CN1327832C - Sibuqumin hydrochloride drip pill - Google Patents
Sibuqumin hydrochloride drip pill Download PDFInfo
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- CN1327832C CN1327832C CNB2006100098999A CN200610009899A CN1327832C CN 1327832 C CN1327832 C CN 1327832C CN B2006100098999 A CNB2006100098999 A CN B2006100098999A CN 200610009899 A CN200610009899 A CN 200610009899A CN 1327832 C CN1327832 C CN 1327832C
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- Prior art keywords
- sibutramine hydrochloride
- hydrochloride
- beta
- sibuqumin
- medicine
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- 239000006187 pill Substances 0.000 title claims abstract description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims description 8
- UWAOJIWUVCMBAZ-UHFFFAOYSA-N [1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl]-dimethylazanium;chloride Chemical compound Cl.C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UWAOJIWUVCMBAZ-UHFFFAOYSA-N 0.000 claims abstract description 31
- 229960003466 sibutramine hydrochloride Drugs 0.000 claims abstract description 31
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 claims abstract description 13
- 229940057838 polyethylene glycol 4000 Drugs 0.000 claims abstract description 13
- 239000000758 substrate Substances 0.000 claims abstract description 13
- 239000000843 powder Substances 0.000 claims abstract description 6
- 229920000858 Cyclodextrin Polymers 0.000 abstract 1
- 239000001116 FEMA 4028 Substances 0.000 abstract 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 abstract 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 abstract 1
- 229960004853 betadex Drugs 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 27
- 238000004090 dissolution Methods 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 230000008859 change Effects 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- 102000010909 Monoamine Oxidase Human genes 0.000 description 2
- 108010062431 Monoamine oxidase Proteins 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000002826 coolant Substances 0.000 description 2
- 229940008099 dimethicone Drugs 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- -1 poly-hydroxyl oxygen Chemical compound 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010020741 Hyperpyrexia Diseases 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000003153 cholinolytic effect Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000640 hydroxylating effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- VZLOAZQEKPRYHD-UHFFFAOYSA-N n-methylmethanamine;hydrate;hydrochloride Chemical compound O.Cl.CNC VZLOAZQEKPRYHD-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000037361 pathway 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
- 108010058237 plasma protein fraction Proteins 0.000 description 1
- 229940081857 plasma protein fraction Drugs 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention provides a sibutramine hydrochloride drop pill which is made from sibutramine hydrochloride fine powder and substrate, wherein the substrate is formed from polyethyleneglycol-4000 accounting for 4 to 6 times of sibutramine hydrochloride by weight and beta-cyclodextrin accounting for 1 to 3 times of the sibutramine hydrochloride by weight. The products of the present invention have the advantages of high stability, long shelf life, high utilizing rate for effective ingredients, etc.
Description
(1) technical field
The present invention relates to a kind of pharmaceutical product and preparation method thereof, specifically describing is Sibuqumin hydrochloride drip pill and preparation method thereof.
(2) background technology
Sibutramine hydrochloride is the bariatrician medicine that acts on maincenter.Main generation effect by its amine (secondary amine and primary amine class) metabolite, its dominant mechanism strengthens satietion for the reuptake that suppresses norepinephrine, 5-hydroxy tryptamine and dopamine, and the release of norepinephrine, 5-hydroxy tryptamine and dopamine is not had obvious influence.Research shows that also this product and amine active metabolite thereof do not have obvious cholinolytic, antihistamine and monoamine oxidase, MAO effect.
Absorb at digestive tract rapidly behind the oral hydrochloride sibutramine, peak reaching time of blood concentration is 1.2 hours, and oral clearance is 1750L/h, and the half-life is 1.1 hours.Single medication is average minimum to absorb 77%.
Sibutramine hydrochloride mainly is the M1 and the M2 of single and dinor-by the metabolism of the Cytochrome P450 of liver (3A4) isozyme through liver first-pass effect.The further hydroxylating of these active metabolites and be non-pharmacologically active metabolite M5 and M6 in conjunction with metabolism.Take that the radioactive substance concentration in the blood plasma is respectively original shape (3%), M1 (6%), M2 (12%), M5 (52%), M6 (27%) behind the radiolabeled Sibutramine hydrochloride.But the plasma concentration of M1 and M2 is peaking in 3～4 hours.Taking medicine, the plasma concentration of M1 and M2 reaches stable state in 4 days, and concentration is the twice of single medication.The elimination half-life of M1 and M2 was respectively 14 and 16 hours, half-life no change behind the multiple dosing.In vitro tests shows that the experiment of animal radio-labeled shows that medicine can be distributed in the tissue rapidly, widely, and what concentration was the highest is to remove organ: liver and kidney.Under the blood drug level of therapeutic dose, the human plasma protein fraction combination rate of Sibutramine hydrochloride, M1, M2 is respectively 97%, 94%, 94%.The radiological dose of about 85% (68～95%) is by urine and defecate behind the single medication, and the main metabolites in the urine is M5 and M6, does not find original shape medicine, M1 and M2.The main excretion pathway of M1 and M2 is a liver metabolism, and M5 and M6 mainly are from renal excretion.
The Sibutramine hydrochloride odorless, slightly soluble in water, its tablet or capsule disintegration time are long, dissolution and stripping three speed 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 Sibutramine hydrochloride curative effect.
In order to overcome the problem that dosage forms such as Sibutramine hydrochloride tablet, capsule exist, number of patent application is in 200410037846.9 the patent of invention file, to disclose a kind of Sibuqumin hydrochloride drip pill.The substrate of selecting in this drop pill is poly-hydroxyl oxygen 40 esters of stearic acid, it have stronger draw moist, make drop pill after, draw wetly easily, medicine generation deliquescence is gone mouldy, influence medicine stability, be unfavorable for the storage of medicine.And it only plays the effect of single excipient, to the medicine active ingredient absorb and do not play a role.
(3) summary of the invention
The object of the present invention is to provide a kind of stability good, long shelf-life, the Sibuqumin hydrochloride drip pill that the utilization rate of active ingredient is high.
The object of the present invention is achieved like this:
It is the drop pill of being made by Sibutramine hydrochloride fine powder and substrate, and it is the drop pill of being made by Sibutramine hydrochloride fine powder and substrate, and described substrate is Polyethylene Glycol-4000 and beta-schardinger dextrin-, its weight be respectively Sibutramine hydrochloride 4-6 doubly with 1-3 doubly.Preferred version of the present invention is that substrate is Polyethylene Glycol-4000 and beta-schardinger dextrin-, its weight be respectively 5 times of Sibutramine hydrochloride with 2 times.
With the Sibutramine hydrochloride fine powder, with the beta-schardinger dextrin-substrate that accounts for the Polyethylene Glycol that the Sibutramine hydrochloride weight portion is 4-6 part-4000 and 1-3 part, fully mixing is condensed into drop pill with dropping preparation method in the coolant dimethicone.
The chemistry of the Sibutramine hydrochloride among the present invention is called (±) N-{1-[1-(4-chlorphenyl) cyclobutyl]-the 3-methyl butyl }-N, the N dimethylamine hydrochloride monohydrate, molecular formula is C
12H
26ClNHClH
2O, molecular weight are 334.33;
The molecular formula of Polyethylene Glycol-4000 is: HO (CH
2CH
2O)
nH
The molecular formula of beta-schardinger dextrin-is: (C
6H
10O
5) 7
Polyoxyethylene stearate 40 esters draw moist strong than Polyethylene Glycol-4000, make drop pill after, draw wetly easily, medicine generation deliquescence is gone mouldy, influence medicine stability, be unfavorable for the storage of medicine.It is substrate that the present invention selects the Polyethylene Glycol-4000 and the mixture of beta-schardinger dextrin-, has good stable, has guaranteed the safety of medicine in storing use.
The beta-schardinger dextrin-molecule is arranged in the form of a ring, and the hydroxyl on the glycoside base is the periphery of position circulus all, so peripherally become hydrophilic, inside is hydrophobicity, much small organic molecules can enclose in internal voids, microcapsule like the formation inclusion.Generally water-soluble with the clathrate that nonpolar drug molecule forms.Sibutramine hydrochloride is soluble in organic solvent, and is slightly water-soluble, beta-schardinger dextrin-can with its formation medicament microcapsule, improve medicine dissolution, increased medicine stability.
Beta-schardinger dextrin-not only can form medicament microcapsule with medicine, but and interlinkage in polymer, carry out chemical modification, increase medicine and the bonded tight type of substrate.
Drop pill of the present invention is in vivo after the disintegrate, Polyethylene Glycol-4000 has been finished the effect of excipient, and beta-schardinger dextrin-medicine enclose micromolecule still exists, because it is a biological micromolecule soluble in water, so accelerated the transport speed of medicine in body fluid greatly, promoted the performance of drug effect.
After considering that Sibutramine hydrochloride is made drop pill, in production, storage and transportation, may be subjected to the influence of light, heat, factor such as wet.Sibutramine hydrochloride crude drug and its adjuvant (mixed-matrix that Polyethylene Glycol-4000 and beta-schardinger dextrin-are formed) have been carried out influence factor's preliminarily stabilised investigation test.
With Sibutramine hydrochloride crude drug and mixed-matrix (1: 7) mixed melting by a certain percentage, make drop pill.Get wherein that a part places plastic bottle respectively, sealing.Carrying out high temperature (60 ℃), high humidity (RH90% ± 5%) and high light (observed 10 days under 4500 ± 500LX) conditions, in the 5th day and sampling in the 10th day, detects its outward appearance with ocular estimate and do not change; High performance liquid chromatography (HPLC method) is checked the situation of change of its content and weight, as following table:
Sibutramine hydrochloride and adjuvant interaction investigation table
| The investigation project | Weight (g) | Content (%) | ||||
| 0 day | 5 days | 10 days | 0 day | 5 days | 10 days | |
| High temperature | 1.0037 | 1.0038 | 1.0037 | 12.3 | 12.2 | 12.4 |
| High humidity | 1.0007 | 1.0007 | 1.0008 | 12.3 | 12.4 | 12.3 |
| High light | 0.9994 | 0.9993 | 0.9993 | 12.3 | 12.5 | 12.3 |
Above-mentioned result of the test shows, the mixed-matrix that Sibutramine hydrochloride and Polyethylene Glycol-4000 and beta-schardinger dextrin-are formed drips the system drop pill, at hyperpyrexia, under high humidity and the high light condition chemical change does not take place, illustrate that raw material and adjuvant are difficult for interacting, can carry out drop pill production.
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 of Chinese Pharmacopoeia version in 2005).
2. dissolution rate: sample thief according to dissolution method (two appendix first methods of Chinese Pharmacopoeia version in 2005), is a solvent with water 500ml, rotating speed is that per minute 50 changes, and operation in accordance with the law is in the time of 10,20,30 minutes, get solution 10ml and filter, get subsequent filtrate as need testing solution; Other gets, and Sibutramine hydrochloride reference substance (pressing anhydride calculates) is an amount of, and accurate the title decides, and being dissolved in water is diluted to the solution that contains 10 μ g among every 1ml approximately, in contrast product solution.Get above-mentioned two kinds of solution,, measure trap respectively, calculate, and result and 1.057 is multiplied each other, calculate dissolution at the wavelength place of 223nm according to spectrophotography (two appendix of Chinese Pharmacopoeia version in 2005).
Two, commercially available Sibutramine hydrochloride sheet check result
1. disintegration time: 37 minutes
2. dissolution rate:
| Time (minute) | 10 | 20 | 30 |
| Dissolution (%) | 45.3 | 70.9 | 91.6 |
Three, sample detection result
1. the molten diffusing time: 2 minutes
2. dissolution rate:
| Time (minute) | 10 | 20 | 30 |
| Dissolution (%) | 68.9 | 96.8 | 99.6 |
(4) specific embodiment
For a more detailed description to the present invention for example below:
Prescription:
Sibutramine hydrochloride 5g
Polyethylene Glycol-4000 25g
Beta-schardinger dextrin-10g
Make 1000
Method for making: Polyethylene Glycol-4000 and beta-schardinger dextrin-are fully mixed, put in 70～80 ℃ of water-baths behind the hot melt, add the Sibutramine hydrochloride fine powder, mixing is a coolant with the dimethicone, the dropping preparation method pill, and drying, promptly.
Claims (2)
1, a kind of Sibuqumin hydrochloride drip pill is characterized in that: it is the drop pill of being made by Sibutramine hydrochloride fine powder and substrate, and described substrate is Polyethylene Glycol-4000 and beta-schardinger dextrin-, its weight be respectively Sibutramine hydrochloride 4-6 doubly with 1-3 doubly.
2, Sibuqumin hydrochloride drip pill according to claim 1 is characterized in that: described substrate is Polyethylene Glycol-4000 and beta-schardinger dextrin-, its weight be respectively 5 times of Sibutramine hydrochloride with 2 times.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100098999A CN1327832C (en) | 2006-04-05 | 2006-04-05 | Sibuqumin hydrochloride drip pill |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100098999A CN1327832C (en) | 2006-04-05 | 2006-04-05 | Sibuqumin hydrochloride drip pill |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1823750A CN1823750A (en) | 2006-08-30 |
| CN1327832C true CN1327832C (en) | 2007-07-25 |
Family
ID=36934695
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100098999A Expired - Fee Related CN1327832C (en) | 2006-04-05 | 2006-04-05 | Sibuqumin hydrochloride drip pill |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1327832C (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1526379A (en) * | 2003-09-23 | 2004-09-08 | 南昌弘益科技有限公司 | Sibutramine hydrochloride dripping pill and its prepn |
| CN1543936A (en) * | 2003-10-29 | 2004-11-10 | 北京正大绿洲医药科技有限公司 | Sibutramine hydrochloride guttate pill |
-
2006
- 2006-04-05 CN CNB2006100098999A patent/CN1327832C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1526379A (en) * | 2003-09-23 | 2004-09-08 | 南昌弘益科技有限公司 | Sibutramine hydrochloride dripping pill and its prepn |
| CN1543936A (en) * | 2003-10-29 | 2004-11-10 | 北京正大绿洲医药科技有限公司 | Sibutramine hydrochloride guttate pill |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1823750A (en) | 2006-08-30 |
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Owner name: TIANNIAN PHARMACEUTICAL ( HARBIN ) CO., LTD. Free format text: FORMER OWNER: ZHAO WEIQING Effective date: 20090925 |
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Effective date of registration: 20090925 Address after: Heilongjiang city of Harbin province Yilan County Tong Road East Patentee after: Tiannian Pharmaceutical (Harbin) Co., Ltd. Address before: Daoli District in Heilongjiang province Harbin City Street No. 12 Room 802 Patentee before: Zhao Weiqing |
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