CN1602845A - Fenfluramine hydrochloride drop pills and its preparation method - Google Patents
Fenfluramine hydrochloride drop pills and its preparation method Download PDFInfo
- Publication number
- CN1602845A CN1602845A CN 200410055336 CN200410055336A CN1602845A CN 1602845 A CN1602845 A CN 1602845A CN 200410055336 CN200410055336 CN 200410055336 CN 200410055336 A CN200410055336 A CN 200410055336A CN 1602845 A CN1602845 A CN 1602845A
- Authority
- CN
- China
- Prior art keywords
- fenfluramine hydrochloride
- preparation
- coolant
- fenfluramine
- polyethylene glycol
- 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
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 239000006187 pill Substances 0.000 title claims abstract description 17
- 229960001877 fenfluramine hydrochloride Drugs 0.000 title claims description 30
- 238000002360 preparation method Methods 0.000 title claims 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
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 6
- 239000004205 dimethyl polysiloxane Substances 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
- 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
- -1 liquid paraffin Substances 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
- 239000000126 substance 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
- 230000000694 effects Effects 0.000 abstract description 5
- 238000005516 engineering process Methods 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 2
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 230000009748 deglutition Effects 0.000 abstract 1
- 229960001582 fenfluramine Drugs 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000009747 swallowing Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 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
- 208000019505 Deglutition disease Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 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 2
- 238000004891 communication Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention uses super micro shattering and drop pills producing technology to produce fenfluramine drop pills, reaching the purposes such as increasing speed, and dissolution of disintegration, increasing the medicine stability, reducing the dose of auxiliary materials and decreasing cost, with rapid effect and convenient use. It can be buccal as well as deglutition, has remarkable conformity, and is especially suitable for children, older man, sicker in bed or with difficulty of swallowing.
Description
Technical field
The present invention relates to a kind of pharmaceutical product and preparation method thereof, specifically fenfluramine hydrochloride drop pill and preparation method thereof.
Background technology
Fenfluramine hydrochloride is the amphetamine appetite suppressant, has the central excitation effect, but intensity a little less than.Can make blood pressure drops, also can increase surrounding tissue to the utilization of glucose and blood sugar lowering also has the effect of triglyceride reducing, cholesterol, total blood plasma lipide.
The fenfluramine hydrochloride oral absorption was good, reached the highest blood drug level through 2-4 hour, and effect was kept 6-8 hour, and 18-30 hour its half-life, blood level can reach stable state after 3-4 days, produced curative effect.Most of with the slowly discharge from urine of metabolite form.List marketing at present tablet, the clinical obese patient who is used for Simple Obesity and suffers from diabetes, hypertension, cardiovascular disease, anxiety neurosis only arranged.
The fenfluramine hydrochloride odorless, in water, dissolve, but 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 fenfluramine hydrochloride therapeutical effect.
The present invention makes the fenfluramine hydrochloride drop pill by using ultramicro communication technique and dropping pill formulation Technology exactly, thereby overcomes the above defective of fenfluramine hydrochloride tablets, and the therapeutical effect of fenfluramine hydrochloride is given full play to.
Summary of the invention
The fenfluramine hydrochloride 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, both can swallow also can buccal, 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 have working condition and production equipment is simple, production cost is low, compare the advantage that supplementary product consumption reduces with tablet, 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 fenfluramine hydrochloride fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, fully mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
The chemical name of fenfluramine hydrochloride is N-ethyl-Alpha-Methyl-3-trifluoromethyl-phenethylamine hydrochlorate among the present invention, and structural formula is
Molecular formula is C
12H
16F
3NHCl, molecular weight are 267.72.
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 first methods of Chinese Pharmacopoeia version in 2000), with 0.1mol/L hydrochloric acid solution 900ml is solvent, rotating speed is that per minute 100 changes, and operation in accordance with the law is in the time of 10,20,30,40 minutes, get solution 10ml, filter, get subsequent filtrate, as need testing solution; Other gets the fenfluramine hydrochloride reference substance, with 0.1mol/L dissolve with hydrochloric acid solution and dilution, makes reference substance solution.According to spectrophotography (two appendix VI of Chinese Pharmacopoeia version in 2000 A), measure trap at the wavelength place of 263nm, calculate stripping quantity.
Two, commercially available fenfluramine hydrochloride tablets testing result
1. disintegration time: 32 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 47.6 84.5 92.3 90.3
Three, example 1 sample detection result
1. the molten diffusing time: 2 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 69.7 99.6 100.5 99.3
Four, example 2 sample detection results
1. the molten diffusing time: 2 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 73.9 98.6 99.2 97.4
Five, example 3 sample detection results
1. the molten diffusing time: 2 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 76.5 98.5 100.0 99.2
Six, example 4 sample detection results
1. the molten diffusing time: 3 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 69.7 97.3 98.6 99.4
Seven, example 5 sample detection results
1. the molten diffusing time: 4 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 72.5 98.7 99.0 98.9
Eight, example 6 sample detection results
1. the molten diffusing time: 4 minutes
2. dissolution rate
Time (minute) 10 20 30 40
Dissolution (%) 69.6 98.4 99.1 99.2
The specific embodiment
One, example 1
Prescription:
Fenfluramine hydrochloride 5g
Polyethylene glycol 6000 15g
Make 1000
Method for making: the fenfluramine hydrochloride 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:
Fenfluramine hydrochloride 5g
Macrogol 4000 15g
Make 1000
Method for making: the fenfluramine hydrochloride 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:
Fenfluramine hydrochloride 5g
Polyethylene glycol 6000 5g
Macrogol 4000 10g
Make 1000
Method for making: the fenfluramine hydrochloride 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:
Fenfluramine hydrochloride 5g
Glyceryl monostearate 15g
Make 1000
Method for making: the fenfluramine hydrochloride 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:
Fenfluramine hydrochloride 5g
Polyethylene glycol 6000 10g
Poloxamer 5g
Make 1000
Method for making: the fenfluramine hydrochloride 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:
Fenfluramine hydrochloride 5g
Glyceryl monostearate 15g
Poloxamer 1g
Make 1000
Method for making: get the mixing fine powders that fenfluramine hydrochloride 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. fenfluramine hydrochloride drop pill and preparation method thereof is characterized in that: the fenfluramine hydrochloride fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, fully mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
2. the chemical name of the described fenfluramine hydrochloride of claim 1 is N-ethyl-Alpha-Methyl-3-trifluoromethyl-phenethylamine hydrochlorate, and structural formula is
, molecular formula is C
12H
16F
3NHCl, molecular weight are 267.72.
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 |
|---|---|---|---|
| CN 200410055336 CN1602845A (en) | 2004-08-23 | 2004-08-23 | Fenfluramine hydrochloride drop pills and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410055336 CN1602845A (en) | 2004-08-23 | 2004-08-23 | Fenfluramine hydrochloride drop pills and its preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1602845A true CN1602845A (en) | 2005-04-06 |
Family
ID=34666168
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410055336 Pending CN1602845A (en) | 2004-08-23 | 2004-08-23 | Fenfluramine hydrochloride drop pills and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1602845A (en) |
-
2004
- 2004-08-23 CN CN 200410055336 patent/CN1602845A/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 |