CN108144064A - A kind of aggregation based on Tween80 and chitosan is the dihydromyricetin medicament and preparation method of carrier - Google Patents
A kind of aggregation based on Tween80 and chitosan is the dihydromyricetin medicament and preparation method of carrier Download PDFInfo
- Publication number
- CN108144064A CN108144064A CN201810123231.XA CN201810123231A CN108144064A CN 108144064 A CN108144064 A CN 108144064A CN 201810123231 A CN201810123231 A CN 201810123231A CN 108144064 A CN108144064 A CN 108144064A
- Authority
- CN
- China
- Prior art keywords
- dihydromyricetin
- chitosan
- water
- release
- medicament
- 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.)
- Granted
Links
- KJXSIXMJHKAJOD-LSDHHAIUSA-N (+)-dihydromyricetin Chemical compound C1([C@@H]2[C@H](C(C3=C(O)C=C(O)C=C3O2)=O)O)=CC(O)=C(O)C(O)=C1 KJXSIXMJHKAJOD-LSDHHAIUSA-N 0.000 title claims abstract description 180
- KQILIWXGGKGKNX-UHFFFAOYSA-N dihydromyricetin Natural products OC1C(=C(Oc2cc(O)cc(O)c12)c3cc(O)c(O)c(O)c3)O KQILIWXGGKGKNX-UHFFFAOYSA-N 0.000 title claims abstract description 90
- 229920001661 Chitosan Polymers 0.000 title claims abstract description 84
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 title claims abstract description 54
- 229920000053 polysorbate 80 Polymers 0.000 title claims abstract description 54
- 230000002776 aggregation Effects 0.000 title claims abstract description 45
- 238000004220 aggregation Methods 0.000 title claims abstract description 45
- 239000003814 drug Substances 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 70
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical group O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000004094 surface-active agent Substances 0.000 claims description 28
- 238000002156 mixing Methods 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 9
- 230000008569 process Effects 0.000 abstract description 6
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 abstract description 4
- 238000010587 phase diagram Methods 0.000 abstract description 2
- 238000001988 small-angle X-ray diffraction Methods 0.000 abstract 1
- 239000004973 liquid crystal related substance Substances 0.000 description 21
- 230000006399 behavior Effects 0.000 description 13
- 230000003578 releasing effect Effects 0.000 description 9
- 238000011067 equilibration Methods 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 238000000235 small-angle X-ray scattering Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 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 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 229940109262 curcumin Drugs 0.000 description 2
- 235000012754 curcumin Nutrition 0.000 description 2
- 239000004148 curcumin Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 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 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- IJMWOMHMDSDKGK-UHFFFAOYSA-N Isopropyl propionate Chemical compound CCC(=O)OC(C)C IJMWOMHMDSDKGK-UHFFFAOYSA-N 0.000 description 1
- 244000270834 Myristica fragrans Species 0.000 description 1
- 235000009421 Myristica fragrans Nutrition 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- OGQYPPBGSLZBEG-UHFFFAOYSA-N dimethyl(dioctadecyl)azanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC OGQYPPBGSLZBEG-UHFFFAOYSA-N 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
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000002535 lyotropic effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 239000001702 nutmeg Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 230000008439 repair process Effects 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
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to the dihydromyricetin medicaments and preparation method that a kind of aggregation based on polyoxyethylene sorbitan monooleate and chitosan is carrier,Medicament prepared by the application is by dihydromyricetin,Polyoxyethylene sorbitan monooleate,Chitosan,Isopropyl myristate,Water forms,Sampling-type is characterized by Phase Diagram Method and small angle X-ray diffraction,Obtain the content of chitosan,Oil content influences,Water content influences,The pH value of system influences the release of dihydromyricetin,Chitosan dissolves in system and forms stable aggregation,The coordination and cooperation of each component of the medicament of preparation can have the function that control the rate of release of dihydromyricetin drug,And release profiles are fitted using different Dynamic model of release,It was found that release process more meets first order kinetics,It is caused by being spread by concentration to illustrate the release of dihydromyricetin in the sample.
Description
Technical field
The invention belongs to pharmaceutical formulation techniques fields, and in particular to a kind of aggregation based on Tween80 and chitosan is
The dihydromyricetin medicament and preparation method of carrier.
Background technology
Dihydromyricetin (DMY) is a kind of compound of the natural flavone extracted from plant, because there is numerous physiology to live
Property and by extensive concern, such as protect liver, adjust blood fat, antibacterial is anti-oxidant etc..However, its dissolubility in water is poor
(0.2mg/mL, 25 DEG C), causes its bioavilability low, greatly limits practice.In recent years, in order to improve the upper of DMY
Problem is stated, DMY is contained by pharmaceutical carrier such as microemulsion, liposome, micella etc. in recent years, realizes the increasing to drug
It is molten, become the hot spot of research with the solubility for improving DMY.
Surfactant is amphiphilic organic compound that is a kind of while having hydrophilic head base and hydrophobic tail, molecule
Hydrophobic tail mutually associates to form micella, when the concentration of surfactant is more than this value, understands spontaneous composition in aqueous solution
Micellar aggregates.It, will there are a lysotropic liquid crystal phases when internal micellar gathers certain critical level.It is short in structure
Cheng Wuxu, the ordered aggregation of long-range order.Hexagonal phase, lamellar phase are broadly divided into, Cubic Lyotropic Liquid Crystals, wherein hexagonal phase are rodlike
Micella in two dimension ordered arrangement and formed, in its hydrophobic kernel can solubilized oil soluble material, in its hydrophilic region
Can solubilized water soluble compound, oil-soluble medicine can both be contained as pharmaceutical carrier according to this feature,
Can be with water soluble medicament-entrapping, and since itself has certain viscoplasticity, the broken of certain external environment can be resisted
It is bad, it plays to protecting the protective effect of drug, and the slow releasing function to drug can be played.
But lysotropic liquid crystal will generally select the green low toxicity physiologically acceptable carrier harmless to organism as pharmaceutical carrier
System, so to be selected with nontoxic, the amphiphile, amphiphilic molecule of biodegradable and biocompatibility to constructing target lysotropic liquid crystal.Its
Middle polyoxyethylene sorbitan derivative of fatty acid (Tween 80), is that a kind of performance is mild, the nonionic of taste slight bitter
Surfactant is usually used as emulsifier and solubilizer and is widely used in drug delivery system.Some researches show that with
Tween 80 can construct pharmaceutical carrier lysotropic liquid crystal for surfactant, can solubilized insoluble drug curcumin, improve medicine
The solubility of object, and there is protective effect to unstable curcumin under light and heat condition, so Tween 80 can conduct
Ideal surfactant is used for constructing the ordered aggregations such as lysotropic liquid crystal.
Chitosan is a kind of naturally occurring macromolecule carbohydrate, is unique existing alkaline mucopolysaccharide in nature, extensively
It is internal to be present in marine organisms shrimp crab etc., exists in the cell wall of some fungies.Chitosan has the spies such as nontoxic, degradable
Point, and there is antibacterial, it is anti-oxidant to wait physiological activity, thus be widely used in food, medicine and cosmetics.But shell gathers
The sugared structure of itself causes water solubility poor, seriously hinders its practice.In recent years, by organic reaction etc. to chitosan
Chitosan derivatives are modified to, improve the dissolubility of chitosan, expand its application range.Hydrophilic sum is carried in chitosan structure
Hydrophobic group, has certain self aggregation ability, and chitosan limits its practice due to dissolubility difference.
Isopropyl myristate (IPM) is used as a kind of food grade additives, is used frequently as in terms of drug delivery system
Bleeding agent and solubilizer during local administration and cutaneous penetration, are widely used in cosmetics industry and medicament transport system
In.Have shown that isopropyl myristate, not only can be a large amount of in the bleeding agent as cutaneous penetration in report before
Solubilized drug, and skin is not damaged in use.
Invention content
For the above-mentioned prior art the problem of, it is an object of the present invention to provide one kind based on Tween80 and
The aggregation of chitosan is the dihydromyricetin medicament of carrier.Lysotropic liquid crystal viscosity is constructed based on Tween 80 larger, microcosmic knot
The lysotropic liquid crystal of structure arrangement improves the solubility of dihydromyricetin, introduces nontoxic, the chitosan with different physiological roles, participation
Aggregation is constructed, the introducing of chitosan increases the viscosity and stability of aggregation, and then has studied the introducing of chitosan to molten
Cause the influence of the behaviors such as Mesomorphic behavior and release.
In order to solve the above technical problems, the technical scheme is that：
Aggregation of the one kind based on polyoxyethylene sorbitan monooleate (Tween80) and chitosan (WCS) is carries
The dihydromyricetin medicament of body, including dihydromyricetin, Tween 80, chitosan (WCS), isopropyl myristate (IPM) and
Water forms.A concentration of 1.5mg/g of dihydromyricetin, Tween 80, WCS, IPM and water composition carrier system, the quality of carrier
It forms and accounts for 34~44 parts for Tween 80, WCS accounts for 0~8 part, and IPM accounts for 2~11 parts, account for 45~53 parts of water；The wherein matter of WCS
Amount is not 0.
Tween80 and WCS is surfactant；Isopropyl myristate is oil phase.
The ratio of surfactant and oil phase is 4:1.
The pH of the medicament is 7.4.
The solubility of the chitosan is 0.04g/g.
A kind of preparation method of aggregation based on Tween80 and chitosan for the dihydromyricetin medicament of carrier：Specifically
Step is：
1) it according to certain mass ratio Tween 80 and IPM, stirs and evenly mixs in a water bath；
2) dihydromyricetin is added in into the mixture that step 1) obtains, is stirred and evenly mixed in a water bath；
3) WCS mixing is added in into the mixture that step 2) obtains to be placed in colorimetric cylinder, and WCS is made to be dispersed in Tween
In 80；
4) redistilled water is added dropwise into the colorimetric cylinder of step 3), it is uniform using magnetic stirrer, then put
It is balanced in water-bath, obtains medicament.
Preferably, the mass ratio of the step 1) Tween80 and chitosan is 9：2~10：1.
Preferably, the temperature of the step 1) is 60-70 DEG C.
Preferably, moisture repeatedly adds in the step 4)；
It is further preferred that the quality of water is divided into several pieces in the step 4), the quality of the water added in every time
Part water is two parts (such as the mass fraction of water is 45 parts in carrier, then adds in 2 parts every time).
Preferably, the bath temperature in the step 3) is 25 DEG C.
Surfactant：Tween80 is as surfactant, in aqueous solution as the interphase state of lysotropic liquid crystal,
Structure is hexagonal phase, and chitosan also serves as surfactant, chitosan and Tween80
The effect of oil phase：The increase of oil phase IPM contents, causes hydrophobic inner core to be swollen, and aggregate structure is loose, under viscoplasticity
Drop, makes the release of DMY become faster.
The effect of chitosan：The introducing of chitosan, under especially high chitosan content, sample has higher elasticity, knot
Structure is relatively stable, slows down so as to cause the rate of release of DMY.
The effect of water：The increase of water content is conducive to the formation of hydrogen bond and unfolding for chitosan, promotes the release speed of DMY
Rate is slack-off.
The effect of pH value：Promote the protonation of amino in chitosan under acid condition, increase the repulsive interaction between molecule,
Become loose so as to cause aggregate structure, promote the release of DMY.
By being analyzed above it is found that the viscoplasticity of system influences the release of DMY, IPM can decline the viscoplasticity of solution, tie
Structure is loose, promotes the release of DMY, and chitosan can increase aggregation viscoplasticity, plays better slow releasing function, chitosan and
Water has the function of to promote hydrogen bond formation simultaneously.
The amino of chitosan protonates under acid condition, and then certain influence is generated to aggregate structure.Make to gather
Aggregate structure is loose.
Beneficial effects of the present invention：
1) the Tween 80/WCS/IPM/H of the application2The coordinative role of each ingredient is to drug dihydromyricetin in O systems
With solubilization, and there is sustained release and controlled release to the release of dihydromyricetin；
2) the Tween 80/WCS/IPM/H of the application2O improves the solubility of chitosan；
3) the result shows that the introducing of chitosan increases the stability for carrying medicine sample, the releases of DMY in the sample are extended
Time, the slowly releasing effect having had to DMY.
Description of the drawings
The accompanying drawings which form a part of this application are used for providing further understanding of the present application, and the application's shows
Meaning property embodiment and its explanation do not form the improper restriction to the application for explaining the application.
Fig. 1 is Tween80/ chitosans (10:1,wt:wt)/IPM/H2O systems pseudoternary phase diagram (25 DEG C)；Wherein
The mass ratio of Tween80 and chitosan is respectively 1:0(a),10:1(b),9:2(c)
Fig. 2 is sample (S at 25 DEG C0And S1) SAXS spectrograms
Fig. 3 constructs Tween80/ chitosans/IPM/ for dihydromyricetin in different chitosan contents (0%, 4%, 8%)
H2Release profiles (25 DEG C) in O systems
Fig. 4 (a) dihydromyricetins are in different surfaces activating agent (Tween80/ chitosans) and IPM contents (8:2,9:1,
9.5:0.5) sample (S is constructed1O1,S1O2,S1O3) in release profiles (25 DEG C)；(b) dihydromyricetin is in different water contents
Sample (the S that (45%, 49%, 53%) is constructed1W1,S1W2,S1W3) in release profiles (25 DEG C)
Fig. 5 is dihydromyricetin under different pH in sample (S2) in release profiles (25 DEG C)
Fig. 6 (a) dihydromyricetins/liquid crystal (S1), blank liquid crystal (BS1), DMY infrared spectrums (DMY), (b) difference shell gathers
Sugared content dihydromyricetin/liquid crystalline sample (S1,S2,S3) infrared spectrum
Fig. 7 (a) differences Tween80:The dihydromyricetin that chitosan/IPM contents are constructed/liquid crystalline sample (S1O1,S1O2,
S1O3) infrared spectrum, (b) difference water content under dihydromyricetin/liquid crystalline sample (S1W1,S1W2,S1W3) infrared spectrum
Specific embodiment
It is noted that following detailed description is all illustrative, it is intended to provide further instruction to the application.It is unless another
It indicates, all technical and scientific terms used herein has usual with the application person of an ordinary skill in the technical field
The identical meanings of understanding.
It should be noted that term used herein above is merely to describe specific embodiment, and be not intended to restricted root
According to the illustrative embodiments of the application.As used herein, unless the context clearly indicates otherwise, otherwise singulative
It is also intended to include plural form, additionally, it should be understood that, when in the present specification using term "comprising" and/or " packet
Include " when, indicate existing characteristics, step, operation, device, component and/or combination thereof.
Polyoxyethylene sorbitan monooleate (Tween 80, Sinopharm Chemical Reagent Co., Ltd.), nutmeg
Isopropyl propionate (IPM, Sinopharm Chemical Reagent Co., Ltd.), chitosan (WCS, deacetylation>85%, Jinan Hai get Bei Hai
Foreign bioengineering Co., Ltd), dihydromyricetin (Nanjing Zelang Pharmaceutical Technology Inc.), water is redistilled water.
Electronic balance (AL104, plum Teller-support benefit Instrument Ltd.), heat collecting type heated at constant temperature blender (DF-
101S types, Ying Yu instrument plants of Gongyi City), centrifuge (TDL-4, Anting Scientific Instrument Factory, Shanghai), ultraviolet specrophotometer (UV-
5500PC, Shanghai Yuan Xi Instrument Ltd.), small angle X ray scattering instrument (SAXSess, Austria, Anton Paar), Fourier becomes
Change infrared spectrometer (AlphaT, Bruker Optik GmbH, Germany), gold leaf board dual pure water water still (SZ- automatically
93A types, Shanghai Yarong Biochemical Instrument Plant).
With reference to embodiment, the present invention is further described
Preparation about carrier
Embodiment 1
Surfactant/oil/water ratio is 44/11/45, and chitosan mass score is 4%, weighs Tween 80 and WCS (makees
For surfactant) it is placed in colorimetric cylinder, mixing makes chitosan be dispersed in Tween 80.IPM is added in thereto,
It is stirred and evenly mixed under 65 DEG C of water-bath.Finally, redistilled water is added dropwise into colorimetric cylinder dropwise, water content is increased with 2% interval,
It is uniform using magnetic stirrer, it is subsequently placed in 25 DEG C of water-bath and balances, observe and record aggregation phase and appearance
Variation needs to extend the equilibration time of aggregation when close to phase boundray.The color presented by estimating aggregation, it is transparent
Degree, hardness, viscosity etc. tentatively judge phase boundray.It is denoted as S1
Embodiment 2
Surfactant/oil/water ratio is 44/11/45, and chitosan mass score is 8%, weighs Tween 80 and WCS (makees
For surfactant) it is placed in colorimetric cylinder, mixing makes chitosan be dispersed in Tween 80.IPM is added in thereto,
It is stirred and evenly mixed under 65 DEG C of water-bath.Finally, redistilled water is added dropwise into colorimetric cylinder dropwise, water content is increased with 2% interval,
It is uniform using magnetic stirrer, it is subsequently placed in 25 DEG C of water-bath and balances, observe and record aggregation phase and appearance
Variation needs to extend the equilibration time of aggregation when close to phase boundray.The color presented by estimating aggregation, it is transparent
Degree, hardness, viscosity etc. tentatively judge phase boundray.It is denoted as S2。
Comparative example 1
Surfactant/oil/water ratio is 44/11/45, and chitosan mass score is 0%, weighs Tween 80 and WCS (makees
For surfactant) it is placed in colorimetric cylinder, mixing makes chitosan be dispersed in Tween 80.IPM is added in thereto,
It is stirred and evenly mixed under 65 DEG C of water-bath.Finally, redistilled water is added dropwise into colorimetric cylinder dropwise, water content is increased with 2% interval,
It is uniform using magnetic stirrer, it is subsequently placed in 25 DEG C of water-bath and balances, observe and record aggregation phase and appearance
Variation needs to extend the equilibration time of aggregation when close to phase boundray.The color presented by estimating aggregation, it is transparent
Degree, hardness, viscosity etc. tentatively judge phase boundray.It is denoted as S0。
Embodiment 3
The ratio of surfactant and oil is 9:1, chitosan mass score is 4.5%, and water content 45% weighs Tween
80 and WCS is placed in (as surfactant) in colorimetric cylinder, and mixing makes chitosan be dispersed in Tween 80.Thereto
IPM is added in, is stirred and evenly mixed under 65 DEG C of water-bath.Finally, redistilled water is added dropwise into colorimetric cylinder dropwise, water content is with 2%
Interval increase, it is uniform using magnetic stirrer, be subsequently placed in 25 DEG C of water-bath and balance, observe and record aggregation phase
The variation of state and appearance needs to extend the equilibration time of aggregation when close to phase boundray.It is presented by estimating aggregation
Color, transparency, hardness, viscosity etc. tentatively judges phase boundray.It is denoted as S1O2.
Embodiment 4
The ratio of surfactant and oil is 9.5:0.5, chitosan mass score is 4.75%, and water content 45% weighs
Tween 80 and WCS are placed in (as surfactant) in colorimetric cylinder, and mixing makes chitosan be dispersed in Tween 80.
IPM is added in thereto, is stirred and evenly mixed under 65 DEG C of water-bath.Finally, redistilled water, water content is added dropwise into colorimetric cylinder dropwise
Increased with 2% interval, it is uniform using magnetic stirrer, it is subsequently placed in 25 DEG C of water-bath and balances, observe and record poly-
The variation of collective's phase and appearance needs to extend the equilibration time of aggregation when close to phase boundray.Assembled by estimating
The color that body is presented, transparency, hardness, viscosity etc. tentatively judge phase boundray.It is denoted as S1O3。
Embodiment 5
The ratio of surfactant and oil is 8:2, chitosan mass score is 3.71%, and water content 49% weighs Tween
80 and WCS is placed in (as surfactant) in colorimetric cylinder, and mixing makes chitosan be dispersed in Tween 80.Thereto
IPM is added in, is stirred and evenly mixed under 65 DEG C of water-bath.Finally, redistilled water is added dropwise into colorimetric cylinder dropwise, water content is with 2%
Interval increase, it is uniform using magnetic stirrer, be subsequently placed in 25 DEG C of water-bath and balance, observe and record aggregation phase
The variation of state and appearance needs to extend the equilibration time of aggregation when close to phase boundray.It is presented by estimating aggregation
Color, transparency, hardness, viscosity etc. tentatively judges phase boundray.It is denoted as S1W2。
Embodiment 6
The ratio of surfactant and oil is 8:2, chitosan mass score is 3.42%, and water content 53% weighs Tween
80 and WCS is placed in (as surfactant) in colorimetric cylinder, and mixing makes chitosan be dispersed in Tween 80.Thereto
IPM is added in, is stirred and evenly mixed under 65 DEG C of water-bath.Finally, redistilled water is added dropwise into colorimetric cylinder dropwise, water content is with 2%
Interval increase, it is uniform using magnetic stirrer, be subsequently placed in 25 DEG C of water-bath and balance, observe and record aggregation phase
The variation of state and appearance needs to extend the equilibration time of aggregation when close to phase boundray.It is presented by estimating aggregation
Color, transparency, hardness, viscosity etc. tentatively judges phase boundray.It is denoted as S1W3。
The drafting of phasor
According to certain mass ratio (10:1 or 9:2), Tween 80 and WCS is weighed to be placed in comparing (as surfactant)
In colour tube, mixing makes chitosan be dispersed in Tween 80.Secondly, according to surfactant than oil phase from 10:0 to 0:10
Variation, adds in IPM, is stirred and evenly mixed under 60-70 DEG C of water-bath thereto successively.Finally, it is added dropwise dropwise into colorimetric cylinder secondary
Distilled water, water content is increased with 2% interval, uniform using magnetic stirrer, is subsequently placed in 25 DEG C of water-bath and is balanced,
The variation of aggregation phase and appearance is observed and recorded, needs to extend the equilibration time of aggregation when close to phase boundray.
The color presented by estimating aggregation, transparency, hardness, viscosity etc. tentatively judge phase boundray.As shown in Figure 1.
Small angle X ray scattering is tested
Small angle X ray scattering instrument chooses copper target as light source, X ray excited wavelength 0.1542nm, operating voltage and electricity
Stream is respectively 40kV and 50mA, and the distance of sample to detector needs under vacuum to prevent air from dissipating for 264.5nm. tests
It penetrates.Studied liquid crystalline sample is measured at 25 DEG C.Measure the structure that obtained SAXS spectrograms can be used for determining lysotropic liquid crystal
Type analyzes the microstructure of liquid crystalline sample and corresponding structural parameters.
The extracorporeal releasing test of dihydromyricetin
By the release in vitro behavior of the technique study dihydromyricetin of extracorporal dialysis, first, weigh about 0.5g and carry liquid
Crystalline substance is placed in the bag filter handled well (small intestine casing).Secondly, it places it in and fills 60mLPBS buffer mediums and (contain
20wt% ethyl alcohol) beaker in, then, magneton is put into beaker and is put into constant temperature in the water-bath of magnetic force heating stirrer and is stirred
It mixes.Finally, 5mL dissolution mediums are taken out at regular intervals, while the dissolution medium for filling into 5mL again maintains constant volume, until
Drug release reaches balance.The absorbance of DMY is measured using ultraviolet specrophotometer at the maximum absorption wavelength 289nm of DMY,
According to the standard absorption curve of DMY, the concentration of DMY is obtained, and the preparation of DMY is calculated according to following formula.
The name of 1 each sample of table and composition
The vitro release kinetics parameter of 2. dihydromyricetin of table in the sample
The first order release kinetics parameter of 3 dihydromyricetin of table in the sample
Experimental result：
As shown in Figure 1a, it finds clear occur in phasor, does not flow, relatively viscous mesophase range, be tentatively judged as
The mesophase range of appearance is hexagonal liquid crystal.And water content changes to 60wt%, the oil of maximum solubilising from 20wt% in the phase region
Content is 32wt%.
As shown in figs. lb and lc, it is larger to occur a viscosity in each phasor, immobilising region of standing upside down, and
The transparency of aggregation is continuously decreased with the increase of chitosan content, and color is gradually deepened.With the increasing of chitosan content
Adding, phase region is gradually moved to high water content area, this is because under conditions of high surface agent content and low water content, it is water-soluble
Property chitosan is completely dissolved not yet, and system is caused not form transparent ordered aggregation, make the alpha region of system become smaller and
It is moved to high water content area.
As shown in Fig. 2, sample S0SAXS spectrograms on show 3 Bragg peaks, the ratio of relative peak positions meetsRelationship, this illustrates sample S0Belong to hexagonal liquid crystal structure.Sample S0Belong to hexagonal liquid crystal structure introducing shell to gather
After sugar, illustrate that the liquid crystal of System forming is imperfect.
Chitosan has the trend gradually dissolved in system as shown in Figure 1.It is each in chitosan influence system as shown in Figure 2
The content of component.The structure of System forming is influenced simultaneously.The structure of system has not been hexagonal phase structure after chitosan adds in, but
The new system of formation is still stable aggregate structure, is only moved to water phase direction, and it is identical with lysotropic liquid crystal to form appearance
State, it is shinny, do not flow, the increased gellike state of viscoplasticity.
Fig. 3 is the release profiles in the sample that DMY is constructed in different chitosan concentrations, it can be seen from the figure that releasing
Put early period (<1000min), DMY is in sample S0,S1And S2In rate of release it is very fast, mainly due to the DMY in boundary layer
Release caused by.With the progress of release, rate of release slows down gradually, and finally release reaches balance, and preparation reaches most
Big value.It can be found that in entire deenergized period, with the increase of chitosan concentration, rates of release of the DMY in hexagonal liquid crystal
It is substantially reduced, and DMY is in sample S2Middle rate of release is most slow, may be since under high chitosan content, sample has higher
Elasticity, structure is relatively stable, slows down so as to cause the rate of release of DMY.The result shows that the introducing of chitosan, which increases, carries medicine sample
The stability of product extends the release times of DMY in the sample, to the slowly releasing effect that DMY has had, thus can be gathered by shell
The introducing of sugar regulates and controls release behavior.
Fig. 4 a are release profiles of the DMY in the sample of different surfaces activating agent/oil such as figure, it can be seen from the figure that with
Sample S1O2And S1O3It compares, DMY is in sample S1O1Release rate is very fast, it may be possible to due to the increase of oil content, hydrophobic inner core
Swelling, aggregate structure is loose, caused by flexibility decrease.
Shown in Fig. 4 b, it can be seen that with the increase of water content, the rate of release of DMY slows down, may be due to water content
Increase make chitosan in aggregation to fully unfolding, the release so as to hinder DMY leads to rate of release and adds up to release
The rate of putting slows down, while also illustrates aggregation can be made to have better slow release effect by increasing water content.
Understand that oil content, chitosan content and water content influence the release behavior of DMY by Fig. 3 and Fig. 4.
Shown in Fig. 5.As can be seen that the rates of release of DMY in the sample are significantly different under different pH value, preparation point
Not Wei 90% (pH value 7.4), 99% (pH value 5.6) has found that with the increase of pH value rate of release is accelerated, cumulative release
Rate increases.By controlling the addition of sodium dihydrogen phosphate and disodium hydrogen phosphate, the dissolution medium of different pH is configured.It can by Fig. 5
Know that pH value influences the release behavior of DMY.
To inquire into release behaviors of the DMY in aggregation, we are with sample S0-S2For, use different kinetic models
It is fitted, mainly include zero order kinetics model (Zero-order), First order dynamic model (First-order),
Higuchi models, Hixson-Crowell models and Korsmeyer-Peppas models are fitted the kinetic parameter such as table of gained
Shown in 2.It was found that it is fitted obtained degree of correlation maximum (R using first order kinetics2>0.9935), illustrate DMY releasing in the sample
It is the process spread by concentration to put.The degree of correlation (the R that Korsmeyer-Peppas models obtain2>0.9316) level-one is only second to move
The degree of correlation obtained by mechanics, illustrates that release processes of the DMY in liquid crystalline sample follows first order kinetics process the most.
First _ order kinetics equation is as follows：
Wherein, K is kinetic constant；N is release index, for characterizing the releasing mechanism of drug；M0/MtIt is drug in t
The release percentage at quarter.
And then choose first _ order kinetics equation and all samples are fitted, the fit equation and relevant parameter of gained are shown in Table
3.Compare obtained related coefficient (R2) find, the degree of correlation R that First order dynamic model is fitted2Both greater than 0.9920, explanation
The release in vitro behavior of DMY more meets with First order dynamic model, and it is to be spread to control by concentration to illustrate release in vitro process.
After introducing chitosan from Fig. 6 a as can be seen that into system ,-OH peak positions are from 3384cm-1(S0) to ebb
3374cm-1(S1) mobile, illustrate to form more hydrogen bonds in system, i.e. the introducing of chitosan is conducive to the formation of hydrogen bond, has
Conducive to the stabilization of aggregation, the chitosan of this and high-content in release in vitro behavior causes rate of release and accumulative release rate slack-off
It is consistent.Wherein in 2851cm-1Place and 2923cm-1The absorption peak at place is respectively-CH on alkyl chain in each component2Symmetrical stretch
Contracting vibration and antisymmetry are stretched symmetrical peak.1461cm-1Locate the bending vibration absorption peak for C-H on alkyl chain.In 1739cm-1Place
There is absorption peak, the stretching vibration peak of-C=O generates predominantly in DMY molecules.1643cm-1For-NH in chitosan2Flexible shake
Dynamic absorption peak, 1437cm-1For the stretching vibration peak of-N-H in chitosan, in 1091cm-1The absorption peak at place is 80 Hes of Tween
The stretching vibration peak of-C-O in DMY molecules.
It can be seen from figure 7 that surfactant and oil content in increase system, the stretching vibration peak position of-OH from
3376cm-1Change 3374cm-1, illustrate to form more hydrogen bonds in system.Increase water content, discovery-OH peaks broaden, explanation
The increase of water content is conducive to the formation of hydrogen bond, and sample structure is more stablized, this causes rate of release slack-off with increasing water content
Result be consistent.
It summarizes：
Medicament prepared by the application has DMY preferable slow releasing function.The release in vitro behavior of DMY and first order kinetics mould
Type more meets, and it is to be spread to control by concentration to illustrate release in vitro process.Chitosan influences the release behavior of DMY in medicament,
Oil content influences the release of DMY, and water content influences the release of DMY, and the pH value of system also influences the release of DMY.So the application
The coordination and cooperation of each component of the medicament of preparation can have the function that control the rate of release of DMY drugs.
The application is that the solubility of lysotropic liquid crystal raising dihydromyricetin is constructed based on Tween 80 first, is had certain micro-
It is larger to see structure, the microemulsion solute liquid crystal viscosity of solubilising power；Introduce nontoxic, the chitosan with different physiological roles, ginseng
With constructing aggregation, the introducing of chitosan increases the viscosity and stability of aggregation, and then has studied the introducing pair of chitosan
The influence of the behaviors such as lysotropic liquid crystal phase behavior and release.
The foregoing is merely the preferred embodiments of the application, are not limited to the application, for the skill of this field
For art personnel, the application can have various modifications and variations.It is all within spirit herein and principle, made any repair
Change, equivalent replacement, improvement etc., should be included within the protection domain of the application.
Claims (10)
1. a kind of aggregation based on Tween 80 and chitosan be carrier dihydromyricetin medicament, including dihydromyricetin,
Tween 80, chitosan, isopropyl myristate and water composition；Tween 80, chitosan, isopropyl myristate and water composition
Carrier system, the quality group of carrier account for 34~44 parts as Tween 80, and chitosan accounts for 0~8 part, and isopropyl myristate accounts for 2
~11 parts, water account for 45~53；Wherein the quality of chitosan is not 0.
2. dihydromyricetin medicament according to claim 1, it is characterised in that：A concentration of 1.5mg/g of dihydromyricetin.
3. dihydromyricetin medicament according to claim 1, it is characterised in that：The ratio of the surfactant and oil phase
It is 4:1.
4. dihydromyricetin medicament according to claim 1, it is characterised in that：The solubility of the chitosan is 0.04g/
g。
5. dihydromyricetin medicament according to claim 1, it is characterised in that：The pH value of medicament is 7.4.
6. a kind of dihydromyricetin medicament preparation method, it is characterised in that：The specific steps are：
1) it according to certain mass ratio Tween 80 and IPM, stirs and evenly mixs in a water bath；
2) dihydromyricetin is added in into the mixture that step 1) obtains, is stirred and evenly mixed in a water bath；
3) WCS mixing is added in into the mixture that step 2) obtains to be placed in colorimetric cylinder, and WCS is made to be dispersed in Tween80；
4) redistilled water is added dropwise into the colorimetric cylinder of step 3), it is uniform using magnetic stirrer, it is subsequently placed in water
It is balanced in bath, obtains medicament.
7. dihydromyricetin medicament according to claim 6, it is characterised in that：Step 1) the Tween80 and chitosan
Mass ratio be 9:2~10:1.
8. dihydromyricetin medicament according to claim 6, it is characterised in that：The temperature of the step 1) is 60-70 DEG C.
9. dihydromyricetin medicament according to claim 6, it is characterised in that：Bath temperature in the step 3) is 25
℃。
10. dihydromyricetin medicament according to claim 6, it is characterised in that：Moisture repeatedly adds in the step 3)；
Preferably, the quality of water is divided into several pieces in the step 3), the mass parts water of the water added in every time is two parts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810123231.XA CN108144064B (en) | 2018-02-07 | 2018-02-07 | Dihydromyricetin medicament taking aggregate of Tween80 and chitosan as carrier and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810123231.XA CN108144064B (en) | 2018-02-07 | 2018-02-07 | Dihydromyricetin medicament taking aggregate of Tween80 and chitosan as carrier and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108144064A true CN108144064A (en) | 2018-06-12 |
| CN108144064B CN108144064B (en) | 2021-01-08 |
Family
ID=62457220
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810123231.XA Active CN108144064B (en) | 2018-02-07 | 2018-02-07 | Dihydromyricetin medicament taking aggregate of Tween80 and chitosan as carrier and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108144064B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109010271A (en) * | 2018-09-25 | 2018-12-18 | 山东师范大学 | A kind of apiolin slow-release medicine carrier and preparation method thereof |
| CN110037982A (en) * | 2019-04-17 | 2019-07-23 | 山东师范大学 | A kind of dihydromyricetin lysotropic liquid crystal preparation and preparation method thereof |
| CN113616797A (en) * | 2021-08-03 | 2021-11-09 | 山东师范大学 | Low-water-solubility polyphenol drug carrier and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007028256A2 (en) * | 2005-09-09 | 2007-03-15 | Les Biotechnologies Oceanova Inc. | Polysaccharides compositions comprising fucans and galactans and their use to reduce extravasation and inflammation |
| CN101129373A (en) * | 2007-08-16 | 2008-02-27 | 华中师范大学 | Method for preparing Imiquimod chitosannano granule |
| CN101173026A (en) * | 2007-11-26 | 2008-05-07 | 天津科技大学 | AKD emulsion and method for producing the same |
| CN101596169A (en) * | 2009-07-06 | 2009-12-09 | 浙江大学 | A kind of chitosan nano of encapsulating adenosine triphosphate and preparation method |
-
2018
- 2018-02-07 CN CN201810123231.XA patent/CN108144064B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007028256A2 (en) * | 2005-09-09 | 2007-03-15 | Les Biotechnologies Oceanova Inc. | Polysaccharides compositions comprising fucans and galactans and their use to reduce extravasation and inflammation |
| CN101129373A (en) * | 2007-08-16 | 2008-02-27 | 华中师范大学 | Method for preparing Imiquimod chitosannano granule |
| CN101173026A (en) * | 2007-11-26 | 2008-05-07 | 天津科技大学 | AKD emulsion and method for producing the same |
| CN101596169A (en) * | 2009-07-06 | 2009-12-09 | 浙江大学 | A kind of chitosan nano of encapsulating adenosine triphosphate and preparation method |
Non-Patent Citations (2)
| Title |
|---|
| LI ZHANG ET AL.: "Construction, in vitro release and rheological behavior of apigenin-encapsulated hexagonal liquid crystal", 《JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY》 * |
| 范军: "药物有序聚集体的释放行为及性能", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109010271A (en) * | 2018-09-25 | 2018-12-18 | 山东师范大学 | A kind of apiolin slow-release medicine carrier and preparation method thereof |
| CN110037982A (en) * | 2019-04-17 | 2019-07-23 | 山东师范大学 | A kind of dihydromyricetin lysotropic liquid crystal preparation and preparation method thereof |
| CN110037982B (en) * | 2019-04-17 | 2021-12-03 | 山东师范大学 | Dihydromyricetin lyotropic liquid crystal preparation and preparation method thereof |
| CN113616797A (en) * | 2021-08-03 | 2021-11-09 | 山东师范大学 | Low-water-solubility polyphenol drug carrier and preparation method and application thereof |
| CN113616797B (en) * | 2021-08-03 | 2024-02-09 | 山东师范大学 | Low-water-solubility polyphenol drug carrier and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108144064B (en) | 2021-01-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108144064A (en) | A kind of aggregation based on Tween80 and chitosan is the dihydromyricetin medicament and preparation method of carrier | |
| CN101066260B (en) | Coenzyme Q10 emulsion and its freeze dried emulsion and their preparation process | |
| CZ298971B6 (en) | Lotions based on Active vitamin D3 emulsions | |
| JPH0552808B2 (en) | ||
| CN104382918B (en) | Adriamycin liposome temperature-sensitive gel for local tumor injection | |
| CA3098108C (en) | Compositions of o-glycosyl flavonoids | |
| CN102697724A (en) | Clopidogrel and salt submicron emulsion injection thereof as well as preparation method of same | |
| CN106491519A (en) | Cubic liquid crystal in-situ gel injection agent of local anesthetic and preparation method thereof | |
| CN106491520A (en) | A kind of coenzyme Q 10 injection liquid formulation and preparation method thereof | |
| BRPI0309406B1 (en) | pharmaceutical composition, process for preparing said composition, obesity treatment kit and use of said composition in the manufacture of compositions useful for the treatment and prevention of obesity | |
| CN104352566A (en) | Oil-in-water compound chlortetracycline nanoemulsion | |
| CN108309954A (en) | A kind of the lecithin aliphatic radical reversed hexagonal liquid crystal medicament and preparation method of tea polyphenols | |
| WO2020004194A1 (en) | External-use composition | |
| CN103054799B (en) | Amiodarone hydrochloride injection emulsion and preparation method thereof | |
| JP6968470B1 (en) | Powdered cosmetics | |
| KR100292027B1 (en) | Liquid suppository composition for prostaglandin e1 | |
| JP2024512659A (en) | Phospholipids as anionic chelating agents in pharmaceutical formulations | |
| JP7350985B2 (en) | Composition containing betamethasone valerate | |
| EP2959911B1 (en) | Compound fructus forsythiae-radix bupleuri oil nanoemulsion preparation | |
| CN118436602A (en) | External honokiol cream and preparation method and application thereof | |
| CN118557454B (en) | Nanometer liquid crystal carrier for improving bioavailability and stability of glabridin | |
| CN101890015A (en) | Liposome injection of pharmaceutical composition comprising piperacillin sodium and tazobactam sodium | |
| Sultan et al. | FORMULATION AND ANTIOXIDANT ACTIVITY EMULGEL SENGGANI LEAF (Melastoma malabathricum L.) WATER FRACTIONS WITH VARIATIONS OF GELLING AGENT USING DPPH METHOD | |
| CA3118255A1 (en) | Isoquercitrin compositions | |
| BR102020001497A2 (en) | PILOCARPINE HYDROCHLORIDE DELIVERED IN SNEDDS NANOCARRECT SYSTEM FOR OPHTHALMOLOGICAL USE AS INTRAOCULAR PRESSURE REDUCER |
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: 20240326 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 |