CN109464408A - A kind of succinic acid SB 209509 piece - Google Patents
A kind of succinic acid SB 209509 piece Download PDFInfo
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- CN109464408A CN109464408A CN201811618547.2A CN201811618547A CN109464408A CN 109464408 A CN109464408 A CN 109464408A CN 201811618547 A CN201811618547 A CN 201811618547A CN 109464408 A CN109464408 A CN 109464408A
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- Prior art keywords
- succinic acid
- parts
- diluent
- adhesive
- piece
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Biophysics (AREA)
- Pain & Pain Management (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
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- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of succinic acid SB 209509 pieces, belong to field of pharmaceutical preparations.The present invention provides a kind of succinic acid SB 209509 pieces, by succinic acid SB 209509, diluent, adhesive, disintegrating agent and lubricant composition, the diluent is made of lactose and sucrose, and described adhesive includes one or both of PVP-VA and Macrogol 6000, and the disintegrating agent includes one of cross-linked pvp and sodium alginate or a variety of.Screening is optimized to diluent and adhesive first in the present invention, it determines and diluent is formed by lactose and sucrose, adhesive is selected from one or both of PVP-VA and Macrogol 6000, then determine that disintegrating agent is selected from one of cross-linked pvp and sodium alginate or a variety of, it is verified by stability test, succinic acid SB 209509 piece performance of the invention is stablized.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of succinic acid SB 209509 piece.
Background technique
Migraine is a kind of common chronic, repeated relapsing disease, is worldwide widely current, seriously affects trouble
The quality of life of person.
Recently the morbidity of migraine is thought originating from central nervous system, and because of cerebral cortex dysfunction, while it is interior to occur together
Secretion and vasomotor dysfunction and cause Headache attacks.It is existing it has proven convenient that with migraine attack it is in close relations be 5-HT1 by
Body.
SB 209509 is second generation triptan drug, belongs to selectivity 5-HT1B and 5-HT1D receptor subtype agonist, with 5-
HT1B and 5-HT1D receptor has high affinity, and the affinity to 5-HT1B is most powerhouse in triptan drug, mechanism of action
Mainly by inhibiting brain outer and the overdistension of entocranial artery achievees the effect that treatment migraine.SB 209509 earliest by
GlaxoSmithKine company exploitation, after transfer Venalis company, in June, 2002 is in U.S.'s Initial Public Offering, trade name
FROVA is clinically used for the acute treatment of the adult migraine with or without tendency, now multiple in Germany and Britain etc.
European countries' listing, by the Menarini company of Italy with trade name Miguard sale.Preclinical and clinical research confirmation,
The product is in treatment adult, the safe and effective drug of severe migraine.
The application form of SB 209509 is succinic acid SB 209509, chemical name are as follows: (R) -3- (methylamino) -2,3,4,
9- tetrahydro -1H- carbazole -6- formamide succinic acid, structural formula is as follows, is a kind of novel new antimigraine drug, main function
In artery outside brain and entocranial artery, and inhibit the overdistension of these blood vessels.As second generation triptan drug, first is overcome
The shortcomings that, half-life short, high recurrence rate low for 5-HT1B/1D receptor stimulating agent oral administration biaavailability.
Lack the stable succinic acid SB 209509 pharmaceutical preparation of performance currently on the market.
Summary of the invention
The purpose of the present invention is to provide a kind of stable succinic acid SB 209509 piece.
To solve this technical problem, the technical solution that the application proposes is:
A kind of succinic acid SB 209509 piece, by succinic acid SB 209509, diluent, adhesive, disintegrating agent and lubricant group
At the diluent is made of lactose and sucrose, and described adhesive includes one of PVP-VA and Macrogol 6000 or two
Kind, the disintegrating agent includes one of cross-linked pvp and sodium alginate or a variety of.
Preferably, described adhesive is selected from PVP-VA.
Preferably, the disintegrating agent is selected from cross-linked pvp.
The composition of each component by weight is as follows:
0.1-10 parts of succinic acid SB 209509
30-70 parts of diluent
20-40 parts of adhesive
5-20 parts of disintegrating agent
0.1-1 parts of lubricant.
Preferably, the composition of each component by weight is as follows:
0.5-5 parts of succinic acid SB 209509
40-60 parts of diluent
25-35 parts of adhesive
10-18 parts of disintegrating agent
0.2-0.6 parts of lubricant.
Most preferably, the composition of each component by weight is as follows:
3 parts of succinic acid SB 209509
50 parts of diluent
30 parts of adhesive
15 parts of disintegrating agent
0.5 part of lubricant.
Wherein, the weight ratio of lactose and sucrose is 10:40-40:10 in diluent.
Preferably, the weight ratio of lactose and sucrose is 15:35-35:15 in diluent.
Beneficial effects of the present invention:
Although mostly there is stability problem there are succinic acid SB 209509 piece in the prior art, this is because amber
Amber acid SB 209509 is incompatible with most of additive of tablet, and there are stability problem, related substance is difficult to solve.The present invention is first
Screening is optimized to diluent and adhesive, determines that the diluent being made of lactose and sucrose, adhesive are selected from PVP-VA
One or both of with Macrogol 6000, then determine that disintegrating agent is selected from one of cross-linked pvp and sodium alginate or more
Kind, it is verified by stability test, succinic acid SB 209509 piece performance of the invention is stablized.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip
Part or according to the normal condition proposed by manufacturer.Unless otherwise stated, otherwise all percentage, ratio, ratio or number is pressed
Poidometer.
Unless otherwise defined, all professional and scientific terms as used herein and meaning familiar to those skilled in the art
Justice is identical.In addition, any method similar to or equal to what is recorded and material can be applied to the method for the present invention.Wen Zhong
The preferred implement methods and materials are for illustrative purposes only.
The optimization of optimization one succinic acid SB 209509 piece diluent and adhesive of experiment
It is pelletized according to the weight formula of table 1, using wet granule compression tablet, prepares the implementation of succinic acid SB 209509 piece
Example 1-9.
1 succinic acid SB 209509 slice prescription (one) of table
The succinic acid SB 209509 piece of Example 1-9 be placed in high temperature (40 DEG C), illumination (4500 ± 500Lx), low temperature (-
18 DEG C) under the conditions of, it samples within the 10th day, each inspection target of stability test is detected, the results are shown in Table 2-3.
2 succinic acid SB 209509 piece accelerated test result (one) of table
3 succinic acid SB 209509 piece accelerated test result (two) of table
According to the above results it is found that embodiment 4, embodiment 6, embodiment 7 and the accelerated test rear stability of embodiment 9 compared with
It is good, thus determine that diluent is screened in lactose and sucrose, adhesive screens in PVP-VA and Macrogol 6000.
It is pelletized according to the weight formula of table 4, using wet granule compression tablet, prepares the implementation of succinic acid SB 209509 piece
Example 10-14.
4 succinic acid SB 209509 slice prescription (two) of table
The succinic acid SB 209509 piece of Example 10-14 is placed in high temperature (40 DEG C), illumination (4500 ± 500Lx), low temperature
Under the conditions of (- 18 DEG C), samples within the 10th day, each inspection target of stability test is detected, the results are shown in Table 5.
5 succinic acid SB 209509 piece accelerated test result (three) of table
According to the above results it is found that the stability of embodiment 10 and embodiment 14 is preferable, in the considerations of simplifying prescription, choosing
Lactose and sucrose are selected as diluent, selects PVP-VA as adhesive.
The optimization of optimization experiment disuccinic acid SB 209509 piece disintegrating agent
It is pelletized according to the weight formula of table 6, using wet granule compression tablet, prepares the implementation of succinic acid SB 209509 piece
Example 15-21.
6 succinic acid SB 209509 slice prescription (three) of table
The succinic acid SB 209509 piece of Example 15-21 is placed in high temperature (40 DEG C), illumination (4500 ± 500Lx), low temperature
Under the conditions of (- 18 DEG C), samples within the 10th day, each inspection target of stability test is detected, the results are shown in Table 7.
7 succinic acid SB 209509 piece accelerated test result (four) of table
According to the above results it is found that the stability of embodiment 16 and embodiment 20 is preferable, in the considerations of simplifying prescription, choosing
Lactose and sucrose are selected as diluent, selects PVP-VA as adhesive, selective cross-linking PVP is as disintegrating agent.
Stability test
It is pelletized according to the weight formula of table 8, using wet granule compression tablet, prepares the implementation of succinic acid SB 209509 piece
Example 22-26.
8 succinic acid SB 209509 slice prescription (four) of table
The succinic acid SB 209509 piece of Example 22-26 is placed in high temperature (40 DEG C), illumination (4500 ± 500Lx), low temperature
Under the conditions of (- 18 DEG C), was sampled respectively at the 5th, 10 day, each inspection target of stability test is detected, the results are shown in Table 9.
9 succinic acid SB 209509 piece accelerated test result of table
The succinic acid SB 209509 piece of Example 22-26 is placed in 40 DEG C, under the conditions of RH75%, respectively at the 0th, 1,2,3
Moon sampling, detects stability test items inspection target.It the results are shown in Table 10.
10 succinic acid SB 209509 tablet stability test result of table
The succinic acid SB 209509 piece of Example 22-26 is placed under room temperature, is sampled respectively at the 0th, 3 months, right
Stability test items inspection target is detected.It the results are shown in Table 11.
11 succinic acid SB 209509 piece of table keeps sample test result for a long time
According to result above it is found that the succinic acid SB 209509 tablet stability test result of the application meets the requirements.
The foregoing is merely illustrative of the preferred embodiments of the present invention, the substantial technological content model being not intended to limit the invention
It encloses, substantial technological content of the invention is broadly defined in the scope of the claims of application, any technology that other people complete
Entity or method also or a kind of equivalent change, will if identical with defined in the scope of the claims of application
It is considered as being covered by among the scope of the claims.
Claims (8)
1. a kind of succinic acid SB 209509 piece, which is characterized in that by succinic acid SB 209509, diluent, adhesive, disintegrating agent and
Lubricant composition, the diluent are made of lactose and sucrose, and described adhesive includes in PVP-VA and Macrogol 6000
One or two, the disintegrating agent include one of cross-linked pvp and sodium alginate or a variety of.
2. succinic acid SB 209509 piece according to claim 1, which is characterized in that described adhesive is selected from PVP-VA.
3. succinic acid SB 209509 piece according to claim 1, which is characterized in that the disintegrating agent is selected from cross-linked pvp.
4. succinic acid SB 209509 piece according to claim 1-3, which is characterized in that it is formed by weight
Are as follows:
0.1-10 parts of succinic acid SB 209509
30-70 parts of diluent
20-40 parts of adhesive
5-20 parts of disintegrating agent
0.1-1 parts of lubricant.
5. succinic acid SB 209509 piece according to claim 1-3, which is characterized in that it is formed by weight
Are as follows:
0.5-5 parts of succinic acid SB 209509
40-60 parts of diluent
25-35 parts of adhesive
10-18 parts of disintegrating agent
0.2-0.6 parts of lubricant.
6. succinic acid SB 209509 piece according to claim 1-3, which is characterized in that it is formed by weight
Are as follows:
3 parts of succinic acid SB 209509
50 parts of diluent
30 parts of adhesive
15 parts of disintegrating agent
0.5 part of lubricant.
7. according to the described in any item succinic acid SB 209509 pieces of claim 4-6, which is characterized in that lactose and sugarcane in diluent
The weight ratio of sugar is 10:40-40:10.
8. according to the described in any item succinic acid SB 209509 pieces of claim 4-6, which is characterized in that lactose and sugarcane in diluent
The weight ratio of sugar is 15:35-35:15.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811618547.2A CN109464408A (en) | 2018-12-28 | 2018-12-28 | A kind of succinic acid SB 209509 piece |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811618547.2A CN109464408A (en) | 2018-12-28 | 2018-12-28 | A kind of succinic acid SB 209509 piece |
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| Publication Number | Publication Date |
|---|---|
| CN109464408A true CN109464408A (en) | 2019-03-15 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811618547.2A Pending CN109464408A (en) | 2018-12-28 | 2018-12-28 | A kind of succinic acid SB 209509 piece |
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| Country | Link |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110898017A (en) * | 2019-12-11 | 2020-03-24 | 正大制药（青岛）有限公司 | Frovatriptan succinate dropping pill and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006042249A2 (en) * | 2004-10-08 | 2006-04-20 | Neuromolecular Pharmaceuticals, Inc. | Methods and compositions for treating migraine pain |
| CN103385876A (en) * | 2012-05-08 | 2013-11-13 | 四川滇虹医药开发有限公司 | Frovatriptan medicine composition and preparation method thereof |
| CN104758268A (en) * | 2015-04-22 | 2015-07-08 | 青岛正大海尔制药有限公司 | Frovatriptan succinate tablet and preparation method thereof |
-
2018
- 2018-12-28 CN CN201811618547.2A patent/CN109464408A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006042249A2 (en) * | 2004-10-08 | 2006-04-20 | Neuromolecular Pharmaceuticals, Inc. | Methods and compositions for treating migraine pain |
| CN103385876A (en) * | 2012-05-08 | 2013-11-13 | 四川滇虹医药开发有限公司 | Frovatriptan medicine composition and preparation method thereof |
| CN104758268A (en) * | 2015-04-22 | 2015-07-08 | 青岛正大海尔制药有限公司 | Frovatriptan succinate tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 方亮主编: "《药剂学 第3版》", 31 March 2016, 中国医药科技出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110898017A (en) * | 2019-12-11 | 2020-03-24 | 正大制药（青岛）有限公司 | Frovatriptan succinate dropping pill and preparation method thereof |
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Application publication date: 20190315 |