CN109125508A - A kind of tea polyphenols lysotropic liquid crystal dispersion and preparation method - Google Patents
A kind of tea polyphenols lysotropic liquid crystal dispersion and preparation method Download PDFInfo
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- CN109125508A CN109125508A CN201811297016.8A CN201811297016A CN109125508A CN 109125508 A CN109125508 A CN 109125508A CN 201811297016 A CN201811297016 A CN 201811297016A CN 109125508 A CN109125508 A CN 109125508A
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- liquid crystal
- water
- tea polyphenols
- dispersion
- oleic acid
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- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 71
- 235000013824 polyphenols Nutrition 0.000 claims description 71
- 241001122767 Theaceae Species 0.000 claims description 68
- 239000004973 liquid crystal related substance Substances 0.000 claims description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 56
- 239000006185 dispersion Substances 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 25
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 23
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 23
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 23
- 239000005642 Oleic acid Substances 0.000 claims description 23
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 23
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 23
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 23
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 22
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 22
- 235000010445 lecithin Nutrition 0.000 claims description 22
- 239000000787 lecithin Substances 0.000 claims description 22
- 229940067606 lecithin Drugs 0.000 claims description 22
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 16
- 229920000136 polysorbate Polymers 0.000 claims description 15
- 239000002245 particle Substances 0.000 claims description 14
- 230000003078 antioxidant effect Effects 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 9
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 9
- 229920000053 polysorbate 80 Polymers 0.000 claims description 9
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 claims description 7
- 239000002105 nanoparticle Substances 0.000 claims description 7
- 238000011067 equilibration Methods 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000003381 stabilizer Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims description 3
- 230000007760 free radical scavenging Effects 0.000 claims description 3
- 239000004976 Lyotropic liquid crystal Substances 0.000 claims 3
- 239000012154 double-distilled water Substances 0.000 claims 3
- 239000004480 active ingredient Substances 0.000 claims 2
- 238000001132 ultrasonic dispersion Methods 0.000 claims 2
- 239000002612 dispersion medium Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000523 sample Substances 0.000 description 18
- -1 ABTS free radical Chemical class 0.000 description 14
- 238000000338 in vitro Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 239000004094 surface-active agent Substances 0.000 description 12
- 238000002835 absorbance Methods 0.000 description 11
- 239000012153 distilled water Substances 0.000 description 10
- 239000003814 drug Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 230000002000 scavenging effect Effects 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000000527 sonication Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000004821 distillation Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- OGQYPPBGSLZBEG-UHFFFAOYSA-N dimethyl(dioctadecyl)azanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC OGQYPPBGSLZBEG-UHFFFAOYSA-N 0.000 description 2
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- LSHVYAFMTMFKBA-TZIWHRDSSA-N (-)-epicatechin-3-O-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=CC=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-TZIWHRDSSA-N 0.000 description 1
- OCZVHBZNPVABKX-UHFFFAOYSA-N 1,1-diphenyl-2-(2,4,6-trinitrophenyl)hydrazine;ethanol Chemical compound CCO.[O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1NN(C=1C=CC=CC=1)C1=CC=CC=C1 OCZVHBZNPVABKX-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000003471 anti-radiation Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000007865 diluting Methods 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
- 238000009472 formulation Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/82—Theaceae (Tea family), e.g. camellia
-
- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Organic Chemistry (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Toxicology (AREA)
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Abstract
本发明提供一种茶多酚溶致液晶分散体及制备方法，该液晶分散体，其为包含药物活性成分、药物载体和稳定剂的乳状纳米颗粒分散体，分散介质为水；所述药物活性成分为茶多酚，所述药物载体为溶致液晶，所述溶致液晶由卵磷脂、油酸、PEG 400和水组成。该茶多酚溶致液晶分散体相较于茶多酚本身抗氧化性能增强，且具有较好的释放和缓释性能。
The invention provides a tea polyphenol lyotropic liquid crystal dispersion and a preparation method. The liquid crystal dispersion is a milky nanoparticle dispersion containing a pharmaceutical active ingredient, a pharmaceutical carrier and a stabilizer, and the dispersion medium is water; the pharmaceutical active The ingredient is tea polyphenol, the drug carrier is lyotropic liquid crystal, and the lyotropic liquid crystal is composed of lecithin, oleic acid, PEG 400 and water. Compared with the tea polyphenol itself, the tea polyphenol lyotropic liquid crystal dispersion has enhanced antioxidant properties, and has better release and sustained release properties.
Description
Technical field
The present invention relates to field of medicaments, and in particular to a kind of tea polyphenols lysotropic liquid crystal dispersion and preparation method thereof.
Background technique
Tea polyphenols are also known as tea tannin, are to have pharmacology and healthcare function in the general name and tealeaves of Polyphenols of Tea
One of main component.Research finds that tea polyphenols have anti-oxidant, anti-inflammatory, antitumor, anti-radiation, lipidemia, anti-aging
Etc. pharmacology and health-care effect, the research in relation to tea polyphenols have become the research hotspot of pharmaceutical field at present.But tea polyphenols is oral
Bioavilability is very low, typically less than 2-5%.Therefore, it in order to preferably apply tea polyphenols, prepares a kind of carrier and comes to tea polyphenols
Encapsulating, can keep its good stability, further increase its bioavilability.
Lysotropic liquid crystal is widely used as pharmaceutical carrier as a kind of self-assembly that amphiphile, amphiphilic molecule is formed in water.It is molten
Cause liquid crystal be usually made of amphiphile, amphiphilic molecule and solvent, can be divided into stratiform, cube, hexagon interphase.Lysotropic liquid crystal is present in me
Body many positions, such as brain, muscle, retina.Their special construction rises emphatically in our key activities
It acts on.In the internal structure of lysotropic liquid crystal, hydrophilic and hydrophobic part may include water soluble drug and oil-soluble medicine respectively
Object.In recent years, lysotropic liquid crystal is received significant attention because of its outstanding load medicine and Release Performance.
Summary of the invention
This application provides a kind of tea polyphenols lysotropic liquid crystal dispersion and preparation methods.Tea polyphenols have been encapsulated in by lecithin
It is nanometer by lysotropic liquid crystal ultrasonic disperse using Tween 80 as stabilizer in the lysotropic liquid crystal that rouge, oleic acid, PEG 400 and water are formed
Particle.The present invention is found through experiments that the inoxidizability for the tea polyphenols being encapsulated in lysotropic liquid crystal dispersion enhances, the present invention
Tea polyphenols lysotropic liquid crystal dispersion remove ABTS free radical IC50It is that tea is more that value, which is both less than 3.778 μ g/mL, 3.778 μ g/mL,
The IC of phenol aqueous solution removing ABTS free radical50Value.Tea polyphenols lysotropic liquid crystal dispersion of the invention removes DPPH free radical IC50
It is the IC that tea polyphenols aqueous solution removes DPPH free radical that value, which is both less than 4.657 μ g/mL, 4.657 μ g/mL,50Value.Also, the present invention
Tea polyphenols lysotropic liquid crystal dispersion physical efficiency slow down the rates of release of tea polyphenols so that tea polyphenols release equilibration time is obviously prolonged.
In addition, tea polyphenols lysotropic liquid crystal dispersion of the invention has the partial size of 164-190nm, compared to simple molten cause
LCD vector, the present invention both can be used as oral preparation, it is also possible to and make intravenous formulations, and there is better stability, this
The tea polyphenols lysotropic liquid crystal dispersion slow-release time of invention is 80 hours or more, slow compared to simple lysotropic liquid crystal carrier
Release effect have be obviously improved.
Specifically, the present invention is realized by technical solution as described below:
In the first aspect of the present invention, the present invention provides a kind of Liquid Crystal dispersions, to include active pharmaceutical ingredient, medicine
The emulsus nanoparticle dispersion of object carrier and stabilizer, decentralized medium are water；The active pharmaceutical ingredient is tea polyphenols, described
Pharmaceutical carrier is lysotropic liquid crystal, and the lysotropic liquid crystal is made of lecithin, oleic acid, PEG 400 and water.
Preferably, in the lysotropic liquid crystal, the mass ratio of oleic acid and PEG 400 are 1:1；
Preferably, the water is secondary distilled water；
Preferably, the stabilizer is tween, preferably Tween 80.
Preferably, the Liquid Crystal dispersion includes or composed of the following components: 57-73wt% lecithin, 2-10wt% oil
Acid, 2-10wt%PEG400,8-25wt% water, 6wt% tween, 1wt% tea polyphenols.
Preferably, the Liquid Crystal dispersion includes or composed of the following components: 57.66-72.54wt% lecithin,
2.325-9.765wt% oleic acid, 2.325-9.765wt%PEG400,8.37-23.25wt% water, 6wt% tween, 1wt% tea
Polyphenol.
Preferably, the Liquid Crystal dispersion includes or composed of the following components: 65.1wt% lecithin, 2.325-
6.045wt% oleic acid, 2.325-6.045wt%PEG400,15.81-23.25wt% water, 6wt% tween, 1wt% tea polyphenols.
Preferably, the partial size of nano particle is 160-200nm, preferably 164-190nm in the dispersion；The nanometer
The PDI of particle is 0.3-0.55, preferably 0.388-0.521；The Zeta potential of the nano particle is -2~-18mV, preferably
For -2.57~-17.2mV.
In the second aspect of the present invention, the present invention provides a kind of methods for preparing above-mentioned Liquid Crystal dispersion comprising with
Lower step: mixing is sufficiently stirred in lecithin, oleic acid and PEG400 in a water bath；Then it is more that tea is successively added into the mixture
Phenol and secondary distilled water are stirred and evenly mixed and are centrifuged repeatedly to drive bubble away；The mixture is stood to balance in water bath with thermostatic control；Add
Enter after tween is thoroughly mixed therewith, takes the mixture to be placed in water, carry out ultrasonic disperse, obtain emulsus Nanodispersion.
Preferably, the additional amount mass ratio of the lecithin, oleic acid and PEG400 are (5.766~7.254): (0.2325
~0.9765): (0.2325~0.9765).
Proportionate relationship between water, oil and surfactant will affect the release rate of Liquid Crystal dispersion of the present invention, through the present invention
Experimental verification, be easy to get more satisfied release when lecithin, oleic acid and PEG400 proportion according to the invention addition
Rate and slow release effect.Preferably, the bath temperature when lecithin, oleic acid and PEG400 are mixed is 60-70 DEG C.
Preferably, the tea polyphenols and the dosage mass ratio of secondary distilled water are 0.1:(0.837~2.325).
Preferably, balance is stood after centrifugation in the water bath with thermostatic control at 37 DEG C, equilibration time is 7 days.
Preferably, the condition of the ultrasonic disperse is pulse mode, per working time 10s, intermittent time 5s, ultrasonic power
400w, total sonication time 18min.
In the third aspect of the present invention, the present invention also provides a kind of pharmaceutical preparations, and it includes above-mentioned Liquid Crystal dispersions.
In the fourth aspect of the present invention, the present invention also provides above-mentioned Liquid Crystal dispersions to prepare answering in pharmaceutical preparation
With；Preferably, the pharmaceutical preparation has the function of anti-oxidant and/or removes ABTS free radical.
Detailed description of the invention
The accompanying drawings constituting a part of this application is used to provide further understanding of the present application, and the application's shows
Meaning property embodiment and its explanation are not constituted an undue limitation on the present application for explaining the application.Hereinafter, coming in conjunction with attached drawing detailed
Describe bright embodiment of the present invention in detail, in which:
Fig. 1 is the particle diameter distribution of tea polyphenols lysotropic liquid crystal dispersion of the invention.
Fig. 2 is the standard curve that absorbance of the tea polyphenols aqueous solution at 273nm is drawn.
Fig. 3 is release behavior of the tea polyphenols in dispersed liquid crystal particle of the invention at 37 DEG C.
Fig. 4 is the relationship for removing ABTS free radical activity and tea polyphenols concentration.
Fig. 5 is the relationship of free radical scavenging and tea polyphenols concentration.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip
Part or according to the normal condition proposed by manufacturer.
Unless otherwise defined, it anticipates known to all professional and scientific terms as used herein and one skilled in the art
Justice is identical.In addition, any method similar to or equal to what is recorded and material can be applied to the method for the present invention.Wen Zhong
The preferred implement methods and materials are for illustrative purposes only.
It is noted that following detailed description is all illustrative, it is intended to provide further instruction to the application.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 singular
Also it is 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 their combination.
Lecithin (SL, purification) is bought from Alfa Aesar Company；Polyethylene glycol 400 (PEG 400 is analyzed pure), spits
Temperature 80 (Tween 80, chemistry are pure), oleic acid (OA is analyzed pure) and ethyl alcohol (analysis is pure) are from the Chinese limited public affairs of traditional Chinese medicines chemical reagent
Department buys；Tea polyphenols (TP, purity 95%) are bought from the careless plant Trade Co., Ltd. of Xuancheng hundred；2,2- joins (the 3- ethyl-benzene of nitrogen-two
And thiazole -6- sulfonic acid) di-ammonium salts (ABTS, purity 98%) and 1,1- diphenyl -2- trinitrophenyl-hydrazine (DPPH, purity 96%) is
It buys from Shanghai Mike's woods biochemical technology Co., Ltd, water is the deionized water that second distillation is crossed.
Embodiment 1
By 6.51g lecithin, 0.2325g oleic acid and 0.2325g PEG400 are placed in the colorimetric cylinder with plug, in 60-70
DEG C water-bath in mixing is sufficiently stirred.Then 0.1g tea polyphenols and 2.325g secondary distilled water are successively added into the mixture,
It stirs and evenly mixs and is centrifuged repeatedly to drive bubble away.The colorimetric cylinder is stood to balance one week in the water bath with thermostatic control at 37 DEG C.It will
After 0.6g tween (Tween 80) is thoroughly mixed therewith, 1g mixture is taken to be placed in 25mL water, on ultrasonic cell disruption instrument
Dispersed, finally obtains milky dispersion.Ultrasonic cell disruption instrument parameter setting are as follows: power 400w, total sonication time
18min, pulse mode (working time 10s, intermittent time 5s).This milky dispersion is denoted as F1, the composition of the dispersion is such as
Shown in table 1.
Embodiment 2
By 6.51g lecithin, 0.6045g oleic acid and 0.6045g PEG400 are placed in the colorimetric cylinder with plug, in 60-70
DEG C water-bath in mixing is sufficiently stirred.Then 0.1g tea polyphenols and 1.581g secondary distilled water are successively added into the mixture,
It stirs and evenly mixs and is centrifuged repeatedly to drive bubble away.The colorimetric cylinder is stood to balance one week in the water bath with thermostatic control at 37 DEG C.It will
After 0.6g tween (Tween 80) is thoroughly mixed therewith, 1g mixture is taken to be placed in 25mL water, on ultrasonic cell disruption instrument
Dispersed, finally obtains milky dispersion.Ultrasonic cell disruption instrument parameter setting are as follows: power 400w, total sonication time
18min, pulse mode (working time 10s, intermittent time 5s).This milky dispersion is denoted as F2, the composition of the dispersion is such as
Shown in table 1.
Embodiment 3
By 6.51g lecithin, 0.9765g oleic acid and 0.9765g PEG400 are placed in the colorimetric cylinder with plug, in 60-70
DEG C water-bath in mixing is sufficiently stirred.Then 0.1g tea polyphenols and 0.837g secondary distilled water are successively added into the mixture,
It stirs and evenly mixs and is centrifuged repeatedly to drive bubble away.The colorimetric cylinder is stood to balance one week in the water bath with thermostatic control at 37 DEG C.It will
After 0.6g tween (Tween 80) is thoroughly mixed therewith, 1g mixture is taken to be placed in 25mL water, on ultrasonic cell disruption instrument
Dispersed, finally obtains milky dispersion.Ultrasonic cell disruption instrument parameter setting are as follows: power 400w, total sonication time
18min, pulse mode (working time 10s, intermittent time 5s).This milky dispersion is denoted as F3, the composition of the dispersion is such as
Shown in table 1.
Embodiment 4
By 5.766g lecithin, 0.9765g oleic acid and 0.9765g PEG400 are placed in the colorimetric cylinder with plug, in 60-
Mixing is sufficiently stirred in 70 DEG C of water-bath.Then 0.1g tea polyphenols and 1.581g second distillation are successively added into the mixture
Water is stirred and evenly mixed and is centrifuged repeatedly to drive bubble away.The colorimetric cylinder is stood to balance one week in the water bath with thermostatic control at 37 DEG C.It will
After 0.6g tween (Tween 80) is thoroughly mixed therewith, 1g mixture is taken to be placed in 25mL water, on ultrasonic cell disruption instrument
Dispersed, finally obtains milky dispersion.Ultrasonic cell disruption instrument parameter setting are as follows: power 400w, total sonication time
18min, pulse mode (working time 10s, intermittent time 5s).This milky dispersion is denoted as F4, the composition of the dispersion is such as
Shown in table 1.
Embodiment 5
By 7.254g lecithin, 0.2325g oleic acid and 0.2325g PEG400 are placed in the colorimetric cylinder with plug, in 60-
Mixing is sufficiently stirred in 70 DEG C of water-bath.Then 0.1g tea polyphenols and 1.581g second distillation are successively added into the mixture
Water is stirred and evenly mixed and is centrifuged repeatedly to drive bubble away.The colorimetric cylinder is stood to balance one week in the water bath with thermostatic control at 37 DEG C.It will
After 0.6g tween (Tween 80) is thoroughly mixed therewith, 1g mixture is taken to be placed in 25mL water, on ultrasonic cell disruption instrument
Dispersed, finally obtains milky dispersion.Ultrasonic cell disruption instrument parameter setting are as follows: power 400w, total sonication time
18min, pulse mode (working time 10s, intermittent time 5s).This milky dispersion is denoted as F5, the composition of the dispersion is such as
Shown in table 1.
The composition of 1 tea polyphenols lysotropic liquid crystal dispersion of table
Experimental example
The measurement of particle size in Liquid Crystal dispersion
The partial size of dispersed liquid crystal particle, polydispersity index (PDI) and Zeta potential are by Malvern laser particle analyzer at 25 DEG C
Under be determined.Solvent is selected as water in instrument parameter, and equilibration time 120s measures 90 ° of angle.Sample (F1, F2, F3, F4,
F5 it contains in sample cell and is measured again after) diluting 20 times with distilled water.The intensity-average particle size that particle size results are selected.
Release in vitro
1. the drafting of tea polyphenols standard curve
Certain density tea polyphenols aqueous solution is prepared, is carried out within the scope of 500-200nm with ultraviolet-uisible spectrophotometer
Spectral scan obtains absorbance-wavelength curve, it is determined that the maximum absorption band of tea polyphenols is 273nm.Prepare a series of concentration ladders
The tea polyphenols aqueous solution of degree surveys its absorbance at the long 273nm of standing wave, draws standard curve.
2. the release in vitro of tea polyphenols
Using release in vitro behavior of the technique study tea polyphenols of dialysis in lysotropic liquid crystal, release in vitro is in biphosphate
It is carried out in the buffer solution of the pH 6.8 of sodium and disodium hydrogen phosphate.Accurately 2mL sample (F1, F2, F3, F4, F5) is pipetted in dialysis
In bag, bag filter is placed in 40mL buffer medium, and using magneton, 37 DEG C of constant temperature discharge under certain speed conditions.When one section
Between take 3mL release liquid, and supplement 3mL buffer.By being released with the method calculating of measurement of ultraviolet-visible spectrophotometer absorbance
The tea polyphenols amount being put into buffer solution calculates the accumulative release rate (CR) of tea polyphenols.
Add up tea polyphenols total amount × 100% in tea polyphenols burst size/lysotropic liquid crystal in CR=sample time
Mt/M∞Indicate that the percentage of the drug release in time t, K are the proportionality coefficients of release, n is the index of release.n
Value difference shows that flooding mechanism is different when drug is discharged from lysotropic liquid crystal.
ABTS radicals scavenging experiment
The ABTS solution 5mL for preparing the potassium persulfate solution 50mL and 0.007mol/L of 0.14mol/L, in ABTS solution
The 88 prepared potassium persulfate solutions of μ L are added, are protected from light 16 hours.Sample (F1, F2, F3, F4, F5) is diluted to one
The solution of series of concentrations gradient, using blank as control.By ABTS solution with secondary distilled water be diluted to absorbance be 0.7 ±
0.02.The ABTS solution that 3mL absorbance is 0.7 ± 0.02 is added in sample solution after 1mL dilution, with eddy blending machine by solution
It is uniformly mixed, is protected from light 30min, surveys its absorbance A at the long 730nm of standing wave.Blank 1mL secondary distilled water, the extinction
Degree is recorded as A0。
Clearance rate=(1-A/A0) × 100%
DPPH radicals scavenging experiment
The concentration of DPPH ethanol solution is configured to 6 × 10-5mol/L.Sample (F1, F2, F3, F4, F5) is diluted to a system
The solution of column concentration gradient, using blank as control.3mL DPPH solution is added in sample after 1mL dilution, is protected from light after mixing
Reaction 60 minutes are stood, survey its absorbance A at the long 517nm of standing wave.Blank 1mL secondary distilled water, the absorbance are recorded as
A0.All samples (F1, F2, F3, F4, F5) are first centrifuged 5 minutes at 3000 turns of centrifuge or more before test.Sample after centrifugation
Cuvette measurement is directly poured into, pays attention to having to gently avoid vibration to allow from the east got off again when test tube is taken out from centrifuge
West suspends again causes sample muddy.Before test, with the mixed liquor zero setting of 3mL ethyl alcohol and 1mL water.
Clearance rate=(1-A/A0) × 100%
Experimental result
The DLS of tea polyphenols lysotropic liquid crystal is characterized
Fig. 1 is the grain size distribution of the tea polyphenols lysotropic liquid crystal dispersion of 1-5 of the embodiment of the present invention, carries medicine dispersed liquid crystal
Grain partial size, PDI and Zeta potential value are shown in table 2.It can be found by data in table, the particle size values of sample are all in 160-200nm
Between, lesser PDI value indicates that tea polyphenols lysotropic liquid crystal has good consistency.Wherein F2 and F4 sample Zeta potential is exhausted
It is maximum to value, illustrate that the stability of the two samples is best.
The partial size of 2 tea polyphenols lysotropic liquid crystal dispersion of table, PDI, Zeta value
Tea polyphenols release in vitro research
1. the foundation of tea polyphenols standard curve
If Fig. 2 is bent by measuring the standard that a series of absorbance of the tea polyphenols aqueous solution of concentration at 273nm is drawn
Line, linear fitting obtains absorbance and the relationship of concentration meets following equation: Abs=21.1229C+0.00736.In 273nm
After place measures the absorbance of tea polyphenols, the concentration of tea polyphenols can be gone out by equation calculation, and then calculate tea polyphenols when different
Between the accumulative release rate put, draw the release profiles of sample.
2. the release in vitro of tea polyphenols
As shown in figure 3, F1, F2, F3 are In-vitro release curves when fixation surface active agent content changes water-oil factor.For
Rate of release early period is discharged for F1, F2, F3 than very fast, after 2500min, rate of release becomes slow.At release initial stage
The rate of release of (before 1000min), F1, F2, F3 are suitable, and the rate of release of F3 starts to become releasing than F1, F2 after 1000min
Put that rate is slow, the rate of release of F1, F2 are still suitable.The accumulative release rate of final F3 is lower than the accumulative release rate of F1, F2, and
The accumulative release rate of F1, F2 are suitable.Generally speaking, fixation surface active agent content, which changes water-oil factor, has shadow to release in vitro behavior
It is loud but unobvious.
F2, F4, F5 be fixed water content change oil and surfactant than when In-vitro release curves.For F2, F4, F5
For release rate of release early period than very fast, but F5 discharge early period it is most fast.Rate of release starts to occur obvious poor after 1000min
Different, F5 rate of release is still most fast, and the rate of release of F2 is very fast, and the rate of release of F4 starts to slow down and difference occurs with F2.?
After 3000min, F5 rate of release becomes extremely slowly, close to zero.After 3500min, F2 rate of release becomes extremely slowly,
Close to zero.After 4500min, F4 rate of release becomes extremely slowly, close to zero.Generally speaking, fixed water content changes
Oil and surfactant compare release in vitro behavior and have a significant effect.Surfactant accounting is bigger, and release in vitro is faster, and tired
It is higher to count release rate.
F1, F5 and F3, F4 be fixed oil content change water and surfactant than when release profiles.F5 compared with F1,
Surfactant accounting is big, and F5 rate of release ratio F1 rate of release is fast and accumulative release rate is high.F3 is compared with F4, surfactant
Accounting is big, but F3 release rate suitable and accumulative with the rate of release of F4 is suitable.
Generally, fixed water content changes oil and the influence of surfactant comparison release in vitro is maximum, and has good
Good slow release effect, as shown in figure 3, the slow-release time of tea polyphenols lysotropic liquid crystal dispersion of the invention be 80 hours with
On.
Antioxidant activity
1. removing ABTS free radical activity
Using clearance rate as ordinate, sample concentration is abscissa, the experimental data of each sample (F1, F2, F3, F4, F5)
Logistic models fitting is all used, finds IC on the curve of fitting50, IC50Be clearance rate be 50% when concentration.IC50Value is got over
Low expression antioxidant activity is better.As shown in figure 4, F2 has best antioxidant activity.Figure 4, it is seen that tea polyphenols
The IC of aqueous solution50Value is 3.778 μ g/mL.The IC of all samples50Value is both less than the IC of tea polyphenols50Value, this illustrates of the invention
The Liquid Crystal dispersion of tea polyphenols has better antioxidant activity.As shown in Figure 4, sample to the scavenging capacity of ABTS free radical with
Its mass concentration increases and improves.
S (Cs, Rs) is the critical point that clearance curve smooths out.Parameter Cs represents elimination efficiency, and parameter Rs representative was removed
The validity of journey, maximum radicals scavenging effect correspond to minimum clearing efficiency.F4 has maximum elimination efficiency, minimum clearing effect
Power.F2 and F3 has minimum clearing efficiency, and maximum removes effect.
2. free radical scavenging
The experimental data of each sample (F1, F2, F3, F4, F5) equally uses Logistic models fitting, in the curve of fitting
On find IC50.As shown in figure 4, sample 1 has best antioxidant activity.From figure 5 it can be seen that the IC of tea polyphenols50Value
For 4.657 μ g/mL.The IC of all samples (F1, F2, F3, F4, F5)50Value is both less than the IC of tea polyphenols50Value, this explanation contain tea
The lysotropic liquid crystal of polyphenol has better antioxidant activity.As shown in Figure 5, sample is to the scavenging capacity of DPPH free radical with its matter
Amount concentration increases and improves.F5 has maximum elimination efficiency, minimum clearing effect.F1 has minimum clearing efficiency, and maximum is removed
Effect.
Conclusion
We are by SL/OA/PEG400/H2The lysotropic liquid crystal that O system is constructed is successfully prepared the dispersed liquid crystal of uniform particle diameter
Particle.Extracorporeal releasing experiment shows to be encapsulated in lysotropic liquid crystal when tea polyphenols, and release equilibration time is obviously prolonged.And it is solid
Determine the influence maximum that water content changes oil and surfactant compares release in vitro, surfactant accounting is bigger, release in vitro
It is faster, and accumulative release rate is higher.The inoxidizability experiment for containing the dispersed liquid crystal particle of tea polyphenols shows tea polyphenols liquid crystal point
Scattered seed has good scavenging effect to ABTS free radical and DPPH free radical.In ABTS radicals scavenging experiment, F2's is anti-
Oxidation activity is best, IC50=0.950 μ g/mL.In DPPH radicals scavenging experiment, the antioxidant activity of F1 is best, IC50=
0.957μg/mL。
Claims (10)
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