CN101530412A - Pharmaceutical composition of blonanserin and preparation method thereof - Google Patents
Pharmaceutical composition of blonanserin and preparation method thereof Download PDFInfo
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- CN101530412A CN101530412A CN200810101631A CN200810101631A CN101530412A CN 101530412 A CN101530412 A CN 101530412A CN 200810101631 A CN200810101631 A CN 200810101631A CN 200810101631 A CN200810101631 A CN 200810101631A CN 101530412 A CN101530412 A CN 101530412A
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Abstract
The invention discloses a [2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5, 6, 7, 8, 9, 10- hexahydro-cycloocta-(b) pyridine), a composition of salts thereof for medical purposes and a preparation method thereof. The pharmaceutical composition has such a stabilizing agent as alkaline substance with a weight not less than 10 percent. The composition has good stability and can block a 5-hydroxytryptamine-2 acceptor and a dopamine-2 acceptor and be applied to the treatment of schizophrenia.
Description
Technical field
The present invention relates to a kind of blonanserin (Blonanserin), chemical name [2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7 of comprising, 8,9,10-six hydrogen cycloocta-[b] pyridines] and the pharmaceutical composition of officinal salt, especially a kind of pharmaceutical composition that contains the alkalescence material.
Background technology
Central nervous system's 5-hydroxy tryptamine and dopamine all have important effect aspect the development of people's emotion and spiritual function, as if the development of the mental disorder that the malfunction of this system is relevant with cerebrovascular disease has confidential relation.
Chemotherapy for the mental disorder relevant with cerebrovascular disease, the report that application dopamine-2 receptor blocking agent (a kind of typical Antipsychotic drug) arranged before, such medicine is effective to a certain extent, but can make suffer from the dysthymic disorder, the conditions of patients deterioration of disease such as spontaneous reductions, so this medicine can not reach desirable therapeutic.
Inventor back after deliberation finds that the mental disorder that the chemical compound of energy blocking 5-hydroxytryptamine-2 receptor and dopamine-2 receptor is followed cerebrovascular disorders can demonstrate significant especially therapeutical effect.Application contains the preparation of preparation of compositions of the present invention, can be used to improve or cure patient by cerebral thrombosis and cerebral embolism and cerebral hemorrhage, simultaneously also can improve or cure other mood disorderss, for example anxiety, nervous, mental state is depressed, act on a momentary impulse, agitation, witless expression etc.; And spontaneous the reduction, for example enthusiasm lowers, desires to ask the interest minimizing of performance minimizing, active enthusiasm reduction, amusement and pastime etc.
The chemical compound of energy blocking 5-hydroxytryptamine-2 receptor and dopamine-2 receptor has a lot, comprises SM-9018, Rispcridonc, Ziprasidone, Seroquel, Olanzapine, Org-5222, blonanserin (Blonanserin), Ampcrozido, HP-873, Carvotroline.CN96101615 discloses with SM-9018, Rispcridonc, Ziprasidone, Seroquel, the pharmaceutical composition of the mental disorder that treatments such as Olanzapine are caused by cerebrovascular disorders, and pointed out that the result shows that this compounds can play definite curative effect really.
EP0385237 discloses new medicinal compound blonanserin and preparation method thereof, with and treat the purposes of spiritual sacred disease.The chemistry of blonanserin is called [2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-six hydrogen cycloocta-[b] pyridines], and its chemical constitution is as follows:
EP0385237 also discloses the employing corn starch, lactose, and crystalline cellulose, hyprolose etc. are the pharmaceutical composition of active component with the blonanserin as pharmaceutic adjuvant.Yet the disclosed technical scheme disease of employing EP0385237 can not obtain the formulation products of stable suitable clinical use, can not satisfy the needs of industrialization.
Summary of the invention
The purpose of this invention is to provide a kind of stable pharmaceutical composition, said composition can be further used for preparing oral solid formulation.
The invention provides a kind of compositions that comprises blonanserin or its officinal salt, contain be no less than 10% weight the alkalescence material as filler, be the alkaline stable environment of 7-9 for active substance provides pH.
The invention provides a kind of compositions that comprises blonanserin or its officinal salt, contain alkalescence materials such as inorganic base and organic base.Inorganic base can be selected from the citrate of sodium or potassium, carbonate, bicarbonate, phosphate, sulfate, benzoate and anti-bad thrombosis salt, and calcium carbonate and magnesium carbonate; Organic base is optional as N-methyl glucoside amine, guanine and arginic amine substance.
The invention provides a kind of compositions that comprises blonanserin or its officinal salt, the alkaline matter that contains is selected from one or more mixture of phosphate or carbonate.
The invention provides a kind of compositions that comprises blonanserin or its officinal salt, the alkaline matter that contains is a calcium hydrogen phosphate.
The invention provides a kind of compositions that comprises blonanserin or its officinal salt, wherein also contain combination greater than the diluent or the diluent of about 30% weight.
The invention provides a kind of compositions that comprises blonanserin or its officinal salt, wherein also can contain as one or more the mixture in diluent lactose monohydrate, Lactis Anhydrous or the microcrystalline Cellulose.
The invention provides a kind of compositions that comprises blonanserin or its officinal salt, wherein can also add lubricant, other adjuvants such as fluidizer.
The invention provides a kind of compositions that comprises blonanserin or its officinal salt, can exist for the form of tablet, capsule particle agent.
Pharmaceutical composition of the present invention can be by wet method or non-slurry pelletizing preparation, and other known any granulating techniques of this area may be used to purpose of the present invention in addition.
Said composition also can be added an amount of correctives and disintegrating agent and is prepared into oral cavity disintegration tablet, and described correctives comprises one or more mixture in sucralose, Ai Saimi, stevioside, the aspartame.Described disintegrating agent such as low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone and carboxymethyl starch sodium.Add filler such as sugar alcohols, starch, microcrystalline Cellulose during the pressing port cavity disintegrating tablet, lubricant such as magnesium stearate, Pulvis Talci, calcium stearate, hydrogenated vegetable oil and light silicic acid anhydride.
Embodiment
The present invention is further elaborated by following examples, but does not limit the scope of the invention.
Embodiment 1:
Preparation technology
Blonanserin was pulverized 100 mesh sieves, and mannitol, lactose, calcium hydrogen phosphate, microcrystalline Cellulose are crossed 80 mesh sieves respectively, and magnesium stearate is crossed 60 orders.Mixing in the mixer granulator fast, add entry system soft material by recipe quantity, cross 18 mesh sieves, in 55 ℃ of baking ovens, after the drying, cross 24 mesh sieve granulate, add the magnesium stearate of recipe quantity, the mixing tabletting, every contains blonanserin 5mg.
Embodiment 2:
Preparation technology
Blonanserin was pulverized 100 mesh sieves; mannitol, lactose, calcium hydrogen phosphate, microcrystalline Cellulose are crossed 80 mesh sieves respectively; mixing in the mixer granulator fast, add entry system soft material by recipe quantity, cross 18 mesh sieves; in 55 ℃ of baking ovens after the drying; cross 24 mesh sieve granulate, obtain evenly full granule of color and luster, add the micropowder silica gel of recipe quantity; mixing incapsulates in the shell.Every contains blonanserin 5mg.
Embodiment 3:
Preparation technology
Blonanserin was pulverized 100 mesh sieves; mannitol, lactose, calcium hydrogen phosphate, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 80 mesh sieves respectively; mixing in the mixer granulator fast by recipe quantity; add entry system soft material, cross 18 mesh sieves, in 55 ℃ of baking ovens after the drying; cross 24 mesh sieve granulate; the magnesium stearate that adds recipe quantity, mixing, tabletting.Every contains blonanserin 10mg
The comparative example 1:
Preparation technology
Blonanserin was pulverized 100 mesh sieves; lactose, corn starch, crystalline cellulose, hyprolose are crossed 80 mesh sieves respectively; mixing in the mixer granulator fast by recipe quantity; add entry system soft material, cross 18 mesh sieves, in 55 ℃ of baking ovens after the drying; cross 24 mesh sieve granulate; the magnesium stearate and the micropowder silica gel that add recipe quantity, mixing, tabletting.
The comparative example 2:
Preparation technology
Blonanserin was pulverized 100 mesh sieves; lactose, corn starch, hyprolose are crossed 80 mesh sieves respectively; mixing in the mixer granulator fast by recipe quantity; add entry system soft material, cross 18 mesh sieves, in 55 ℃ of baking ovens after the drying; cross 24 mesh sieve granulate; the magnesium stearate and the micropowder silica gel that add recipe quantity, mixing, fill capsule.
With the preparation produced among embodiment 1～3, the comparative example 1～2 in accelerated tests (40 ± 2 ℃ of temperature, humidity 75% ± 5%) related substance growth pattern is shown in table 1, the table 2 respectively and in the long-time stability experiment (25 ± 2 ℃ of temperature, humidity 60% ± 5%).
Table 1. accelerated tests result
| 1 month | 2 months | 3 months | 6 months | |
| Embodiment 1 | — | — | — | — |
| Embodiment 2 | — | — | — | — |
| Embodiment 3 | — | — | — | — |
| The comparative example 1 | — | — | + | + |
| The comparative example 2 | — | + | + | ++ |
Table 2. long-time stability experimental result
| 0 month | 3 months | 6 months | 9 months | 12 months | 18 months | |
| Embodiment 1 | — | — | — | — | — | — |
| Embodiment 2 | — | — | — | — | — | — |
| Embodiment 3 | — | — | — | — | — | — |
| The comparative example 1 | — | — | — | + | + | ++ |
| The comparative example 2 | — | — | + | + | ++ | ++ |
Annotate :-: the related substance growth was compared with 0 day and is no more than 0.05%
+: related substance increased with 0 day to be compared above 0.1%
++: related substance increased with 0 day to be compared above 0.5%
Therefore, from the result shown in table 1～table 2 as can be seen, the Orally-administered solid composition that contains blonanserin of the present invention is relatively stable, and other every assays also prove by the preparation of said composition preparation very stablely simultaneously, are a kind of good preparations therefore.
Claims (6)
1, the compositions of a kind of chemistry that comprises [2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-six hydrogen cycloocta-[b] pyridines] by name or its officinal salt contains the alkalescence material that is no less than 10% weight.
The mixture of one or more that 2, compositions as claimed in claim 1, wherein said alkalescence material are phosphate or carbonate.
3, as each described compositions of claim 1, wherein said alkalescence material is a calcium hydrogen phosphate.
4, compositions as claimed in claim 1 wherein also comprises the combination greater than the diluent or the diluent of about 30% weight.
5, compositions as claimed in claim 4, wherein said diluent are selected from one or more the mixture in lactose monohydrate, Lactis Anhydrous or the microcrystalline Cellulose.
6, compositions as claimed in claim 1 wherein can also add lubricant, and other adjuvants such as fluidizer can tablet or capsule form existence.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN200810101631A CN101530412A (en) | 2008-03-10 | 2008-03-10 | Pharmaceutical composition of blonanserin and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN200810101631A CN101530412A (en) | 2008-03-10 | 2008-03-10 | Pharmaceutical composition of blonanserin and preparation method thereof |
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| CN101530412A true CN101530412A (en) | 2009-09-16 |
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| CN200810101631A Pending CN101530412A (en) | 2008-03-10 | 2008-03-10 | Pharmaceutical composition of blonanserin and preparation method thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102038685A (en) * | 2010-11-29 | 2011-05-04 | 天津市汉康医药生物技术有限公司 | Blonanserin medicine composition with capacity of improving oral absorbability |
| CN102240270A (en) * | 2010-05-13 | 2011-11-16 | 丽珠医药集团股份有限公司 | Blonanserin tablet and preparation method thereof |
| CN101766626B (en) * | 2008-12-30 | 2012-03-07 | 丽珠医药集团股份有限公司 | Blonanserin-contained oral preparation for treating schizophrenia |
| CN102727453A (en) * | 2011-04-01 | 2012-10-17 | 北京德众万全医药科技有限公司 | Blonanserin dispersible tablet and its preparation method |
| CN102949392A (en) * | 2012-11-27 | 2013-03-06 | 西安泰科迈医药科技有限公司 | Medicinal composition for treating schizophrenia and preparation method thereof |
| JP2018203706A (en) * | 2017-06-08 | 2018-12-27 | 高田製薬株式会社 | Tablet containing blonanserin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0385237A2 (en) * | 1989-03-03 | 1990-09-05 | Dainippon Pharmaceutical Co., Ltd. | 2-(1-piperazinyl)-4-phenylcycloalkanopyridine derivatives, processes for the production thereof, and pharmaceutical composition containing the same |
| WO2006096439A2 (en) * | 2005-03-04 | 2006-09-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for the treatment and/or prevention of schizophrenia and related diseases |
-
2008
- 2008-03-10 CN CN200810101631A patent/CN101530412A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0385237A2 (en) * | 1989-03-03 | 1990-09-05 | Dainippon Pharmaceutical Co., Ltd. | 2-(1-piperazinyl)-4-phenylcycloalkanopyridine derivatives, processes for the production thereof, and pharmaceutical composition containing the same |
| WO2006096439A2 (en) * | 2005-03-04 | 2006-09-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for the treatment and/or prevention of schizophrenia and related diseases |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766626B (en) * | 2008-12-30 | 2012-03-07 | 丽珠医药集团股份有限公司 | Blonanserin-contained oral preparation for treating schizophrenia |
| CN102240270A (en) * | 2010-05-13 | 2011-11-16 | 丽珠医药集团股份有限公司 | Blonanserin tablet and preparation method thereof |
| CN102240270B (en) * | 2010-05-13 | 2013-01-02 | 丽珠医药集团股份有限公司 | Blonanserin tablet and preparation method thereof |
| CN102038685A (en) * | 2010-11-29 | 2011-05-04 | 天津市汉康医药生物技术有限公司 | Blonanserin medicine composition with capacity of improving oral absorbability |
| CN102727453A (en) * | 2011-04-01 | 2012-10-17 | 北京德众万全医药科技有限公司 | Blonanserin dispersible tablet and its preparation method |
| CN102949392A (en) * | 2012-11-27 | 2013-03-06 | 西安泰科迈医药科技有限公司 | Medicinal composition for treating schizophrenia and preparation method thereof |
| JP2018203706A (en) * | 2017-06-08 | 2018-12-27 | 高田製薬株式会社 | Tablet containing blonanserin |
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Application publication date: 20090916 |