CN109453112A - A kind of selective serotonin 3(5-HT3) receptor antagonist and preparation method - Google Patents
A kind of selective serotonin 3(5-HT3) receptor antagonist and preparation method Download PDFInfo
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- CN109453112A CN109453112A CN201811514640.9A CN201811514640A CN109453112A CN 109453112 A CN109453112 A CN 109453112A CN 201811514640 A CN201811514640 A CN 201811514640A CN 109453112 A CN109453112 A CN 109453112A
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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
- A61K9/08—Solutions
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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Abstract
A kind of selective serotonin 3 (5-HT3) receptor antagonist of the invention, including following component:
Description
Technical field
The present invention relates to a kind of selective serotonin 3 (5-HT3) receptor antagonists, belong to antiemetic technical field.
Background technique
Nausea and vomiting is common adverse reaction during disease treatment, serious vomiting not only makes patient not feel good,
It is demoralized, and will lead to electrolyte imbalance, nutritional deficiency, seriously undermine itself resistance of patient's body.
Currently used known antiemetic is broadly divided into three categories: 5-HT3 receptor antagonist, nk 1 receptor antagonist and
Traditional antiemetic.Wherein 5-HT3 receptor antagonist passes through the 5-HT3 receptor of selective exclusion periphery and maincenter, to effectively control
Vomiting caused by inhibition and generation is treated, significant effect, adverse reaction are small, thus have obtained preferable clinical application.
Dolasetron mesilate and its active metabolite Reduced dolasetron (MDL-74156) be selective 5-HT3 by
Body antagonist, and other known 5-HT receptor is not acted on, it is low with dopamine receptor compatibility.It is generally acknowledged that chemotherapeutic
Object causes small enterochromaffin cell to discharge serotonin, and serotonin activation causes to vomit positioned at the 5-HT3 receptor that fan walks efferent nerve
Reflection is spat, to generate nausea and vomiting.Dolasetron mesilate mechanism of action be by antagonism periphery vagus nerve ending and
5-HT3 receptor is removed in the impression of maincenter emetic chemical, to inhibit the generation of Nausea and vomiting.
There are colour changed into yellow especially under illumination condition during preservation for existing dolasetron mesilate injection, related
The problems such as substance increases.
Summary of the invention
In order to overcome the deficiencies of the prior art, the present invention proposes a kind of selective serotonin 3 (5-HT3) receptor antagonist,
Property is stablized, and light resistance is good, and color change and related substance increased feelings will not be generated under the influence of long-term undesirable element
Condition.
To achieve the above object, a kind of selective serotonin 3 (5-HT3) receptor antagonist, including following component:
Further, department's fine jade class medicament includes Granisetron Hydrochloride, Tropisetron, Ondansetron, hydrochloric acid Pa Luonuosi
Fine jade, dolasetron mesilate, it is preferred to use dolasetron mesilate.
Further, the usage amount of dolasetron mesilate is 12.5g.
Further, stabilizer includes mannitol, sorbierite, glucose, it is preferred to use mannitol.
Further, the usage amount of mannitol is 38.2g.
Further, the acetate buffer solution that buffer is configured using sodium acetate and glacial acetic acid, the concentration of buffer are
50mmol/L, the pH value of buffer are 3.0~3.3.
The present invention also proposes that a kind of preparation method of selective serotonin 3 (5-HT3) receptor antagonist, feature exist
In, comprising the following steps:
S1: the acetate buffer solution of 50mmol/L is configured；
S2: measuring 80% water for injection, is cooled to room temperature, and mannitol, stirring to achromaticity and clarification is added；
S3: dolasetron mesilate, stirring to achromaticity and clarification are added in the water for injection into S2；
S4: being added acetate buffer solution obtained in step S1 in the water for injection into S3, adjusts pH value to 3.2
~3.8；
S5: 1000mL is added water for injection to；
S6: injection made from S5 is potted；
S7: the sample after encapsulating is put into sterilizing cabinet, is hunted leak and is sterilized；
S8: lamp inspection.
Further, in step s 6, potting process whole process nitrogen charging, and product remaining oxygen need to be controlled within 3%.
Further, in the step s 7, sterilising temp is 115 DEG C or more, and sterilization time is 15min or more.
A kind of selective serotonin 3 (5-HT3) receptor antagonist property of the invention is stablized, and light resistance is good, long-term
Undesirable element under the influence of will not generate color change and related substance increase the case where.And one of present invention selects
Property serotonin 3 (5-HT3) receptor antagonist preparation method simple and reliable process, be made product stablize effectively, be suitable for work
Industry large-scale production.
Specific embodiment
Below by by the description to the preferred embodiment of the present invention, skill of the invention is more clearly and completely illustrated
Art scheme.
Embodiment 1: the preparation of selective serotonin 3 (5-HT3) receptor antagonist, comprising the following steps:
S1: weighing 0.0732g sodium acetate, measures 2.8mL glacial acetic acid and is dissolved into appropriate water for injection, and is diluted to
The acetate buffer solution of 50mmol/L is made in 1000mL；
S2: weighing the water for injection of 80% total amount, be cooled to room temperature, and the mannitol of 38.2g, stirring and dissolving is added；
S3: the dolasetron mesilate of 12.5g, stirring and dissolving is added；
S4: acetate buffer solution, adjustment pH value to 3.2~3.8 is added；
S5: benefit injects water to 1000mL；
S6: encapsulating, nitrogen charging before and after encapsulating, and control remaining oxygen≤3% of product；
S7: hunting leak to the injection after encapsulating, and the 30min that sterilizes under conditions of 115 DEG C；
S8: lamp inspection.
Embodiment 2: the preparation of selective serotonin 3 (5-HT3) receptor antagonist, comprising the following steps:
S1: weighing 0.0732g sodium acetate, measures 2.8mL glacial acetic acid and is dissolved into appropriate water for injection, and is diluted to
The acetate buffer solution of 50mmol/L is made in 1000mL；
S2: weighing the water for injection of 80% total amount, be cooled to room temperature, and the mannitol of 40g, stirring and dissolving is added；
S3: the dolasetron mesilate of 20g, stirring and dissolving is added；
S4: acetate buffer solution, adjustment pH value to 3.2~3.8 is added；
S5: benefit injects water to 1000mL；
S6: encapsulating, nitrogen charging before and after encapsulating, and control remaining oxygen≤2% of product；
S7: hunting leak to the injection after encapsulating, and the 30min that sterilizes under conditions of 115 DEG C；
S8: lamp inspection.
Embodiment 3: the preparation of selective serotonin 3 (5-HT3) receptor antagonist, comprising the following steps:
S1: weighing 0.0732g sodium acetate, measures 2.8mL glacial acetic acid and is dissolved into appropriate water for injection, and is diluted to
The acetate buffer solution of 50mmol/L is made in 1000mL；
S2: weighing the water for injection of 80% total amount, be cooled to room temperature, and the mannitol of 30g, stirring and dissolving is added；
S3: the dolasetron mesilate of 10g, stirring and dissolving is added；
S4: acetate buffer solution, adjustment pH value to 3.2~3.8 is added；
S5: benefit injects water to 1000mL；
S6: encapsulating, nitrogen charging before and after encapsulating, and control remaining oxygen≤1% of product；
S7: hunting leak to the injection after encapsulating, and the 30min that sterilizes under conditions of 115 DEG C；
S8: lamp inspection.
Embodiment 4: the preparation of selective serotonin 3 (5-HT3) receptor antagonist, comprising the following steps:
S1: weighing 0.0732g sodium acetate, measures 2.8mL glacial acetic acid and is dissolved into appropriate water for injection, and is diluted to
The acetate buffer solution of 50mmol/L is made in 1000mL；
S2: weighing the water for injection of 80% total amount, be cooled to room temperature, and the mannitol of 35g, stirring and dissolving is added；
S3: the dolasetron mesilate of 15g, stirring and dissolving is added；
S4: acetate buffer solution, adjustment pH value to 3.2~3.8 is added；
S5: benefit injects water to 1000mL；
S6: encapsulating, nitrogen charging before and after encapsulating, and control remaining oxygen≤3% of product；
S7: hunting leak to the injection after encapsulating, and the 15min that sterilizes under conditions of 121 DEG C；
S8: lamp inspection.
Embodiment 5: the preparation of selective serotonin 3 (5-HT3) receptor antagonist, comprising the following steps:
S1: weighing 0.0732g sodium acetate, measures 2.8mL glacial acetic acid and is dissolved into appropriate water for injection, and is diluted to
The acetate buffer solution of 50mmol/L is made in 1000mL；
S2: weighing the water for injection of 80% total amount, be cooled to room temperature, and the mannitol of 30g, stirring and dissolving is added；
S3: the dolasetron mesilate of 20g, stirring and dissolving is added；
S4: acetate buffer solution, adjustment pH value to 3.2~3.8 is added；
S5: benefit injects water to 1000mL；
S6: encapsulating, nitrogen charging before and after encapsulating, and control remaining oxygen≤2% of product；
S7: hunting leak to the injection after encapsulating, and the 15min that sterilizes under conditions of 121 DEG C；
S8: lamp inspection.
Embodiment 6: the preparation of selective serotonin 3 (5-HT3) receptor antagonist, comprising the following steps:
S1: weighing 0.0732g sodium acetate, measures 2.8mL glacial acetic acid and is dissolved into appropriate water for injection, and is diluted to
The acetate buffer solution of 50mmol/L is made in 1000mL；
S2: weighing the water for injection of 80% total amount, be cooled to room temperature, and the mannitol of 40g, stirring and dissolving is added；
S3: the dolasetron mesilate of 10g, stirring and dissolving is added；
S4: acetate buffer solution, adjustment pH value to 3.2~3.8 is added；
S5: benefit injects water to 1000mL；
S6: encapsulating, nitrogen charging before and after encapsulating, and control remaining oxygen≤1% of product；
S7: hunting leak to the injection after encapsulating, and the 15min that sterilizes under conditions of 121 DEG C；
S8: lamp inspection.
Comparative example: reference substance uses commercial product, the dolasetron mesilate of Liaoning Hasco Pharmaceutical Co., Ltd.'s production
Injection, trade name: it is vertical to answer, tear label off.
Test method: carrying out influence factor exposure experiments to light, and illumination condition is 4500Lux ± 500Lux, is investigated.
Test result see the table below:
Test result analysis: experiments have shown that after illumination in 30 days, embodiment 1, embodiment 4 and comparative example color become yellowish
Color, related substance increase obvious.After remaining oxygen reduces in the product of embodiment 2 and embodiment 5, though related substance is also increased
Add, but increasing degree becomes smaller.Product remaining oxygen in embodiment 3 and embodiment 6 controls when within 1%, does not generate new miscellaneous
Matter.Illustrate to control the remaining oxygen in product, solution turned yellow and the increase in relation to substance can be slowed down.Comparative example 3 and example 6 are found
Different sterilising conditions are on product quality without influence.It further proves, when the nitrogen charging before and after encapsulating, and product remaining oxygen is lower than 1%
When, it can effectively avoid solution turned yellow and increase of the reduction in relation to substance.
A kind of selective serotonin 3 (5-HT3) receptor antagonist property of the invention is stablized, and light resistance is good, long-term
Undesirable element under the influence of without color change, do not occur yet related substance increase the case where.And one of present invention selects
Property serotonin 3 (5-HT3) receptor antagonist preparation method simple and reliable process, be made product stablize effectively, be suitable for work
Industry large-scale production.
Only preferred embodiments of the present invention will be described for above-mentioned specific embodiment, and not to guarantor of the invention
Shield range is defined.Under the premise of not departing from design concept of the present invention and scope, those skilled in the art
Provided verbal description various modifications to made by technical solution of the present invention, substitution and improvement according to the present invention, should all
Belong to protection category of the invention.Protection scope of the present invention is determined by claim.
Claims (9)
1. a kind of selective serotonin 3 (5-HT3) receptor antagonist, which is characterized in that including following component:
2. a kind of selective serotonin 3 (5-HT3) receptor antagonist as described in claim 1, which is characterized in that the department
Fine jade class medicament includes Granisetron Hydrochloride, Tropisetron, Ondansetron, palonosetron Hcl, dolasetron mesilate, preferably
Using dolasetron mesilate.
3. a kind of selective serotonin 3 (5-HT3) receptor antagonist as claimed in claim 2, which is characterized in that the first
The usage amount of sulfonic acid Dolasetron is 12.5g.
4. a kind of selective serotonin 3 (5-HT3) receptor antagonist as described in claim 1, which is characterized in that described steady
Determining agent includes mannitol, sorbierite, glucose, it is preferred to use mannitol.
5. a kind of selective serotonin 3 (5-HT3) receptor antagonist as claimed in claim 4, which is characterized in that described sweet
The usage amount for revealing alcohol is 38.2g.
6. a kind of selective serotonin 3 (5-HT3) receptor antagonist as described in claim 1, which is characterized in that described slow
The acetate buffer solution that fliud flushing is prepared using sodium acetate and glacial acetic acid, the concentration of the buffer are 50mmol/L, described slow
The pH value of fliud flushing is 3.0~3.3.
7. a kind of preparation method of selective serotonin 3 (5-HT3) receptor antagonist, which comprises the following steps:
S1: the acetate buffer solution of 50mmol/L is configured；
S2: measuring 80% water for injection, be cooled to room temperature, and the mannitol of recipe quantity, stirring to achromaticity and clarification is added；
S3: the dolasetron mesilate of recipe quantity, stirring to achromaticity and clarification are added in the water for injection into S2；
S4: being added acetate buffer solution obtained in step S1 in the water for injection into S3, adjusts pH value to 3.2~3.8；
S5: 1000mL is added water for injection to；
S6: injection made from S5 is potted；
S7: the sample after encapsulating is put into sterilizing cabinet, is hunted leak and is sterilized；
S8: lamp inspection.
8. a kind of selective serotonin 3 (5-HT3) receptor antagonist as claimed in claim 7, which is characterized in that in step
In S6, potting process whole process nitrogen charging, and product remaining oxygen need to be controlled within 3%.
9. a kind of selective serotonin 3 (5-HT3) receptor antagonist as claimed in claim 7, which is characterized in that in step
In S7, sterilising temp is 121 DEG C, sterilization time 15min.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2018115019189 | 2018-12-10 | ||
| CN201811501918 | 2018-12-10 |
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| Publication Number | Publication Date |
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| CN109453112A true CN109453112A (en) | 2019-03-12 |
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| CN201811514640.9A Pending CN109453112A (en) | 2018-12-10 | 2018-12-12 | A kind of selective serotonin 3(5-HT3) receptor antagonist and preparation method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111789812A (en) * | 2020-09-01 | 2020-10-20 | 南京恩泰医药科技有限公司 | Dolasetron mesylate oral solution and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1843356A (en) * | 2006-02-21 | 2006-10-11 | 成都欣捷高新技术开发有限公司 | Powder injection of dolasetron and its pharmaceutically acceptable salt, and its preparation method |
| CN103006547A (en) * | 2011-09-28 | 2013-04-03 | 辽宁海思科制药有限公司 | Dolasetron mesylate containing injection, as well as preparation method and quality control method thereof |
| CN103040721A (en) * | 2012-12-17 | 2013-04-17 | 海南百思特医药科技有限公司 | Dolasetron mesylate lipidosome injection |
| CN103360392A (en) * | 2013-06-21 | 2013-10-23 | 辽宁海思科制药有限公司 | Dolasetron mesylate compound |
-
2018
- 2018-12-12 CN CN201811514640.9A patent/CN109453112A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1843356A (en) * | 2006-02-21 | 2006-10-11 | 成都欣捷高新技术开发有限公司 | Powder injection of dolasetron and its pharmaceutically acceptable salt, and its preparation method |
| CN103006547A (en) * | 2011-09-28 | 2013-04-03 | 辽宁海思科制药有限公司 | Dolasetron mesylate containing injection, as well as preparation method and quality control method thereof |
| CN103040721A (en) * | 2012-12-17 | 2013-04-17 | 海南百思特医药科技有限公司 | Dolasetron mesylate lipidosome injection |
| CN103360392A (en) * | 2013-06-21 | 2013-10-23 | 辽宁海思科制药有限公司 | Dolasetron mesylate compound |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111789812A (en) * | 2020-09-01 | 2020-10-20 | 南京恩泰医药科技有限公司 | Dolasetron mesylate oral solution and preparation method thereof |
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Application publication date: 20190312 |