detected to a detector is 264.5nm, and the measurement temperature is set to be 37 ℃. The SAXS spectrogram obtained by measurement can be used for analyzing the microstructure and corresponding structural parameters of the liquid crystal sample.
Determination of rheological Properties
The rheological properties of the liquid crystals were measured using a U.S. Discovery HR-2 rheometer. The lamina diameter used for the measurement was 20mm and the cone angle was 2 °. The sample was slowly applied to the peltier plate, the handpiece was slowly lowered to the measurement position, and the excess sample was scraped off with a scraper. The temperature is controlled by a thermostatic water bath connected with a Peltier plate, the maximum error is controlled to be +/-0.1 ℃, the sample is kept at the constant temperature in a sensor for 10min before measurement, dynamic frequency scanning is carried out under the stress value in a linear viscoelastic region obtained by stress scanning, and the scanning range is 0.01-600 rad/s. The steady state scanning measurement range is from 0.01 to 1000S-1.
In vitro release of curcumin
The in vitro release behavior of curcumin is researched by an in vitro dialysis method, a medium released in vitro is a PBS solution with the ethanol content of 40%, about 0.5g of drug-loaded liquid crystal is weighed in a treated small intestine semipermeable membrane, a dialysis bag containing a sample is placed in a beaker containing 60mL of PBS buffer solution, the beaker is placed in a constant-temperature water bath kettle at a certain constant temperature and is stirred, the curcumin is released under the constant temperature condition, 5mL of release medium is taken out at regular intervals, meanwhile, 5mL of fresh release medium is added to ensure that the volume of the release medium is constant, and the absorbance of the curcumin in the taken out release medium is measured at the maximum absorption wavelength of the curcumin by using an ultraviolet spectrophotometer.
Cumulative drug release rate% cumulative drug released/total drug in vehicle 100
Characterization results
Sample BL0And BL1As shown in FIG. 2, sample BL0Shows 3 Bragg peaks on the SAXS spectrum,the relation of the position ratio of the Bragg peak is 1:2:3, which indicates that the sample BL0 belongs to a lamellar phase liquid crystal structure, and after the WCS is introduced, the sample BL is1The position of the peak did not change significantly and was still lamellar.
As can be seen from fig. 3, the temperature varied from 10 ℃ to 70 ℃. The values of the elastic modulus and the viscous modulus of the lamellar liquid crystal are basically independent of temperature, which shows that the lamellar phase structure of the lamellar liquid crystal is stable in the temperature range to be researched, and no phase transition occurs. The samples with chitosan had a higher viscous modulus and a higher elastic modulus than the samples without chitosan.
As can be seen from FIG. 4, as the shear rate increases, the sample BL0And BL1The viscosity number of (a) gradually decreases, showing shear thinning behavior. It can be interpreted that since the lamellar liquid crystal is composed of a lamellar structure layer by layer, sliding can occur in any direction along the aqueous phase or the oil phase. Therefore, under the shearing action, the internal microstructure units of the sample are positioned in parallel with the shearing direction, so that the interlayer sliding occurs, and the viscosity is reduced. And BL1Has a shear viscosity higher than BL in the measurement range0This suggests that the introduction of WCS increases the interaction between molecules in lamellar phase liquid crystal and hinders the degree of sliding thereof, presumably because the water-soluble chitosan reduces the thickness of the aqueous layer at the hydrophilic head group of the surfactant and the aqueous layer, and sliding between layers becomes difficult, so that sample BL1Has a viscosity greater than that of the sample BL0. The introduction of chitosan improves the stability of lamellar phase liquid crystal. The lyotropic liquid crystal loaded with the drug can stably exist for a long time under the shearing environment (such as living bodies), and is beneficial to the continuous slow release of the drug in the carrier. Corresponding to its release.
From FIG. 5 it can be seen that BL is for the sample0,BL1In the frequency sweep range, the elastic modulus and viscous modulus increase slowly with increasing frequency, and in the measured frequency range, G 'is higher than G', the complex viscosity decreases linearly with frequency, which is a rheological property of a typical lamellar liquid crystal phase, and the elastic modulus and viscous modulus of lyotropic liquid crystal after chitosan introduction are comparedThe modulus values show that the value of the viscous modulus of the lyotropic liquid crystal decreases and the value of the elastic modulus increases after the chitosan is introduced, i.e. the sample point BL1Having maximum elastic properties and minimum viscous properties, the higher the elastic properties and the slower the release rate due to lyotropic liquid crystals as drug carriers. Therefore, the slow release effect of the drug from the sample may be increased after the chitosan is introduced.
As can be seen from figure 6, the curcumin ethanol solution has very fast release rate, reaches the maximum cumulative release rate within about 2.5 hours, has the phenomenon of fast release, and has poor slow release effect on the medicament. The lyotropic liquid crystal has a good slow release effect on curcumin. And the two lamellar phase-soluble liquid crystals have different slow release effects on the medicament and are good medicament carriers. We further investigated the release behavior of the drug under different conditions without and after WCS introduction.
Fig. 6 is a graph showing the cumulative release rate (CR) of curcumin in the lamellar phase liquid crystal at 37 ℃ as a function of time. Sample L compared to curcumin ethanol solution0And L1Has sustained release effect on curcumin. Sample L0In the early stage of release (before 500 min), the release rate of curcumin is high, reaches 70%, then gradually slows down, and finally reaches a platform. Sample L1In the early stage of release (first 1100min), the release rate of curcumin is higher, and gradually becomes slower along with the release rate; finally, the cumulative release rate is substantially unchanged. This is due to: in the early stage of release, part of curcumin adhered to the lyotropic liquid crystal is easier to escape through molecular movement, so that the release rate of curcumin is faster in this stage. In the middle release period, the medicine solubilized in the oil phase gradually diffuses into the interface layer, and the release speed gradually slows down. In the later release period, the cumulative release rate of curcumin is basically kept unchanged, and the release reaches the balance. Furthermore, it can also be seen that L1And L0This indicates that its introduction of WCS can prolong the release time of the drug, compared to its longer release time. Consistent with the increase in shear viscosity of the aggregates following the introduction of chitosan. At the same time, sample L in terms of cumulative release rate1Is significantly lower than that of sample L0. This suggests that the introduction of WCS reduces the cumulative release rate of curcumin. This result is associated with the sample L in the frequency sweep1The higher the elastic modulus value of (A) is, the more uniform.
FIG. 7(a) is curcumin in sample L at 37 ℃0The release curve in (1) shows that the in vitro release curve of curcumin has no obvious change under different pH values, the influence of changing the pH value on the release behavior of curcumin is not obvious, the release curve of the drug after introducing the WCS is shown in figure 7(b), the cumulative release rate of curcumin reaches 82% when the pH value is 6.5, the cumulative release rate changes to 62% when the pH value is increased to 7.5, and the curcumin in the sample L can be seen to increase along with the increase of the pH value1The reason why the release is reduced in the process is that the water-soluble chitosan contains amino groups, and the amino groups are protonated at a lower pH value, so that the repulsion among molecules in lamellar phase liquid crystal is increased, the aggregate structure is loosened, and the release of curcumin is promoted. The release rate and the cumulative release rate of the medicine are improved. This is due to the fact that at higher pH, WCS forms a tight layer, hindering curcumin release.
As can be seen from fig. 8, the release rate and the cumulative release rate of curcumin in the lamellar liquid crystal increased with increasing temperature. The release rate at 37 c is significantly higher than 25 c, 30 c, probably because molecular motion is affected by temperature, and when the temperature is raised, molecular motion is accelerated, curcumin escapes more easily from the interfacial film, the release rate of the drug is accelerated, and the cumulative release rate is increased.
The results of the effect of the ratio of the surfactant to the oil on the release behavior of the drug are shown in fig. 9(a), and it can be seen that, first, lyotropic liquid crystal has good sustained-release properties as a carrier of curcumin as a drug, and it can be found that the release behavior of curcumin is affected by the mass ratio of the surfactant to the oil, and the release rate and cumulative release rate of curcumin increase as the ratio of the surfactant to the oil decreases, because as the oil content increases, the structure of lyotropic liquid crystal swells, and curcumin more easily escapes from the interfacial film to reach the aqueous phase, so the release rate and cumulative release rate thereof increase.
Since the composition and composition of the drug carrier has a significant effect on the release behavior of the drug, to find a more optimal composition of the elemental carrier for curcumin, the surfactant to oil ratio was fixed at 9:1, and the sample (L) was selected1,L4,L5) The effect of water content on drug release was further explored. As can be seen from fig. 9(b), the release rate and the cumulative release rate of curcumin decreased as the water content increased. The potential is that the macromolecular chitosan gradually stretches in water as the water content increases, preventing the curcumin molecules from escaping from the interfacial film.
The above description is only a preferred embodiment of the present application and is not intended to limit the present application, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application shall be included in the protection scope of the present application.
Claims (7)
1. The drug carrier based on the alkyl glycoside lyotropic liquid crystal is characterized in that a lamellar liquid crystal is formed by mixing a surfactant, ethyl oleate and water, wherein the mass percentage of the surfactant, the ethyl oleate and the water is 63:7:30, the surfactant is a mixture of dodecyl mixed glycoside and chitosan, and the mass ratio of the dodecyl mixed glycoside to the chitosan is 9: 1; the dodecyl mixed glycoside is a mixture of dodecyl single glycoside and dodecyl polyglycoside; the chitosan is water-soluble chitosan, and the deacetylation degree is more than 85%.
2. The method for preparing the drug carrier according to claim 1, wherein the drug carrier is obtained by uniformly mixing dodecyl mixed glycoside, chitosan, ethyl oleate and water at 60-70 ℃, and removing air bubbles.
3. The method of claim 2, wherein the bubbles are removed by centrifugation.
4. The use of the pharmaceutical carrier of claim 1 in loading curcumin to prepare a carrier drug.
5. A drug carrier, wherein the drug carrier of claim 1 carries curcumin.
6. The carrier drug of claim 5, wherein curcumin is 1X 10 of the mass of the drug carrier -3%~2×10 -3%。
7. The preparation method of the drug carrier according to claim 2 or 3, adding curcumin into the drug carrier, stirring at 37 ± 0.5 ℃ until the curcumin is completely dissolved, removing bubbles, and standing for 6-8 days to obtain the carrier drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810236053.1A CN108478550B (en) | 2018-03-21 | 2018-03-21 | Medicine carrier based on alkyl glycoside lyotropic liquid crystal and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810236053.1A CN108478550B (en) | 2018-03-21 | 2018-03-21 | Medicine carrier based on alkyl glycoside lyotropic liquid crystal and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108478550A CN108478550A (en) | 2018-09-04 |
| CN108478550B true CN108478550B (en) | 2021-06-25 |
Family
ID=63318989
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810236053.1A Active CN108478550B (en) | 2018-03-21 | 2018-03-21 | Medicine carrier based on alkyl glycoside lyotropic liquid crystal and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108478550B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108420787B (en) * | 2018-05-15 | 2021-05-11 | 华中科技大学鄂州工业技术研究院 | Cell factor type wound repair drug lyotropic liquid crystal gel nano preparation and preparation method thereof |
| CN111205378B (en) * | 2020-01-15 | 2021-11-30 | 南京清研高分子新材料有限公司 | Liquid crystal polymer having lyotropic liquid crystal property and method for preparing same |
| CN112480895B (en) * | 2020-11-27 | 2022-02-01 | 中国石油大学(北京) | PH-responsive oil displacement agent composition, oil displacement agent, and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002066014A2 (en) * | 2001-02-20 | 2002-08-29 | The Procter & Gamble Company | Cubic liquid crystalline compositions and methods for their preparation |
| WO2012112319A1 (en) * | 2011-02-04 | 2012-08-23 | Aegis Therapeutics, Llc | Orally bioavailable peptide drug compositions and methods thereof |
| CN103285401A (en) * | 2013-05-27 | 2013-09-11 | 沈阳药科大学 | Composition capable of improving solubility and bioavailability of insoluble medicament |
| CN106822044A (en) * | 2017-03-15 | 2017-06-13 | 山东师范大学 | Curcumin sustained release aggregation and the preparation method of a kind of chitosan-containing |
-
2018
- 2018-03-21 CN CN201810236053.1A patent/CN108478550B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002066014A2 (en) * | 2001-02-20 | 2002-08-29 | The Procter & Gamble Company | Cubic liquid crystalline compositions and methods for their preparation |
| WO2012112319A1 (en) * | 2011-02-04 | 2012-08-23 | Aegis Therapeutics, Llc | Orally bioavailable peptide drug compositions and methods thereof |
| CN103285401A (en) * | 2013-05-27 | 2013-09-11 | 沈阳药科大学 | Composition capable of improving solubility and bioavailability of insoluble medicament |
| CN106822044A (en) * | 2017-03-15 | 2017-06-13 | 山东师范大学 | Curcumin sustained release aggregation and the preparation method of a kind of chitosan-containing |
Non-Patent Citations (1)
| Title |
|---|
| 表面活性剂聚集体的性质及作药物载体的研究;成朋;《中国优秀硕士学位论文全文数据库》;20110815(第8期);第1-71页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108478550A (en) | 2018-09-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108478550B (en) | Medicine carrier based on alkyl glycoside lyotropic liquid crystal and preparation method and application thereof | |
| JP6634138B2 (en) | Highly branched α-D-glucan | |
| Kabiri et al. | A stimulus-responsive, in situ-forming, nanoparticle-laden hydrogel for ocular drug delivery | |
| Yao et al. | Enzymatically degradable alginate/gelatin bioink promotes cellular behavior and degradation in vitro and in vivo | |
| EA012450B1 (en) | Process for the manufacture of cellulose sulfate with improved characteristics | |
| Zhao et al. | Digestion degree is a key factor to regulate the printability of pure tendon decellularized extracellular matrix bio-ink in extrusion-based 3D cell printing | |
| CN106822044B (en) | A kind of the curcumin sustained release aggregation and preparation method of chitosan-containing | |
| CN108144064B (en) | Dihydromyricetin medicament taking aggregate of Tween80 and chitosan as carrier and preparation method thereof | |
| CN108113964B (en) | Construction of Tween 80-based biocompatible microemulsion, in-vitro release of apigenin and research on antioxidant performance | |
| KR20230016937A (en) | Microalgae-derived exosome analogue and method for preparing the same | |
| Vadodaria et al. | Fabrication of surfactant-polyelectrolyte complex using valvejet 3D printing-aided colloidal self assembly | |
| CN109172526B (en) | Lyotropic liquid crystal drug carrier, preparation method and application | |
| CN111939128B (en) | Temperature-sensitive lyotropic liquid crystal drug carrier and preparation method and application thereof | |
| EP3356440B1 (en) | Hydrophobic highly branched carbohydrate polymers | |
| Schwoerer et al. | Influence of degree of substitution of HES–HEMA on the release of incorporated drug models from corresponding hydrogels | |
| CN108524312A (en) | A kind of sulforaphen pik woods micro emulsion and preparation method thereof | |
| CN109010271B (en) | Apigenin slow-release type drug carrier and preparation method thereof | |
| EP3068223B1 (en) | Glycol chitin based thermosensitive hydrogel for vaginal delivery of progesterone | |
| US11896685B2 (en) | Core-shell network structure comprising biopolymer and composition comprising same | |
| CN109589301B (en) | Apigenin slow-release aggregate with responsiveness and preparation method thereof | |
| Jyothi et al. | Formulation and evaluation of curcumin emulgel for topical delivery | |
| CN113616797B (en) | Low-water-solubility polyphenol drug carrier and preparation method and application thereof | |
| Valentini et al. | Development of hydroxypropylmethylcellulose acetate succinate and kappa carrageenan films loaded with curcumin for wound healing | |
| RU2745124C1 (en) | Bioactive composition based on a crosslinked hyaluronic acid salt containing resveratrol and a method of its preparation | |
| CN110507601B (en) | Paclitaxel-loaded Korean pine pinecone polysaccharide-A gel and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20240325 Address after: 2081, building a, 88 Jianghai West Road, Liangxi District, Wuxi City, Jiangsu Province, 214000 Patentee after: Wuxi Xiangyuan Information Technology Co.,Ltd. Country or region after: China Address before: 250014 No. 88, Wenhua East Road, Lixia District, Shandong, Ji'nan Patentee before: SHANDONG NORMAL University Country or region before: China |