CN110141600A - Nanocrystalline self-stabilization Pickering lotion of Salvia root P.E and preparation method thereof - Google Patents
Nanocrystalline self-stabilization Pickering lotion of Salvia root P.E and preparation method thereof Download PDFInfo
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- CN110141600A CN110141600A CN201910411261.5A CN201910411261A CN110141600A CN 110141600 A CN110141600 A CN 110141600A CN 201910411261 A CN201910411261 A CN 201910411261A CN 110141600 A CN110141600 A CN 110141600A
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- salvia root
- lotion
- nanocrystalline
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- oil
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- 239000006210 lotion Substances 0.000 title claims abstract description 167
- 241001072909 Salvia Species 0.000 title claims abstract description 125
- 235000017276 Salvia Nutrition 0.000 title claims abstract description 125
- 238000002360 preparation method Methods 0.000 title claims abstract description 70
- 238000011105 stabilization Methods 0.000 title claims abstract description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 84
- 239000000839 emulsion Substances 0.000 claims abstract description 43
- AIGAZQPHXLWMOJ-UHFFFAOYSA-N Tanshinone I Chemical compound C1=CC2=C(C)C=CC=C2C(C(=O)C2=O)=C1C1=C2C(C)=CO1 AIGAZQPHXLWMOJ-UHFFFAOYSA-N 0.000 claims abstract description 42
- DOUMFZQKYFQNTF-WUTVXBCWSA-N (R)-rosmarinic acid Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-WUTVXBCWSA-N 0.000 claims abstract description 14
- 239000002253 acid Substances 0.000 claims abstract description 11
- PAFLSMZLRSPALU-MRVPVSSYSA-N (2R)-3-(3,4-dihydroxyphenyl)lactic acid Chemical compound OC(=O)[C@H](O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-MRVPVSSYSA-N 0.000 claims abstract description 7
- GVKKJJOMQCNPGB-JTQLQIEISA-N Cryptotanshinone Chemical compound O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1[C@@H](C)CO2 GVKKJJOMQCNPGB-JTQLQIEISA-N 0.000 claims abstract description 7
- GVKKJJOMQCNPGB-UHFFFAOYSA-N Cryptotanshinone Natural products O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1C(C)CO2 GVKKJJOMQCNPGB-UHFFFAOYSA-N 0.000 claims abstract description 7
- PAFLSMZLRSPALU-QMMMGPOBSA-N Danshensu Natural products OC(=O)[C@@H](O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-QMMMGPOBSA-N 0.000 claims abstract description 7
- ZZAFFYPNLYCDEP-HNNXBMFYSA-N Rosmarinsaeure Natural products OC(=O)[C@H](Cc1cccc(O)c1O)OC(=O)C=Cc2ccc(O)c(O)c2 ZZAFFYPNLYCDEP-HNNXBMFYSA-N 0.000 claims abstract description 7
- PAFLSMZLRSPALU-UHFFFAOYSA-N Salvianic acid A Natural products OC(=O)C(O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-UHFFFAOYSA-N 0.000 claims abstract description 7
- DOUMFZQKYFQNTF-MRXNPFEDSA-N rosemarinic acid Natural products C([C@H](C(=O)O)OC(=O)C=CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-MRXNPFEDSA-N 0.000 claims abstract description 7
- TVHVQJFBWRLYOD-UHFFFAOYSA-N rosmarinic acid Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=Cc2ccc(O)c(O)c2)C=O TVHVQJFBWRLYOD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003921 oil Substances 0.000 claims description 83
- 239000000725 suspension Substances 0.000 claims description 67
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 37
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 claims description 34
- 244000138993 panchioli Species 0.000 claims description 34
- 238000000265 homogenisation Methods 0.000 claims description 33
- 238000003756 stirring Methods 0.000 claims description 19
- 239000005642 Oleic acid Substances 0.000 claims description 18
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 17
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 17
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 17
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 17
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 17
- 239000003960 organic solvent Substances 0.000 claims description 17
- 239000000284 extract Substances 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 11
- 239000002023 wood Substances 0.000 claims description 11
- 235000019441 ethanol Nutrition 0.000 claims description 10
- 239000000341 volatile oil Substances 0.000 claims description 10
- AZEZEAABTDXEHR-UHFFFAOYSA-M sodium;1,6,6-trimethyl-10,11-dioxo-8,9-dihydro-7h-naphtho[1,2-g][1]benzofuran-2-sulfonate Chemical compound [Na+].C12=CC=C(C(CCC3)(C)C)C3=C2C(=O)C(=O)C2=C1OC(S([O-])(=O)=O)=C2C AZEZEAABTDXEHR-UHFFFAOYSA-M 0.000 claims description 9
- HYXITZLLTYIPOF-UHFFFAOYSA-N Tanshinone II Natural products O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1C(C)=CO2 HYXITZLLTYIPOF-UHFFFAOYSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 125000005909 ethyl alcohol group Chemical group 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 22
- 239000004615 ingredient Substances 0.000 abstract description 13
- 239000000203 mixture Substances 0.000 abstract description 12
- 238000009472 formulation Methods 0.000 abstract description 5
- 239000002156 adsorbate Substances 0.000 abstract description 4
- 238000002835 absorbance Methods 0.000 description 27
- 229940079593 drug Drugs 0.000 description 27
- 238000005119 centrifugation Methods 0.000 description 25
- 239000002245 particle Substances 0.000 description 23
- 239000000523 sample Substances 0.000 description 17
- 235000013339 cereals Nutrition 0.000 description 12
- 239000003643 water by type Substances 0.000 description 11
- 238000002296 dynamic light scattering Methods 0.000 description 10
- 238000005457 optimization Methods 0.000 description 8
- 238000009826 distribution Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 6
- 241000212948 Cnidium Species 0.000 description 5
- 229930183118 Tanshinone Natural products 0.000 description 5
- 239000012296 anti-solvent Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 238000009830 intercalation Methods 0.000 description 5
- 230000002687 intercalation Effects 0.000 description 5
- 239000006070 nanosuspension Substances 0.000 description 5
- 230000001376 precipitating effect Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 235000014899 silybin Nutrition 0.000 description 4
- 230000006641 stabilisation Effects 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- FDQAOULAVFHKBX-UHFFFAOYSA-N Isosilybin A Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC(=CC=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 FDQAOULAVFHKBX-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- VLGROHBNWZUINI-UHFFFAOYSA-N Silybin Natural products COc1cc(ccc1O)C2OC3C=C(C=CC3OC2CO)C4Oc5cc(O)cc(O)c5C(=O)C4O VLGROHBNWZUINI-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000004519 grease Substances 0.000 description 3
- 239000002105 nanoparticle Substances 0.000 description 3
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 description 3
- 229940043175 silybin Drugs 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 241000304195 Salvia miltiorrhiza Species 0.000 description 2
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008033 biological extinction Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 2
- 238000005189 flocculation Methods 0.000 description 2
- 230000016615 flocculation Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- -1 glycol glycerin ester Chemical class 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 239000002159 nanocrystal Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 239000012898 sample dilution Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000218646 Cedrus deodara Species 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- RXUWDKBZZLIASQ-UHFFFAOYSA-N Puerarin Natural products OCC1OC(Oc2c(O)cc(O)c3C(=O)C(=COc23)c4ccc(O)cc4)C(O)C(O)C1O RXUWDKBZZLIASQ-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000320380 Silybum Species 0.000 description 1
- 235000010841 Silybum marianum Nutrition 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 230000000739 chaotic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940126678 chinese medicines Drugs 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 229910052570 clay Inorganic materials 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- STORWMDPIHOSMF-UHFFFAOYSA-N decanoic acid;octanoic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC(O)=O.CCCCCCCCCC(O)=O STORWMDPIHOSMF-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 229940056319 ferrosoferric oxide Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229910021389 graphene Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011835 investigation 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
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229950000628 silibinin Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000019710 soybean protein Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 238000012360 testing method 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- 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)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Heart & Thoracic Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dispersion Chemistry (AREA)
- Cosmetics (AREA)
Abstract
The invention belongs to formulation arts, and in particular to nanocrystalline self-stabilization Pickering lotion of Salvia root P.E and preparation method thereof.It is 60-100mg/g that the present invention, which is with the content of tanshin polyphenolic acid B, the content of danshensu is 3-10mg/g, the content of Rosmarinic acid is 3-10mg/g;The content of Tanshinone I I A is 5-20mg/g, the content of Cryptotanshinone is 2-10mg/g, the Salvia root P.E that the content of Tanshinone I is 3-10mg/g is bulk pharmaceutical chemicals, with the Pickering lotion of oil-in-water type made of oily phase and water phase, the present invention is the nanocrystalline self-stabilization Pickering lotion with stability property that the Salvia root P.E of a kind of water-soluble effective component using simultaneously containing Radix Salviae Miltiorrhizae and slightly solubility effective component is prepared as bulk pharmaceutical chemicals, wherein the water soluble ingredients such as tanshin polyphenolic acid B are distributed in water phase, the refractory components such as tanshinone part is distributed in oily phase, partial adsorbates are in emulsion droplet interface, stable emulsion.
Description
Technical field
The invention belongs to formulation arts, and in particular to the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E and its system
Preparation Method.
Background technique
Pickering lotion be it is a kind of by oil-water interface adsorbent solid particle stablize, form membrane structure
Lotion.Solia particle used mainly has three categories 1. inorganic salts, such as silica, clay, ferroso-ferric oxide;2. nanometer
Synthetic material, such as carbon nanotube, nanometer sheet, Jenner's grain of rice-graphene oxide heterocomplex;3. biodegradation material, as starch,
Cellulose, soybean protein, fat, chitosan etc..Compared with conventional emulsion, Pickering lotion is not needed using surface-active
Agent has better safety, and has better anti-merging stability, is a kind of potential superior drug transmission system, and
For being administered orally.Such as Simovic is by Miglyol 812N and SiO containing Indomethacin2Aqueous dispersions mixing, through high pressure cream
Even obtained Pickering lotion, spray drying, obtains micro-capsule.The Oral Administration in Rats bioavilability of Pickering lotion micro-capsule is
101.13%, the 64.57% of 53.54% and emulsion of significantly larger than former drug suspension.However, tradition Pickering
Lotion there will still likely be the problem of following 2 aspect: 1. Pickering lotion uses silica dioxide nano particle to be administered orally mostly
As the solid particle for stablizing emulsion droplet, there are potential safety problems;2. drug is dissolved mainly in oily phase, the dissolution energy of oily phase
Power directly limits the Drug loading capacity of lotion.
It can be formed in view of insoluble drug itself nanocrystalline, seminar where the present inventor proposes that establishing drug receives
The brilliant self-stabilization Pickering lotion of rice.The lotion is using the nanocrystalline stable as solia particle of insoluble drug itself
Pickering lotion.In the Pickering lotion of the nanocrystalline self-stabilization of this newtype drug, only 3 kinds of substances, water, oil and
Drug, without other auxiliary materials, such as surfactant, xenogenesis solia particle, some of drugs are dissolved in oil, high amount of drug then with
The form of nanocrystal is adsorbed on oil droplets, coating is formed on oil droplet, and stablize Pickering lotion.With traditional rouge
Matter preparation is compared, and safety problem caused by surfactant is avoided;Compared with traditional Pickering lotion, xenogenesis is not used
Nano particle avoids the security risk of nano particle, can effectively improve drugloading rate.Seminar where inventor successfully will
Medicament nano crystalline substance self-stabilization Pickering emulsion applications are in slightly solubility monomer: such as with silibinin, Puerarin, tanshinone IIA
It is made nanocrystalline as solia particle, and nanocrystalline self-stabilization Pickering lotion is prepared using high pressure homogenization;With milk thistle
For guest, manufactured silybin nanostructured crystalline substance self-stabilization Pickering lotion (silybin nanocrystalline self-
Silybin nanostructured brilliant suspension of the stability of stabilizing Pickering emulsion, SN-NSSPE than no stabilizer
Liquid is high, can at least stablize 40 days or more.The in-vitro release rate of SN-NSSPE is similar to nanocrystalline suspension, more significant than bulk pharmaceutical chemicals
Accelerate.Result of study, which shows that insoluble drug is nanocrystalline, can stablize Pickering lotion.Medicament nano crystalline substance self-stabilization
Pickering lotion has broad application prospects in terms of the oral administration biaavailability for improving insoluble drug.With tanshinone
The manufactured nanocrystalline self-stabilization Pickering lotion of tanshinone IIA is also significantly increased on preparation stability for II A.So
And seminar where inventor is all to prepare nanocrystalline self-stabilization Pickering by bulk pharmaceutical chemicals of monomeric compound all the time
New this medicament nano crystalline substance self-stabilization Pickering emulsion formulations are not yet applied to the traditional Chinese medicine extraction of complicated component by lotion
Object.Compared with monomer, extract component is complicated, often simultaneously containing there are many water soluble ingredient and refractory components, there are also albumen,
The big molecular impurities such as polysaccharide;Either extract nano crystalline substance suspension or its Pickering lotion is all without report.
Seminar where inventor attempts to prepare nanocrystalline self-stabilization Pickering lotion by bulk pharmaceutical chemicals of Chinese medical extract
It is found when preparation, the suspension, auxiliary material and dosage that can not replicate existing nanocrystalline self-stabilization Pickering emulsion formulations are realized
Stable nanocrystalline self-stabilization Pickering emulsion formulations are prepared, after repeatedly failing, are realized finally with Salvia root P.E
The pharmacy purpose of the nanocrystalline self-stabilization Pickering lotion of stable Salvia root P.E is prepared for bulk pharmaceutical chemicals.
Summary of the invention
Technical problem solved by the invention be to provide a kind of nanocrystalline self-stabilization Pickering lotion of Salvia root P.E and
Preparation method, the emulsion droplet of the nanocrystalline self-stabilization Pickering lotion can be steadily distributed forms stable cream in water
Liquid.
The nanocrystalline self-stabilization Pickering lotion of Salvia root P.E of the present invention is using Salvia root P.E, oil phase and water system
At oil-in-water type Pickering lotion, preparation method includes the following steps:
A, it prepares primary suspension: Salvia root P.E is dissolved in organic solvent, being added with stirring pH value is 9-13's
In water, continues heating stirring and wave except organic solvent, obtain primary suspension A;
B, it prepares nanocrystalline suspension: primary suspension A obtained by step A is obtained into nanocrystalline suspension B through high-pressure homogeneous;
C, it prepares nanocrystalline self-stabilization Pickering lotion: nanocrystalline suspension B obtained by step B and oily phase oleic acid is gathered
The mixing of glycol glycerin ester obtains the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E through high-pressure homogeneous.
In above-mentioned preparation method:
Organic solvent in step A is acetone, any one or its mixing in ethyl alcohol;Salvia root P.E and organic solvent
Mass volume ratio ,≤30:1 is calculated as with mg/ml;It is preferred that using acetone solution Salvia root P.E.
High-pressure homogeneous condition in step B is that homogenization pressure is 600-1200bar, and homogenization cycles are 10-30 times;Further
It is preferred that it is 800-1000bar that high-pressure homogeneous condition, which is homogenization pressure, 20-30 times.
High-pressure homogeneous pressure in step C is 600-1200bar, and homogenization cycles are 10-30 times;Further preferred high pressure is equal
It is 800-1000bar that matter condition, which is homogenization pressure, 20-30 times.
The mass volume ratio of Salvia root P.E described in step A and oil phase described in step C is calculated as 20:1-60:1 with mg/ml.
Oil described in step C is mutually 0.5:10-2:10 with the volume ratio of nanocrystalline suspension B;Further preferably, step C
The oil is mutually 1:10 with the volume ratio of nanocrystalline suspension B.
There are a kind of special situation, Radix Salviae Miltiorrhizae and dalbergia wood to treat cardiovascular phase in field of Chinese medicines compatibility in lotion preparation of the present invention
Related disorders have specific drug effect significantly to report, therefore inventor attempts dalbergia wood volatile oil adding preparation in oil inlet phase.But
It is found in trial-manufacturing process, the nanocrystalline self-stabilization for the tanshinone IIA monomer completed with seminar where inventor
Pickering lotion needs to add many cnidium oils just on the contrary, in the Pickering lotion for preparing tanshinone IIA
Stable lotion can be prepared.And additive amount cannot be excessive when lotion of the present invention addition dalbergia wood volatile oil, otherwise can not form stabilization
Lotion.The study found that the oil in step C can mutually use dalbergia wood volatile oil and oleic acid LABRAFIL M 1944CS mixture;Its
Volume ratio is 1:2-1:8.The addition of dalbergia wood volatile oil not only increases effective component, moreover it is possible to play the role of stable emulsion, compared with
It is applied alone oily phase oleic acid LABRAFIL M 1944CS stability higher.
In preparation method of the present invention, the Salvia root P.E used is to use the ethyl alcohol of 70-100% to be molten by Chinese medicine Radix Salviae Miltiorrhizae
Agent, 60-90 DEG C of refluxing extraction.Wherein, the content of the tanshin polyphenolic acid B in Salvia root P.E is the content of 60-100mg/g, danshensu
Content for 3-10mg/g, Rosmarinic acid is 3-10mg/g;The content of Tanshinone I I A is 5-20mg/g, the content of Cryptotanshinone
For 2-10mg/g, the content of Tanshinone I is 3-10mg/g.
The nanocrystalline self-stabilization Pickering lotion of Salvia root P.E obtained by preparation method of the present invention is wrapped in oil in lotion
The nanocrystalline partial size of the Salvia root P.E of phase surface is 300nm-1000nm, and the emulsion droplet size in the lotion is 1 μm -10 μm.Into
One step, the nanocrystalline partial size of Salvia root P.E for being wrapped in oily phase surface is 300nm-500nm, the emulsion droplet size in the lotion
It is 1 μm -5 μm.
Preparation method of the present invention overcomes in extract that there are many nanocrystalline to tanshinone in oil droplet interface at branch
When seminar's discovery is using monomeric compound where adsorbing the influence generated, especially inventor, only with high pressure homogenization
Preparation meets the nanocrystalline of Particle size requirements, and as there are many extract of ingredient, the nanocrystal obtained using high pressure homogenization
Diameter is bigger, can not be successfully the subsequent preparation process of progress and obtains stable lotion;Along with multicomponent is to nanocrystalline Interfacial Adsorption
Influence so that the preparation crystalline substance self-stabilization that can not be successfully of extract of the preparation with compound or containing multicomponent ingredient
Pickering lotion, the present invention exactly solves nanocrystalline self-stabilization Pickering lotion can only be using monomeric compound as raw material
The drawbacks of medicine, specific nanometer crystal preparation method, aqueous pH values are used, oil is mutually (i.e. oily with the volume ratio of nanocrystalline suspension B
Water volume ratio), the content of Salvia root P.E and tanshinone component in the mass volume ratio and extract of oily phase realizes nothing
Surfactant, without additional solid particle stabilizers, also available stable Pickering lotion, especially tanshin polyphenolic acid B etc.
Water soluble ingredient is distributed in water phase, and the refractory components such as tanshinone part is distributed in oily phase, and partial adsorbates are in emulsion droplet interface, surely
Determine lotion, can the control of preparation method above-mentioned steps parameter of the present invention be the key that influence obtain stablizing Pickering lotion.
To sum up, the present invention, which has rewritten Pickering lotion, to prepare nanocrystalline self-stabilization using monomeric compound
The history of Pickering lotion provides a kind of water-soluble effective component and slightly solubility effective component with simultaneously containing Radix Salviae Miltiorrhizae
Salvia root P.E be bulk pharmaceutical chemicals preparation the nanocrystalline self-stabilization Pickering lotion with stability property, wherein tanshin polyphenolic acid B
Equal water soluble ingredients are distributed in water phase, and the refractory components such as tanshinone part is distributed in oily phase, partial adsorbates in emulsion droplet interface,
Stable emulsion.
Detailed description of the invention
Fig. 1 Salvia root P.E utilizes cnidium oil: oleic acid LABRAFIL M 1944CS (9:1) or dalbergia heartwood oil: oleic acid polyethylene glycol
Glyceride (9:1) is the result of oily phase.
The Pickering lotion that Fig. 2 difference Salvia root P.E suspension liquid and preparation method thereof obtains be placed at room temperature for during it is outer
See variation.
Wherein, A, B, C, D, E be respectively Probe Ultrasonic Searching method, it is high pressure homogenization, Probe Ultrasonic Searching joint high pressure homogenization, anti-molten
Agent joint high pressure homogenization, water bath sonicator method prepare Salvia root P.E nanosuspension
After the Pickering lotion 4000g centrifugation 15min that Fig. 3 difference Salvia root P.E suspension liquid and preparation method thereof obtains
Appearance.
Wherein, A, B, C, D, E are respectively Probe Ultrasonic Searching method, high pressure homogenization, anti-solvent method, anti-solvent joint high pressure homogenization
Method, water bath sonicator method prepare Salvia root P.E nanosuspension
The cosmetic variation figure of Salvia root P.E Pickering lotion made from nine kinds of Fig. 4 different oily matcheds.
Wherein, A, B, C, D, E, F, G, H, I are respectively dalbergia heartwood oil, dalbergia heartwood oil: Labrafil M 1944CS=10:0,8:
1、4:1、2:1、1:1、1:2、1:4、1:8、Labrafil M 1944CS。
Outside drawing after Salvia root P.E Pickering lotion centrifugation made from nine kinds of Fig. 5 different oily phase compositions.
Wherein, A, B, C, D, E, F, G, H, I are respectively dalbergia heartwood oil, dalbergia heartwood oil: Labrafil M 1944CS=10:1,8:
1、4:1、2:1、1:1、1:2、1:4、1:8、Labrafil M 1944CS。
The cosmetic variation figure of Salvia root P.E Pickering lotion made from the different initial water phase pH of Fig. 6.
Outside drawing after Salvia root P.E Pickering lotion centrifugation made from the different initial water phase pH of Fig. 7.
The cosmetic variation of Salvia root P.E Pickering lotion made from Fig. 8 different pharmaceutical additional amount.
Outside drawing after the centrifugation of Salvia root P.E Pickering lotion made from Fig. 9 different pharmaceutical additional amount.
Radix Salviae Miltiorrhizae made from Figure 10 difference grease volume ratio (oil is mutually 0.5:10,1:10,2:10,4:10 with the ratio of water phase)
The cosmetic variation figure of extract Pickering lotion.
Radix Salviae Miltiorrhizae made from Figure 11 difference grease volume ratio (oil is mutually 0.5:10,1:10,2:10,4:10 with the ratio of water phase)
Extract 4000 × g of Pickering lotion is centrifuged the outside drawing after 15min.
Figure 12 optimizes outside drawing of the three batches of Salvia root P.E Pickering lotions of technique preparation at room temperature storage 3 months.
Figure 13 optimizes the appearance after three crowdes of Salvia root P.E 4000 × g of Pickering lotion centrifugation 15min of technique preparation
Figure.
Figure 14 optimizes the Salvia root P.E Pickering lotion brand-new sample of technique preparation and after room temperature storage 3 month
Emulsion droplet aspect graph.
Specific embodiment
Illustrate below by way of specific description of embodiments of the present invention but does not limit the present invention.
The nanocrystalline self-stabilization Pickering lotion of Salvia root P.E of the present invention is using Salvia root P.E, oil phase and water system
At oil-in-water type Pickering lotion, emulsion droplet can be steadily distributed forms stable lotion in water.
The preparation method of the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E of the present invention includes the following steps:
A, it prepares primary suspension: Salvia root P.E is dissolved in organic solvent, being added with stirring pH value is 9-13's
In water, continues heating stirring and wave except organic solvent, obtain primary suspension A;
B, it prepares nanocrystalline suspension: primary suspension A obtained by step A is obtained into nanocrystalline suspension B through high-pressure homogeneous;
C, it prepares nanocrystalline self-stabilization Pickering lotion: nanocrystalline suspension B obtained by step B and oily phase oleic acid is gathered
The mixing of glycol glycerin ester obtains the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E through high-pressure homogeneous.
In above-mentioned preparation method:
Organic solvent in step A is acetone, any one or its mixing in ethyl alcohol;Salvia root P.E and organic solvent
Mass volume ratio ,≤30:1 is calculated as with mg/ml;It is preferred that using acetone solution Salvia root P.E.
High-pressure homogeneous condition in step B is that homogenization pressure is 600-1200bar, and homogenization cycles are 10-30 times;Further
It is preferred that it is 800-1000bar that high-pressure homogeneous condition, which is homogenization pressure, 20-30 times.
High-pressure homogeneous pressure in step C is 600-1200bar, and homogenization cycles are 10-30 times;Further preferred high pressure is equal
It is 800-1000bar that matter condition, which is homogenization pressure, 20-30 times.
The mass volume ratio of Salvia root P.E described in step A and oil phase described in step C is calculated as 20:1-60:1 with mg/ml.
Oil described in step C is mutually 0.5:10-2:10 with the volume ratio of nanocrystalline suspension B;Further preferably, step C
The oil is mutually 1:10 with the volume ratio of nanocrystalline suspension B.
In preparation method of the present invention, the Salvia root P.E used is to use the ethyl alcohol of 70-100% to be molten by Chinese medicine Radix Salviae Miltiorrhizae
Agent, 60-90 DEG C of refluxing extraction.Wherein, the content of the tanshin polyphenolic acid B in Salvia root P.E is the content of 60-100mg/g, danshensu
Content for 3-10mg/g, Rosmarinic acid is 3-10mg/g;The content of Tanshinone I I A is 5-20mg/g, the content of Cryptotanshinone
For 2-10mg/g, the content of Tanshinone I is 3-10mg/g.
Originally, when preparing the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E as raw material using Salvia root P.E, reference
The Master degree candidate that seminar where inventor replied on May 27th, 2018 replies, and paper " promote blood circulation Fang Zhongsan kind by influence
The Elements research of refractory components nanocrystalline self-stabilization Pickering lotion preparation " in record, with particular reference to Tanshinone I I A
Lotion preparation process, the unstable phenomenon such as merging, layering, flocculation, equal nothing has occurred in obtained lotion in various degree
Method prepares stable lotion.In particular, in the reply paper, investigation obtains cnidium oil: Fabrafil for tanshinone IIA
M 1944CS=9:1 (v/v) is as oily phase;The self-emulsifying ability of water phase basic condition oil phase significantly increases, and water phase pH can lead to
Cross partial size, the charge for influencing solia particle, and oily phase self-emulsifying ability and influence the building of NSSPE;Drug concentration can lead to
Cross influence the partial size of solia particle, charge and suspension pH and influence NSSPE at cream and stability, and this influence is to tool
Having the drug of certain acid-base property may become apparent from;Oily Phase Proportion is excessive or too small, is unfavorable for the building and stabilization of lotion;Water phase pH
It is 12.0, water oil volume ratio is tanshinone IIA-NSSPE made from 85:15, and being placed at room temperature for after 90d still has outside good lotion
It sees and emulsion droplet form, partial size is declined slightly without significant change, only drugs content.But Salvia root P.E can not but utilize Rhizoma Chuanxiong
Oil-oleic acid LABRAFIL M 1944CS oil, which is mutually realized, obtains stable lotion, sees Fig. 1: left figure is the technique by tanshinone IIA
The condition of (i.e. cnidium oil: oleic acid LABRAFIL M 1944CS=9:1) prepares Salvia root P.E: being unable to get stable lotion.It is right
Figure is that cnidium oil in left figure is changed into the condition of dalbergia heartwood oil (i.e. dalbergia heartwood oil: oleic acid LABRAFIL M 1944CS=9:1) to prepare Radix Salviae Miltiorrhizae
Extract: still it is unable to get stable lotion.
Especially in the reply paper, inventor seminar thinks the property for the solia particle that Pickering lotion uses
The influence result of confrontation Pickering lotion is inconsistent, and reason is still not clear.And Pickering emulsion intercalation method is evaluated
System is chaotic, and influence of the drug to stability of emulsion there is no research after Pickering lotion carries medicine, is project where inventor
Group breaks through the heavy difficult point changed from monomer to the extract with composite parts.
On this basis, seminar where inventor is solved finally by studying, groping for a long time with Salvia root P.E
The nanocrystalline self-stabilization Pickering lotion of stable Salvia root P.E is prepared for bulk pharmaceutical chemicals.Test process is as follows:
One, main material
Dalbergia heartwood oil (the natural medicinal oil Co., Ltd of Jiangxi deodar).
Salvia root P.E (Xi'an Honson Biotechnology Co., Ltd.) meets following content through detection Salvia root P.E and wants
Ask: the content of tanshin polyphenolic acid B is 60-100mg/g, the content of danshensu is 3-10mg/g, the content of Rosmarinic acid is 3-10mg/g;
The content of Tanshinone I I A is 5-20mg/g, and the content of Cryptotanshinone is 2-10mg/g, and the content of Tanshinone I is 3-10mg/g.
Oleic acid LABRAFIL M 1944CS (hereinafter referred to as Labrafil M 1944CS, French GATTEFOSSE).
Remaining reagent is that analysis is pure.
Remarks: in following preparation method, the proportion relation between oily phase is volume ratio;The proportion of Salvia root P.E and oily phase
Relationship is mass volume ratio, in terms of mg/ml;Oily is mutually volume ratio with the proportion relation of nanocrystalline suspension.
Two, experimental method
1, the evaluation index of process optimization
(1) appearance
It by sample obtained loaded in vial, is stored at room temperature, phenomena such as being layered, flocculate, precipitating is observed in 0,1,14d,
Appearance photo is shot with digital camera, the height of emulsion layer is measured, group-index is calculated by formula: group-index 1-Ht/Ho,
Middle Ht, Ho are respectively the height of t, 0 moment emulsion layer.
(2) centrifugal stability
Take l mL it is freshly prepared go out sample in the centrifuge tube of 1.5mL, 4000 × g is centrifuged 15min, has seen whether point
Phenomena such as layer, precipitating.While emulsion layer is taken, absorbance is measured in 500nm after dilution certain multiple.
2, process optimization
(1) influence of solia particle suspension liquid and preparation method thereof
The solia particle suspension of Salvia root P.E is prepared with following 5 kinds of methods respectively, laser particle size analyzer measurement is solid
The partial size of body particle.
Method A: taking 200mg Salvia root P.E to be added in 50ml pure water, Probe Ultrasonic Searching (1200w, work 5s, interval 5s,
Total 6min).
Method B: take 200mg Salvia root P.E that 50ml pure water, the high-pressure homogeneous 6min of 800bar is added.
Method C: taking 200mg Salvia root P.E that 10ml acetone is added, and 50 DEG C of waters bath with thermostatic control vibrate 4h, are all injected into 50ml
In pure water, stirring is waved except acetone at 60 DEG C.
Method D: taking 200mg Salvia root P.E that 10ml acetone is added, and 50 DEG C of water bath with thermostatic control oscillations for 24 hours, are all injected into
In 50ml pure water, stirring is waved except acetone at 60 DEG C, then it carries out the high-pressure homogeneous 3min of 800bar.
Method E: take 200mg Salvia root P.E that 50ml pure water, water bath sonicator 3min is added.
It takes above-mentioned Salvia root P.E suspension 40ml respectively, is added 4ml dalbergia heartwood oil, 18000rpm high shear 2min, then
Samples of latex is made in the high-pressure homogeneous 6min of 800bar.Lotion is carried out by the method under the evaluation index of process optimization " 1, " item
Evaluation.
(2) influence of oily phase composition
160mg Salvia root P.E is taken, 10ml acetone is added, 50 DEG C of waters bath with thermostatic control are vibrated 4h, are injected into 40ml pure water, 60
Stirring is waved except acetone at DEG C, and Salvia root P.E suspension is made then at the high-pressure homogeneous 3min of 800bar;It is directly added into 4ml oil phase again
(respectively dalbergia heartwood oil;Dalbergia heartwood oil: Labrafil M 1944CS volume ratio=8:1,4:1,2:1,1:1,1:2,1:4,1:8;
Labrafil M 1944CS), the high-pressure homogeneous 6min of 800bar after 18000rpm high shear 2min.
(3) influence of the initial pH of water phase
Take 60mg Salvia root P.E, 10ml acetone be added, 4h are vibrated in 50 DEG C of waters bath with thermostatic control, be injected into the initial pH of 40ml be 5,
7, in 9,11,12 pure water, stirring is waved except acetone at 60 DEG C, then at the high-pressure homogeneous 3min of 800bar;It is directly added into 4ml oil phase again
(dalbergia heartwood oil: Labrafil M 1944CS volume ratio=2:1), the high-pressure homogeneous 6min of 800bar after 1800rpm high shear 2min.
(4) influence of drug additional amount
The Salvia root P.E of 40,80,160,320,640mg is taken, 10ml acetone is added, 4h is vibrated in 50 DEG C of waters bath with thermostatic control, point
It is not added in the 40ml pure water that pH is 9, stirring is waved except acetone at 60 DEG C, then at the high-pressure homogeneous 3min of 800bar;Directly add again
Enter 4ml oil phase (dalbergia heartwood oil: Labrafil M 1944CS=2:1), 800bar is high-pressure homogeneous after 18000rpm high shear 2min
6min。
(5) influence of water oil volume ratio
The Salvia root P.E of 240mg is taken, 10ml acetone is added, 4h is vibrated in 50 DEG C of waters bath with thermostatic control, and being added separately to pH is 9
In 41.9,40,36.67,31.43ml pure water, stirring is waved except acetone at 60 DEG C, then at the high-pressure homogeneous 3min of 800bar;Distinguish again
Oily phase (dalbergia heartwood oil: Labrafil M 1944CS=2:1) is added, makes ratio 0.5:10,1:10, the 2:10 of oily phase and water phase,
The high-pressure homogeneous 6min of 800bar after 4:10,1800rpm high shear 2min.
(6) final optimization technique
According to the above results, it determines the more excellent value of each factor, determines optimization technique, prepare 3 batches of Salvia root P.Es
Pickering lotion.
3, the emulsion intercalation method evaluation of optimization technique preparation
(1) centrifugal stability
Take l mL it is freshly prepared go out sample in the centrifuge tube of 1.5mL, 4000 × g is centrifuged 15min, has seen whether point
Phenomena such as layer, precipitating.While emulsion layer is taken, absorbance is measured in 500nm after 100 multiples of dilution.
(2) stability being stored at room temperature
Lotion is stored at room temperature, carries out properties evaluations, including appearance, emulsion droplet form and particle diameter distribution respectively at 0,1 and 3m.
4, distribution research of each ingredient in Pickering lotion
25mL emulsion layer is taken, 4 DEG C, 50000rpm is centrifuged 1h, and careful separation oil phase, water phase collect medicine layer, super with methanol
Sound dissolution, constant volume, measure each content of active component.Using the total content in lotion as reference, calculate each ingredient oily phase, water phase and
The distributive law of adsorption layer.
5, result and analysis
1) influence of solia particle suspension liquid and preparation method thereof
Salvia root P.E suspension particle size results made from 5 kinds of methods are shown in Table 1.
The partial size of Salvia root P.E suspension made from 15 kinds of methods of table and distribution (n=3)
Method | D0.5/μm | D4,3/μm | Span | Percentage/% of particle less than 1 μm |
A Probe Ultrasonic Searching | 1.69±0.13 | 2.05±0.07 | 2.72±0.18 | 18.01±2.23 |
B high pressure homogenization | 1.30±0.31 | 1.66±0.31 | 2.78±0.25 | 33.40±0.92 |
C anti-solvent method | 1.79±0.47 | 2.08±0.47 | 3.05±0.47 | 10.26±3.49 |
D anti-solvent combines high pressure homogenization | 0.38±0.27 | 0.45±0.12 | 2.12±1.06 | 93.17±0.85 |
E water bath sonicator | 2.43±0.31 | 2.59±0.25 | 1.70±0.84 | 7.01±0.83 |
3 batches of lotions of five kinds of different Salvia root P.E suspensions preparations are placed at room temperature for the appearance after 0,1 and 14d and see Fig. 2,
Appearance after 4000 × g centrifugation 15min is shown in Fig. 3.
The Pickering samples of latex of different Salvia root P.E suspension preparations places the group-index and 4000 after 14d
Absorbance after the lotion of × g centrifugation 15min dilutes 100 times the results are shown in Table 2.
Group-index after 2 sample of table placement 14d and the sample after centrifugation dilute the absorbance (n=3) after 100 times
Method | A | B | C | D | E |
Group-index | 0.091±0.018 | 0.073±0.031 | 0.145±0.083 | 0.079±0.010 | 0.091±0.048 |
Absorbance | 0.272±0.052 | 0.130±0.011 | 0.242±0.089 | 0.211±0.110 | 0.505±0.344 |
From Fig. 1, table 2 it is found that the Salvia root P.E nanosuspension grain that method D is prepared using anti-solvent joint high pressure homogenization
Diameter is minimum, and group-index is smaller after placing 14d with the Pickering lotion of this nanosuspension preparation, and newborn layer absorbance is opposite
Higher, stability of emulsion is quite a lot of compared with remaining method.Therefore determine that the preparation method of nanosuspension is method D.
2) oily phase composition
Salvia root P.E Pickering lotion made from nine kinds of different oily phase compositions 0,1, the outside drawing of 14d see Fig. 4,
Appearance after 4000 × g centrifugation 15min is shown in Fig. 5.
After newborn layer sample dilutes 100 times after the Salvia root P.E Pickering lotion centrifugation of different oil matched preparations
Absorbance, changes of contents are shown in Table 3.
Fig. 4 and table 3 show that single poor for the stability of emulsion of oil phase preparation with dalbergia heartwood oil, appearance is apparent clear after placing 14d
Bright water layer and oil reservoir, group-index reach 0.152.After the amount for increasing Labrafil M 1944CS, group-index gradually becomes
It is small, when dalbergia heartwood oil and Labrafil M 1944CS ratio reach 1:1, group-index 0.Stabilization in remaining sample 14d
Property it is all preferable, apparent oil or water are not precipitated.For layer absorbance newborn after centrifugation, Labrafil M is added in dalbergia heartwood oil
After 1944CS, newborn layer absorbance increases after centrifugation, is illustrated as milkiness enhancing, and Labrafil M 1944CS, which is added, in dalbergia heartwood oil is
Reach maximum value, slightly above 2:1 when 4:1.The content for increasing Labrafil M 1944CS is continued thereafter with, newborn layer extinction after centrifugation
Degree declines instead, and absorbance is down to 1.026 from 2.199 after the lotion centrifugation of pure Labrafil M 1944CS preparation, but is still higher than
The 0.257 of pure dalbergia heartwood oil.To sum up, the ratio of pure dalbergia heartwood oil and Labrafil M 1944CS is selected to make for the oily phase composition of 2:1
Obtain the nanocrystalline Pickering lotion of Salvia root P.E.
Absorbance (n=3) after the different oily phase composition lotion centrifugations of table 3
Dalbergia heartwood oil: Labrafil M 1944CS | Group-index | Absorbance |
10:0 | 0.152±0.038 | 0.257±0.234 |
8:1 | 0.033±0.005 | 0.885±0.250 |
4:1 | 0.016±0.003 | 2.199±0.158 |
2:1 | 0.009±0.000 | 1.901±0.377 |
1:1 | 0.007±0.056 | 1.062±0.444 |
1:2 | 0 | 1.343±0.314 |
1:4 | 0 | 1.451±0.160 |
1:8 | 0 | 1.249±0.045 |
0:10 | 0 | 1.026±0.093 |
3) influence of water phase pH
Outside drawing of the Salvia root P.E Pickering lotion made from five kinds of different water phase pH in each time (0,1 and 14d)
See Fig. 6, the appearance after 4000 × g centrifugation 15min is shown in Fig. 7.
The Pickering lotion of the preparation of Salvia root P.E suspension made from different water phase pH, the sample dilution after centrifugation
Absorbance, group-index after 100 times are shown in Table 4.
Absorbance and group-index (n=3) after lotion centrifugation is made in the different initial water phase pH of table 4
Water phase pH | 5 | 7 | 9 | 11 | 13 |
Group-index | 0.008±0.039 | 0.003±0.012 | 0 | 0 | 0 |
Absorbance | 1.396±0.054 | 0.827±0.031 | 1.476±0.293 | 1.115±0.114 | 1.173±0.143 |
Fig. 6 and table 4 show that the initial pH of water phase is not very big, stabilization of the sample in 14d on emulsion intercalation method influence
Property it is all preferable, apparent oil or water are not precipitated.Again by the absorbance of lotion in table 4 it is found that as pH value increases, the extinction of lotion
Degree becomes larger, and reaches highest 1.476 when pH is 9.Later again as pH value increases, lotion absorbance is gradually become smaller.Again by Fig. 7
It is found that centrifugal stability is preferable when pH is 9,13.To sum up, initial pH value is selected to be made receiving for Salvia root P.E for 9 water phase
Rice crystalline substance pickering lotion.
4) influence of drug additional amount
Salvia root P.E Pickering lotion made from different pharmaceutical additional amount 0,1, the outside drawing of 14d see Fig. 8,
Appearance after 4000 × g centrifugation 15min is shown in Fig. 9.
The Pickering lotion of the preparation of Salvia root P.E suspension made from five kinds of different pharmaceutical additional amounts, after centrifugation
Absorbance, group-index after 100 times of sample dilution are shown in Table 5.
Absorbance and group-index (n=3) after lotion centrifugation is made in 5 different pharmaceutical additional amount of table
Drug additional amount | 40 | 80 | 160 | 320 | 640 |
Group-index | 0 | 0 | 0.003±0.011 | 0.009±0.008 | 0.016±0.003 |
Absorbance | 1.528±0.081 | 2.037±0.277 | 2.076±0.247 | 1.548±0.338 | 1.514±0.148 |
Fig. 8-9 and table 5 are shown, with the increase of drug additional amount, emulsion intercalation method variation in the range of 40-60mg
It is not very big, but there is fraction of oil to be mutually precipitated after medication amount increases to 320mg, when arriving 640mg, group-index reaches 0.016.
With the increase of drug additional amount, the absorbance of lotion is being gradually increased, and when 80-160mg, the newborn layer absorbance of centrifugation reaches
It is 2.076 to maximum.Continue to increase dosage, newborn layer absorbance reduces instead.After lotion places 14d, in the sample of 160mg
It has no that apparent drug falls to bottom of bottle, but observes apparent drug sedimentation when 320mg.To sum up, the medication amount being added is selected
The nanocrystalline pickering lotion of Salvia root P.E is made between 160-320mg.
5) influence of water oil volume ratio
Outside drawing of the different water oil volumes than Salvia root P.E Pickering lotion obtained in each time is shown in Figure 10,
Appearance after 4000 × g centrifugation 15min is shown in Figure 11.
Sample of the different water oil volumes than Pickering lotion prepared by Salvia root P.E suspension obtained, after centrifugation
Absorbance, group-index after 100 times of dilution are shown in Table 6.
Absorbance, group-index (n=3) after 100 times of 6 sample of table dilution
Water oil volume ratio | 0.5:10 | 1:10 | 2:10 | 4:10 |
Group-index | 0.082±0.035 | 0.091±0.029 | 0.143±0.021 | 0.278±0.014 |
Absorbance | 1.253±0.180 | 2.096±0.260 | 1.490±0.236 | 0.628±0.123 |
Figure 10 and table 6 are shown, with the increase of dampening oil volume ratio, are affected to emulsion intercalation method, when water oil volume
When than for 2:10, there is apparent oil to be mutually precipitated, when to water oil volume ratio being 4:10, group-index reaches 0.278.With dampening oil body
The increase of product ratio, the absorbance of lotion first increases after by reducing, when water oil volume ratio is 1:10, reach maximum 2.096.Again by
Figure 11 is it is found that centrifugal stability is preferable when water oil volume ratio is 1:10.To sum up, water oil volume ratio is selected to prepare Radix Salviae Miltiorrhizae for 1:10
The nanocrystalline Pickering lotion of extract.
6) optimize the determination of technique
240mg Salvia root P.E is taken, 10ml acetone is added, 50 DEG C of waters bath with thermostatic control vibrate 4h, are injected into 40ml initial pH value
For in 9 pure water, at 60 DEG C stirring wave except in the high-pressure homogeneous 6min of 800bar, added after acetone 4ml oil phase (pure dalbergia heartwood oil with
The volume ratio of Labrafil M 1944CS be 2:1), the high-pressure homogeneous 6min of 800bar to get.
7) estimation of stability result
Outside drawing of the Salvia root P.E Pickering lotion in each time of three batches preparation is shown in Figure 12,4000 × g from
Appearance after heart 15min is shown in that Figure 13 brand-new sample and the emulsion droplet aspect graph after room temperature storage 3 months are shown in Figure 14.Optimize technique preparation
Particle diameter distribution of three batches of Salvia root P.E Pickering lotions in each time be shown in Table 7.
Table 7 optimizes the room temperature storage 3 months particle diameter distribution (n of three batches of Salvia root P.E Pickering lotions of technique preparation
=3)
Time/m | D0.5/μm | D4,3/μm | Span |
0 | 0.848±0.179 | 1.019±0.147 | 2.764±0.327 |
1 | 0.459±0.078 | 0.921±0.193 | 4.012±0.452 |
3 | 0.580±0.068 | 0.959±0.260 | 2.602±0.197 |
Aforementioned stable Journal of Sex Research is the results show that Salvia root P.E solia particle self-stabilization prepared by Figure 13 display optimization technique
4000 × g of Pickering lotion centrifugation 15min after, lotion without layering, precipitating etc. wild effects;Figure 12 shows that room temperature is put
After setting 3 months, appearance is still in uniform emulsion form, and emulsion-stabilizing is layered without obvious, also oil-free phase precipitation or Salvia root P.E
The unstable phenomenons such as flocculation, aggregation, precipitating, the visible D of table 84,3Emulsion droplet size is without significant changes after about 1 μm, three months.It says
Bright, lotion has preferable stability.
8) distribution of each ingredient in Pickering lotion
Table 8 optimizes distribution percentage/% of each ingredient in 3 crowdes of Salvia root P.E Pickering of technique preparation
Ingredient | Oil | Water | Adsorption layer |
Danshensu | 0.92 | 98.71 | 0.37 |
Rosmarinic acid | 3.96 | 94.93 | 1.11 |
Tanshin polyphenolic acid B | 3.97 | 95.28 | 0.75 |
Cryptotanshinone | 33.59 | 14.10 | 52.31 |
Salvia miltiorrhiza bge I | 32.83 | 12.28 | 54.89 |
Tanshinone IIA | 33.14 | 15.05 | 51.81 |
Table 8 shows that in Pickering lotion obtained, water-soluble danshensu, Rosmarinic acid, tanshin polyphenolic acid B mainly divide
It is distributed in water phase;Fat-soluble Cryptotanshinone, salvia miltiorrhiza bge I, tanshinone IIA part are distributed in oily phase, are largely adsorbed in oil
Water termination.Confirm that lotion obtained has by the nanocrystalline structure for being adsorbed in oil-water interfaces stable emulsion of insoluble drug.
More than, Pickering lotion preparation process that the present invention optimizes are as follows: take the Salvia root P.E of 240mg, 10ml is added
4h are vibrated in acetone, 50 DEG C of waters bath with thermostatic control, are injected into the pure water that 40ml initial pH value is 9, at 60 DEG C stirring wave except after acetone in
The mixing of 4ml dalbergia heartwood oil and oleic acid LABRAFIL M 1944CS (Labrafil M 1944CS) is added in the high-pressure homogeneous 6min of 800bar
Oily phase (2:1, v/v), the high-pressure homogeneous 6min of 800bar.Salvia root P.E self-stabilization Pickering lotion made from final optimization pass
Emulsion droplet D4,3For (1.019 ± 0.147) μm, after being placed at room temperature for 3m, appearance, partial size there are no significant variation.
On this basis, inventor repeatedly prepares within the scope of the claimed invention, obtains stable Radix Salviae Miltiorrhizae
Extract nano crystalline substance self-stabilization Pickering lotion, referring to following preparating example.
The preparation method of the nanocrystalline self-stabilization Pickering lotion of 1 Salvia root P.E of embodiment, comprising the following steps:
(1) 80mg Salvia root P.E bulk pharmaceutical chemicals are weighed, are added in 5mL ethyl alcohol, 4h is vibrated in 50 DEG C of waters bath with thermostatic control, is injected into
In the pure water that 40ml initial pH value is 9,60 DEG C of stirrings are waved except ethyl alcohol, and primary suspension A is obtained;
(2) under the conditions of 600bar nanocrystalline suspension B is made homogenisation cycle 10 times in primary suspension A;
(3) by obtained nanocrystalline suspension B and 4ml miscella phase (dalbergia wood volatile oil: oleic acid LABRAFIL M 1944CS
=2:1) mixing, it reuses high pressure homogenizer and is recycled 10 times under the conditions of 600bar, can be prepared by self-stabilization Pickering lotion
Preparation.
Partial size, gained are detected using photon correlation spectroscopy (photon correlation spectroscopy, PCS)
The average grain diameter of lotion is 1.8 ± 0.2 μm, wherein nanocrystalline average grain diameter is 350nm ± 28.2nm.Lotion room temperature obtained
It is still stable after placing 1 month.
The preparation method of the nanocrystalline self-stabilization Pickering lotion of 2 Salvia root P.E of embodiment, comprising the following steps:
(1) 160mg Salvia root P.E bulk pharmaceutical chemicals are weighed, 5ml acetone: the mixed solvent of ethyl alcohol (1:1), 50 DEG C of constant temperature is added
4h is vibrated in water-bath, is injected into the pure water that 40ml initial pH value is 9,60 DEG C of stirrings are waved except organic solvent, and primary suspension A is obtained;
(2) under the conditions of 800bar nanocrystalline suspension B is made homogenisation cycle 20 times in primary suspension A;
(3) by obtained nanocrystalline suspension B and 4ml miscella phase (dalbergia wood volatile oil: oleic acid LABRAFIL M 1944CS
=1:2) mixing, it reuses high pressure homogenizer and is recycled 20 times under the conditions of 800bar, can be prepared by self-stabilization Pickering lotion
Preparation.
Partial size, gained are detected using photon correlation spectroscopy (photon correlation spectroscopy, PCS)
The average grain diameter of lotion is 2.4 ± 0.7 μm, wherein nanocrystalline average grain diameter is 430 ± 25.3nm.Lotion room temperature obtained is put
It is still stable after setting 1 month.
The preparation method of the nanocrystalline self-stabilization Pickering lotion of 3 Salvia root P.E of embodiment, comprising the following steps:
(1) 200mg Salvia root P.E bulk pharmaceutical chemicals are taken, 5ml acetone is added, 50 DEG C of waters bath with thermostatic control vibrate 4h, are injected into 40ml
In the pure water that initial pH value is 11,60 DEG C of stirrings are waved except organic solvent, and primary suspension A is obtained;
(2) under the conditions of 1000bar nanocrystalline suspension B is made homogenisation cycle 15 times in primary suspension A;
(3) by obtained nanocrystalline suspension B and 4ml miscella phase (dalbergia wood volatile oil: oleic acid LABRAFIL M 1944CS
=1:4) mixing, it reuses high pressure homogenizer and is recycled 20 times under the conditions of 1000bar, can be prepared by self-stabilization Pickering cream
Liquid formulation.
Partial size, gained are detected using photon correlation spectroscopy (photon correlation spectroscopy, PCS)
The average grain diameter of lotion is 5.5 ± 1.8 μm, wherein nanocrystalline average grain diameter is 530.8 ± 38.4nm.Lotion room temperature obtained
It is still stable after placing 1 month.
The preparation method of the nanocrystalline self-stabilization Pickering lotion of 4 Salvia root P.E of embodiment, comprising the following steps:
(1) 300mg Salvia root P.E bulk pharmaceutical chemicals are weighed, 10ml acetone is added, 50 DEG C of waters bath with thermostatic control are vibrated 4h, are injected into
In the pure water that 40ml initial pH value is 12,60 DEG C of stirrings are waved except organic solvent, and primary suspension A is obtained;
(2) under the conditions of 800bar nanocrystalline suspension B is made homogenisation cycle 20 times in primary suspension A;
(3) primary suspension B is mixed with 3ml miscella phase (dalbergia wood volatile oil: oleic acid LABRAFIL M 1944CS=1:8)
It closes, can be prepared by preparation homogenisation cycle 20 times under the conditions of 1000bar.
Partial size, gained are detected using photon correlation spectroscopy (photon correlation spectroscopy, PCS)
The average grain diameter of lotion is 6.5 ± 1.7 μm, wherein nanocrystalline average grain diameter is 526.4 ± 25.6nm.Lotion room temperature obtained
It is still stable after placing 1 month.
The preparation method of the nanocrystalline self-stabilization Pickering lotion of 5 conopsea extraction of embodiment, comprising the following steps:
(1) 400mg Salvia root P.E bulk pharmaceutical chemicals are weighed, 15ml acetone is added, 50 DEG C of waters bath with thermostatic control are vibrated 4h, are injected into
In the pure water that 40ml initial pH value is 13,60 DEG C of stirrings are waved except organic solvent, and primary suspension A is obtained;
(2) under the conditions of 1000bar nanocrystalline suspension B is made homogenisation cycle 20 times in primary suspension A;
(3) primary suspension B is mixed with 2ml miscella phase (dalbergia wood volatile oil: oleic acid LABRAFIL M 1944CS=1:8)
It closes, can be prepared by preparation homogenisation cycle 25 times under the conditions of 1200bar.
Partial size, gained are detected using photon correlation spectroscopy (photon correlation spectroscopy, PCS)
The average grain diameter of lotion is 4.5 ± 2.1 μm, wherein nanocrystalline average grain diameter is 474.5 ± 28.4nm.Lotion obtained is placed
It is still stable after 1 month.
To sum up, the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E of the present invention be using Salvia root P.E, oil mutually and
The Pickering lotion of oil-in-water type made of water, specific nanometer crystal preparation method, aqueous pH values, oil are mutually mixed with nanocrystalline
The volume ratio (i.e. grease volume ratio) of suspension B, Salvia root P.E and tanshinone in the mass volume ratio and extract of oily phase
The content of ingredient realizes surfactant-free, without additional solid particle stabilizers, also available stable Pickering
The water soluble ingredients such as lotion, especially tanshin polyphenolic acid B are distributed in water phase, and the refractory components such as tanshinone part is distributed in oily phase,
Partial adsorbates are in emulsion droplet interface, stable emulsion.
Claims (10)
1. the preparation method of the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E, it is characterised in that: the lotion is to use
The Pickering lotion of oil-in-water type made of Salvia root P.E, oil phase and water;Tanshin polyphenolic acid B contains in the Salvia root P.E
Amount is 60-100mg/g, the content of danshensu is 3-10mg/g, the content of Rosmarinic acid is 3-10mg/g;Tanshinone IIA contains
Amount is 5-20mg/g, the content of Cryptotanshinone is 2-10mg/g, the content of Tanshinone I is 3-10mg/g;
Preparation method includes the following steps:
A, it prepares primary suspension: Salvia root P.E is dissolved in organic solvent, be added with stirring in the water that pH value is 9-13,
Continue heating stirring to wave except organic solvent, obtains primary suspension A;
B, it prepares nanocrystalline suspension: primary suspension A obtained by step A is obtained into nanocrystalline suspension B through high-pressure homogeneous;
C, nanocrystalline self-stabilization Pickering lotion is prepared: by nanocrystalline suspension B obtained by step B and the poly- second two of oily phase oleic acid
The mixing of alcohol glyceride obtains the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E through high-pressure homogeneous.
2. the preparation method of the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E according to claim 1, feature
It is: in step A, meets following any one:
The organic solvent is ethyl alcohol, any one or its mixing in acetone;
The mass volume ratio of the Salvia root P.E and organic solvent is calculated as≤30:1 with mg/ml;
The preferred acetone of organic solvent.
3. the preparation method of the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E according to claim 1, feature
It is: in step B,;High-pressure homogeneous condition is that homogenization pressure is 600-1200bar, and homogenization cycles are 10-30 times;
It is 800-1000bar that further preferred high-pressure homogeneous condition, which is homogenization pressure, 20-30 times.
4. the preparation method of the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E according to claim 1, feature
Be: in step C, high-pressure homogeneous pressure is 600-1200bar, and homogenization cycles are 10-30 times;
It is 800-1000bar that further preferred high-pressure homogeneous condition, which is homogenization pressure, 20-30 times.
5. the preparation method of the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E according to claim 1, feature
Be: the mass volume ratio of Salvia root P.E described in step A and oil phase described in step C is calculated as 20:1-60:1 with mg/ml.
6. the preparation method of the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E according to claim 1, feature
Be: oil described in step C is mutually 0.5:10-2:10 with the volume ratio of nanocrystalline suspension B;
Further preferably, oil described in step C is mutually 1:10 with the volume ratio of nanocrystalline suspension B.
7. the preparation method of the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E according to claim 1, feature
Be: oil described in step C is mutually using dalbergia wood volatile oil and oleic acid LABRAFIL M 1944CS;Its volume ratio is 1:2-1:8.
8. the preparation side of the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E described in -7 Arbitrary Terms according to claim 1
Method, it is characterised in that: the Salvia root P.E uses the ethyl alcohol of 70-100% for solvent by Chinese medicine Radix Salviae Miltiorrhizae, 60-90 DEG C of reflux
It extracts.
9. the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E of claim 1-8 Arbitrary Term the method preparation, special
Sign is: the nanocrystalline partial size of Salvia root P.E that oily phase surface is wrapped in the lotion is 300nm-1000nm, the lotion
In emulsion droplet size be 1 μm -10 μm.
10. the nanocrystalline self-stabilization Pickering lotion of Salvia root P.E according to claim 9, it is characterised in that: described
The nanocrystalline partial size of Salvia root P.E that oily phase surface is wrapped in lotion is 300nm-500nm, the emulsion droplet size in the lotion
It is 1 μm -5 μm.
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