CN105125500A - Medicine hydrochloric acid fasudil composite dry suspension for treating ischemic cerebrovascular disease - Google Patents
Medicine hydrochloric acid fasudil composite dry suspension for treating ischemic cerebrovascular disease Download PDFInfo
- Publication number
- CN105125500A CN105125500A CN201510632895.5A CN201510632895A CN105125500A CN 105125500 A CN105125500 A CN 105125500A CN 201510632895 A CN201510632895 A CN 201510632895A CN 105125500 A CN105125500 A CN 105125500A
- Authority
- CN
- China
- Prior art keywords
- fasudic hydrochloride
- dry suspension
- crystal
- weight portion
- medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Landscapes
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses medicine hydrochloric acid fasudil composite dry suspension for treating ischemic cerebrovascular disease, and belongs to the technical field of medicine. The composite dry suspension is prepared from hydrochloric acid fasudil, mannitol, sodium alginate, locust bean gum, sodium stearyl alcohol sulfonate, steviosin and 95% ethyl alcohol. Hdrochloric acid fasudil is a new-crystal-form compound; an X-ray powder diffraction pattern obtained through measurement of Cu-K alpha rays is shown in figure 1, and hydrochloric acid fasudil is different from hydrochloric acid fasudil reported in the prior art; it is found through experiments that the new-crystal-form compound is high in purity, mobility and stability, low in impurity content, not prone to moisture absorption and safe and reliable in clinical application; the dry suspension prepared from the new-crystal-form compound is high in stability and bioavailability and quite suitable for clinical application.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine Fasudic hydrochloride compositions dry suspension for the treatment of ischemic cerebrovascular.
Background technology
Fasudic hydrochloride (fasudilhydrochloride, 1) is a kind of novel isoquinoline sulphonamide derivatives of Japanese Asahi Kasei Corporation and Nagoya University cooperative development.As Ca in a kind of RHO inhibitors of kinases and novel cell
2+antagonist, this medicine, by increasing the active blood vessel dilating of Myosin light chain phosphatase, reduces the tension force of endotheliocyte, improves cerebral tissue microcirculation, protection ischemic tissue of brain, simultaneously can antagonism inflammatory factor, and neuroprotective anti-apoptotic, promotes neuranagenesis.June nineteen ninety-five is gone on the market by Japanese Asahi Kasei Corporation, and within 2004, in Discussion on Chinese Listed, be mainly used in the improvement of the ischemic cerebrovascular symptom that cerebral vasospasm after subarachnoid hemorrhage etc. causes, its clinical application range also will constantly be expanded, and market prospect is had an optimistic view of.
Draw moist because Fasudic hydrochloride has, the change of the physicochemical properties such as the decline of caking, mobility, deliquescence, crystal formation change can be caused after moisture absorption, thus affect the interior qualities such as product stability, effectiveness, safety.But prior art does not propose corresponding solution, the crystal formation involved by prior art does not also improve this.
Material owing to affecting by various factors, makes in molecule or molecular linkage mode changes when crystallization, cause molecule or atom different in lattice vacancy arrangement, form different crystal structures.Polymorph in pharmaceuticals phenomenon is one of key factor affecting drug quality and clinical efficacy, and therefore in Control of drug quality, crystal formation is one of them important quality control index.The quality of polymorphism on product of medicine has important impact.The compound that crystal structure is different, due to the difference of its molecules align order, be in different energy state respectively, usual unformed medicine has larger potential energy, interparticle bond strength is little compared with crystal formation, total per surface free energy is comparatively large, surface easily aquation between particle, thus causes the difference with crystalline azithromycin dissolubility.In the structure cell of different crystal forms, molecule is different from arrangement in steric configuration, conformation, its dissolubility is made to there is significant difference, preparation is caused to have different dissolution rates in vivo, directly affect preparation absorption in vivo, distribution, excretion and metabolism, finally cause the difference of clinical drug effect because its bioavailability is different.
The present inventor starts with from Fasudic hydrochloride crude drug, has carried out a large amount of tests, obtains a kind of Fasudic hydrochloride crystalline compounds being different from prior art, the purity of this fasudil hydrochloride compound is high, good fluidity, good stability, not easily moisture absorption, impurity content is low, and the preparation for preparation brings conveniently, and clinical practice is safe and reliable, utilize the dry suspension that this crystal compound is obtained, good stability, bioavailability is high, is very suitable for clinical practice.
In prior art, for the crystal formation of Fasudic hydrochloride, 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 Fasudic hydrochloride crystalline compounds being different from prior art, the purity of this fasudil hydrochloride compound is high, good fluidity, good stability, not easily moisture absorption, impurity content is low, preparation for preparation brings conveniently, clinical practice is safe and reliable, utilizes the dry suspension that this crystal compound is obtained, good stability, bioavailability is high, is very suitable for clinical practice.
Summary of the invention
Goal of the invention of the present invention is the medicine Fasudic hydrochloride compositions dry suspension providing treatment ischemic cerebrovascular.
In order to complete object of the present invention, the technical scheme of employing is:
Treat a medicine Fasudic hydrochloride compositions dry suspension for ischemic cerebrovascular, described compositions dry suspension is made up of Fasudic hydrochloride, mannitol, sodium alginate, locust bean gum, stearyl alcohol sodium sulfonate, steviosin, 95% ethanol; Described Fasudic hydrochloride 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, described compositions dry suspension is made up of the Fasudic hydrochloride of 3 weight portions, the mannitol of 18-20 weight portion, the sodium alginate of 4-6 weight portion, the locust bean gum of 1.5-1.7 weight portion, the stearyl alcohol sodium sulfonate of 0.9-1.0 weight portion, the steviosin of 0.25-0.35 weight portion, 95% ethanol of 9-10 weight portion.
Preferably, described compositions dry suspension is made up of the Fasudic hydrochloride of 3 weight portions, the mannitol of 19 weight portions, the sodium alginate of 5 weight portions, the locust bean gum of 1.6 weight portions, the stearyl alcohol sodium sulfonate of 0.95 weight portion, the steviosin of 0.3 weight portion, 95% ethanol of 9.5 weight portions.
Preferably, the preparation method of described compositions dry suspension comprises the following steps:
(1) supplementary material process: sieve Fasudic hydrochloride 100 orders;
(2) weigh: weigh according to prescription;
(3) granulate: Fasudic hydrochloride, mannitol, sodium alginate, locust bean gum, stearyl alcohol sodium sulfonate, steviosin are added in wet mixing pelletizer, be dry mixed 10 minutes, 95% ethanol is joined wet mixing pelletizer wet mixing cutting, select 18 orders granulation soft material processed;
(4) dry granulate: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 60-65 DEG C, dry total time is 3-3.5 hour, by material 20 order granulate after drying;
(5) mix: granule after granulate is dropped into three-dimensional motion mixer, premixing speed 15 revs/min, incorporation time 5 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
Preferably, the preparation method of the crystal of described Fasudic hydrochloride comprises the following steps:
(1) be dissolved in by Fasudic hydrochloride in the mixed solvent of methanol and propyl acetate, the solvent load that needs of every gram of Fasudic hydrochloride is 120ml, and the volume ratio of methanol and propyl acetate is 5:3;
(2), after being heated to 30 DEG C of dissolvings, after cool to room temperature, crystal seed is added;
(3) be cooled to less than-5 DEG C, stirring and crystallizing, the temperature of crystallize is-10 DEG C, filters, dry, collects crystal and namely obtains Fasudic hydrochloride crystal.
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 Fasudic hydrochloride 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 Fasudic hydrochloride crystal
(1) be dissolved in by Fasudic hydrochloride in the mixed solvent of methanol and propyl acetate, the solvent load that needs of every gram of Fasudic hydrochloride is 120ml, and the volume ratio of methanol and propyl acetate is 5:3;
(2), after being heated to 30 DEG C of dissolvings, after cool to room temperature, crystal seed is added;
(3) be cooled to less than-5 DEG C, stirring and crystallizing, the temperature of crystallize is-10 DEG C, filters, dry, collects crystal and namely obtains Fasudic hydrochloride crystal.
The X-ray powder diffraction pattern that the Fasudic hydrochloride crystal prepared uses the measurement of Cu-K alpha ray to obtain as shown in Figure 1.
embodiment 2:the preparation of Fasudic hydrochloride dry suspension, step is as follows:
Prescription: Fasudic hydrochloride crystal-form compound, the mannitol of 18 weight portions, the sodium alginate of 4 weight portions, the locust bean gum of 1.5 weight portions, the stearyl alcohol sodium sulfonate of 0.9 weight portion, the steviosin of 0.25 weight portion, 95% ethanol of 9 weight portions that the embodiment 1 of 3 weight portions is obtained.
Preparation method:
(1) supplementary material process: sieve Fasudic hydrochloride 100 orders;
(2) weigh: weigh according to prescription;
(3) granulate: Fasudic hydrochloride, mannitol, sodium alginate, locust bean gum, stearyl alcohol sodium sulfonate, steviosin are added in wet mixing pelletizer, be dry mixed 10 minutes, 95% ethanol is joined wet mixing pelletizer wet mixing cutting, select 18 orders granulation soft material processed;
(4) dry granulate: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 60-65 DEG C, dry total time is 3-3.5 hour, by material 20 order granulate after drying;
(5) mix: granule after granulate is dropped into three-dimensional motion mixer, premixing speed 15 revs/min, incorporation time 5 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
embodiment 3:the preparation of Fasudic hydrochloride dry suspension, step is as follows:
Prescription: Fasudic hydrochloride crystal-form compound, the mannitol of 19 weight portions, the sodium alginate of 5 weight portions, the locust bean gum of 1.6 weight portions, the stearyl alcohol sodium sulfonate of 0.95 weight portion, the steviosin of 0.3 weight portion, 95% ethanol of 9.5 weight portions that the embodiment 1 of 3 weight portions is obtained.
Preparation method:
(1) supplementary material process: sieve Fasudic hydrochloride 100 orders;
(2) weigh: weigh according to prescription;
(3) granulate: Fasudic hydrochloride, mannitol, sodium alginate, locust bean gum, stearyl alcohol sodium sulfonate, steviosin are added in wet mixing pelletizer, be dry mixed 10 minutes, 95% ethanol is joined wet mixing pelletizer wet mixing cutting, select 18 orders granulation soft material processed;
(4) dry granulate: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 60-65 DEG C, dry total time is 3-3.5 hour, by material 20 order granulate after drying;
(5) mix: granule after granulate is dropped into three-dimensional motion mixer, premixing speed 15 revs/min, incorporation time 5 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
embodiment 4:the preparation of Fasudic hydrochloride dry suspension, step is as follows:
Prescription: Fasudic hydrochloride crystal-form compound, the mannitol of 20 weight portions, the sodium alginate of 6 weight portions, the locust bean gum of 1.7 weight portions, the stearyl alcohol sodium sulfonate of 1.0 weight portions, the steviosin of 0.35 weight portion, 95% ethanol of 10 weight portions that the embodiment 1 of 3 weight portions is obtained.
Preparation method:
(1) supplementary material process: sieve Fasudic hydrochloride 100 orders;
(2) weigh: weigh according to prescription;
(3) granulate: Fasudic hydrochloride, mannitol, sodium alginate, locust bean gum, stearyl alcohol sodium sulfonate, steviosin are added in wet mixing pelletizer, be dry mixed 10 minutes, 95% ethanol is joined wet mixing pelletizer wet mixing cutting, select 18 orders granulation soft material processed;
(4) dry granulate: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 60-65 DEG C, dry total time is 3-3.5 hour, by material 20 order granulate after drying;
(5) mix: granule after granulate is dropped into three-dimensional motion mixer, premixing speed 15 revs/min, incorporation time 5 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
experimental example 1:fluidity test
The mobility of this experimental example to the Fasudic hydrochloride 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 Fasudic hydrochlorides (batch: 1,2,3,4,5 and 6), sample from 6 batches of obtained Fasudic hydrochlorides respectively, adopt fixed funnel method, funnel is placed in the suitable height on graph paper, Fasudic hydrochloride 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 Fasudic hydrochloride accumulation horizon.The results are shown in Table 1:
The fluidity test result of table 1 Fasudic hydrochloride
From the interpretation of table 1, the mobility of Fasudic hydrochloride crystal of the present invention is fine.
experimental example 2:influence factor tests
1, hot test
The Fasudic hydrochloride 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 Fasudic hydrochloride 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 Fasudic hydrochloride 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 Fasudic hydrochloride 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 Fasudic hydrochloride 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 Fasudic hydrochloride 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 Fasudic hydrochloride crystalline compounds prepared by the present invention is low, good stability.
Claims (5)
1. treat the medicine Fasudic hydrochloride compositions dry suspension of ischemic cerebrovascular, it is characterized in that: described compositions dry suspension is made up of Fasudic hydrochloride, mannitol, sodium alginate, locust bean gum, stearyl alcohol sodium sulfonate, steviosin, 95% ethanol; Described Fasudic hydrochloride 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. the medicine Fasudic hydrochloride compositions dry suspension for the treatment of ischemic cerebrovascular according to claim 1, is characterized in that: described compositions dry suspension is made up of the Fasudic hydrochloride of 3 weight portions, the mannitol of 18-20 weight portion, the sodium alginate of 4-6 weight portion, the locust bean gum of 1.5-1.7 weight portion, the stearyl alcohol sodium sulfonate of 0.9-1.0 weight portion, the steviosin of 0.25-0.35 weight portion, 95% ethanol of 9-10 weight portion.
3. the medicine Fasudic hydrochloride compositions dry suspension for the treatment of ischemic cerebrovascular according to claim 2, is characterized in that: described compositions dry suspension is made up of the Fasudic hydrochloride of 3 weight portions, the mannitol of 19 weight portions, the sodium alginate of 5 weight portions, the locust bean gum of 1.6 weight portions, the stearyl alcohol sodium sulfonate of 0.95 weight portion, the steviosin of 0.3 weight portion, 95% ethanol of 9.5 weight portions.
4. the medicine Fasudic hydrochloride compositions dry suspension of the treatment ischemic cerebrovascular according to any one of claim 1-3, it is characterized in that, the preparation method of described compositions dry suspension comprises the following steps:
(1) supplementary material process: sieve Fasudic hydrochloride 100 orders;
(2) weigh: weigh according to prescription;
(3) granulate: Fasudic hydrochloride, mannitol, sodium alginate, locust bean gum, stearyl alcohol sodium sulfonate, steviosin are added in wet mixing pelletizer, be dry mixed 10 minutes, 95% ethanol is joined wet mixing pelletizer wet mixing cutting, select 18 orders granulation soft material processed;
(4) dry granulate: the wet granular of granulation gained is evenly split on the drip pan of baking oven, set temperature 60-65 DEG C, dry total time is 3-3.5 hour, by material 20 order granulate after drying;
(5) mix: granule after granulate is dropped into three-dimensional motion mixer, premixing speed 15 revs/min, incorporation time 5 minutes are set;
(6) pack: carry out subpackage according to after the theoretical loading amount scope of total mixed gained material cubage.
5. the medicine Fasudic hydrochloride compositions dry suspension for the treatment of ischemic cerebrovascular according to claim 1, it is characterized in that, the preparation method of the crystal of described Fasudic hydrochloride comprises the following steps:
(1) be dissolved in by Fasudic hydrochloride in the mixed solvent of methanol and propyl acetate, the solvent load that needs of every gram of Fasudic hydrochloride is 120ml, and the volume ratio of methanol and propyl acetate is 5:3;
(2), after being heated to 30 DEG C of dissolvings, after cool to room temperature, crystal seed is added;
(3) be cooled to less than-5 DEG C, stirring and crystallizing, the temperature of crystallize is-10 DEG C, filters, dry, collects crystal and namely obtains Fasudic hydrochloride crystal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510632895.5A CN105125500A (en) | 2015-09-30 | 2015-09-30 | Medicine hydrochloric acid fasudil composite dry suspension for treating ischemic cerebrovascular disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510632895.5A CN105125500A (en) | 2015-09-30 | 2015-09-30 | Medicine hydrochloric acid fasudil composite dry suspension for treating ischemic cerebrovascular disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105125500A true CN105125500A (en) | 2015-12-09 |
Family
ID=54711330
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510632895.5A Withdrawn CN105125500A (en) | 2015-09-30 | 2015-09-30 | Medicine hydrochloric acid fasudil composite dry suspension for treating ischemic cerebrovascular disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105125500A (en) |
-
2015
- 2015-09-30 CN CN201510632895.5A patent/CN105125500A/en not_active Withdrawn
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10961192B2 (en) | (R)-4-hydroxy-2-oxo-1-pyrrolidineacetamide crystal form, preparation method therefor, and application thereof | |
| CN108368061A (en) | The solid form of substituted 5,6- dihydros -6- phenyl benzo [F] isoquinolin -2- amine compounds | |
| CN105125500A (en) | Medicine hydrochloric acid fasudil composite dry suspension for treating ischemic cerebrovascular disease | |
| CN105055337A (en) | Medicament namely fasudil hydrochloride composite granules for treating cerebral ischemia | |
| UA125938C2 (en) | Crystalline form of n-butyldeoxygalactonojirimycin | |
| CN105012310A (en) | Angiectasis medicine fasudil hydrochloride composition | |
| CN105055425A (en) | Medicine hydroxyfasudil composition granula for treating cerebral ischemia | |
| CN105213404A (en) | A kind of medicine Fasudic hydrochloride compositions for the treatment of cerebrovascular disease | |
| CN105106155A (en) | Fasudil hydrochloride composition tablets capable of improving cerebral vasospasm | |
| CN105055369A (en) | Vasodilatation medicament namely fasudil hydrochloride composition capsules | |
| CN105055332A (en) | Hydroxyfasudil composition dry suspension for treating ischemic cerebrovascular diseases | |
| CN105168176A (en) | Pharmaceutical fasudil hydrochloride composition capsule for angiectasis | |
| CN104983704A (en) | Medicine fasudil hydrochloride composition tablet capable of relieving cerebral angiospasm | |
| CN105193737A (en) | Medicinal tropisetron hydrochloride composition dry suspension for treating nausea and emesis | |
| CN104945397B (en) | Medicine Tropiseiron hydrochloride compound for the treatment of nausea and vomiting and preparation method thereof | |
| CN105147699A (en) | Medicinal fasudil hydrochloride composition for treating cerebral ischemia | |
| CN105125518A (en) | Medicinal tropisetron hydrochloride composition capsule for treating nausea and vomiting | |
| CN105055334A (en) | Postoperative antiemetic tropisetron hydrochloride composition granule | |
| CN105125496A (en) | Medicinal fasudil hydrochloride composition for treating ischemic cerebrovascular diseases | |
| CN105859748B (en) | Polycyclic compound sodium salt and its polymorphic, preparation method and application | |
| CN105193729A (en) | Pharmaceutical tropisetron hydrochloride composition dry suspension for treating nausea and vomiting both caused by chemotherapy | |
| CN105193711A (en) | Medicine fasudil hydrochloride composition water injection for treating cerebrovascular disease | |
| CN105125561A (en) | Fasudil hydrochloride composition freeze-dried powder injection for treating cerebrovascular diseases | |
| CN105078921A (en) | Medical tropisetron hydrochloride composition capsule for treating nausea and vomiting | |
| CN105147685A (en) | Tropisetron hydrochloride composition granules serving as postoperative vomit-stopping medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20151209 |
|
| WW01 | Invention patent application withdrawn after publication |