CN1528292A - Simvastatin drop pill and preparing method thereof - Google Patents
Simvastatin drop pill and preparing method thereof Download PDFInfo
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- CN1528292A CN1528292A CNA2003101009236A CN200310100923A CN1528292A CN 1528292 A CN1528292 A CN 1528292A CN A2003101009236 A CNA2003101009236 A CN A2003101009236A CN 200310100923 A CN200310100923 A CN 200310100923A CN 1528292 A CN1528292 A CN 1528292A
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- simvastatin
- coolant
- polyethylene glycol
- pill
- dissolution
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- 239000006187 pill Substances 0.000 title claims abstract description 18
- 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 title claims description 38
- 229960002855 simvastatin Drugs 0.000 title claims description 38
- 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 title claims description 37
- 238000000034 method Methods 0.000 title description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 12
- 239000002826 coolant Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 8
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 6
- 229940008099 dimethicone Drugs 0.000 claims description 6
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 6
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 6
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 claims description 6
- 229960000502 poloxamer Drugs 0.000 claims description 6
- 229920001983 poloxamer Polymers 0.000 claims description 6
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 4
- 239000011159 matrix material Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- IQXJCCZJOIKIAD-UHFFFAOYSA-N 1-(2-methoxyethoxy)hexadecane Chemical compound CCCCCCCCCCCCCCCCOCCOC IQXJCCZJOIKIAD-UHFFFAOYSA-N 0.000 claims description 2
- 239000001828 Gelatine Substances 0.000 claims description 2
- 241000238631 Hexapoda Species 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 229950009789 cetomacrogol 1000 Drugs 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 229960005150 glycerol Drugs 0.000 claims description 2
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 claims description 2
- -1 liquid paraffin Substances 0.000 claims description 2
- 229940057995 liquid paraffin Drugs 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229940093430 polyethylene glycol 1500 Drugs 0.000 claims description 2
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 claims description 2
- 229940080350 sodium stearate Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 2
- 239000008158 vegetable oil Substances 0.000 claims description 2
- 239000001993 wax Substances 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 20
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000001514 detection method Methods 0.000 description 7
- 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 6
- 230000000694 effects Effects 0.000 description 6
- 229940075507 glyceryl monostearate Drugs 0.000 description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 108010010234 HDL Lipoproteins Proteins 0.000 description 3
- 102000015779 HDL Lipoproteins Human genes 0.000 description 3
- 108010028554 LDL Cholesterol Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 101710095342 Apolipoprotein B Proteins 0.000 description 2
- 102100040202 Apolipoprotein B-100 Human genes 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 2
- 150000001277 beta hydroxy acids Chemical class 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 201000001386 familial hypercholesterolemia Diseases 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- SYKWLIJQEHRDNH-KRPIADGTSA-N glutaryl-coa Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSC(=O)CCCC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 SYKWLIJQEHRDNH-KRPIADGTSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000013546 non-drug therapy Methods 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- XWLXKKNPFMNSFA-HGQWONQESA-N simvastatin hydroxy acid Chemical class C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)C(C)(C)CC)C[C@@H](C)C=C21 XWLXKKNPFMNSFA-HGQWONQESA-N 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention utilizes ultramicropulverization and dripping pill preparation production process to make simvastatinie dripping pills, and can attain the goal of raising disintegration and dissolution speed, quickly obtaining therapeutic effect, raising stability of medicine, reducing dose of auxiliary material, reducing production cost and convenient administration. Said pill not only can be sucked, but also can be swallowed, and its compliance property is good.
Description
Technical field
The present invention relates to a kind of pharmaceutical product and preparation method thereof, specifically drop pills of simvastatin and preparation method thereof.
Background technology
The non-activity of simvastatin own, hydrolyzate after the oral absorption suppresses the rate-limiting enzyme hydroxyl first glutaryl CoA reductase of cholesterol building-up process in vivo competitively, make the synthetic minimizing of cholesterol, also make the synthetic increase of low density lipoprotein receptor, main site of action is at liver, the result reduces cholesterolemia and low-density lipoprotein cholesterol level, and moderate reduces serum triglyceride level and increases the blood hdl level.Thus to the control generation effect of atherosclerosis and coronary heart disease.
The simvastatin oral absorption is good, and the concentration that absorbs in the liver of back is higher than its hetero-organization, and extensive first pass metabolism in liver is hydrolyzed to metabolite, based on three kinds of metabolites of β-hydroxy acid activity is arranged.The protein binding rate of simvastatin and β-hydroxy acid metabolite is up to 95%, and peak time is 1.3～2.4 hours, and T1/2 is 3 hours.60% from the feces discharge, and 13% discharges from urine.2 weeks of treatment are curative effect as seen, and 4～6 weeks reached the peak, drug withdrawal after the long-term treatment, and effect continued for 4～6 weeks.
List marketing at present simvastatin tablet and capsule arranged, clinical being used for:
1. hyperlipemia
(1) for the patient of primary hypercholesterolemia, heterozygote familial hypercholesterolemia or Combination hypercholesterolemia, when diet control and other non-drug therapies were undesirable, simvastatin can be used for reducing T-CHOL, low-density lipoprotein cholesterol, apolipoprotein B and the triglyceride of rising.And simvastatin high density lipoprotein increasing cholesterol, thereby the ratio of reduction low density lipoprotein, LDL/high density lipoprotein and T-CHOL/high density lipoprotein.
(2) for homozygote familial hypercholesterolemia patient, when diet control and non-dietetic therapy were undesirable, simvastatin can be used for reducing T-CHOL, low-density lipoprotein cholesterol and the apolipoprotein B of rising.
2. coronary heart disease
(1) reduces dead danger.
(2) danger of minimizing coronary heart disease death and non-lethality myocardial infarction.
(3) danger of minimizing apoplexy and transient ischemic attack.
(4) reduce the myocardial vascular danger of logical operation (bypass operation of coronary artery and percutaneous air bag coronary angioplasty) again.
(5) delay atherosclerotic progress, comprise new focus and full generation of stopping up.
Simvastatin is insoluble in water, its tablet or capsule disintegration time are long, dissolution and dissolution rate are low, absorption difference, bioavailability is low, and the supplementary product consumption ratio is big, and child, old people, bed patient and dysphagia patients are taken inconvenience, compliance is poor, has influenced the performance of Simvastatin Treatment effect.
The present invention makes the drop pills of simvastatin agent by using ultramicro communication technique and dropping pill formulation Technology exactly, thereby overcomes simvastatin sheet and capsular above defective, and the therapeutical effect of simvastatin is given full play to.
Summary of the invention
The drop pills of simvastatin of making by using ultramicro communication technique and dropping pill formulation Technology not only have disintegrate molten loose fast, dissolution and dissolution rate improve, steady quality, the pill volume is little, both can swallow also can buccal, easy to carry and use, onset is rapid, compliance is good, be particularly suitable for the child, the old people, the characteristics that bed patient and dysphagia patients are taken, but also have working condition and production equipment is simple, production cost is low, compare the advantage that supplementary product consumption reduces with tablet or capsule, demonstrated fully the new drug research exploitation spirit that people-oriented.
For achieving the above object, the present invention by the following technical solutions: the simvastatin fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, abundant mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
The chemical name of simvastatin among the present invention (Simvastatin) is 2, and 2-acid dimethyl-8-{ (4R, 6R)-6-(2-[(1S, 2S, 6R, 8S, 8aR)-1,2,6,7,8,8-α-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl] ethyl) tetrahydrochysene-4-hydroxyl-2H-pyran-2-one ester, molecular formula is C
25H
38O
5, molecular weight is 418.57, structural formula is
Substrate among the present invention includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.
Coolant among the present invention includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.
Below through detecting to beneficial effect of the present invention as directed
One, detects index and method
1. disintegrate (molten loosing) time limit: check according to inspection technique disintegration (two appendix XA of Chinese Pharmacopoeia version in 2000).
2. dissolution rate: sample thief, according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2000), (get potassium dihydrogen phosphate 1.36g with phosphate buffer, add water 900ml and make dissolving, regulate pH value to 4.5, add water to 1000ml with hydrochloric acid or sodium hydroxide solution, shake up, promptly)-and normal propyl alcohol (2: 1) 900ml is a solvent, rotating speed is that per minute 50 changes, operation in accordance with the law, in the time of 10,20,30,40 and 50 minutes, get solution 10ml, filter, get subsequent filtrate as need testing solution.It is an amount of that other gets the simvastatin reference substance, accurate claims surely, adds above-mentioned solution dissolving and make the solution product solution in contrast that contains 6 μ g among every 1ml approximately.Get each 20 μ l of need testing solution and reference substance solution respectively and inject chromatograph of liquid, measure according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2000).With octadecylsilane chemically bonded silica is filler; With acetonitrile-0.025mol/L sodium dihydrogen phosphate (pH4.5) (65: 35) is mobile phase; The detection wavelength is 238nm; Number of theoretical plate calculates by the simvastatin peak should be not less than 2000.Press external standard method with the calculated by peak area stripping quantity.
Two, commercially available simvastatin sheet testing result
1. disintegration time: 57 minutes
2. dissolution rate:
Time (minute) 10 20 30 40 50
Dissolution (%) 22.3 37.6 61.4 73.5 87.2
Three, example 1 sample detection result
1. the molten diffusing time: 4 minutes
2. dissolution rate:
Time (minute) 10 20 30 40 50
Dissolution (%) 46.5 71.2 95.4 99.7 100.5
Four, example 2 sample detection results
1. the molten diffusing time: 4 minutes
2. dissolution rate:
Time (minute) 10 20 30 40 50
Dissolution (%) 46.3 71.2 93.4 98.6 99.0
Five, example 3 sample detection results
1. the molten diffusing time: 5 minutes
2. dissolution rate:
Time (minute) 10 20 30 40 50
Dissolution (%) 38.9 69.4 91.2 99.7 98.6
Six, example 4 sample detection results
1. the molten diffusing time: 7 minutes
2. dissolution rate:
Time (minute) 10 20 30 40 50
Dissolution (%) 35.1 59.2 84.5 96.3 97.8
Seven, example 5 sample detection results
1. the molten diffusing time: 8 minutes
2. dissolution rate:
Time (minute) 10 20 30 40 50
Dissolution (%) 37.2 60.4 83.5 95.3 97.6
Eight, example 6 sample detection results
1. the molten diffusing time: 10 minutes
2. dissolution rate
Time (minute) 10 20 30 40 50
Dissolution (%) 40.4 58.2 80.1 95.3 96.7
The specific embodiment
One, example 1
Prescription:
Simvastatin 5g
Polyethylene glycol 6000 15g
Make 1000
Method for making: the simvastatin fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused polyethylene glycol 6000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Two, example 2
Prescription:
Simvastatin 5g
Macrogol 4000 15g
Make 1000
Method for making: the simvastatin fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused Macrogol 4000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Three, example 3
Prescription:
Simvastatin 5g
Polyethylene glycol 6000 5g
Macrogol 4000 10g
Make 1000
Method for making: the simvastatin fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in fused Macrogol 4000 and the polyethylene glycol 6000 mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Four, example 4
Prescription:
Simvastatin 5g
Glyceryl monostearate 15g
Make 1000
Method for making: the simvastatin fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused glyceryl monostearate substrate, and mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.
Five, example 5
Prescription:
Simvastatin 5g
Polyethylene glycol 6000 10g
Poloxamer 5g
Make 1000
Method for making: the simvastatin fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in fused polyethylene glycol 6000 and the poloxamer mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Six, example 6
Prescription:
Simvastatin 5g
Glyceryl monostearate 15g
Poloxamer 1g
Make 1000
Method for making: get the mixing fine powders that simvastatin and poloxamer cross 200 mesh sieves through micronizing and be added in the fused glyceryl monostearate substrate, mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.
Claims (4)
1. drop pills of simvastatin and preparation method thereof is characterized in that: the simvastatin fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, and abundant mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
2. the molecular formula of the described simvastatin Simvastatin of claim 1 is C
25H
38O
5, molecular weight is 418.57, structural formula is
3. the described substrate of claim 1 includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.
4. the described coolant of claim 1 includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2003101009236A CN1528292A (en) | 2003-10-08 | 2003-10-08 | Simvastatin drop pill and preparing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2003101009236A CN1528292A (en) | 2003-10-08 | 2003-10-08 | Simvastatin drop pill and preparing method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1528292A true CN1528292A (en) | 2004-09-15 |
Family
ID=34304116
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2003101009236A Pending CN1528292A (en) | 2003-10-08 | 2003-10-08 | Simvastatin drop pill and preparing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1528292A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1872052B (en) * | 2005-06-01 | 2010-09-29 | 天津天士力制药股份有限公司 | Drop pills of simvastatin, and preparation method |
| CN102106835A (en) * | 2009-12-29 | 2011-06-29 | 张凤文 | Method for preparing simvastatin tablet by employing micronizing and power direct compressing technologies |
| CN102641250A (en) * | 2012-04-12 | 2012-08-22 | 兴安药业有限公司 | Simvastatin dropping pill and preparation method thereof |
| CN104771378A (en) * | 2015-04-20 | 2015-07-15 | 鲁南贝特制药有限公司 | Simvastatin tablet |
| CN106727398A (en) * | 2017-02-21 | 2017-05-31 | 鲁南制药集团股份有限公司 | A kind of simvastatin tablet |
-
2003
- 2003-10-08 CN CNA2003101009236A patent/CN1528292A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1872052B (en) * | 2005-06-01 | 2010-09-29 | 天津天士力制药股份有限公司 | Drop pills of simvastatin, and preparation method |
| CN102106835A (en) * | 2009-12-29 | 2011-06-29 | 张凤文 | Method for preparing simvastatin tablet by employing micronizing and power direct compressing technologies |
| CN102641250A (en) * | 2012-04-12 | 2012-08-22 | 兴安药业有限公司 | Simvastatin dropping pill and preparation method thereof |
| CN104771378A (en) * | 2015-04-20 | 2015-07-15 | 鲁南贝特制药有限公司 | Simvastatin tablet |
| CN104771378B (en) * | 2015-04-20 | 2018-03-20 | 鲁南贝特制药有限公司 | A kind of simvastatin tablet |
| CN106727398A (en) * | 2017-02-21 | 2017-05-31 | 鲁南制药集团股份有限公司 | A kind of simvastatin tablet |
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