CN108567763A - A kind of Paeoniflorin nanocrystal and preparation method thereof - Google Patents
A kind of Paeoniflorin nanocrystal and preparation method thereof Download PDFInfo
- Publication number
- CN108567763A CN108567763A CN201810597904.5A CN201810597904A CN108567763A CN 108567763 A CN108567763 A CN 108567763A CN 201810597904 A CN201810597904 A CN 201810597904A CN 108567763 A CN108567763 A CN 108567763A
- Authority
- CN
- China
- Prior art keywords
- paeoniflorin
- nanocrystal
- stabilizer
- preparation
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- YKRGDOXKVOZESV-UHFFFAOYSA-N paeoniflorin Natural products O1C(C)(C2(CC34)OC5C(C(O)C(O)C(CO)O5)O)CC3(O)OC1C24COC(=O)C1=CC=CC=C1 YKRGDOXKVOZESV-UHFFFAOYSA-N 0.000 title claims abstract description 120
- YKRGDOXKVOZESV-WRJNSLSBSA-N Paeoniflorin Chemical compound C([C@]12[C@H]3O[C@]4(O)C[C@](O3)([C@]1(C[C@@H]42)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)C)OC(=O)C1=CC=CC=C1 YKRGDOXKVOZESV-WRJNSLSBSA-N 0.000 title claims abstract description 117
- 239000002159 nanocrystal Substances 0.000 title claims abstract description 71
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000003381 stabilizer Substances 0.000 claims abstract description 27
- 239000000725 suspension Substances 0.000 claims abstract description 19
- 239000012074 organic phase Substances 0.000 claims abstract description 15
- 239000013078 crystal Substances 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 9
- 239000008346 aqueous phase Substances 0.000 claims abstract description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 21
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 8
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- 229930003427 Vitamin E Natural products 0.000 claims description 6
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 6
- -1 hydroxyl Propyl Chemical group 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- 229920000136 polysorbate Polymers 0.000 claims description 6
- 150000003900 succinic acid esters Chemical class 0.000 claims description 6
- 229940046009 vitamin E Drugs 0.000 claims description 6
- 235000019165 vitamin E Nutrition 0.000 claims description 6
- 239000011709 vitamin E Substances 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 229940069328 povidone Drugs 0.000 claims description 4
- 229920001400 block copolymer Polymers 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 150000002148 esters Chemical group 0.000 claims description 3
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 241000416162 Astragalus gummifer Species 0.000 claims description 2
- 229920001503 Glucan Polymers 0.000 claims description 2
- 235000001630 Pyrus pyrifolia var culta Nutrition 0.000 claims description 2
- 240000002609 Pyrus pyrifolia var. culta Species 0.000 claims description 2
- 229920001615 Tragacanth Polymers 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 239000012153 distilled water Substances 0.000 claims description 2
- 210000003928 nasal cavity Anatomy 0.000 claims description 2
- 229950008882 polysorbate Drugs 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 235000010487 tragacanth Nutrition 0.000 claims description 2
- 239000000196 tragacanth Substances 0.000 claims description 2
- 229940116362 tragacanth Drugs 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims 1
- 239000001913 cellulose Substances 0.000 claims 1
- 229920002678 cellulose Polymers 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 235000009508 confectionery Nutrition 0.000 claims 1
- 239000003995 emulsifying agent Substances 0.000 claims 1
- 229920001451 polypropylene glycol Polymers 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 239000001384 succinic acid Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 13
- 229940079593 drug Drugs 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 8
- 210000004027 cell Anatomy 0.000 abstract description 4
- 238000001727 in vivo Methods 0.000 abstract description 3
- 210000000170 cell membrane Anatomy 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 235000013339 cereals Nutrition 0.000 description 20
- 239000012071 phase Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 238000004090 dissolution Methods 0.000 description 9
- 238000009826 distribution Methods 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 6
- 238000003760 magnetic stirring Methods 0.000 description 6
- 241000209094 Oryza Species 0.000 description 5
- 235000007164 Oryza sativa Nutrition 0.000 description 5
- 241000209140 Triticum Species 0.000 description 5
- 235000021307 Triticum Nutrition 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 235000009566 rice Nutrition 0.000 description 5
- 108010061711 Gliadin Proteins 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 235000006484 Paeonia officinalis Nutrition 0.000 description 3
- 239000012296 anti-solvent Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 2
- 241000736199 Paeonia Species 0.000 description 2
- 229920003081 Povidone K 30 Polymers 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000006069 physical mixture Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010006100 Bradykinesia Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 240000005001 Paeonia suffruticosa Species 0.000 description 1
- 235000003889 Paeonia suffruticosa Nutrition 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 241000218201 Ranunculaceae Species 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 238000012661 block copolymerization Methods 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229930003658 monoterpene Natural products 0.000 description 1
- 235000002577 monoterpenes Nutrition 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Physics & Mathematics (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Molecular Biology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of Paeoniflorin nanocrystal, the Paeoniflorin nanocrystal includes Paeoniflorin and stabilizer, and the weight ratio of Paeoniflorin and stabilizer is 0.5~20：1.The Paeoniflorin nanocrystal of the present invention is made using following methods：First Paeoniflorin is dissolved in organic solvent, forms organic phase solution A；Stabilizer is added in water again, forms aqueous phase solution B；Then high-speed stirred solution B, while solution A is injected, Paeoniflorin crystal is precipitated, obtains Paeoniflorin nanocrystal suspension；After filtering by above-mentioned Paeoniflorin nanocrystal suspension finally, it is lyophilized and nanocrystal is lyophilized to get Paeoniflorin.Paeoniflorin nanocrystal grain size prepared by the present invention is small, can penetrate cell membrane rapidly, discharge drug in the cell, be rapidly reached effective concentration in vivo, improve the bioavilability of drug.The preparation method of the present invention simultaneously：Step is simple, and auxiliary material used is few, it is only necessary to which stabilizer reduces cost of manufacture.
Description
Technical field
The present invention relates to pharmaceutical technologies, and in particular to a kind of Paeoniflorin nanocrystal and preparation method thereof.
Background technology
Paeoniflorin is the activated monomer extracted in Ranunculaceae Paeonia plant peony root, tree peony root, and molecular formula is
C23H28O11, belong to monoterpenes compound.Under room temperature, Paeoniflorin is white amorphous powder, easy to moisture absorption, and is compared heat, soda acid
Sensitivity is oxidized easily.
Many preclinical laboratories prove Paeoniflorins can anti-histocyte oxidativestress damage, inhibit swashing for astroglia
Living, enhancing protection nerve, has apparent antagonism, and can for the damage of corpus straitum and nigral dopamine energy nerve cell
Improve bradykinesia, thus can be used for treating the brain diseases such as Alzheimer's disease, Parkinson's disease, epilepsy.In addition, Paeoniflorin is also
It can the autoimmune diseases such as antitumor, rheumatoid arthritis and ankylosing spondylitis.Zoopery also confirms that Paeoniflorin can
It is substantially reduced blood-sugar content, there is important protective effect to cardiopulmonary cell.
Pharmacokinetics research find that Paeoniflorin is although water-soluble, but cannot easily penetrate the physiologic barrier of body,
Bioavilability is very low, even intravenously administrable, is also metabolized as Chinese herbaceous peony metabolism element-I quickly.
Domestic at present few to the preparation research of Paeoniflorin, document report has Paeoniflorin micro emulsion, Paeoniflorin lipid liquid crystal to receive
Paeoniflorin solution, Paeoniflorin wheat gliadin nanoparticle containing sorbefacient is perfused in the grain of rice, intranasal.Although Paeoniflorin micro emulsion
It is with slow releasing function but limited through the ability of raw physical barriers, to limit its application；Paeoniflorin lipid liquid crystal nanoparticle can
Improve the availability of Paeoniflorin, extend Paeoniflorin work in vivo and utilize the time, but preparation process is more complex, influence factor compared with
It is more；Paeoniflorin solution containing sorbefacient is absorbed by Passive diffusion in nasal membrane, the improvement of bioavilability
It is limited；Prepared by Paeoniflorin wheat gliadin nanoparticle is the liposome vesicle packaging medicine formed using wheat gliadin,
Again with the water dissolution containing 50% ethyl alcohol, vesica is set to be scattered in the water containing 50% ethyl alcohol using Pluronic F68 or PVA-0486,
It finally also needs to be added trehalose and forms colloidal solution and can just make to wrap up in anther sac and steep to form stabilising system, the Paeoniflorin of gained after freeze-drying
Nano-colloid grain diameter is mostly in 200nm or more, the intermediate product wheat that preparation process is complicated, operating procedure is more and obtained
The molecular weight of alcohol soluble protein is not easy to control, so as to keep medicaments uniformity degree poor.
Medicament nano crystal technology refers to that micron-sized drug granule can be made grain size by grinding distribution or precipitated crystal
It is reduced to millimicro meter level (1~100nm), and is stabilized under the action of stabilizer.Preparing the technology of nanocrystal can be divided into
Method (such as high-pressure uniform or media milling process) from up to down and bottom-to-top method (such as good solvent-anti-solvent addition
Method, supercritical fluid method).Good solvent-anti-solvent addition method is easy to operate, manufacturing cycle compared with the advantage of other technologies of preparing
It is short, do not need that carrier material, particle size be small and epigranular.Its principle is using drug in pure organic solvent containing no water
It after being completely dissolved in (good solvent), is added rapidly in the water containing stabilizer (anti-solvent), because drug is in good solvent and resists
Dissolubility difference in solvent is larger, therefore drug is analysed in aqueous solution in the form of the nanocrystal of a small amount of stabilizer of surface band
Go out, forms suspension.Tablet, granule, capsule, injection, nose can be further made in the nanocrystal prepared by this method
Chamber drug-delivery preparation, preparation capable of permeating skin etc..
Invention content
There is provided it is an object of the invention to overcome in place of above-mentioned the deficiencies in the prior art a kind of Paeoniflorin nanocrystal and
Preparation method.
To achieve the above object, the technical solution adopted by the present invention is：A kind of Paeoniflorin nanocrystal, including Paeoniflorin and
The weight ratio of stabilizer, the Paeoniflorin and stabilizer is 0.5~20：1.
Preferably, the grain size of the Paeoniflorin nanocrystal is 1~200nm.
Preferably, the stabilizer is hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyoxyethylene polyoxypropylene block copolymerization
Object, povidone, polysorbate, vitamin E polyethylene glycol succinic acid ester, tween, polyvinyl alcohol, neopelex,
Arabic gum, sodium alginate, sodium carboxymethylcellulose, glucan, mannitol, tragacanth, poly yamanashi esters, polyoxyethylene castor
The mixture of any one or two or more arbitrary proportions in sesame oil class.
Preferably, the stabilizer is hydroxypropyl methylcellulose, polyoxyethylene polyoxypropylene block copolymer, povidone, dimension
The mixture of any one or two or more arbitrary proportions of raw element E polyethanediol succinates, tween or polyvinyl alcohol.
The present invention also provides a kind of preparation methods of Paeoniflorin nanocrystal, include the following steps：
(1) Paeoniflorin is dissolved in organic solvent, forms organic phase solution A；
(2) stabilizer is added in water, forms aqueous phase solution B；
(3) high-speed stirred solution B, while solution A is injected, Paeoniflorin crystal is precipitated, obtains the suspension of Paeoniflorin nanocrystal
Liquid；
(4) after filtering by above-mentioned Paeoniflorin nanocrystal suspension, it is lyophilized and nanocrystal is lyophilized to get to Paeoniflorin.
Preferably, the water is distilled water or deionized water.
Preferably, the organic solvent be water-free methanol, acetone, acetonitrile, ethyl acetate, propylene glycol, n-butanol or
Chloroform.
Preferably, the mixing speed in the step (3) is 400-2000 revs/min.
In addition, the present invention also provides a kind of pharmaceutical preparation, in order to achieve this, the technical solution that the present invention takes is：One
Kind pharmaceutical preparation, the pharmaceutical preparation include above-mentioned Paeoniflorin nanocrystal.
Preferably, the pharmaceutical preparation is tablet, granule, capsule, injection, nasal cavity administrated preparation or preparation capable of permeating skin.
Compared with prior art, the invention has the advantages that：
Paeoniflorin nanocrystal grain size prepared by the present invention is small, can penetrate cell membrane rapidly, discharge drug in the cell,
It is rapidly reached effective concentration in vivo, improves the bioavilability of drug.Stabilizer good biocompatibility used in the present invention, low toxicity peace
Entirely, preparation provided by the invention can increase the internal external stability of Paeoniflorin.
Paeoniflorin nanocrystal prepared by the present invention, the Paeoniflorin nano-carrier prepared with other methods, it is advantageous that：
1, step is simple：The present invention, which need not be prepared separately, to be carried medicine intermediate, load medicine intermediate need not be made repeatedly to be scattered in water, be not required to
Dispersant to be added in water, colloidal dispersion need not be formed；2, auxiliary material used in the present invention is few, it is only necessary to which stabilizer reduces system
Make cost；3, the grain size of Paeoniflorin nanocrystal produced by the present invention is small compared with Paeoniflorin wheat gliadin nanoparticle, can be more preferable
Raising bioavilability.
Description of the drawings
Fig. 1 is the Paeoniflorin nanocrystal grain size distribution of embodiment 1.
Fig. 2 is the Paeoniflorin nanocrystal grain size distribution of embodiment 2.
Fig. 3 is the Paeoniflorin nanocrystal grain size distribution of embodiment 3.
Fig. 4 is the Paeoniflorin nanocrystal grain size distribution of embodiment 4.
Fig. 5 is the Paeoniflorin nanocrystal grain size distribution of embodiment 5.
Fig. 6 is the Paeoniflorin nanocrystal grain size distribution of embodiment 6.
Fig. 7 is the Paeoniflorin nanocrystal Dissolution Rate Testing curve graph of embodiment 1.
Specific implementation mode
In order to more concisely show technical scheme of the present invention, objects and advantages, with reference to specific embodiment
And attached drawing is described in further detail the present invention.
Embodiment 1
Weigh the Paeoniflorin 20mg of recipe quantity, organic solvent-acetone 0.4mL, stabilizer hydroxypropyl methylcellulose E310mg, water
20mL。
Prepare Paeoniflorin nanocrystal：
(1) in acetone by Paeoniflorin dissolving, organic phase is formed；
(2) hydroxypropyl methylcellulose E3 is dissolved in water, forms water phase；
(3) under 800 revs/min of magnetic stirring speeds, by organic phase rapid dispersion in water phase, Paeoniflorin nanometer is obtained
Crystal suspension；
(4) after filtering by above-mentioned Paeoniflorin nanocrystal suspension, it is lyophilized and nanocrystal is lyophilized to get to Paeoniflorin.
Embodiment 2
Weigh the Paeoniflorin 30mg of recipe quantity, organic solvent methanol 0.5mL, stabilizer vitamin E polyethylene glycol succinic acid
Ester 10mg, water 20mL.
Prepare Paeoniflorin nanocrystal：
(1) in methyl alcohol by Paeoniflorin dissolving, organic phase is formed；
(2) vitamin E polyethylene glycol succinic acid ester is dissolved in water, forms water phase；
(3) it under 1000 revs/min of magnetic stirring speeds, by organic phase rapid dispersion in water phase, obtains Paeoniflorin and receives
Rice crystal suspension；
(4) after filtering by above-mentioned Paeoniflorin nanocrystal suspension, it is lyophilized and nanocrystal is lyophilized to get to Paeoniflorin.
Embodiment 3
Weigh the Paeoniflorin 20mg of recipe quantity, organic solvent acetonitrile 0.8mL, stabilizer PVP K30 20mg, water 20mL.
Prepare Paeoniflorin nanocrystal：
(1) Paeoniflorin is dissolved in acetonitrile, forms organic phase；
(2) PVP K30 is dissolved in water, forms water phase；
(3) under 600 revs/min of magnetic stirring speeds, by organic phase rapid dispersion in water phase, Paeoniflorin nanometer is obtained
Crystal suspension；
(4) after filtering by above-mentioned Paeoniflorin nanocrystal suspension, it is lyophilized and nanocrystal is lyophilized to get to Paeoniflorin.
Embodiment 4
Weigh the Paeoniflorin 20mg of recipe quantity, organic solvent propylene glycol 0.6mL, stabilizer Tween 80 10mg, water 20mL.
Prepare Paeoniflorin nanocrystal：
(1) Paeoniflorin is dissolved in propylene glycol, forms organic phase；
(2) Tween 80 is dissolved in water, forms water phase；
(3) it under 1200 revs/min of magnetic stirring speeds, by organic phase rapid dispersion in water phase, obtains Paeoniflorin and receives
Rice crystal suspension；
(4) after filtering by above-mentioned Paeoniflorin nanocrystal suspension, it is lyophilized and nanocrystal is lyophilized to get to Paeoniflorin.
Embodiment 5
Weigh the Paeoniflorin 15mg of recipe quantity, organic solvent-acetone 0.5mL, stabilizer lauryl sodium sulfate 20mg, water
20mL。
Prepare Paeoniflorin nanocrystal：
(1) in acetone by Paeoniflorin dissolving, organic phase is formed；
(2) lauryl sodium sulfate is dissolved in water, forms water phase；
(3) it under 1500 revs/min of magnetic stirring speeds, by organic phase rapid dispersion in water phase, obtains Paeoniflorin and receives
Rice crystal suspension；
(4) after filtering by above-mentioned Paeoniflorin nanocrystal suspension, it is lyophilized and nanocrystal is lyophilized to get to Paeoniflorin.
Embodiment 6
The Paeoniflorin 10mg of recipe quantity, organic solvent-acetone 0.4mL, stabilizer hydroxypropyl methylcellulose E15 20mg are weighed,
Water 20mL.
Prepare Paeoniflorin nanocrystal：
(1) in acetone by Paeoniflorin dissolving, organic phase is formed；
(2) hydroxypropyl methylcellulose E15 is dissolved in water, forms water phase；
(3) it under 2000 revs/min of magnetic stirring speeds, by organic phase rapid dispersion in water phase, obtains Paeoniflorin and receives
Rice crystal suspension；
(4) after filtering by above-mentioned Paeoniflorin nanocrystal suspension, it is lyophilized and nanocrystal is lyophilized to get to Paeoniflorin.
The Paeoniflorin nanocrystal obtained in above-described embodiment is detected, to its grain size, polydispersity index PDI, molten
Out-degree is evaluated, and test method is as follows with result：
1. the measurement of grain size and polydispersity index
1mL Paeoniflorin nanocrystal solutions are taken to be placed in sample cell, using Nano-Zetasizer dynamic optical particle size determinations
Instrument measures grain size, PDI and Zeta potential, and each sample is parallel to be prepared 3 times, and each sample measures 3 times.As a result such as Fig. 1-Fig. 6 institutes
Show, average grain diameter and the PDI of each embodiment are shown in Table 1：
Table 1：The average grain diameter and PDI of each embodiment
| Embodiment | Average grain diameter (nm) | PDI |
| Embodiment 1 | 171.7 | 0.238 |
| Embodiment 2 | 149.3 | 0.068 |
| Embodiment 3 | 163.6 | 0.341 |
| Embodiment 4 | 187.5 | 0.126 |
| Embodiment 5 | 182.3 | 0.204 |
| Embodiment 6 | 163.9 | 0.242 |
The above result shows that the average grain diameter of the Paeoniflorin nanocrystal in all embodiments is respectively less than 200nm, and granularity
It is evenly distributed, wherein stabilizer used is the Paeoniflorin nanocrystal of vitamin E polyethylene glycol succinic acid ester in example 2,
Its grain size is down to 149.3nm, PDI 0.068.
2. Dissolution Rate Testing
It will implement the Chinese herbaceous peony nanocrystal in 1 and carry out Dissolution Rate Testing, according to USP XXV Type II paddle method, with dissolution
It spends analyzer and dissolution determination is carried out to Paeoniflorin nanocrystal.0.2% sodium dodecyl sulfate solution is selected to be situated between as dissolution
Matter (750mL), to form sink conditions, temperature is maintained at 37 ± 0.5 DEG C, and rotating speed is 100 revs/min.Paeoniflorin, Paeoniflorin with
Stabilizer physical mixture as a control group, took dissolution fluid 2ml at the 5th, 10,15,20,30,45 and 60 minute respectively, does not mend
Liquid.The dissolution fluid of taking-up passes through 0.45 μm of membrane filtration, discards primary filtrate, collects subsequent filtrate, uses high effective liquid chromatography for measuring
Paeoniflorin content.
The results are shown in Figure 7, and in embodiment 1, organic solvent used is acetone, under 800 revs/min of shear action
It is made Paeoniflorin nanocrystal, 15 minutes accumulative release rates are up to 91%, and the accumulative release rate of active compound and physical mixture
Only 4% or so.
Several embodiments of the invention above described embodiment only expresses, the description thereof is more specific and detailed, but simultaneously
It cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the art
It says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the protection of the present invention
Range.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (10)
1. a kind of Paeoniflorin nanocrystal, which is characterized in that the Paeoniflorin nanocrystal includes Paeoniflorin and stabilizer, described
The weight ratio of Paeoniflorin and stabilizer is 0.5~20：1.
2. Paeoniflorin nanocrystal as described in claim 1, which is characterized in that the grain size of the Paeoniflorin nanocrystal is 1-
200nm。
3. Paeoniflorin nanocrystal as described in claim 1, which is characterized in that the stabilizer is hydroxypropyl methylcellulose, hydroxyl
Propyl cellulose, polyoxyethylene polyoxypropylene block copolymer, povidone, polysorbate, vitamin E polyethylene glycol succinic acid
It is ester, tween, polyvinyl alcohol, neopelex, Arabic gum, sodium alginate, sodium carboxymethylcellulose, glucan, sweet
Reveal alcohol, tragacanth, at least one of poly yamanashi esters, Emulsifier EL-60 class.
4. Paeoniflorin nanocrystal as described in claim 1, which is characterized in that the stabilizer is hydroxypropyl methylcellulose, gathers
In ethylene oxide polyoxypropylene block copolymers, povidone, vitamin E polyethylene glycol succinic acid ester, tween or polyvinyl alcohol extremely
Few one kind.
5. a kind of preparation method of Paeoniflorin nanocrystal as described in any one of claims 1-3, which is characterized in that including following
Step：
(1) Paeoniflorin is dissolved in organic solvent, forms organic phase solution A；
(2) stabilizer is added in water, forms aqueous phase solution B；
(3) high-speed stirred solution B, while solution A is injected, Paeoniflorin crystal is precipitated, obtains Paeoniflorin nanocrystal suspension；
(4) after filtering by above-mentioned Paeoniflorin nanocrystal suspension, it is lyophilized and nanocrystal is lyophilized to get Paeoniflorin.
6. the preparation method of Paeoniflorin nanocrystal as claimed in claim 5, which is characterized in that the water is distilled water or goes
Ionized water.
7. the preparation method of Paeoniflorin nanocrystal as claimed in claim 5, which is characterized in that the organic solvent be without
Methanol, acetone, acetonitrile, ethyl acetate, propylene glycol, n-butanol or the chloroform of water.
8. the preparation method of Paeoniflorin nanocrystal as claimed in claim 5, which is characterized in that stirring in the step (3)
It is 400-2000 revs/min to mix speed.
9. a kind of pharmaceutical preparation, which is characterized in that include the Paeoniflorin nanocrystal as described in claim 1-4 is any.
10. pharmaceutical preparation as claimed in claim 9, which is characterized in that the pharmaceutical preparation is tablet, granule, capsule, note
Penetrate agent, nasal cavity administrated preparation or preparation capable of permeating skin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810597904.5A CN108567763A (en) | 2018-06-12 | 2018-06-12 | A kind of Paeoniflorin nanocrystal and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810597904.5A CN108567763A (en) | 2018-06-12 | 2018-06-12 | A kind of Paeoniflorin nanocrystal and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108567763A true CN108567763A (en) | 2018-09-25 |
Family
ID=63573112
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810597904.5A Pending CN108567763A (en) | 2018-06-12 | 2018-06-12 | A kind of Paeoniflorin nanocrystal and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108567763A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112426427A (en) * | 2020-06-24 | 2021-03-02 | 中国人民解放军军事科学院军事医学研究院 | Application of midazolam nanocrystal in preparation of medicine for improving blood brain barrier permeability |
| CN113069415A (en) * | 2021-04-09 | 2021-07-06 | 湖北中医药大学 | Insoluble drug nanosuspension and preparation method thereof |
| CN114588196A (en) * | 2020-12-03 | 2022-06-07 | 山东益康药业股份有限公司 | A kind of total aglycone of scutellariae and its preparation method and application |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101322682A (en) * | 2008-07-29 | 2008-12-17 | 沈阳药大制剂新技术有限公司 | Preparation method of poorly soluble drug nanoparticles |
| WO2010151653A2 (en) * | 2009-06-24 | 2010-12-29 | Board Of Supervisors Of Louisiana State University & Agricultural & Mechanical College | Terpene glycosides and their combinations as solubilizing agents |
| CN103637984A (en) * | 2013-12-24 | 2014-03-19 | 宁夏医科大学 | Baicalin nanometer crystal and preparation method thereof |
| CN106265599A (en) * | 2016-08-29 | 2017-01-04 | 苏州求是玉泉健康科技有限公司 | The preparation technology of a kind of peoniflorin wheat gliadin nanoparticle and purposes |
-
2018
- 2018-06-12 CN CN201810597904.5A patent/CN108567763A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101322682A (en) * | 2008-07-29 | 2008-12-17 | 沈阳药大制剂新技术有限公司 | Preparation method of poorly soluble drug nanoparticles |
| WO2010151653A2 (en) * | 2009-06-24 | 2010-12-29 | Board Of Supervisors Of Louisiana State University & Agricultural & Mechanical College | Terpene glycosides and their combinations as solubilizing agents |
| CN103637984A (en) * | 2013-12-24 | 2014-03-19 | 宁夏医科大学 | Baicalin nanometer crystal and preparation method thereof |
| CN106265599A (en) * | 2016-08-29 | 2017-01-04 | 苏州求是玉泉健康科技有限公司 | The preparation technology of a kind of peoniflorin wheat gliadin nanoparticle and purposes |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112426427A (en) * | 2020-06-24 | 2021-03-02 | 中国人民解放军军事科学院军事医学研究院 | Application of midazolam nanocrystal in preparation of medicine for improving blood brain barrier permeability |
| CN114588196A (en) * | 2020-12-03 | 2022-06-07 | 山东益康药业股份有限公司 | A kind of total aglycone of scutellariae and its preparation method and application |
| CN114588196B (en) * | 2020-12-03 | 2024-04-05 | 山东益康药业股份有限公司 | A kind of total aglycone of scutellaria baicalensis and its preparation method and application |
| CN113069415A (en) * | 2021-04-09 | 2021-07-06 | 湖北中医药大学 | Insoluble drug nanosuspension and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Pharmacokinetics and biodistribution of surface modification polymeric nanoparticles | |
| CN104136012B (en) | The method that preparation is mounted with the nano particle of active material | |
| CN101053553B (en) | Biodegradable fluorourcacil polyester medicine-carried nanospheres and its preparation method | |
| CN105106117B (en) | A kind of quercetin nano grain and preparation method thereof | |
| CN103550223B (en) | The purposes of the eye medicinal of erythrocyte membrane parcel | |
| CN108567763A (en) | A kind of Paeoniflorin nanocrystal and preparation method thereof | |
| CN104398477B (en) | A kind of usnic acid nanosuspension and its production and use | |
| CN108186605B (en) | Medicine-carrying nano-particles based on tannic acid and preparation method and application thereof | |
| CN101259279A (en) | Biocompatible monodisperse nanopolymer carrier and its preparation and drug loading method | |
| US9283190B2 (en) | Highly efficient and long-acting slow-release formulation of poorly soluble drugs and preparation method thereof | |
| Contado et al. | Influence of secondary preparative parameters and aging effects on PLGA particle size distribution: a sedimentation field flow fractionation investigation | |
| CN112386586A (en) | Preparation method of albumin nanoparticles | |
| Bao et al. | A facile strategy to generate high drug payload celecoxib micelles for enhanced corneal permeability | |
| Yan et al. | Dual drug-loaded core-shell nanofibers membranes via emulsion electrospinning and their controllable sustained release property | |
| CN106389336B (en) | Liquid crystal nanoparticle precursor particles, self-assembled liquid crystal nanoparticles and preparation method thereof | |
| Shi et al. | Progress in the study of drug nanocrystals | |
| CN108379227B (en) | Rutin-entrapped polymer micelle and preparation method thereof | |
| CN117530933A (en) | Pirenpazide long-acting slow-release microsphere, preparation method and slow-release injection | |
| CN102008454A (en) | Daidzein-entrapped PLGA nanoparticles and preparation method thereof | |
| Mandal et al. | Development and physical characterization of chloramphenicol loaded biodegradable nanoparticles for prolonged release | |
| CN113546060B (en) | Naltrexone microspheres | |
| CN108498455A (en) | A kind of water-soluble medicament nano crystalline substance of oiliness and preparation method thereof | |
| CN107157930A (en) | A kind of mithramycin nano granule suspension and preparation method thereof | |
| CN102727446B (en) | Solid preparation containing poorly soluble drug and preparation method thereof | |
| CN107582542B (en) | PLGA nano-microspheres of Delamani and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180925 |