CN101045134A - Method for preparing medicine to treat atherosclerosis - Google Patents
Method for preparing medicine to treat atherosclerosis Download PDFInfo
- Publication number
- CN101045134A CN101045134A CN 200710098038 CN200710098038A CN101045134A CN 101045134 A CN101045134 A CN 101045134A CN 200710098038 CN200710098038 CN 200710098038 CN 200710098038 A CN200710098038 A CN 200710098038A CN 101045134 A CN101045134 A CN 101045134A
- Authority
- CN
- China
- Prior art keywords
- filtrate
- thick paste
- coating
- controlled
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims description 52
- 201000001320 Atherosclerosis Diseases 0.000 title abstract description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 178
- 239000000463 material Substances 0.000 claims abstract description 50
- 238000001035 drying Methods 0.000 claims abstract description 49
- 239000006228 supernatant Substances 0.000 claims abstract description 21
- 239000007788 liquid Substances 0.000 claims abstract description 20
- 238000000576 coating method Methods 0.000 claims description 117
- 239000011248 coating agent Substances 0.000 claims description 115
- 239000000706 filtrate Substances 0.000 claims description 90
- 239000008187 granular material Substances 0.000 claims description 77
- 239000000284 extract Substances 0.000 claims description 74
- 238000003756 stirring Methods 0.000 claims description 48
- 238000002360 preparation method Methods 0.000 claims description 45
- 230000008901 benefit Effects 0.000 claims description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
- 238000010438 heat treatment Methods 0.000 claims description 36
- 229940079593 drug Drugs 0.000 claims description 32
- 239000007941 film coated tablet Substances 0.000 claims description 32
- 238000009501 film coating Methods 0.000 claims description 32
- 239000003826 tablet Substances 0.000 claims description 32
- 239000000725 suspension Substances 0.000 claims description 31
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 30
- 230000003143 atherosclerotic effect Effects 0.000 claims description 19
- -1 filter Substances 0.000 claims description 19
- 239000002244 precipitate Substances 0.000 claims description 19
- 239000007921 spray Substances 0.000 claims description 19
- 241000756943 Codonopsis Species 0.000 claims description 18
- 241000628997 Flos Species 0.000 claims description 18
- 239000009636 Huang Qi Substances 0.000 claims description 18
- 239000000890 drug combination Substances 0.000 claims description 18
- 239000012530 fluid Substances 0.000 claims description 18
- 238000004064 recycling Methods 0.000 claims description 18
- 238000001291 vacuum drying Methods 0.000 claims description 18
- 239000010409 thin film Substances 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 239000007888 film coating Substances 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 15
- 229920002472 Starch Polymers 0.000 claims description 15
- UHZZMRAGKVHANO-UHFFFAOYSA-M chlormequat chloride Chemical compound [Cl-].C[N+](C)(C)CCCl UHZZMRAGKVHANO-UHFFFAOYSA-M 0.000 claims description 15
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 15
- 238000004090 dissolution Methods 0.000 claims description 15
- 238000005469 granulation Methods 0.000 claims description 15
- 230000003179 granulation Effects 0.000 claims description 15
- 235000019359 magnesium stearate Nutrition 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 15
- 239000008188 pellet Substances 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 239000000741 silica gel Substances 0.000 claims description 15
- 229910002027 silica gel Inorganic materials 0.000 claims description 15
- 239000008107 starch Substances 0.000 claims description 15
- 235000019698 starch Nutrition 0.000 claims description 15
- 210000002784 stomach Anatomy 0.000 claims description 15
- 238000005303 weighing Methods 0.000 claims description 15
- 239000000080 wetting agent Substances 0.000 claims description 15
- 230000002572 peristaltic effect Effects 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 14
- 239000002671 adjuvant Substances 0.000 claims description 12
- 239000006187 pill Substances 0.000 claims description 5
- 239000007901 soft capsule Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000006196 drop Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 1
- 238000000151 deposition Methods 0.000 abstract description 4
- 238000001914 filtration Methods 0.000 abstract 2
- 241000213006 Angelica dahurica Species 0.000 abstract 1
- 241000205585 Aquilegia canadensis Species 0.000 abstract 1
- 229940107666 astragalus root Drugs 0.000 abstract 1
- 238000007493 shaping process Methods 0.000 abstract 1
- 229960004756 ethanol Drugs 0.000 description 55
- 241000700159 Rattus Species 0.000 description 24
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 20
- 210000002966 serum Anatomy 0.000 description 19
- 231100000915 pathological change Toxicity 0.000 description 15
- 230000036285 pathological change Effects 0.000 description 15
- 210000000709 aorta Anatomy 0.000 description 13
- 238000012360 testing method Methods 0.000 description 11
- 102000015696 Interleukins Human genes 0.000 description 10
- 108010063738 Interleukins Proteins 0.000 description 10
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 10
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 9
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 9
- 108010023302 HDL Cholesterol Proteins 0.000 description 8
- 108010028554 LDL Cholesterol Proteins 0.000 description 8
- 238000011552 rat model Methods 0.000 description 8
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 7
- 229960002855 simvastatin Drugs 0.000 description 7
- 210000004026 tunica intima Anatomy 0.000 description 7
- 230000004087 circulation Effects 0.000 description 6
- 210000003038 endothelium Anatomy 0.000 description 6
- 208000004434 Calcinosis Diseases 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000002308 calcification Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000010408 film Substances 0.000 description 5
- 239000013618 particulate matter Substances 0.000 description 5
- 208000031481 Pathologic Constriction Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 239000012188 paraffin wax Substances 0.000 description 4
- 210000001215 vagina Anatomy 0.000 description 4
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 3
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 3
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 3
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 3
- 210000002808 connective tissue Anatomy 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 208000025494 Aortic disease Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 208000000501 Lipidoses Diseases 0.000 description 2
- 206010024585 Lipidosis Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 2
- KNAHARQHSZJURB-UHFFFAOYSA-N Propylthiouracile Chemical compound CCCC1=CC(=O)NC(=S)N1 KNAHARQHSZJURB-UHFFFAOYSA-N 0.000 description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000009514 concussion Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 239000002932 luster Substances 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 229960002662 propylthiouracil Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000012109 statistical procedure Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000018152 Cerebral disease Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 101100117236 Drosophila melanogaster speck gene Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282894 Sus scrofa domesticus Species 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 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 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 210000001765 aortic valve Anatomy 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 210000003017 ductus arteriosus Anatomy 0.000 description 1
- 210000004177 elastic tissue Anatomy 0.000 description 1
- 210000003725 endotheliocyte Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000000630 fibrocyte Anatomy 0.000 description 1
- 210000000497 foam cell Anatomy 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003118 histopathologic effect Effects 0.000 description 1
- 210000003090 iliac artery Anatomy 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 229960003753 nitric oxide Drugs 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 201000009442 piebaldism Diseases 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 235000021395 porridge Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 108700022737 rat Fat1 Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A Chinese medicine for treating atherosclerosis is prepared from 8 Chinese-medicinal materials including astragalus root, Chinese angelica root, pilose asiabell root, honeysuckle flower, etc through decocting and filtering twice, collecting liquid, concentrating, depositing in alcohol, taking supernatant, filtering for recovering alcohol, concentrating, drying, adding auxiliaries, and shaping.
Description
Technical field
The present invention relates to a kind of preparation of drug combination method, the atherosclerotic preparation of drug combination method of particularly a kind of treatment.
Background technology
Arteriosclerosis is that ductus arteriosus wall thickens, hardening, the degeneration that tube chamber dwindles and the general name of proliferative lesion, atherosclerosis (atherosclerosis) is a type common in the arteriosclerosis, for the main diseases of myocardial infarction and cerebral infarction because of.Treating atherosclerotic medicine TONGSAIMAI PIAN is State Food and Drug Administration's standard medicine, discloses the medicine composition in the standard, but does not disclose drug ratio relation and preparation method; Application number is the patent application of 03113176.X " application of TONGSAIMAI extractum in preparation treatment apoplexy medicine " by name, discloses medicine and has formed and proportion relation, but had defectives such as preparation method is simple, substantive distinguishing features is not outstanding.
Summary of the invention
The object of the invention is to provide a kind of preparation of drug combination method; Another object of the present invention is to provide a kind of treatment atherosclerotic preparation of drug combination method.
The present invention seeks to be achieved through the following technical solutions:
The atherosclerotic preparation of drug combination method of a kind of treatment of the present invention is:
A, decoction: crude drug is added in the multi-function extractor, add 4-6 times of water gaging, heating decocted 0.5-2.5 hour, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; Medicinal residues are added with the decocting that 2-4 doubly measures and boiled 0.5-1.5 hour, filter, merge with filtrate I, filtrate II, medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 50-70%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make clinical acceptable forms, include but not limited to concentrated pill, capsule, drop pill, granule, tablet, soft capsule, slow releasing agent, oral liquid or lyophilized injectable powder according to common process;
Wherein crude drug consists of: Radix Astragali 400-550 weight portion, Radix Angelicae Sinensis 400-550 weight portion, Radix Codonopsis 400-550 weight portion, Radix Scrophulariae 400-550 weight portion, Flos Lonicerae 400-550 weight portion, Herba Dendrobii 400-550 weight portion, Radix Achyranthis Bidentatae 400-550 weight portion, Radix Glycyrrhizae 400-550 weight portion.
The A-E step is preferably in the atherosclerotic preparation of drug combination method of above-mentioned a kind of treatment:
A, decoction: crude drug is added in the multi-function extractor, add 6 times of water gagings, heating decocted 0.5 hour, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 4 times of amounts boiled 0.5 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 70%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make clinical acceptable preparation according to common process.
The atherosclerotic preparation of drug combination method of a kind of treatment of the present invention A-E step is preferably:
A, decoction: crude drug is added in the multi-function extractor, add 4 times of water gagings, heating decocted 2.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 2 times of amounts boiled 1.5 hours, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 50%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make the clinical preparation of accepting according to common process.
The atherosclerotic preparation of drug combination method of a kind of treatment of the present invention A-E step is preferably:
A, decoction: crude drug is added in the multi-function extractor, add 5 times of water gagings, heating decocted 1.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 3 times of amounts boiled 1 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 60%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make the clinical preparation of accepting according to common process.
The invention described above pharmaceutical composition is made in the preparation method of Film coated tablets the E step is replaced with:
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 1-3% starch, 0.5-1.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added the 0.5-1.5% Pulvis Talci, the 0.1-0.3% magnesium stearate was mixed 10 minutes with 10-20 rev/min rotating speed start;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, with water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by the 4-5% of plain sheet weight is Opadry; The Diluted Alcohol liquid that adds 5-15% is mixed with the suspension of 10-30%, and continuous stirring 40-50 minute, stir, standby; Plain sheet is added in the coating pan, and the rotation coating pan sprays bag with the Opadry suspension of 10%-40%, and after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got clinical acceptable Film coated tablets.
The preparation method F-J step that the invention described above pharmaceutical composition is made Film coated tablets is preferably:
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 1% starch, 1.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 0.5% Pulvis Talci, 0.3% magnesium stearate was mixed 10 minutes with 10 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 4.5% of plain sheet weight is Opadry; Add 10% Diluted Alcohol liquid and be mixed with 20% suspension, continuous stirring 45 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 20% Opadry suspension, after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got clinical acceptable Film coated tablets.
The invention described above pharmaceutical composition makes that the F-J step is preferably in the preparation method of Film coated tablets:
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 3% starch, 0.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 1.5% Pulvis Talci, 0.1% magnesium stearate was mixed 10 minutes with 20 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 4% of plain sheet weight is Opadry; Add 12% Diluted Alcohol liquid and be mixed with 15% suspension, continuous stirring 48 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 12% Opadry suspension, after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got clinical acceptable Film coated tablets.
The invention described above pharmaceutical composition makes that the F-J step is preferably in the preparation method of Film coated tablets:
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 2.3% starch, 1% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 1% Pulvis Talci, 0.2% magnesium stearate was mixed 10 minutes with 13 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 5% of plain sheet weight is Opadry; Add 6% Diluted Alcohol liquid and be mixed with 28% suspension, continuous stirring 40 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 35% Opadry suspension, after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got clinical acceptable Film coated tablets.
Coating parameter when the invention described above pharmaceutical composition is made in the preparation method of Film coated tablets spray bag in the J step is: inlet temperature is 25-70 ℃, and leaving air temp is 25-60 ℃, and peristaltic pump speed is 1.0-20.0 rev/min; The sheet bed tempertaure is 25-50 ℃, 2-15 rev/min of coating pan rotating speed, and the slice temperature is below 35 ℃, 4-8 hour coating time.
Coating parametric optimization when the invention described above pharmaceutical composition is made in the preparation method of Film coated tablets spray bag in the J step is: inlet temperature is 45 ℃, and leaving air temp is 40 ℃, and peristaltic pump speed is 10.0 rev/mins; The sheet bed tempertaure is 35 ℃, 9 rev/mins of coating pan rotating speeds, and the slice temperature is below 35 ℃, 6 hours coating time.
Coating parametric optimization when the invention described above pharmaceutical composition is made in the preparation method of Film coated tablets spray bag in the J step is: inlet temperature is 60 ℃, leaving air temp is 30 ℃, peristaltic pump speed is 18.0 rev/mins, the sheet bed tempertaure is 30 ℃, 12 rev/mins of coating pan rotating speeds, the slice temperature is below 35 ℃, 5 hours coating time.
Coating parametric optimization when the invention described above pharmaceutical composition is made in the preparation method of Film coated tablets spray bag in the J step is: inlet temperature is 30 ℃, leaving air temp is 50 ℃, peristaltic pump speed is 5.0 rev/mins, the sheet bed tempertaure is 45 ℃, 5 rev/mins of coating pan rotating speeds, the slice temperature is below 35 ℃, 8 hours coating time.
Crude drug in the preparation of pharmaceutical compositions method of the present invention is formed and can also be preferably: the Radix Astragali 420 weight portions, Radix Angelicae Sinensis 530 weight portions, Radix Codonopsis 420 weight portions, Radix Scrophulariae 530 weight portions, Flos Lonicerae 420 weight portions, Herba Dendrobii 530 weight portions, Radix Achyranthis Bidentatae 420 weight portions, Radix Glycyrrhizae 530 weight portions; The Radix Astragali 530 weight portions, Radix Angelicae Sinensis 420 weight portions, Radix Codonopsis 530 weight portions, Radix Scrophulariae 420 weight portions, Flos Lonicerae 530 weight portions, Herba Dendrobii 420 weight portions, Radix Achyranthis Bidentatae 530 weight portions, Radix Glycyrrhizae 420 weight portions or the Radix Astragali 480 weight portions, Radix Angelicae Sinensis 480 weight portions, Radix Codonopsis 480 weight portions, Radix Scrophulariae 480 weight portions, Flos Lonicerae 480 weight portions, Herba Dendrobii 480 weight portions, Radix Achyranthis Bidentatae 480 weight portions, Radix Glycyrrhizae 480 weight portions.
Preparation of pharmaceutical compositions method of the present invention has overcome cardio-cerebral diseases that coated tablet exists and has had diabetics concurrently and should not take, adjuvant is many, production cost is big, it is unfavorable to health too much to take in, easily the moisture absorption is unfavorable for defectives such as product maintenance and sale, it is few to have weightening finish, the coating time is short, moisture resistance is good, the bioavailability height, cost reduces, take advantages such as crowd's expanded range, preparation of pharmaceutical compositions method of the present invention selects for use Opadry II to make thin film coating material, compare with coated tablet and to possess following advantage: 1. make the water packaging technique, satisfy the requirement of tablet protection against the tide, use simply, quickly disintegrating tablet; 2. complete safer, pollution-free, low-cost, the more environmental protection of water film coating; 3. solid content is higher and can not increase viscosity, saves 25% even the higher coating time, improves production capacity and production efficiency, reduces the coating water; 4. label require lower, difficult wear and tear, ftracture and other-a little infringements that in the coating process, may be subjected to, reach a coating effect preferably; 5. have higher adhesive force, overcome problems such as aqueous coatings common " bridge joint ", " thin film comes off "; 6. have better gloss and slickness, good fluidity is convenient to packing; 7. increase the stability of color; 8. simplify the coating solution preparation process; 9. simplify handling of goods and materials.
The preparation (TONGSAIMAI PIAN) that uses preparation of pharmaceutical compositions method of the present invention to make forms by suppressing lipidosis and speckle, reduce peripheral circulation endotheliocyte quantity, regulate the lipid metabolism of Atherosclerosis Model rat, reduce TC, TG and LDL-C content, increase HDL-C content, improve the function of vascular endothelial cell, suppress NOS activity and NO and generate, reduce the links such as expression of cytokine TNF-α, IL-6, ICAM, intervene atherosclerotic formation.
Following experimental example and embodiment are used to further specify the present invention but are not limited to the present invention.
Experimental example 1 TONGSAIMAI PIAN Film coated tablets and coated tablet quality investigation are relatively
Outward appearance: the coated tablet color and luster is even, and is bright-coloured bright and clean; Film coated tablets fineness is better, but color and luster is darker, slightly is inferior to coated tablet.
Average hardness: coated tablet 5.20kg; Film coated tablets 6.80kg.
Disintegration: press regulation under tablet item of Chinese Pharmacopoeia version in 2000, two kinds of coated tablet are tested, the sugar-coat agreement that contracts a film or TV play to an actor or actress needs 50 minutes as a result, and the film-coat agreement that contracts a film or TV play to an actor or actress needs 10 minutes.
The test of resistance to wearing: the results are shown in Table 1.
The test of resistance to wearing of two kinds of coated tablet of table 1
| Time (min) | Film coated tablets | Coated tablet |
| 10 30 60 | No change fineness reduces, the dark slightly fineness of unilateral gloss reduces, unilateral gloss is dark slightly | Surface staining is unilateral to have piebaldism, fluffing partly damaged |
Hygroscopicity compares: two kinds of samples are not added packing place RH75%, investigate 3 months under 40 ℃ of conditions, there are numerous black speck (the inner extractum moisture absorption is oozed out) on the coated tablet surface as a result, and label is softer; And the only accidental superfine little black patches of Film coated tablets, the sheet heart is still harder.Show the moisture resistance coated tablet not as good as Film coated tablets, good packaging material are packed but two kinds of coated tablet all need be selected moisture resistance for use.
The influence experiment of 2 pairs of Atherosclerosis Model rat arteries of experimental example lesion degree
1. experiment material
1.1 drug material and reagent
TONGSAIMAI PIAN extractum: 5g crude drug/g, joint stock company limited provides by the Rhizoma Arisaematis Pharmaceutical.Lot number: be made into corresponding concentration with 0.5%CMC-Na during gastric infusion.
Simvastatin Hangzhou Mo Shadong pharmaceutical Co. Ltd lot number: P1076
Cholesterol Huaibei Bo Aogaoke biochemistry corporation,Ltd. lot number: 20060124
Sodium cholate Huaibei Bo Aogaoke biochemistry corporation,Ltd. lot number: 20060202
Propylthiouracil Nantong China peaking worker Co., Ltd lot number: 20051204
Vitamin D3 Beijing Jia Kang source development in science and technology company limited lot number: 20051009
Oil red O SCRC Chemical Reagent Co., Ltd., Sinopharm Group lot number: 20060307
East, TG test kit Zhejiang bowl biological engineering company limited lot number: 2006030210
East, TCH test kit Zhejiang bowl biological engineering company limited lot number: 2006030212
East, LDL-C test kit Zhejiang bowl biological engineering company limited lot number: 2005120133
East, HDL-C test kit Zhejiang bowl biological engineering company limited lot number: 2006020304
Bio-engineering research institute lot number is built up in NO test kit Nanjing: 20060417
Bio-engineering research institute lot number is built up in NOS test kit Nanjing: 20060410
ICAM test kit Senxiong Science ﹠ Technology Industry Co., Ltd., Shanghai lot number: 0604212
IL-6 test kit Senxiong Science ﹠ Technology Industry Co., Ltd., Shanghai lot number: 0604213
1.2 laboratory animal
Cleaning level SD rat, male, body weight 270-300g is provided credit number by Nanjing Medical University's Experimental Animal Center: SCXK (Soviet Union) 2002-0031.
1.3 test group and drug dose setting
Blank group normal saline (NS)
Model group normal saline (NS)
Simvastatin group 0.009g/kg
High dose group 12.44g crude drug/kg
Middle dosage group 6.22g crude drug/kg
Low dose group 3.11g crude drug/kg
1.4 route of administration: the gastric infusion volume is 10ml/kg.
2. test method
2.1 the foundation of rat bait Atherosclerosis Model
[1]
Rat is divided into 6 groups at random, normal control group feeding plain particles feedstuff, and experimental group and model group feeding high lipid food add weekly and irritate vitamin D liquid (by 150,000 IU/kg) 1 time simultaneously.High lipid food processes in 3% cholesterol, 0.5% sodium cholate, 0.2% propylthiouracil, 5% white sugar, 10% Adeps Sus domestica, 81.3% normal diet ratio.Began to give gastric infusion the same day at the feeding high lipid food, every day 1 time, dosage as previously mentioned, isometric 0.5% sodium carboxymethyl cellulose of normal control group and model group rat oral gavage, continuous 1 month.Rat is anaesthetized with 10% chloral hydrate lumbar injection (0.3g/kg) then, and carotid artery is got blood and put to death, preparation serum, and-20 ℃ are frozen, peel off aorta simultaneously, 10% formaldehyde fixed, the observation of marking.
2.2 detection index
2.2.1 aortic disease degree detecting
[2]
Peel off the total length tremulous pulse along aortic valve to iliac artery bifurcation, vertically cut off, fixing in 10% formalin, oil red O stain is determined lipid speckle position and area.
Carry out the pathological changes classification by gross examination of skeletal muscle, following provisions are pressed in classification:
0 grade: intimal surface is smooth, no red dying
0.5 level: inner membrance has slight red dying, but does not have the speckle that protrudes the surface
1 grade: the red specking piece of tangible projection is arranged, and area is less than 3mm
2
2 grades: plaque area is greater than 3mm
2Protruding red specking piece
3 grades: speckle merges in flakes, and most of plaque area is greater than 3mm
2
4 grades: speckle almost covers whole endarterium.
Blood vessel wall pathological changes thickness and blood vessel wall thickness measure: get the wax section by Olympus BX41 image acquisition, use auspicious medical courses in general skill image analysis system, measure the thickness and the pathological changes thickness of blood vessel, same specimen random measurement 6 times, average, unit represents with millimicron.
2.2.2 circulation endothelium cell (CEC) counting
[3]
Adopt the Hladovec method, carotid artery is got blood 2.5ml, add in the anticoagulant tube (3.8% sodium citrate), 4 ℃, the centrifugal 18min of 400g, collect 2/3 supernatant, adenosine diphosphate (ADP) (ADP) the liquid 0.2ml of adding 0.1% in 1ml is rich in hematoblastic blood plasma, concussion 5min, the centrifugal 18min of 400g, get supernatant with the centrifugal 18min of 2100g, in precipitate, add 0.9% sodium chloride 0.1ml, concussion 1min, resuspended after, getting a little suspension splashes in the Burker blood countng chamber, (10 * 10) counting under the inverted microscope, same specimen counting is averaged for twice, and unit represents with individual/0.9 μ l.
2.2.3 the detection of serum index
Get serum, measure T-CHOL (TC), serum levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), HDL-C (HDL-C), nitric oxide (NO), nitricoxide synthase (NOS), tumor necrosis factor-alpha (TNF-α), interleukin (IL-6), cell adhesion factor (ICAM) according to the detection method of corresponding reagent box respectively.
2.3 histopathologic examination:
2.3.1 after laboratory animal is put to death, get aorta, heart and be positioned in 4% the neutral formalin.
2.3.2 dehydration: the process of removing contained humidity before being organized in of fixing or washing immersed paraffin is called dehydration.Because of containing large quantity of moisture after the fixation of tissue, and water and paraffin can not be miscible, must drive away thoroughly that contained humidity just can make paraffin be penetrated in the tissue in the tissue.The most frequently used dehydrant is an ethanol.Should be during dehydration earlier from the lower ethanol of concentration (50% or 70%), with constantly increasing progressively until dehydrated alcohol of its concentration, every grade was dewatered 2-4 hour.
2.3.3 transparent: the tissue after will dewatering, put into dimethylbenzene, each 30 minutes, totally 3 times.
2.3.4 waxdip: the tissue after transparent moves in the paraffin that dissolves and soaks, and the waxdip process needs to carry out in the incubator that keeps uniform temperature (about about 60 ℃).The 4 hours waxdip time of piece of tissue.
2.3.5 cut into slices: paraffin-embedded tissue is cut into 4 microns tissue slice by microtome.
2.3.6HE dyeing: the colourless tissue slice that cuts immerses in the different dye liquors, makes different tissues or cell show different colours.
2.4 statistical procedures
Data are represented with X ± SD, carry out statistical procedures with the student-T check, relatively use the least significant difference method in twos between each group.
3. result
The most aortectasias of model group rat, sclerosis, elasticity is relatively poor, and as seen fixing dyeing back is observed: aorta wall has the red specking piece of tangible projection, is streak.Each administration group aortic disease all has alleviating in various degree, and TONGSAIMAI height, middle dosage group and model group comparing difference all have significance.See Table 2.
Table 2 TONGSAIMAI PIAN is to the influence of Atherosclerosis Model rat aorta lesion degree (X ± SD)
| Group | The example number | Dosage (g/kg) | The pathological changes score value |
| Dosage TONGSAIMAI low dosage in the normal model simvastatin TONGSAIMAI high dose TONGSAIMAI | 10 12 12 10 11 10 | Isometric(al) isometric(al) 0.009 12.44 6.22 3.11 | 0 2.17±0.83 0.71±0.94 ** 0.90±1.15 ** 1.18±1.25 * 1.65±1.65 |
Annotate: compare * p＜0.05 with model group, * * p＜0.01 (down together)
The influence experiment of 3 pairs of Atherosclerosis Model rats of experimental example circulation endothelium cell number
Model group rat circulation endothelium cell number obviously increases, and with normal control group comparing difference highly significant is arranged.TONGSAIMAI PIAN height, middle dosage all can significantly reduce circulation endothelium cell number in the rat model blood, have compared significant difference with model group; Low dosage also has the trend that reduces circulation endothelium cell quantity in the rat model blood, does not have significance (seeing Table 3) but compare difference with model group.
Table 3 TONGSAIMAI PIAN is to the influence of Atherosclerosis Model rat circulation endothelium cell (X ± SD)
| Group | The example number | Dosage (g/kg) | CEC (individual/0.9ul) |
| Dosage TONGSAIMAI low dosage in the normal model simvastatin TONGSAIMAI high dose TONGSAIMAI | 10 12 12 10 11 10 | Isometric(al) isometric(al) 0.009 12.44 6.22 3.11 | 2.9±1.125 ** 5.54±2.116 2.833±1.231 ** 3.3±1.378 * 3.72±1.253 * 4.5±1.354 |
The influence experiment of 4 pairs of Atherosclerosis Model Serum TC of experimental example, TG, LDL-C, HDL-C
TC, TG, LDL-C content obviously raise in the model group rat blood serum, and HDL-C obviously reduces, and with normal group significant difference are arranged more all.Compare with model group, TONGSAIMAI PIAN height, middle dosage all can significantly reduce TC, TG in the Atherosclerosis Model rat blood serum, LDL-C content, can significantly increase HDL-C content (p＜0.05) simultaneously; The TONGSAIMAI PIAN low dosage also can lower T-CHOL in the rat model serum, total triglyceride, low density lipoprotein, LDL content, and can increase hdl concentration, does not have significant difference (seeing Table 4) but compare with model group.
Table 4 TONGSAIMAI PIAN is to the influence of Atherosclerosis Model rat fat (X ± SD)
| Group | Dosage (g/kg) | The example number | TC | TG | LDL-C | HDL-C |
| Dosage Tongsaimai low dosage in the normal model Simvastatin Tongsaimai high dose Tongsaimai | Isometric(al) isometric(al) 0.009 12.44 6.22 3.11 | 10 12 12 10 11 10 | 1.248±0.168 ** 7.804±3.086 4.879±1.393 ** 4.983±1.747 * 5.461±1.780 * 7.025±3.143 | 0.673±0.353 **2.584±0.925 1.536±1.241 * 1.498±0.853 * 1.654±0.956 * 2.144±0.977 | 1.613±0.273 ** 3.593±0.764 2.714±0.532 ** 2.780±0.627 * 2.770±0.979 * 3.239±0.827 | 0.791±0.213 ** 0.548±0.142 0.718±0.213 * 0.682±0.191 * 0.636±0.192 0.589±0.325 |
The influence experiment of 5 pairs of Atherosclerosis Model rat blood serums of experimental example NO, NOS
NO in the model group rat blood serum, NOS content are obvious, with normal group significant difference are arranged more all.TONGSAIMAI PIAN height, middle dosage all can significantly reduce rat model serum NO content and NOS vigor, compare with model group, and there is remarkable statistical significance in its difference; Low dosage also can reduce rat model serum NO content and NOS vigor, but compares there was no significant difference with model group (seeing Table 5).
Table 5 TONGSAIMAI PIAN is to the influence of atherosclerotic rat serum NO levels and NOS vigor (X ± SD)
| Group | The example number | Dosage (g/kg) | NO(umol/L) | NOS(U/ml) |
| Dosage TONGSAIMAI low dosage in the normal model simvastatin TONGSAIMAI high dose TONGSAIMAI | 10 12 12 10 11 10 | Isometric(al) isometric(al) 0.009 12.44 6.22 3.11 | 35.504±23.137 ** 90.181±33.201 48.32±15.152 ** 51.78±25.501 ** 59.098±21.774 * 66.667±27.938 | 19.5±4.722 ** 25.31±3.447 21.07±3.613 ** 20.77±7.886 ** 21.63±4.422 * 24.23±3.027 |
The influence experiment of 6 pairs of Atherosclerosis Model rat blood serums of experimental example TNF-α, ICAM-1, IL-6
TNF-α, ICAM-1, IL-6 content obviously raise in the model group rat blood serum, with normal group significant difference are arranged more all.TONGSAIMAI PIAN height, middle dosage all can significantly reduce TNF-α, ICAM in the rat model serum, IL-6 content, compare with model group, and there is remarkable statistical significance in its difference; Low dosage also can significantly reduce TNF-alpha content in the rat model serum, and in addition, the TONGSAIMAI PIAN low dosage is compared there was no significant difference (seeing Table 6) to the reduction of ICAM, IL-6 content in the rat model serum with model group.
Table 6 TONGSAIMAI PIAN is to the influence of Atherosclerosis Model rat blood serum TNF-α, ICAM, IL-6 content (X ± SD)
| Group | The example number | Dosage (g/kg) | TNF-α(pg/ml) | ICAM-1(pg/ml) | IL-6(pg/ml) |
| Dosage TONGSAIMAI low dosage in the normal model simvastatin TONGSAIMAI high dose TONGSAIMAI | 10 12 12 10 11 10 | Isometric(al) isometric(al) 0.009 12.44 6.22 3.11 | 8.721±0.308 ** 15.818±0.995 11.123±2.610 ** 11.554±3.612 ** 12.530±4.120 * 12.916±3.253 * | 19.188±5.732 ** 189.19±9.532 29.493±21.065 ** 72.711±43.372 ** 87.962±37.995 * 111.23±51.173 | 24.895±2.993 ** 68.794±7.433 38.23±21.248 ** 41.644±12.985 ** 49.085±13.196 ** 59.927±15.859 |
The experiment of experimental example 7 pathological examination results
The normal control group: the sick damage of the smooth no medicated porridge sample of rat aorta inner membrance, naked eyes do not have the lipid speckle and form; Light microscopic undertissue learns section and shows that normal aorta wall, inner membrance, middle film, adventitia are all high-visible, and each layer structure is normal.Inner membrance does not have lipidosis and changes, and contains a small amount of collagen fiber and smooth muscle fiber, and elastic fibers is evenly distributed, marshalling, and no abnormality seen changes.
Model group: the coarse injustice of rat aorta inner membrance, as seen naked eyes have a large amount of lark striated fat stricture of vaginas, significantly swell to intimal surface, under the light microscopic, inner membrance significantly thickens, edema, the focus surface constitutes thin fibrous cap by fibrocyte, collagen fiber, and the visible understain amorphous substance of lesion region, calcification particulate matter have a little lymphocyte, neutrophilic granulocyte near the bottom.
Positive controls: though visible this of naked eyes is organized each routine rat aorta lark striated fat stricture of vagina is arranged, the striated fat stricture of vagina of most routine aortic tunica intimas is few than model group, has only indivedual case focus scopes big slightly.Under the light microscopic, every routine aortic tunica intima all thickens slightly.The visible surface fibre medicated cap of focus is thinner, the visible understain amorphous substance in the focal zone of pathological changes, calcification particulate matter.
Low dose group: the naked eyes tunica intima is rough and uneven in surface, and be the fibrous plaque phase and change, focally be the rough and uneven in surface atherosis phase and change, other have the aorta of pathological changes, its pathological changes is all light than model group relatively, under the light microscopic, the pathological changes aortic tunica intima slightly thickens, endothelial denudation, the small amount of foam cell aggregation is arranged under it, and calcification particulate matter deposition is seen at this place.
Middle dosage group: naked eyes do not have the lipid speckle and form, and are early stage fat stricture of vagina phase change.Other have the aorta of pathological changes, and its pathological changes is all light than model group, low dose group relatively, and under the light microscopic, no pathological changes aorta wall, inner membrance, middle film, adventitia are all high-visible, and each layer structure is normal; The pathological changes aortic tunica intima slightly thickens, and local endothelial denudation has focal calcification particulate matter deposition under it.
High dose group: naked eyes do not have the lipid speckle and form the tunica intima smoother.Special mess tunica intima protuberance, other have the aorta of pathological changes, and its pathological changes is all light than model group, low dose group relatively, under the light microscopic, most of aorta wall, inner membrance, middle film, adventitia are all high-visible, and each layer structure is normal, marshalling, the calcification particulate matter deposition of special mess.
Table 7 TONGSAIMAI PIAN is to Atherosclerosis Model rat pathology statistical result (N=6)
| Group | N | Pathological changes thickness/blood vessel wall thickness |
| Dosage group TONGSAIMAI high dose group in the positive group of the normal group model group TONGSAIMAI low dose group TONGSAIMAI | 6 6 6 6 6 6 | 0.129±0.056*** 0.713±0.058* 0.496±0.125** 0.553±0.154* 0.395±0.102** 0.246±0.086*** |
Compare with normal group: * P＜0.001; Compare with model group: * * p＜0.001; Compare with low dose group: * * * p＜0.001.Illustrate that all medicines all have effect to AS, the most obvious with the TONGSAIMAI PIAN high dose group, and be better than the positive drug group.In the TONGSAIMAI PIAN, low dosage has effect to AS, but DeGrain.
Following embodiment all can realize the effect of above-mentioned experimental example.
The specific embodiment
Embodiment 1:
Radix Astragali 420kg, Radix Angelicae Sinensis 530kg, Radix Codonopsis 420kg, Radix Scrophulariae 530kg, Flos Lonicerae 420kg, Herba Dendrobii 530kg, Radix Achyranthis Bidentatae 420kg, Radix Glycyrrhizae 530kg;
A, decoction: crude drug is added in the multi-function extractor, add 6 times of water gagings, heating decocted 0.5 hour, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 4 times of amounts boiled 0.5 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 70%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make the oral liquid formulations of clinical acceptance according to common process.
Embodiment 2:
Radix Astragali 530kg, Radix Angelicae Sinensis 420kg, Radix Codonopsis 530kg, Radix Scrophulariae 420kg, Flos Lonicerae 530kg, Herba Dendrobii 420kg, Radix Achyranthis Bidentatae 530kg, Radix Glycyrrhizae 420kg;
A, decoction: crude drug is added in the multi-function extractor, add 4 times of water gagings, heating decocted 2.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 2 times of amounts boiled 1.5 hours, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 50%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make the concentrated pill of clinical acceptance according to common process.
Embodiment 3:
Radix Astragali 480kg, Radix Angelicae Sinensis 480kg, Radix Codonopsis 480kg, Radix Scrophulariae 480kg, Flos Lonicerae 480kg, Herba Dendrobii 480kg, Radix Achyranthis Bidentatae 480kg, Radix Glycyrrhizae 480kg;
A, decoction: crude drug is added in the multi-function extractor, add 5 times of water gagings, heating decocted 1.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 3 times of amounts boiled 1 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 60%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make the soft capsule of clinical acceptance according to common process.
Embodiment 4:
Radix Astragali 530kg, Radix Angelicae Sinensis 420kg, Radix Codonopsis 530kg, Radix Scrophulariae 420kg, Flos Lonicerae 530kg, Herba Dendrobii 420kg, Radix Achyranthis Bidentatae 530kg, Radix Glycyrrhizae 420kg;
A, decoction: crude drug is added in the multi-function extractor, add 6 times of water gagings, heating decocted 0.5 hour, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 4 times of amounts boiled 0.5 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 70%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 1% starch, 1.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 0.5% Pulvis Talci, 0.3% magnesium stearate was mixed 10 minutes with 10 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 4% of plain sheet weight is Opadry; Add 12% Diluted Alcohol liquid and be mixed with 15% suspension, continuous stirring 48 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 12% Opadry suspension, inlet temperature is 60 ℃, leaving air temp is 30 ℃, peristaltic pump speed is 18.0 rev/mins, and the sheet bed tempertaure is 30 ℃, 12 rev/mins of coating pan rotating speeds, the slice temperature is below 35 ℃, 5 hours coating time, after coating finishes, the coated tablet drying, drying room humidity should be controlled in 50%, gets clinical acceptable Film coated tablets.
Embodiment 5:
Radix Astragali 530kg, Radix Angelicae Sinensis 420kg, Radix Codonopsis 530kg, Radix Scrophulariae 420kg, Flos Lonicerae 530kg, Herba Dendrobii 420kg, Radix Achyranthis Bidentatae 530kg, Radix Glycyrrhizae 420kg;
A, decoction: crude drug is added in the multi-function extractor, add 4 times of water gagings, heating decocted 2.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 2 times of amounts boiled 1.5 hours, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 50%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 3% starch, 0.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 1.5% Pulvis Talci, 0.1% magnesium stearate was mixed 10 minutes with 20 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 5% of plain sheet weight is Opadry; Add 6% Diluted Alcohol liquid and be mixed with 28% suspension, continuous stirring 40 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 35% Opadry suspension, inlet temperature is 30 ℃, leaving air temp is 50 ℃, peristaltic pump speed is 5.0 rev/mins, and the sheet bed tempertaure is 45 ℃, 5 rev/mins of coating pan rotating speeds, the slice temperature is below 35 ℃, 8 hours coating time, after coating finishes, the coated tablet drying, drying room humidity should be controlled in 50%, gets clinical acceptable Film coated tablets.
Embodiment 6:
Radix Astragali 480kg, Radix Angelicae Sinensis 480kg, Radix Codonopsis 480kg, Radix Scrophulariae 480kg, Flos Lonicerae 480kg, Herba Dendrobii 480kg, Radix Achyranthis Bidentatae 480kg, Radix Glycyrrhizae 480kg;
A, decoction: crude drug is added in the multi-function extractor, add 5 times of water gagings, heating decocted 1.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 3 times of amounts boiled 1 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 60%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 2.3% starch, 1% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 1% Pulvis Talci, 0.2% magnesium stearate was mixed 10 minutes with 13 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 4.5% of plain sheet weight is Opadry; Add 10% Diluted Alcohol liquid and be mixed with 20% suspension, continuous stirring 45 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 20% Opadry suspension, inlet temperature is 45 ℃, and leaving air temp is 40 ℃, and peristaltic pump speed is 10.0 rev/mins; The sheet bed tempertaure is 35 ℃, 9 rev/mins of coating pan rotating speeds, and the slice temperature is below 35 ℃, and 6 hours coating time, after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got clinical acceptable Film coated tablets.
Embodiment 7:
Radix Astragali 530kg, Radix Angelicae Sinensis 420kg, Radix Codonopsis 530kg, Radix Scrophulariae 420kg, Flos Lonicerae 530kg, Herba Dendrobii 420kg, Radix Achyranthis Bidentatae 530kg, Radix Glycyrrhizae 420kg;
A, decoction: crude drug is added in the multi-function extractor, add 6 times of water gagings, heating decocted 0.5 hour, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 4 times of amounts boiled 0.5 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 70%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 3% starch, 0.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 1.5% Pulvis Talci, 0.1% magnesium stearate was mixed 10 minutes with 20 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 4.5% of plain sheet weight is Opadry; Add 10% Diluted Alcohol liquid and be mixed with 20% suspension, continuous stirring 45 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 20% Opadry suspension, inlet temperature is 45 ℃, and leaving air temp is 40 ℃, and peristaltic pump speed is 10.0 rev/mins; The sheet bed tempertaure is 35 ℃, 9 rev/mins of coating pan rotating speeds, and the slice temperature is below 35 ℃, and 6 hours coating time, after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got the Film coated tablets of clinical acceptance.
Embodiment 8:
Radix Astragali 530kg, Radix Angelicae Sinensis 420kg, Radix Codonopsis 530kg, Radix Scrophulariae 420kg, Flos Lonicerae 530kg, Herba Dendrobii 420kg, Radix Achyranthis Bidentatae 530kg, Radix Glycyrrhizae 420kg;
A, decoction: crude drug is added in the multi-function extractor, add 4 times of water gagings, heating decocted 2.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 2 times of amounts boiled 1.5 hours, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 50%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 2.3% starch, 1% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 1% Pulvis Talci, 0.2% magnesium stearate was mixed 10 minutes with 13 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 4% of plain sheet weight is Opadry; Add 12% Diluted Alcohol liquid and be mixed with 15% suspension, continuous stirring 48 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 12% Opadry suspension, inlet temperature is 60 ℃, leaving air temp is 30 ℃, peristaltic pump speed is 18.0 rev/mins, and the sheet bed tempertaure is 30 ℃, 12 rev/mins of coating pan rotating speeds, the slice temperature is below 35 ℃, 5 hours coating time, after coating finishes, the coated tablet drying, drying room humidity should be controlled in 50%, gets the Film coated tablets of clinical acceptance.
Embodiment 9:
Radix Astragali 480kg, Radix Angelicae Sinensis 480kg, Radix Codonopsis 480kg, Radix Scrophulariae 480kg, Flos Lonicerae 480kg, Herba Dendrobii 480kg, Radix Achyranthis Bidentatae 480kg, Radix Glycyrrhizae 480kg;
A, decoction: crude drug is added in the multi-function extractor, add 5 times of water gagings, heating decocted 1.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 3 times of amounts boiled 1 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 60%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 1% starch, 1.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 0.5% Pulvis Talci, 0.3% magnesium stearate was mixed 10 minutes with 10 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 5% of plain sheet weight is Opadry; Add 6% Diluted Alcohol liquid and be mixed with 28% suspension, continuous stirring 40 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 35% Opadry suspension, inlet temperature is 30 ℃, leaving air temp is 50 ℃, peristaltic pump speed is 5.0 rev/mins, and the sheet bed tempertaure is 45 ℃, 5 rev/mins of coating pan rotating speeds, the slice temperature is below 35 ℃, 8 hours coating time, after coating finishes, the coated tablet drying, drying room humidity should be controlled in 50%, gets the Film coated tablets of clinical acceptance.
Embodiment 10:
Radix Astragali 480kg, Radix Angelicae Sinensis 480kg, Radix Codonopsis 480kg, Radix Scrophulariae 480kg, Flos Lonicerae 480kg, Herba Dendrobii 480kg, Radix Achyranthis Bidentatae 480kg, Radix Glycyrrhizae 480kg;
A, decoction: crude drug is added in the multi-function extractor, add 5 times of water gagings, heating decocted 1.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 3 times of amounts boiled 1 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 60%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 2.3% starch, 1% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 1% Pulvis Talci, 0.2% magnesium stearate was mixed 10 minutes with 13 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 4.5% of plain sheet weight is Opadry; Add 10% Diluted Alcohol liquid and be mixed with 20% suspension, continuous stirring 45 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 20% Opadry suspension, inlet temperature is 45 ℃, and leaving air temp is 40 ℃, and peristaltic pump speed is 10.0 rev/mins; The sheet bed tempertaure is 35 ℃, 9 rev/mins of coating pan rotating speeds, and the slice temperature is below 35 ℃, and 6 hours coating time, after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got the Film coated tablets of clinical acceptance.
Claims (12)
1, the atherosclerotic preparation of drug combination method of a kind of treatment is characterized in that this method is:
A, decoction: crude drug is added in the multi-function extractor, add 4-6 times of water gaging, heating decocted 0.5-2.5 hour, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; Medicinal residues are added with the decocting that 2-4 doubly measures and boiled 0.5-1.5 hour, filter, merge with filtrate I, filtrate II, medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 50-70%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make the dosage form of clinical acceptance, include but not limited to concentrated pill, capsule, drop pill, granule, tablet, soft capsule, slow releasing agent, oral liquid or lyophilized injectable powder according to common process;
Wherein crude drug consists of: Radix Astragali 400-550 weight portion, Radix Angelicae Sinensis 400-550 weight portion, Radix Codonopsis 400-550 weight portion, Radix Scrophulariae 400-550 weight portion, Flos Lonicerae 400-550 weight portion, Herba Dendrobii 400-550 weight portion, Radix Achyranthis Bidentatae 400-550 weight portion, Radix Glycyrrhizae 400-550 weight portion.
2, the atherosclerotic preparation of drug combination method of a kind of treatment as claimed in claim 1 is characterized in that the A-E step is in this method:
A, decoction: crude drug is added in the multi-function extractor, add 6 times of water gagings, heating decocted 0.5 hour, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 4 times of amounts boiled 0.5 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 70%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make the preparation of clinical acceptance according to common process.
3, the atherosclerotic preparation of drug combination method of a kind of treatment as claimed in claim 1 is characterized in that the A-E step is in this method:
A, decoction: crude drug is added in the multi-function extractor, add 4 times of water gagings, heating decocted 2.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 2 times of amounts boiled 1.5 hours, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 50%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make the clinical preparation of accepting according to common process.
4, the atherosclerotic preparation of drug combination method of a kind of treatment as claimed in claim 1 is characterized in that the A-E step is in this method:
A, decoction: crude drug is added in the multi-function extractor, add 5 times of water gagings, heating decocted 1.5 hours, and kettle temperature picks up counting when reaching 100 ℃; Filter, get filtrate I, standby in the input fluid reservoir; The decocting that medicinal residues are added with 3 times of amounts boiled 1 hour, filtered, and merged with filtrate I, got filtrate II, and medicinal residues discard;
B, concentrated: filtrate II is imported in the economic benefits and social benefits concentrator, and temperature is controlled at below 70 ℃, and the above heating of vacuum-0.05Mpa is concentrated into 50～60 ℃ of relative densities 1.10～1.29, collects thick paste I;
C, precipitate with ethanol: get thick paste I and put in the Alcohol-settling tank, add ethanol and reach 60%, fully stir evenly, leave standstill more than 24 hours to containing the alcohol amount; Get supernatant, filter, filtrate recycling ethanol also is concentrated into the thick paste II of 50～60 ℃ of relative densities 1.30～1.50, and thick paste II is collected in the container;
D, drying: get thick paste II and be sub-packed in the mid-baking temperature of drip pan and be controlled at below 80 ℃, dry in the above vacuum drying oven of vacuum-0.05MPa, after the oven dry dry extract;
E, dry extract is added conventional adjuvant,, make the preparation of clinical acceptance according to common process.
5, as the atherosclerotic preparation of drug combination method of the arbitrary described a kind of treatment of claim 1-4, it is characterized in that this method replaces with the E step:
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 1-3% starch, 0.5-1.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added the 0.5-1.5% Pulvis Talci, the 0.1-0.3% magnesium stearate was mixed 10 minutes with 10-20 rev/min rotating speed start;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, with water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by the 4-5% of plain sheet weight is Opadry; The Diluted Alcohol liquid that adds 5-15% is mixed with the suspension of 10-30%, and continuous stirring 40-50 minute, stir, standby; Plain sheet is added in the coating pan, and the rotation coating pan sprays bag with the Opadry suspension of 10%-40%, and after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got the Film coated tablets of clinical acceptance.
6, the atherosclerotic preparation of drug combination method of a kind of treatment as claimed in claim 5 is characterized in that the F-J step is in this method:
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 1% starch, 1.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 0.5% Pulvis Talci, 0.3% magnesium stearate was mixed 10 minutes with 10 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 4.5% of plain sheet weight is Opadry; Add 10% Diluted Alcohol liquid and be mixed with 20% suspension, continuous stirring 45 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 20% Opadry suspension, after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got the Film coated tablets of clinical acceptance.
7, the atherosclerotic preparation of drug combination method of a kind of treatment as claimed in claim 5 is characterized in that the F-J step is in this method:
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 3% starch, 0.5% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 1.5% Pulvis Talci, 0.1% magnesium stearate was mixed 10 minutes with 20 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 4% of plain sheet weight is Opadry; Add 12% Diluted Alcohol liquid and be mixed with 15% suspension, continuous stirring 48 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 12% Opadry suspension, after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got the Film coated tablets of clinical acceptance.
8, the atherosclerotic preparation of drug combination method of a kind of treatment as claimed in claim 5 is characterized in that the F-J step is in this method:
F, granulation: dry extract is pulverized, got dry extract, dry extract adds 2.3% starch, 1% micropowder silica gel, granulates at the efficient wet mixer-granulator as wetting agent with ethanol, and pellet moisture is controlled at and is no more than 4.5%;
G, granulate: with 14 mesh sieve oscillating granulator granulate;
H, total mixing: granule is put in the three-dimensional motion mixer, added 1% Pulvis Talci, 0.2% magnesium stearate was mixed 10 minutes with 13 rev/mins rotating speed starts;
I, tabletting: granule is pressed into the plain sheet of the 0.36g of plate core weight ± 4.0%, and operation room humidity is controlled at and is no more than 50%;
J, usefulness water solublity thin film coating material bag film-coat, coating material is a stomach dissolution type Opadry film coating pre-mix dose, taking by weighing coating material by 5% of plain sheet weight is Opadry; Add 6% Diluted Alcohol liquid and be mixed with 28% suspension, continuous stirring 40 minutes stirs, and is standby; Plain sheet is added in the coating pan, rotate coating pan and spray bag with 35% Opadry suspension, after coating finished, coated tablet drying, drying room humidity should be controlled in 50%, got the Film coated tablets of clinical acceptance.
9, pharmaceutical composition as claimed in claim 5 is made the preparation method of Film coated tablets, it is characterized in that the coating parameter when the J step is sprayed bag in this method is: inlet temperature is 25-70 ℃, leaving air temp is 25-60 ℃, and peristaltic pump speed is 1.0-20.0 rev/min; The sheet bed tempertaure is 25-50 ℃, 2-15 rev/min of coating pan rotating speed, and the slice temperature is below 35 ℃, 4-8 hour coating time.
10, make the preparation method of Film coated tablets as claim 6,7 or 8 described pharmaceutical compositions, it is characterized in that the coating parameter when the J step is sprayed bag in this method is: inlet temperature is 25-70 ℃, leaving air temp is 25-60 ℃, and peristaltic pump speed is 1.0-20.0 rev/min; The sheet bed tempertaure is 25-50 ℃, 2-15 rev/min of coating pan rotating speed, and the slice temperature is below 35 ℃, 4-8 hour coating time.
11, pharmaceutical composition as claimed in claim 9 is made the preparation method of Film coated tablets, and it is characterized in that the coating parameter when the J step is sprayed bag in this method is: inlet temperature is 45 ℃, and leaving air temp is 40 ℃, and peristaltic pump speed is 10.0 rev/mins; The sheet bed tempertaure is 35 ℃, 9 rev/mins of coating pan rotating speeds, and the slice temperature is below 35 ℃, 6 hours coating time.
12, as claim 1,2,3,4,6,7,8, the atherosclerotic preparation of drug combination method of 9 or 11 arbitrary described a kind of treatments, it is characterized in that crude drug consists of in this method:
The Radix Astragali 420 weight portions, Radix Angelicae Sinensis 530 weight portions, Radix Codonopsis 420 weight portions, Radix Scrophulariae 530 weight portions, Flos Lonicerae 420 weight portions, Herba Dendrobii 530 weight portions, Radix Achyranthis Bidentatae 420 weight portions, Radix Glycyrrhizae 530 weight portions; The Radix Astragali 530 weight portions, Radix Angelicae Sinensis 420 weight portions, Radix Codonopsis 530 weight portions, Radix Scrophulariae 420 weight portions, Flos Lonicerae 530 weight portions, Herba Dendrobii 420 weight portions, Radix Achyranthis Bidentatae 530 weight portions, Radix Glycyrrhizae 420 weight portions or the Radix Astragali 480 weight portions, Radix Angelicae Sinensis 480 weight portions, Radix Codonopsis 480 weight portions, Radix Scrophulariae 480 weight portions, Flos Lonicerae 480 weight portions, Herba Dendrobii 480 weight portions, Radix Achyranthis Bidentatae 480 weight portions, Radix Glycyrrhizae 480 weight portions.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710098038A CN101045134B (en) | 2007-04-26 | 2007-04-26 | Method for preparing medicine to treat atherosclerosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710098038A CN101045134B (en) | 2007-04-26 | 2007-04-26 | Method for preparing medicine to treat atherosclerosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101045134A true CN101045134A (en) | 2007-10-03 |
| CN101045134B CN101045134B (en) | 2010-05-26 |
Family
ID=38770236
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200710098038A Active CN101045134B (en) | 2007-04-26 | 2007-04-26 | Method for preparing medicine to treat atherosclerosis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101045134B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103007571A (en) * | 2012-12-19 | 2013-04-03 | 温州市天龙轻工设备有限公司 | Alcohol-recyclable medicine extracting device and process thereof |
| CN107334932A (en) * | 2017-08-18 | 2017-11-10 | 上海交通大学医学院附属瑞金医院 | Preparation method of traditional Chinese medicine granules containing astragalus membranaceus |
| CN110917296A (en) * | 2019-12-03 | 2020-03-27 | 江苏康缘药业股份有限公司 | Application of traditional Chinese medicine composition in preparation of medicine for treating diabetic nephropathy |
| CN112472766A (en) * | 2020-12-11 | 2021-03-12 | 合肥华润神鹿药业有限公司 | Preparation process and detection method of radix salviae miltiorrhizae and blood slices |
| CN113813330A (en) * | 2021-10-03 | 2021-12-21 | 王钢柱 | Industrial-grade preparation method and product of traditional Chinese medicine composition for preventing and treating diabetic peripheral neuropathy |
| CN118178543A (en) * | 2023-11-30 | 2024-06-14 | 上海诚联生物医药科技有限公司 | A stem cell drug for treating atherosclerosis |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1442183A (en) * | 2003-04-11 | 2003-09-17 | 江苏南中医大药业有限责任公司 | Application of tongsaimai ectract in preparation of meticine for treating celebral wind stroke |
-
2007
- 2007-04-26 CN CN200710098038A patent/CN101045134B/en active Active
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103007571A (en) * | 2012-12-19 | 2013-04-03 | 温州市天龙轻工设备有限公司 | Alcohol-recyclable medicine extracting device and process thereof |
| CN103007571B (en) * | 2012-12-19 | 2014-09-10 | 汪振朴 | Alcohol-recyclable medicine extracting device and process thereof |
| CN107334932A (en) * | 2017-08-18 | 2017-11-10 | 上海交通大学医学院附属瑞金医院 | Preparation method of traditional Chinese medicine granules containing astragalus membranaceus |
| CN107334932B (en) * | 2017-08-18 | 2021-03-19 | 上海交通大学医学院附属瑞金医院 | Preparation method of traditional Chinese medicine granules containing astragalus |
| CN110917296A (en) * | 2019-12-03 | 2020-03-27 | 江苏康缘药业股份有限公司 | Application of traditional Chinese medicine composition in preparation of medicine for treating diabetic nephropathy |
| CN112472766A (en) * | 2020-12-11 | 2021-03-12 | 合肥华润神鹿药业有限公司 | Preparation process and detection method of radix salviae miltiorrhizae and blood slices |
| CN113813330A (en) * | 2021-10-03 | 2021-12-21 | 王钢柱 | Industrial-grade preparation method and product of traditional Chinese medicine composition for preventing and treating diabetic peripheral neuropathy |
| CN118178543A (en) * | 2023-11-30 | 2024-06-14 | 上海诚联生物医药科技有限公司 | A stem cell drug for treating atherosclerosis |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101045134B (en) | 2010-05-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101045134A (en) | Method for preparing medicine to treat atherosclerosis | |
| CN1390594A (en) | Mixture for improving blood circulation | |
| CN101057926A (en) | Gynaecologic menstruation regulating preparation for treating gynecopathy and its preparation method and quality control method | |
| CN1245198C (en) | Chinese medicine composition for treating diabetes and its preparing method | |
| CN100349598C (en) | Medicine for treating high lipemia and its production method | |
| CN1876161A (en) | Pharmaceutical formulation and preparing method for breast nodules for treating hyperplasia of mammary glands, and its quality control method | |
| CN101040999A (en) | Medicine compound for treating snoring and the preparing method and the quality control method | |
| CN1290517C (en) | Combination of propolis, preparation method and usage | |
| CN1785249A (en) | A new application of medicinal composition containing salvia miltiorrhiza | |
| CN1562310A (en) | Soft capsule preparation of Tibet medicine 'unique taste' | |
| CN1954867A (en) | Medical preparation of nodules of breast for treating gynaopathy and preparation method and quality control method | |
| CN1335161A (en) | Deer bone powder capsule | |
| CN1319560C (en) | Chinese medicine compound rheumatism preparation for improving bioavailability and medicine effect and preparing method | |
| CN1857609A (en) | Chinese medicine composition with nourishing health function and its preparing method | |
| CN1827147A (en) | Dispersible tablet with gastrodia tuber for treating headache, its preparation and quality control method | |
| CN1294925C (en) | Chinese medicine for treating hypertension and hyperlipemia and preparation thereof | |
| CN1562144A (en) | Chinese medicinal composition for treating intestine irritable syndrome and its preparing method | |
| CN1698709A (en) | A kind of compound Scutellaria baicalensis preparation | |
| CN1616018A (en) | Preparation for improving bioavailability and medicine effect for treating gynecopathy and preparing method | |
| CN1931233A (en) | Medicine composition of red sage and epimedium for treating cardiac and cerebral vascular diseases | |
| CN1583036A (en) | Composite panaxadiol and saponin with physiologic activity and its use and preparation | |
| CN1239197C (en) | Oral preparation for cerebral embolism and its preparing method | |
| CN1726987A (en) | Combined of Chinese traditional medicine for lowering blood sugar, preparation and discrimination method | |
| CN1698714A (en) | 'Rukuaixiao' preparation for treating mammary disease and its preparation process | |
| CN1546116A (en) | Traditional Chinese medicine composition for treating migraine and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: JIANGSU KANGYUAN YANGGUANG PHARMACEUTICAL CO., LTD Free format text: FORMER NAME: NANXING PHARMACEUTICAL CO., LTD., JIANGSU PROVINCE |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 210046 No. 29, Heng Jing Road, Nanjing economic and Technological Development Zone, Jiangsu, China Patentee after: JIANGSU KANION YANGGUANG PHARMACEUTICAL CO., LTD. Address before: 210046 No. 29, Heng Jing Road, Nanjing economic and Technological Development Zone, Jiangsu, China Patentee before: Nanxing Pharmaceutical Co., Ltd., Jiangsu Province |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20190626 Address after: No. 29 Hengjinglu, Nanjing Economic and Technological Development Zone, Jiangsu Province Co-patentee after: Kangyuan Pharmceutical Co., Ltd. Patentee after: JIANGSU KANION YANGGUANG PHARMACEUTICAL CO., LTD. Address before: No. 29 Hengjing Road, Nanjing Economic and Technological Development Zone, Jiangsu Province Patentee before: JIANGSU KANION YANGGUANG PHARMACEUTICAL CO., LTD. |