CN111249322B - 一种芹菜籽油固体分散体及其制备方法 - Google Patents
一种芹菜籽油固体分散体及其制备方法 Download PDFInfo
- Publication number
- CN111249322B CN111249322B CN201911280118.3A CN201911280118A CN111249322B CN 111249322 B CN111249322 B CN 111249322B CN 201911280118 A CN201911280118 A CN 201911280118A CN 111249322 B CN111249322 B CN 111249322B
- Authority
- CN
- China
- Prior art keywords
- seed oil
- celery seed
- solid dispersion
- celery
- solubility
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000001387 apium graveolens Substances 0.000 title claims abstract description 132
- 235000015112 vegetable and seed oil Nutrition 0.000 title claims abstract description 130
- 239000007962 solid dispersion Substances 0.000 title claims abstract description 95
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 238000001694 spray drying Methods 0.000 claims abstract description 37
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 28
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 28
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 28
- 239000012876 carrier material Substances 0.000 claims abstract description 14
- 239000007864 aqueous solution Substances 0.000 claims abstract description 8
- 239000007787 solid Substances 0.000 claims abstract description 8
- 239000000843 powder Substances 0.000 claims abstract description 7
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 30
- 238000000889 atomisation Methods 0.000 claims description 26
- 238000002347 injection Methods 0.000 claims description 21
- 239000007924 injection Substances 0.000 claims description 21
- 239000000706 filtrate Substances 0.000 claims description 19
- 238000001914 filtration Methods 0.000 claims description 19
- 240000007087 Apium graveolens Species 0.000 claims description 15
- 235000015849 Apium graveolens Dulce Group Nutrition 0.000 claims description 13
- 235000010591 Appio Nutrition 0.000 claims description 13
- 239000007921 spray Substances 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 238000007873 sieving Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 2
- 230000002572 peristaltic effect Effects 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 19
- 229920000858 Cyclodextrin Polymers 0.000 abstract description 10
- 239000000341 volatile oil Substances 0.000 abstract description 7
- YZOUYRAONFXZSI-SBHWVFSVSA-N (1S,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31S,33R,35R,36R,37S,38R,39S,40R,41S,42R,43S,44R,45S,46R,47S,48R,49S)-5,10,15,20,25,30,35-heptakis(hydroxymethyl)-37,39,40,41,42,43,44,45,46,47,48,49-dodecamethoxy-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,38-diol Chemical compound O([C@@H]([C@H]([C@@H]1OC)OC)O[C@H]2[C@@H](O)[C@@H]([C@@H](O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3O)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O3)O[C@@H]2CO)OC)[C@H](CO)[C@H]1O[C@@H]1[C@@H](OC)[C@H](OC)[C@H]3[C@@H](CO)O1 YZOUYRAONFXZSI-SBHWVFSVSA-N 0.000 abstract description 5
- SATHPVQTSSUFFW-UHFFFAOYSA-N 4-[6-[(3,5-dihydroxy-4-methoxyoxan-2-yl)oxymethyl]-3,5-dihydroxy-4-methoxyoxan-2-yl]oxy-2-(hydroxymethyl)-6-methyloxane-3,5-diol Chemical compound OC1C(OC)C(O)COC1OCC1C(O)C(OC)C(O)C(OC2C(C(CO)OC(C)C2O)O)O1 SATHPVQTSSUFFW-UHFFFAOYSA-N 0.000 abstract description 5
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 abstract description 5
- 229920000189 Arabinogalactan Polymers 0.000 abstract description 5
- 239000001904 Arabinogalactan Substances 0.000 abstract description 5
- 239000001116 FEMA 4028 Substances 0.000 abstract description 5
- 229920001612 Hydroxyethyl starch Polymers 0.000 abstract description 5
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 abstract description 5
- 229940043377 alpha-cyclodextrin Drugs 0.000 abstract description 5
- 235000019312 arabinogalactan Nutrition 0.000 abstract description 5
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 abstract description 5
- 235000011175 beta-cyclodextrine Nutrition 0.000 abstract description 5
- 229960004853 betadex Drugs 0.000 abstract description 5
- 229940050526 hydroxyethylstarch Drugs 0.000 abstract description 5
- 229920006316 polyvinylpyrrolidine Polymers 0.000 abstract description 5
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 abstract description 5
- 210000004400 mucous membrane Anatomy 0.000 abstract description 3
- 239000002245 particle Substances 0.000 abstract description 3
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 abstract description 2
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 abstract description 2
- 230000036772 blood pressure Effects 0.000 abstract description 2
- 230000007794 irritation Effects 0.000 abstract description 2
- 229940116269 uric acid Drugs 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 60
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 43
- 229940117893 apigenin Drugs 0.000 description 43
- XADJWCRESPGUTB-UHFFFAOYSA-N apigenin Natural products C1=CC(O)=CC=C1C1=CC(=O)C2=CC(O)=C(O)C=C2O1 XADJWCRESPGUTB-UHFFFAOYSA-N 0.000 description 43
- 235000008714 apigenin Nutrition 0.000 description 43
- 229940087305 limonene Drugs 0.000 description 30
- 235000001510 limonene Nutrition 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 238000012360 testing method Methods 0.000 description 19
- 239000012153 distilled water Substances 0.000 description 18
- 238000003756 stirring Methods 0.000 description 17
- 238000004090 dissolution Methods 0.000 description 10
- 238000005063 solubilization Methods 0.000 description 7
- 230000007928 solubilization Effects 0.000 description 7
- 238000001514 detection method Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- 239000006069 physical mixture Substances 0.000 description 4
- 230000003381 solubilizing effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 201000001431 Hyperuricemia Diseases 0.000 description 3
- 238000000498 ball milling Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 229920000856 Amylose Polymers 0.000 description 1
- 241000208173 Apiaceae Species 0.000 description 1
- 235000002764 Apium graveolens Nutrition 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 235000019484 Rapeseed oil Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- -1 cyclic polysaccharide Chemical class 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 238000004134 energy conservation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Images
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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/35—Extraction with lipophilic solvents, e.g. Hexane or petrol ether
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Preparation (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
本发明公开了一种芹菜籽油固体分散体及其制备方法。由芹菜籽油和高分子载体材料的饱和水溶液混合均质后经喷雾干燥后获得的粉末状固体;所述固体分散体中芹菜籽油与高分子载体材料的质量比为1:1‑100;所述高分子载体材料选自阿拉伯半乳聚糖、羟乙基淀粉、聚乙烯吡咯烷酮K30、透明质酸、α‑环糊精、β‑环糊精、羟丙基‑β‑环糊精或甲基‑β‑环糊精中的一种。本发明通过喷雾干燥,获得干燥微小粉粒,通过载体的包合作用形成复合物,抑制芹菜籽油的挥发。对降尿酸,降血压效果显著,能提高精油有效剂量并掩盖其刺激性气味,降低对人体黏膜的刺激性,市场前景广阔。
Description
技术领域
本发明属于药物制剂技术领域,具体涉及一种能够提高芹菜籽油水溶液溶出度,并降低其挥发性的芹菜籽油固体分散体及其制备方法。
背景技术
随着人们生活水平的提高,生活压力增大,人们对生活方式和饮食习惯的不重视,使得高尿酸血症,三高人群不断增多,但现有化学药物仍无法很好的对其进行治疗,需长期用药,副作用较大。因此急需一种安全有效的药物保健品对其进行预防和治疗。
芹菜籽油,由伞形花科草本植物芹菜(Apium graveolens.Linn)的种子中蒸馏提取得到的棕绿色油状液体,具有强烈持久辛香、药草香气,其主要有效成分为柠檬烯(31%),芹菜甲素(13%)。研究表明,芹菜籽油具有很好的利尿抗菌作用,不易产生耐药性,对人体无害。对于治疗高尿酸血症,高血脂,高血压有特别疗效。但芹菜籽油的有效成分水溶性差,在水溶液中以油滴的形式存在,且气味刺激,沸点低,易挥发,直接服用对黏膜有刺激性损伤,极大的限制了芹菜籽油的应用,药效降低。因此开发水溶性不易挥发的芹菜籽油固体分散体对解决上述问题具有实际的意义。
传统的固体分散体的制备方法有熔融法,溶剂法,超声法,冷冻干燥法等,这些方法需实验要求较高,时间较长,工业化困难,而且有制备过程复杂,过程中芹菜籽油的损失率较高,所以如何避免上述问题是芹菜籽油固体分散体开发中面临的最大障碍。然而利用冷冻干燥法制备固体分散体,过程简单,速度快,含水量低,固体分散体粒径更小,更均匀,水溶性好,精油损失减少,易工业化生产,无需使用有机溶剂,更加绿色安全。因此,该方法不仅是对传统固体分散体制备工艺创新,同时也实现了芹菜籽油固体分散体制备工艺的重大突破。
发明内容
针对现有技术中存在的芹菜籽油水溶性差且易挥发等问题,本发明的目的在于提供一种芹菜籽油固体分散体及其制备方法,它能提高芹菜籽油水溶液溶出度,并降低其挥发性,其制备中避免了有机溶剂的使用,达到绿色环保的要求。
一种芹菜籽油固体分散体,由芹菜籽油和高分子载体材料的饱和水溶液混合均质后经喷雾干燥后获得的粉末状固体;所述的固体分散体中芹菜籽油与高分子载体材料的质量比为1:1-100;所述的高分子载体材料选自阿拉伯半乳聚糖、羟乙基淀粉、聚乙烯吡咯烷酮K30、透明质酸以及α-环糊精,β-环糊精,羟丙基-β-环糊精或甲基-β-环糊精中的一种。
进一步,所述的芹菜籽油提取自芹菜的种子,提取工艺采用传统的溶剂萃取法,所述的溶剂萃取法为:芹菜籽粉碎后过40目筛,采用正己烷冷浸提取4h,重复三次,减压蒸馏除去正己烷,所得棕绿色油状液体即为芹菜籽油。
进一步,所述的芹菜籽油与高分子载体材料的质量比优选为1:10。
进一步,所述芹菜籽油固体分散体的制备方法,具体按照如下步骤进行:按质量比配置芹菜籽油和高分子载体材料的饱和水溶液的混合物进行过滤,所得滤液通入喷雾干燥机,在0.15-4BAR雾化压力下进行喷雾干燥,得到芹菜籽油固体粉末;所述的喷雾干燥机的进风口温度为100-220℃,进样量为500-1800mL/h,出风口温度为60-90℃,风机功率为0.5-1.5KW。
进一步,喷雾干燥机为压力式喷雾干燥,进风口温度优选为140℃。
进一步,所述的喷雾干燥进样方式为蠕动泵进样,进样量优选为1000mL/h。
进一步,所述的喷雾干燥过程中,雾化压力优选为2.5BAR。
进一步,所述的喷雾干燥过程中,出风口温度优选为85℃。
进一步,所述的喷雾干燥过程中,风机功率优选为1.0KW。
进一步,所述的高分子载体材料优选为透明质酸。
本发明所述的固体分散体制成的临床上的药物剂型包括散剂、颗粒剂或水剂,还可以是其他固体口服制剂,主要为人用内服外用药。
通过采用上述技术,与现有技术相比,本发明有益效果体现在:
1)本发明的芹菜籽油固体分散体,它可以制成各种药物剂型,如散剂、颗粒剂或水剂,还可以是其他固体口服制剂,主要为人用内服外用药,其使用方便,灵活性好,对降尿酸,降血压效果显著,能够提高精油有效剂量并且掩盖其刺激性气味,降低对人体黏膜的刺激性,其市场前景广阔;
2)本发明通过限定的制备方法制备固体分散体,其操作简单,与捏合法、冷冻干燥法等常规制备方法相比避免了使用有机溶剂,即避免了除去溶剂的过程中极易导致的挥发油损失、对环境产生污染等问题;
3)本发明通过喷雾干燥快速去除水分,获得干燥微小粉粒,增加药物与载体的分散均一度,增加可湿润性等作用促进芹菜籽油的溶出,并且通过载体的包合作用形成复合物,从而抑制芹菜籽油的挥发,大大减少芹菜籽油在制剂制备过程中的损耗,具有操作简单、制备时间短、生产安全可靠、生产成本低、污染少等优点,是一种具有较好推广应用前景的固体分散体的制备方法。
附图说明
图1是不同高分子载体制备的固体分散体中芹菜籽油的芹菜甲素与柠檬烯溶解度(溶解度测定方法见实施例1);
图2是不同比例的透明质酸与芹菜籽油制备的固体分散体中芹菜籽油的芹菜甲素与柠檬烯溶解度;
图3是喷雾干燥机进风口温度对制备的固体分散体中芹菜籽油的芹菜甲素与柠檬烯溶解度的影响;
图4是喷雾干燥机进料量对制备的固体分散体中芹菜籽油的芹菜甲素与柠檬烯溶解度的影响;
图5是喷雾干燥机雾化压力对制备的固体分散体中芹菜籽油的芹菜甲素与柠檬烯溶解度的影响;
图6是喷雾干燥机出风口温度对制备的固体分散体中芹菜籽油的芹菜甲素与柠檬烯溶解度的影响;
图7是喷雾干燥机风机功率对制备的固体分散体中芹菜籽油的芹菜甲素与柠檬烯溶解度的影响;
图8是芹菜籽油与实施例8固体分散体中芹菜甲素的溶出曲线;
图9是芹菜籽油与透明质酸1:10物理混合物与实施例8固体分散体放置不同时间后其中芹菜甲素的剩余含量曲线图。
具体实施方式
下面结合具体实施例对本发明进行进一步描述,但本发明的保护范围并不仅限于此:
本发明所述的芹菜籽油的提取方法为:芹菜籽粉碎后过40目筛,采用正己烷冷浸提取4h,重复三次,减压蒸馏除去正己烷,所得棕绿色油状液体即为芹菜籽油。
实施例1:羟丙基-β-环糊精为载体的固体分散体的制备(1:10)
在烧杯中加入羟丙基-β-环糊精(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.6g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。取适量该粉末置于锥形瓶中,加入10mL蒸馏水,于摇床37℃,150rpm条件下,震荡24h。取上清液过0.45μm膜后使用高效液相色谱检测其中主要抗菌成分芹菜甲素与柠檬烯的浓度,以此来作为芹菜甲素与柠檬烯的溶解度,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为6.65g/L,柠檬烯的溶解度为7.28g/L。
实施例2:α-环糊精为载体的固体分散体的制备(1:10)
在烧杯中加入α-环糊精(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.6g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。溶解度测定的步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为5.10g/L,柠檬烯的溶解度为6.78g/L。
实施例3:β-环糊精为载体的固体分散体的制备(1:10)
在烧杯中加入β-环糊精(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.6g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为2.82g/L,柠檬烯的溶解度为3.34g/L。
实施例4:甲基-β-环糊精为载体的固体分散体的制备(1:10)
在烧杯中加入甲基-β-环糊精(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.6g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为5.03g/L,柠檬烯的溶解度为6.55g/L。
实施例5:阿拉伯半乳聚糖为载体的固体分散体的制备(1:10)
在烧杯中加入阿拉伯半乳聚糖(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.6g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为4.35g/L,柠檬烯的溶解度为5.11g/L。
实施例6:聚乙烯吡咯烷酮K30为载体的固体分散体的制备(1:10)
在烧杯中加入聚乙烯吡咯烷酮K30(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.6g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为2.23g/L,柠檬烯的溶解度为3.06g/L。
实施例7:羟乙基淀粉为载体的固体分散体的制备(1:10)
在烧杯中加入羟乙基淀粉(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.6g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为4.77g/L,柠檬烯的溶解度为5.26g/L。
实施例8:透明质酸为载体的固体分散体的制备(1:10)
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.6g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为8.12g/L,柠檬烯的溶解度为9.71g/L。
实施例9:固体分散体载体优选
选择阿拉伯半乳聚糖(支链多糖)、羟乙基淀粉(直链多糖)、聚乙烯吡咯烷酮K30(聚维酮)以及透明质酸(酸性粘多糖)、α-环糊精、β-环糊精、羟丙基-β-环糊精、甲基-β-环糊精(环状多糖)等不同空间结构的高分子作为载体,制备芹菜籽油固体分散体,并通过其中芹菜甲素与柠檬烯的溶解度,如图1所示,优选高分子载体为透明质酸。以其为载体制备的芹菜籽油固体分散体中芹菜甲素溶解度8.12g/L,柠檬烯的溶解度为9.71g/L。
实施例10:透明质酸为载体的固体分散体的制备(1:1)
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(6.0g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为3.67g/L,柠檬烯的溶解度为4.12g/L。
实施例11:透明质酸为载体的固体分散体的制备(1:5)
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.2g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为6.88g/L,柠檬烯的溶解度为7.34g/L。
实施例12:透明质酸为载体的固体分散体的制备(1:50)
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.12g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为8.01g/L,柠檬烯的溶解度为9.52g/L。
实施例13:透明质酸为载体的固体分散体的制备(1:100)
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.06g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,试验结果表明,制备的芹菜籽油固体分散体中芹菜甲素的溶解度为8.09g/L,柠檬烯的溶解度为9.60g/L。
实施例14:透明质酸用量的优选
如图2所示,透明质酸用量提高能够显著的增加芹菜籽油中芹菜甲素与柠檬烯的溶解度,但是当用量提升至一定程度后,增溶作用趋于平缓,所以考虑到用药剂量问题,优选芹菜籽油:透明质酸=1:10作为最佳的药辅比。
实施例15:喷雾干燥进风口温度的优选
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.06g),不断搅拌30min后过滤。将滤液进行喷雾干燥,控制进风口温度分别为:100℃,110℃,120℃,140℃,160℃,180℃,200℃,220℃,进样量为1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,制备的芹菜籽油固体分散体中芹菜甲素与柠檬烯的溶解度如图3。试验结果表明,进风口温度过低,样品含水量过高,喷雾干燥效果差,增溶效果差;而进风口温度过高,造成样品受热分解,含量降低,增溶的效果变差,所以优选进风口温度为140℃。
实施例16:喷雾干燥进料量的优选
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.06g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,控制进样量分别为500ml/h,600ml/h,700ml/h,800ml/h,1000ml/h,1200ml/h,1400ml/h,1600ml/h,1800ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,制备的一系列芹菜籽油固体分散体中芹菜甲素与柠檬烯的溶解度如图4。试验结果表明,随着进样量的增加,溶解度平稳增加,但在1000ml/h以后便开始明显降低,这是因为进样量过大,导致干燥不完全,含水量高,产率低,增溶效果降低。所以优选进样量为1000ml/h。
实施例17:喷雾干燥雾化压力的优选
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.06g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为1000ml/h,控制雾化压力分别为:0.15BAR,1.0BAR,2.0BAR,2.5BAR,3.0BAR,3.5BAR,4BAR,出风口温度为:85℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,不同球磨时间下的芹菜籽油固体分散体中芹菜甲素与柠檬烯的溶解度如图5。试验结果表明,雾化压力过小,进料液滴比表面积小,不能进行充分的热交换,干燥效果差,粒径较大,导致增溶效果差;而随着雾化压力的增大,增溶效果逐渐趋于平缓,所以综合考虑节约能源与机器保养,优选雾化压力为2.5BAR。
实施例18:喷雾干燥出风口温度的优选
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.06g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为:1000ml/h,雾化压力为:2.5BAR,控制出风口温度分别为:60℃,65℃,70℃,75℃,80℃,85℃,90℃,风机功率为:1.0KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,不同球磨时间下的芹菜籽油固体分散体中芹菜甲素与柠檬烯的溶解度如图6。试验结果表明,出风口温度过小,干燥不充分,导致增溶效果差;而出风口温度过高,会导致有效成分损失,增溶效果降低,所以优选出风口温度为85℃。
实施例19:喷雾干燥风机功率的优选
在烧杯中加入透明质酸(6.0g),加入蒸馏水至饱和,缓慢加入芹菜籽油(0.06g),不断搅拌30min后过滤。将滤液进行喷雾干燥,进风口温度为:140℃,进样量为:1000ml/h,雾化压力为:2.5BAR,出风口温度为:85℃,控制风机功率分别为:0.5KW,0.7KW,1.0KW,1.3KW,1.5KW。得到芹菜籽油固体分散体。检测溶解度步骤同实施例1,不同球磨时间下的芹菜籽油固体分散体中芹菜甲素与柠檬烯的溶解度如图7。试验结果表明,风机功率过低,空气流量较小,效率低,有效成分易损失,导致增溶效果较差;而风机功率过高,空气流量过快,会导致干燥不充分,包合较差,增溶效果低,所以优选风机功率为1KW。
实施例20:溶出度实验
以芹菜籽油精油中主要成分芹菜甲素为指标,测定固体分散体中芹菜籽油的溶出速率,其方法如下:分别精密称取芹菜籽油(50mg)、实施例8(0.55g,相当于药物约50mg)以及芹菜籽油(50mg)与透明质酸(0.5g)物理混合物进行溶出度(一定量药在不同时间内的溶解度曲线)实验,采用桨法:即以900mL纯化水为溶出介质,温度为37℃,转速100rpm,溶出时间120min;分别于5min,10min,20min,30min,60min,75min,90min和120min时取各溶液5ml,取样后随即向溶出槽中补加37℃纯化水5ml,取样液经0.45um的微孔滤膜滤过后作为供试品,采用HPLC进行其中芹菜甲素含量的检测。获得以溶解度为衡量指标的芹菜籽油中代表物质芹菜甲素的溶出曲线见图8。由对芹菜籽油主要成分芹菜甲素的增溶效果可知,本实施例固体分散体不仅显著提高了芹菜籽油的溶解度,还能有效的促进芹菜籽油迅速溶出。
实施例21:芹菜籽油固体分散体的挥发性
取50mg芹菜籽油,使用95%的乙醇溶解,定容至100mL,稀释至一定的浓度,记下稀释倍数,使用HPLC测定其中芹菜甲素的质量m0。随后分别取芹菜籽油与透明质酸1:10物理混合物(5.5g,其中芹菜籽油约0.5g)和实施例8固体分散体(5.5g,其中芹菜籽油含量约为0.5g),将样品平铺使厚度均匀,放置室温(约30℃)分别于0小时,5小时,10小时,20小时,30小时取样0.55g,使用95%的乙醇溶解,定容至100mL,稀释至一定的浓度,记下稀释倍数,使用HPLC测定取样样品中芹菜甲素的质量mt,芹菜甲素剩余量=(mt/m0)×100%;由于芹菜甲素易挥发且它也是芹菜籽油中的主要成分,可以根据其含量的变化情况表征芹菜籽油的挥发情况。
其结果如图9所示,物理混合物中的芹菜籽油在30h后,其芹菜甲素剩余量仅为9.6%,而实施例8中由于载体的包合作用,芹菜籽油的挥发性大大减弱,放置30小时后,其芹菜甲素的剩余量仍可达97.3%。试验结果可以确定本实施例中分散体的形成降低了芹菜籽挥发油挥发损失,从而减轻其味道。
Claims (8)
1.一种芹菜籽油固体分散体,其特征在于:由芹菜籽油和高分子载体材料的饱和水溶液混合均质后经喷雾干燥后获得的粉末状固体;所述的固体分散体中芹菜籽油与高分子载体材料的质量比为1:10-100;所述的高分子载体材料为透明质酸;所述芹菜籽油固体分散体按如下方法制备:
按质量比配制芹菜籽油和高分子载体材料的饱和水溶液的混合物,然后过滤,所得滤液通入喷雾干燥机,在2.5-4 BAR雾化压力下进行喷雾干燥,得到芹菜籽油固体粉末;所述的喷雾干燥机的进风口温度为120-160℃,进样量为500-1200mL/h,出风口温度为60-90℃,风机功率为0.5-1.5KW。
2.如权利要求1所述的芹菜籽油固体分散体,其特征在于:所述的芹菜籽油提取自芹菜的种子,所述的提取方法为:将芹菜籽粉碎后过40目筛,采用正己烷冷浸提取4h,重复三次,减压蒸馏除去正己烷,所得油状液体即为芹菜籽油。
3.如权利要求1所述的芹菜籽油固体分散体,其特征在于:所述的芹菜籽油与高分子载体材料的质量比为1:10。
4.如权利要求1所述的芹菜籽油固体分散体,其特征在于:喷雾干燥机为压力式喷雾干燥,进风口温度为140℃,出风口温度为85℃。
5.如权利要求1所述的芹菜籽油固体分散体,其特征在于:所述的雾化压力为2.5 BAR。
6.如权利要求1所述的芹菜籽油固体分散体,其特征在于:所述的喷雾干燥进样方式为蠕动泵进样,所述进样量为1000mL/h。
7.如权利要求1所述的芹菜籽油固体分散体,其特征在于:所述的喷雾干燥过程中,所述风机功率为1.0 KW。
8.一种包含如权利要求1~3任一项所述的芹菜籽油固体分散体的制剂,其特征在于:药物剂型为散剂、颗粒剂或其他固体口服制剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911280118.3A CN111249322B (zh) | 2019-12-13 | 2019-12-13 | 一种芹菜籽油固体分散体及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911280118.3A CN111249322B (zh) | 2019-12-13 | 2019-12-13 | 一种芹菜籽油固体分散体及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111249322A CN111249322A (zh) | 2020-06-09 |
CN111249322B true CN111249322B (zh) | 2022-02-11 |
Family
ID=70945067
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911280118.3A Active CN111249322B (zh) | 2019-12-13 | 2019-12-13 | 一种芹菜籽油固体分散体及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111249322B (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106420633A (zh) * | 2016-12-20 | 2017-02-22 | 广州中大南沙科技创新产业园有限公司 | 固体分散体及其制备方法和应用 |
CN107496361A (zh) * | 2017-08-11 | 2017-12-22 | 浙江工业大学 | 一种百里香精油固体分散体及其制备方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110025644A (zh) * | 2019-04-02 | 2019-07-19 | 江苏圣典医药科技有限公司 | 一种具有抗衰老作用的复合芹菜籽油脂肪乳制剂及其制备方法 |
-
2019
- 2019-12-13 CN CN201911280118.3A patent/CN111249322B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106420633A (zh) * | 2016-12-20 | 2017-02-22 | 广州中大南沙科技创新产业园有限公司 | 固体分散体及其制备方法和应用 |
CN107496361A (zh) * | 2017-08-11 | 2017-12-22 | 浙江工业大学 | 一种百里香精油固体分散体及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN111249322A (zh) | 2020-06-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102391385B (zh) | 一种霍山石斛中生物活性多糖的提取、纯化方法 | |
Ding et al. | Kinetics of ultrasound-assisted extraction of flavonoids and triterpenes and structure characterization of Chinese northeast black bee propolis | |
CN102805767B (zh) | 具有抗淋球菌作用的热淋清颗粒原料头花蓼提取物 | |
CN111249322B (zh) | 一种芹菜籽油固体分散体及其制备方法 | |
CN102488712A (zh) | 一种人工牛黄包合物、其制备方法及其应用 | |
CN105902562A (zh) | 一种葡甘露聚糖在制备防治白细胞减少症药物中的应用 | |
CN1850838A (zh) | 一种野黄芩苷原料药的制备方法 | |
CN103977359B (zh) | 一种提高机体免疫力的中兽药组合物及其制备方法和用途 | |
CN102805836B (zh) | 一种治疗原发性肝癌的中药组合物及其制备方法 | |
CN100581587C (zh) | 一种综合生产利用纳米生物活性材料的方法 | |
CN107802678A (zh) | 一种喉康散的制备方法 | |
CN103623345B (zh) | 抗病毒口服液的制备方法 | |
CN113712999A (zh) | 一种壮药血党干膏粉在制备抗炎镇痛药物中的应用 | |
CN1169873A (zh) | 一种治疗皮肤病的药物及制备方法 | |
CN1552363A (zh) | 辛芳鼻炎丸及制备方法 | |
CN101647997A (zh) | 感冒疏风胶囊及其制备方法和质量控制方法 | |
CN112402515A (zh) | 一种含虫类药中药提取物及其制剂的制备方法 | |
CN107626220B (zh) | 一种促进黄酮或苷类化合物溶解的方法及其应用 | |
CN111053795A (zh) | 一种四季青提取物的制备方法及其应用 | |
CN1267120C (zh) | 一种鱼腥草冻干粉针剂及其制备方法 | |
CN1267102C (zh) | 一种具有抗病毒作用的复合物及其制备方法 | |
CN1456236A (zh) | 妇乐泡腾颗粒的制备方法 | |
CN1739748A (zh) | 一种感冒治疗药物及其制备方法 | |
CN108283680A (zh) | 血竭粉直接口服中药饮片 | |
CN1456231A (zh) | 寒痹停胶囊的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |