CN1528301A - Nicorandic drop pill and preparing method thereof - Google Patents
Nicorandic drop pill and preparing method thereof Download PDFInfo
- Publication number
- CN1528301A CN1528301A CNA2003101009128A CN200310100912A CN1528301A CN 1528301 A CN1528301 A CN 1528301A CN A2003101009128 A CNA2003101009128 A CN A2003101009128A CN 200310100912 A CN200310100912 A CN 200310100912A CN 1528301 A CN1528301 A CN 1528301A
- Authority
- CN
- China
- Prior art keywords
- nicorandil
- coolant
- polyethylene glycol
- pill
- drop pill
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000006187 pill Substances 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 title description 11
- 229960002497 nicorandil Drugs 0.000 claims abstract description 33
- LBHIOVVIQHSOQN-UHFFFAOYSA-N nicorandil Chemical compound [O-][N+](=O)OCCNC(=O)C1=CC=CN=C1 LBHIOVVIQHSOQN-UHFFFAOYSA-N 0.000 claims abstract description 33
- 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
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- -1 liquid paraffin 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
- 239000002253 acid Substances 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
- 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 3
- 238000001514 detection method Methods 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 208000019505 Deglutition disease Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 239000003218 coronary vasodilator agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000003890 Coronary Vasospasm Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 201000011634 coronary artery vasospasm Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 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
- 230000001732 thrombotic effect Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention utilizes ultramicropulverization and dripping pill preparation production process to make nicorandil dripping pills, and can attain the goal of raising disintegration and dissolution speed, quickly obtaining therapeutic effect, raising 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 nicorandil drop pill and preparation method thereof.
Background technology
Nicorandil is an anti-anginal drug, belong to nitrate compound, it is free to have the intracellular calcium of prevention, increase the permeability of cell membrane to potassium ion, the expansion coronary vasodilator, the persistence coronary blood flow increasing suppresses the effect of coronary vasospasm, when the expansion coronary vasodilator, do not influence blood pressure, heart rate, myocardial contraction and myocardial oxygen consumption.Nicorandil also has anticoagulant and prevents thrombotic effect.
The nicorandil oral absorption is fast, and bioavailability is 7 5% and complete, 0.5～1 hour blood drug level peaking in back of taking medicine, half-life (t
1/2) be about 1 hour.Mainly be distributed in liver, the heart, kidney, adrenal gland and the blood.Slough nitro through hydrolysis in vivo, the metabolite pharmacologically active is very little, mainly drains from urine.List marketing at present tablet, the clinical treatment that is used for coronary heart disease, angor only arranged.
The nicorandil bitter in the mouth, molten in the water part omitted, its disintegration of tablet time is long, dissolution and dissolution rate are low, absorption difference, and bioavailability is low, the supplementary product consumption ratio is big, child, old people, bed patient and dysphagia patients are taken inconvenience, and compliance is poor, have influenced the performance of nicorandil therapeutical effect.
The present invention makes the nicorandil drop pill by using ultramicro communication technique and dropping pill formulation Technology exactly, thereby overcomes the above defective of nicorandil tablet, and the therapeutical effect of nicorandil is given full play to.
Summary of the invention
The nicorandil drop pill 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, easy to carry and use, onset is rapid, compliance is good, be particularly suitable for the characteristics that child, old people, bed patient and dysphagia patients are taken, but also has working condition and production equipment is simple, production cost is low, compares the advantage that supplementary product consumption reduces with tablet, has 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 nicorandil 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 nicorandil among the present invention (Nicorandil) is N-(2-hydroxyethyl) Nicorandil, and structural formula is
Molecular formula is C
8H
9N
3O
4, molecular weight is 211.2.
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 of Chinese Pharmacopoeia version in 2000 three therapeutic methods of traditional Chinese medicine), 250ml is a solvent with hydrochloric acid solution (dilute hydrochloric acid 24 → 1000), and rotating speed is that per minute 50 changes, operation in accordance with the law, in the time of 10,20,30 and 40 minutes, get solution 10ml, filter, get subsequent filtrate, according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), measure trap at the wavelength place of 261nm, press C
8H
9N
3O
4Absorptance (E
1cm 1%) be 281 calculating stripping quantities.
Two, commercially available nicorandil tablet testing result
1. disintegration time: 53 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 32.4 51.2 73.5 81.3
Three, example 1 sample detection result
1. the molten diffusing time: 4 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 46.4 78.9 95.6 99.6
Four, example 2 sample detection results
1. the molten diffusing time: 4 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 51.2 81.3 97.4 100.6
Five, example 3 sample detection results
1. the molten diffusing time: 4 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 41.1 76.2 93.5 99.2
Six, example 4 sample detection results
1. the molten diffusing time: 4 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 47.3 86.5 97.6 102.3
Seven, example 5 sample detection results
1. the molten diffusing time: 6 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 40.5 72.4 91.3 98.9
Eight, example 6 sample detection results
1. the molten diffusing time: 9 minutes
2. dissolution rate
Time (minute) 10 20 30 40
Dissolution (%) 39.6 73.4 86.5 98.8
The specific embodiment
One, example 1
Prescription:
Nicorandil 5g
Polyethylene glycol 6000 15g
Make 1000
Method for making: the nicorandil 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:
Nicorandil 5g
Macrogol 4000 15g
Make 1000
Method for making: the nicorandil 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:
Nicorandil 5g
Polyethylene glycol 6000 5g
Macrogol 4000 10g
Make 1000
Method for making: the nicorandil 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:
Nicorandil 5g
Glyceryl monostearate 15g
Make 1000
Method for making: the nicorandil 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:
Nicorandil 5g
Polyethylene glycol 6000 10g
Poloxamer 5g
Make 1000
Method for making: the nicorandil 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:
Nicorandil 5g
Glyceryl monostearate 15g
Poloxamer 1g
Make 1000
Method for making: get the mixing fine powders that nicorandil 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. nicorandil drop pill and preparation method thereof is characterized in that: the nicorandil 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 nicorandil Nicorandil of claim 1 is C
8H
9N
3O
4, molecular weight is 211.2, 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 |
|---|---|---|---|
| CNA2003101009128A CN1528301A (en) | 2003-10-08 | 2003-10-08 | Nicorandic drop pill and preparing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2003101009128A CN1528301A (en) | 2003-10-08 | 2003-10-08 | Nicorandic drop pill and preparing method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1528301A true CN1528301A (en) | 2004-09-15 |
Family
ID=34304105
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2003101009128A Pending CN1528301A (en) | 2003-10-08 | 2003-10-08 | Nicorandic drop pill and preparing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1528301A (en) |
-
2003
- 2003-10-08 CN CNA2003101009128A patent/CN1528301A/en active Pending
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |