CN105012302A - Tropisetron hydrochloride composition for vomit-stopping medicine - Google Patents
Tropisetron hydrochloride composition for vomit-stopping medicine Download PDFInfo
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- CN105012302A CN105012302A CN201510550155.7A CN201510550155A CN105012302A CN 105012302 A CN105012302 A CN 105012302A CN 201510550155 A CN201510550155 A CN 201510550155A CN 105012302 A CN105012302 A CN 105012302A
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- soz
- navoban
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- dihydrogen phosphate
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Abstract
The invention discloses tropisetron hydrochloride composition for a vomit-stopping medicine and belongs to the technical field of medicines. The composition comprises tropisetron hydrochloride and sodium dihydrogen phosphate, wherein tropisetron hydrochloride is crystals, and an X-ray powder diffraction pattern obtained through measurement of Cu=K-alpha rays is shown in Figure 1. The new crystal form of tropisetron hydrochloride is different from a crystal form structure in the prior art, tests verify that the purity of the composition with the new crystal form is high, the fluidity is good, the stability is good, the content of impurities is low, moisture absorption is unlikely to occur, clinical applications are safe and reliable, and a powder injection prepared from the composition with the new crystal form is good in stability even after being mixed with a solvent, contains few insoluble particles and is very suitable for clinical application.
Description
Technical field
The invention belongs to medical art, relate to a kind of antiemetic Navoban (Soz) compositions.
Background technology
Navoban (Soz) is selectivity peripheral neurons and central nervous system's 5-seretonine receptor 5 antagonist, can selectively block vomiting reflex maincenter, the excitement of peripheral neurons presynaptic 5-seretonine receptor 5, act on 5-seretonine receptor 5 of the vagal activity importing nervus centralis area postrema into, can the nausea and vomiting that caused by chemotherapy of Prevention and Curation, do not cause extrapyramidal system untoward reaction.
In prior art, for the crystal formation of Navoban (Soz), had many research, but the hygroscopicity of impurity content, stability and crystal formation is still undesirable, brings difficulty also to while have impact on self stability the preparation of preparation.
The present invention is through a large amount of experimental studies, and obtained a kind of Navoban (Soz) crystalline compounds being different from prior art, the purity of this Tropiseiron hydrochloride compound is high, good fluidity, good stability, not easily moisture absorption, impurity content is low, preparation for preparation brings conveniently, and clinical practice is safe and reliable, utilizes the injectable powder that this crystal compound is obtained, good stability, good with solvent compatibility rear stability, particulate matter content is extremely low, is very suitable for clinical practice.
In prior art, for the crystal formation of Navoban (Soz), had many research, but the hygroscopicity of impurity content, stability and crystal formation is still undesirable, brings difficulty also to while have impact on self stability the preparation of preparation.
The present invention, through a large amount of experimental studies, has obtained a kind of Navoban (Soz) crystalline compounds being different from prior art, has passed through verification experimental verification, surprisingly find that this crystal compound purity is high, good fluidity, good stability, impurity content is low, not easily moisture absorption, clinical practice is safe and reliable, utilizes the injectable powder that this crystal compound is obtained, good stability, good with solvent compatibility rear stability, particulate matter content is extremely low, is very suitable for clinical practice.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of antiemetic Navoban (Soz) compositions.
In order to complete object of the present invention, the technical scheme of employing is:
A kind of antiemetic Navoban (Soz) compositions, consisting of of described compositions: Navoban (Soz) 1 weight portion, sodium dihydrogen phosphate 0.03-0.07 weight portion; Described Navoban (Soz) is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
Preferably, consisting of of described compositions: Navoban (Soz) 1 weight portion, sodium dihydrogen phosphate 0.04-0.06 weight portion.
Preferably, consisting of of described compositions: Navoban (Soz) 1 weight portion, sodium dihydrogen phosphate 0.05 weight portion.
Preferably, the dosage form of described compositions is injection, and the preparation method of described injection comprises the following steps:
(1) take Navoban (Soz) crystal and sodium dihydrogen phosphate in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
The preparation method of the Navoban (Soz) crystal in described compositions comprises the following steps:
1) dimethyl formamide and water are mixed with mixed solution A with the volume ratio of 1:4;
2) Navoban (Soz) crude drug is got, add the mixed solution A that step 1) is prepared, the volume of wherein said mixed solution A is 10ml:1g with the ratio of the quality of Navoban (Soz), stirring makes all to dissolve in backward gained solution to add 0.1%g/ml activated carbon decolorizing, filtration, obtains settled solution;
3) diisopropyl ether and isopropyl alcohol are mixed with mixed solution B with the volume ratio of 2:3.5;
4) under room temperature, be to step 2 at power under the ultrasonic field of 0.8KW) add mixed solution B in the settled solution of gained, wherein the addition of mixed solution B is 5 times of the volume of mixed solution A, finish closedown ultrasonic field, be cooled to 0 DEG C, leave standstill 3 hours, crystallize out, drying obtains described Tropiseiron hydrochloride compound.
The polymorphism of solid chemical is the natural phenomena that a kind of general material exists, this phenomenon refers to that a kind of solid chemical can exist 2 kinds or two or more crystal form state, be also called the polymorphic state of material, the polymorphic state of material is also referred to as " allomorphism " phenomenon.Although its chemical nature of allomorphous solid matter is identical, its physicochemical property may be different.For " allomorphism medicine " that physicochemical property is different, also can show the curative effect of different disease preventing and treating clinically, directly affect application and the clinical effectiveness of medicine.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction that the Navoban (Soz) crystal of the embodiment of the present invention 1 preparation uses the measurement of Cu-K alpha ray to obtain.
Detailed description of the invention
Below by specific embodiment, summary of the invention of the present invention is described in further detail, but does not therefore limit content of the present invention.
embodiment 1:the preparation of Navoban (Soz) crystal
1) dimethyl formamide and water are mixed with mixed solution A with the volume ratio of 1:4;
2) Navoban (Soz) crude drug is got, add the mixed solution A that step 1) is prepared, the volume of wherein said mixed solution A is 10ml:1g with the ratio of the quality of Navoban (Soz), stirring makes all to dissolve in backward gained solution to add 0.1%g/ml activated carbon decolorizing, filtration, obtains settled solution;
3) diisopropyl ether and isopropyl alcohol are mixed with mixed solution B with the volume ratio of 2:3.5;
4) under room temperature, be to step 2 at power under the ultrasonic field of 0.8KW) add mixed solution B in the settled solution of gained, wherein the addition of mixed solution B is 5 times of the volume of mixed solution A, finish closedown ultrasonic field, be cooled to 0 DEG C, leave standstill 3 hours, crystallize out, drying obtains described Tropiseiron hydrochloride compound.
As shown in Figure 1, its purity of high-performance liquid chromatogram determination is 99.9% to the X-ray powder diffraction pattern that the Navoban (Soz) crystal prepared uses the measurement of Cu-K alpha ray to obtain.
embodiment 2:the preparation of Navoban (Soz) compositions:
Consist of: Navoban (Soz) crystal 1 weight portion prepared by the present invention, sodium dihydrogen phosphate 0.03 weight portion.
Preparation method is:
(1) take Navoban (Soz) crystal and sodium dihydrogen phosphate in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 3:the preparation of Navoban (Soz) compositions:
Consist of: Navoban (Soz) crystal 1 weight portion prepared by the present invention, sodium dihydrogen phosphate 0.04 weight portion.
Preparation method is:
(1) take Navoban (Soz) crystal and sodium dihydrogen phosphate in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 4:the preparation of Navoban (Soz) compositions:
Consist of: Navoban (Soz) crystal 1 weight portion prepared by the present invention, sodium dihydrogen phosphate 0.05 weight portion.
Preparation method is:
(1) take Navoban (Soz) crystal and sodium dihydrogen phosphate in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 5:the preparation of Navoban (Soz) compositions:
Consist of: Navoban (Soz) crystal 1 weight portion prepared by the present invention, sodium dihydrogen phosphate 0.06 weight portion.
Preparation method is:
(1) take Navoban (Soz) crystal and sodium dihydrogen phosphate in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 6:the preparation of Navoban (Soz) compositions:
Consist of: Navoban (Soz) crystal 1 weight portion prepared by the present invention, sodium dihydrogen phosphate 0.07 weight portion.
Preparation method is:
(1) take Navoban (Soz) crystal and sodium dihydrogen phosphate in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
experimental example 1:fluidity test
The mobility of this experimental example to the Navoban (Soz) crystal that the embodiment of the present invention 1 obtains detects.
Method: according to the embodiment of the present invention 1 method continuous production 6 batches of Navoban (Soz)s (batch: 1,2,3,4,5 and 6), sample from 6 batches of obtained Navoban (Soz)s respectively, adopt fixed funnel method, funnel is placed in the suitable height on graph paper, Navoban (Soz) crystal is freely flowed down from bell mouth, until the cone top formed contacts with bell mouth, measure hypotenuse and the horizontal angle (θ angle of repose) of Navoban (Soz) accumulation horizon.The results are shown in Table 1:
The fluidity test result of table 1 Navoban (Soz)
From the interpretation of table 1, the mobility of Navoban (Soz) crystal of the present invention is fine.
experimental example 2:influence factor tests
1, hot test
The Navoban (Soz) crystalline compounds that Example 1 prepares, simulation listing packaging, puts in sealing clean container, place 10 days at 40 ± 2 DEG C of temperature, in the 5th day and sampling in the 10th day, detect by stability high spot reviews project, result of the test compared with 0 day.
2, high humility test
The Navoban (Soz) crystalline compounds that Example 1 prepares, simulation listing packaging, put in sealing clean container, place 10 days under the condition of 25 ± 2 DEG C of relative humiditys 90% ± 5%, in the 5th day and sampling in the 10th day, detect by stability high spot reviews project, result of the test compared with 0 day.
3, strong illumination test
The Navoban (Soz) crystalline compounds that Example 1 prepares, simulation listing packaging, puts in sealing clean container, being placed in illumination is place 10 days under the condition of 4500lx, in the 5th day and sampling in the 10th day, detect by stability high spot reviews project, result compared with 0 day.The results are shown in Table 2
Table 2 influence factor result of the test
Result shows: the Navoban (Soz) crystalline compounds that the present invention prepares, and its stability is good, and under high temperature, high humidity, high light conditions, equal retention is stablized.
experimental example 3:acceleration study
The Navoban (Soz) crystalline compounds that Example 1 prepares 3 batches and marketable material, simulation listing packaging, put in sealing clean container, in 40 DEG C ± 2 DEG C, place 6 months under relative humidity 70% ± 5% condition, at duration of test respectively at 1,2,3,6 sampling at the end of month once, each stability high spot reviews project is tested.The results are shown in Table 3.
Table 3 accelerated test result
Result shows: the Navoban (Soz) crystalline compounds that the present invention prepares, known through accelerated test result, its good stability, and total assorted content is low.
experimental example 4:wettability test
1 instrument
PL203 electronic balance, LRH-250-S constant temperature and humidity incubator, HH-400SD testing chamber for medicine stability;
2 methods
Get the glass desicator (for ensureing that saline solution is saturated, excessive salt should be had bottom exsiccator to exist) that bottom fills salt supersaturated solution, the built-in weighing botle of exsiccator, places 48h to constant humidity in calorstat.Sample thief is about 2g, puts in weighing botle, accurately weighed, bottle cap is opened, puts into exsiccator top, put in 25 DEG C of constant temperature and humidity incubators or 20 DEG C of stability test casees by different temperatures requirement and preserve, operation repetitive 3 parts, weighs respectively at different time, calculates the hydroscopicity of different time.
Computing formula: hydroscopicity=(medicated powder weight after moisture absorption-moisture absorption prodrug grain weight amount)/moisture absorption prodrug grain weight amount × 100%.Result is as table 4:
Table 4 hygroscopicity test results
According to above-mentioned experiment, the hygroscopicity of Navoban (Soz) crystalline compounds prepared by the present invention is low, good stability.
Claims (5)
1. an antiemetic Navoban (Soz) compositions, is characterized in that: described compositions consist of Navoban (Soz) 1 weight portion, sodium dihydrogen phosphate 0.03-0.07 weight portion; Described Navoban (Soz) is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
2. antiemetic Navoban (Soz) compositions according to claim 1, is characterized in that: described compositions consist of Navoban (Soz) 1 weight portion, sodium dihydrogen phosphate 0.04-0.06 weight portion.
3. antiemetic Navoban (Soz) compositions according to claim 2, is characterized in that: described compositions consist of Navoban (Soz) 1 weight portion, sodium dihydrogen phosphate 0.05 weight portion.
4. antiemetic Navoban (Soz) compositions according to claim 1, is characterized in that, the dosage form of described compositions is injection, and the preparation method of described injection comprises the following steps:
(1) take Navoban (Soz) and sodium dihydrogen phosphate in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
5. antiemetic Navoban (Soz) compositions according to claim 1, is characterized in that, the crystal preparation method of described Navoban (Soz) is:
1) dimethyl formamide and water are mixed with mixed solution A with the volume ratio of 1:4;
2) Navoban (Soz) crude drug is got, add the mixed solution A that step 1) is prepared, the volume of wherein said mixed solution A is 10ml:1g with the ratio of the quality of Navoban (Soz), stirring makes all to dissolve in backward gained solution to add 0.1%g/ml activated carbon decolorizing, filtration, obtains settled solution;
3) diisopropyl ether and isopropyl alcohol are mixed with mixed solution B with the volume ratio of 2:3.5;
4) under room temperature, be to step 2 at power under the ultrasonic field of 0.8KW) add mixed solution B in the settled solution of gained, wherein the addition of mixed solution B is 5 times of the volume of mixed solution A, finish closedown ultrasonic field, be cooled to 0 DEG C, leave standstill 3 hours, crystallize out, drying obtains described Tropiseiron hydrochloride compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510550155.7A CN105012302A (en) | 2015-09-01 | 2015-09-01 | Tropisetron hydrochloride composition for vomit-stopping medicine |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510550155.7A CN105012302A (en) | 2015-09-01 | 2015-09-01 | Tropisetron hydrochloride composition for vomit-stopping medicine |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102351857A (en) * | 2011-08-23 | 2012-02-15 | 天津市汉康医药生物技术有限公司 | Tropiseiron hydrochloride compound |
| CN102367252A (en) * | 2011-11-03 | 2012-03-07 | 天津市汉康医药生物技术有限公司 | Tropisetron hydrochloride compound |
| CN103360386A (en) * | 2013-07-18 | 2013-10-23 | 珠海金鸿药业股份有限公司 | Tropisetron hydrochloride compound, its preparation method, and pharmaceutical composition containing the same |
| CN104844591A (en) * | 2014-02-17 | 2015-08-19 | 中国医学科学院药物研究所 | Tropisetron hydrochloride crystal form II substance, preparation method, composition and uses thereof |
-
2015
- 2015-09-01 CN CN201510550155.7A patent/CN105012302A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102351857A (en) * | 2011-08-23 | 2012-02-15 | 天津市汉康医药生物技术有限公司 | Tropiseiron hydrochloride compound |
| CN102367252A (en) * | 2011-11-03 | 2012-03-07 | 天津市汉康医药生物技术有限公司 | Tropisetron hydrochloride compound |
| CN103360386A (en) * | 2013-07-18 | 2013-10-23 | 珠海金鸿药业股份有限公司 | Tropisetron hydrochloride compound, its preparation method, and pharmaceutical composition containing the same |
| CN104844591A (en) * | 2014-02-17 | 2015-08-19 | 中国医学科学院药物研究所 | Tropisetron hydrochloride crystal form II substance, preparation method, composition and uses thereof |
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