CN1836651A - Levogyration sulpiride injection and its preparation method - Google Patents
Levogyration sulpiride injection and its preparation method Download PDFInfo
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- CN1836651A CN1836651A CN 200610026137 CN200610026137A CN1836651A CN 1836651 A CN1836651 A CN 1836651A CN 200610026137 CN200610026137 CN 200610026137 CN 200610026137 A CN200610026137 A CN 200610026137A CN 1836651 A CN1836651 A CN 1836651A
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Abstract
The preparation process of levosulpiride injection features that levosulpiride is dissolved with injection water containing pharmaceutically acceptable acid of the same molar amount to regulate the pH value of the injection to 4-6. The said process can prepare water injection and frozen powder for injection with less side effect and high stability.
Description
Technical field
The present invention relates to a kind of preparation method of Levogyration sulpiride injection and its, more specifically relate to the preparation method of a kind of left-handed sulpiride aqueous injection and lyophilized injectable powder.
Background technology
The chemical name of left-handed sulpiride is: (S)-(-)-5-(amino-sulfonyl)-N-[(1-ethyl-2-pyrrolidinyl) methyl]-the 2-methoxy benzamide, its structure is as follows:
Clinical vomiting and the gastric dynamic dysfunction of being used for the treatment of of left-handed sulpiride, heavy dose of as tranquilizer.Because the left-handed sulpiride utmost point is insoluble in water, volume ratio meter by weight, therefore its dissolubility in water can not directly be configured to aqueous solution for muscle or intravenous injection less than 0.01%.At present commercially available left-handed sulpiride preparation mostly is oral formulations such as tablet, capsule, and regular meeting the patient occurs and is difficult to case of oral administration in the clinical practice.Therefore significant by intramuscular injection or intravenous administration.Use the left-handed sulpiride of high dose as ataractic psychotic or other serious diseases patient for needs, drug administration by injection also is unusual important mode.
Because left-handed sulpiride has the utmost point and is insoluble in water, and its amido link such as can be hydrolyzed at characteristic in strong acid-alkali medium, is difficult to be mixed with injection, has not yet to see the report of relevant Levogyration sulpiride injection and its preparation method.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of Levogyration sulpiride injection and its.Utilize this method can prepare favorable solubility and stay-in-grade left-handed sulpiride aqueous injection or lyophilized injectable powder.
The inventive method comprises the left-handed sulpiride of dissolving, regulates pH, adds activated carbon filtration, use the microporous filter membrane fine straining, and resulting injection is sterilized through packing and made aqueous injection or make step such as injectable powder through lyophilization, and its characteristics are as follows:
(1) left-handed sulpiride is dissolved in the water for injection that contains pharmaceutically acceptable acid, and said pharmaceutically acceptable acid refers to pharmaceutically acceptable ore deposit acid or acid strong organic acid, wherein preferred hydrochloric acid or sulphuric acid or benzenesulfonic acid or citric acid, most preferably hydrochloric acid.In mole, the consumption of pharmaceutically acceptable acid and left-handed sulpiride equates that the mol ratio of promptly pharmaceutically acceptable acid and left-handed sulpiride is 1: 1; In the water for injection of mole pharmaceutically acceptable acids such as containing, the dissolubility of left-handed sulpiride can be increased to 0.025%～3% (bulking value specific concentration).
(2) regulate pH to 4.0-6.0, in this pH scope, prepared left-handed sulpiride injection has good stability, store 2 years and degraded does not take place yet or separate out precipitation, and this injection can stand 30 minutes 115 ℃ of flowing steam sterilizations and not degrade after packing is finished, manufactured goods can not produce zest and anaphylaxis to blood vessel yet, are suitable for muscle or intravenous injection; According to the present invention, preferred pH regulator is to 4.0-5.0, and under preferred pH scope, active carbon is minimum to the adsorption rate of left-handed sulpiride, i.e. the loss minimum of medicine in the course of processing.Can regulate left-handed sulpiride solution with hydrochloric acid or the sodium hydroxide of 0.1M.
According to the present invention, add activated carbon filtration, use the microporous filter membrane fine straining, resulting injection is made aqueous injection or is made step such as injectable powder through lyophilization and adopt the conventional method operation through packing sterilization, be 0.01%～0.05% (w/v) with the consumption of removing the active carbon of pyrogen wherein in order to adsorption bleaching, adsorption treatment is 15 minutes under the room temperature, and the filtrate of the microporous filter membrane that can adopt 0.22 micron or 0.45 micron after to adsorption treatment is carried out fine straining.
Utilize the inventive method can prepare aqueous injection or lyophilized injectable powder, wherein aqueous injection is injection with small volume or low capacity sodium chloride injection or high capacity sodium chloride injection or high capacity glucose injection.Wherein the example of injection with small volume is every milliliter of injection that contains 25mg or the left-handed sulpiride of 12.5mg, and the example of low capacity sodium chloride injection is every milliliter of injection that contains 25mg or left-handed sulpiride of 12.5mg and 7mg sodium chloride; The example of high-capacity injection is the used for intravenous injection transfusion that contains 25mg/100ml or left-handed sulpiride of 50mg/100ml and 900mg/100ml sodium chloride; Contain the used for intravenous injection transfusion of left-handed sulpiride of 25mg/100ml or 50mg/100ml and 5g/100ml or 10g/100ml glucose.When preparation sodium chloride or glucose injection, adding proper amount of sodium chloride or glucose are made drug solution in the left-handed sulpiride of dissolving.Conventional bracket agent such as use mannitol are carried out lyophilizing to left-handed sulpiride injection, can make every injectable powder that contains 25mg or the left-handed sulpiride of 50mg.
Beneficial effect
1, the inventive method is dissolved left-handed sulpiride with the water for injection of mole pharmaceutically acceptable acids such as will containing, has obviously increased the dissolubility of left-handed sulpiride in water, improves its water solublity.
2, it is low to utilize the inventive method can prepare side effect, and the Levogyration sulpiride injection and its that has good stability has been realized muscle or intravenous administration, has expanded the medicinal scope of left-handed sulpiride.
3, the inventive method technology is simple, operation is gentle, avoids violent condition such as strong acid, heating.
The specific embodiment
The present invention is further elaborated below in conjunction with specific embodiment, but do not limit the present invention.
The preparation of embodiment 1 left-handed sulpiride low capacity sodium chloride injection
Prescription is formed
| Supplementary material | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 |
| Left-handed sulpiride sodium chloride 1mol/L hydrochloric acid is set solution pH value needle-use activated carbon water for injection | 25g 14g 73.2ml 6.0 1g 2000ml | 25g 14g 73.2ml 5.0 1g 2000ml | 25g 14g 73.2ml 4.0 1g 2000ml | 25g 14g 73.2ml 3.5 1g 2000ml |
Preparation method:
(1) left-handed sulpiride, 1mol/L hydrochloric acid, the sodium chloride of getting recipe quantity adds in about 1500ml water for injection, treats that levosulpiride all after the dissolving, adds the injection water to 2000ml, regulates pH value to setting value with 0.1M hydrochloric acid and 0.1M sodium hydroxide solution;
(2) the active carbon stirring and adsorbing of adding recipe quantity is 15 minutes, after the excellent coarse filtration of sand, and with the microporous filter membrane fine straining of 0.45um, the clarity of check medicinal liquid;
(3) medicine liquid irrigation is encapsulated in the ampoule, 2ml/ props up;
(4) 115 ℃ of flowing steam sterilizations 30 minutes are stopped leakage in the roof, lamp inspection, lettering, packing.
The injection that each prescription makes is colorless cleared solution, and the evaluation index of its sterilization back pH value and medicine active carbon adsorption rate is measured and seen Table 1:
Table 1
| The prescription number | Sterilization back pH value | Activated carbon adsorption rate % |
| 1 2 3 4 | 5.63 4.15 3.65 3.07 | 5.2 2.1 2.2 2.2 |
As shown in table 1, when the pH value of solution regulated value was 6.0, active carbon was higher to the adsorption rate of left-handed sulpiride, if further improve the pH setting value, can separate out left-handed sulpiride crystallization and made the activated carbon adsorption drug loss excessive; And when the pH value of solution regulated value was 3.5, pH dropped near 3 behind the injection high temperature sterilize, and at this moment injection has zest to muscle.Therefore selectable pH value of solution range of accommodation should be 4-6, and wherein when pH was 4-5, drug loss was less.
The preparation of embodiment 2 left-handed sulpiride sodium chloride transfusions
Prescription: left-handed sulpiride 25.0g
1mol/L sulphuric acid 73.2ml
Sodium chloride 900.0g
Water for injection 100000ml
Make 1000 bottles altogether
Preparation method:
(1) take by weighing left-handed sulpiride and 1mol/L hydrochloric acid according to recipe quantity, add in about 4500ml water for injection, stirring makes it to dissolve fully, this solution is added in about 250000ml water for injection again, mixes;
(2) sodium chloride of adding recipe quantity stirs and makes dissolving;
(3) regulate pH to 4.5 with hydrochloric acid or the sodium hydroxide of 0.1mol/L;
(4) the active carbon stirring and adsorbing of adding 0.03% (w/v) is 15 minutes, filters and removes active carbon, measures left-handed sulpiride content;
(5) add to the full amount of water for injection;
(6) filter with 0.45 micron microporous filter membrane, filtrate measure content qualified after, fill is in infusion bottle, the 100ml/ bottle is jumped a queue, gland, 115 ℃ of circulation steam sterilizations 30 minutes.
After measured, active carbon is 2.8% to the adsorption rate of levosulpiride, and the pH value after the transfusion sterilization is 4.2.
The preparation of embodiment 3 left-handed sulpiride lyophilized injectable powders
Prescription: left-handed sulpiride 25.0g
1mol/L benzenesulfonic acid 73.2ml
Mannitol 250.0g
Water for injection 1000ml
Active carbon 0.5g
Make 1000 bottles altogether
Preparation method:
(1) the left-handed sulpiride of getting recipe quantity adds in about 800ml water for injection, adds recipe quantity 1mol/L methanesulfonic acid, stirs to make it to dissolve fully, the mannitol that adds recipe quantity, add the injection water to 1000ml, mix, add 1M hydrochloric acid or sodium hydroxide and regulate pH value to 4.5 ± 0.5;
(2) active carbon of adding recipe quantity, after the excellent coarse filtration of sand, by microporous filter membrane fine straining with 0.45um, the clarity of check medicinal liquid;
(3) medicinal liquid is sub-packed in the cillin bottle, the 1ml/ bottle;
(4) solution after the packing places the freeze dryer that is cooled to-50 ℃, makes rapidly and freezes.Wait to freeze the product temperature and reduce to-35 ℃, kept 2 hours, be evacuated to 13.33Pa, give and to freeze product and heat and slowly be warming up to-15 ℃ and carry out drying, this process is about 12 hours, slowly is warming up to about 30 ℃, keeps 4 hours, be warming up to room temperature gradually, kept 2 hours, jump a queue gland promptly.
The preparation of embodiment 4 left-handed sulpiride injection with small volume
Prescription: left-handed sulpiride 25.0g
1mol/L citric acid 73.2ml
Water for injection 1000ml
Active carbon 0.5g
Make 1000 altogether
Preparation method:
(1) the left-handed sulpiride of getting recipe quantity adds in about 800ml water for injection, adds recipe quantity 1mol/L citric acid, stirs to make it to dissolve fully, adds the injection water to 1000ml, mixes, and regulates pH value to 4.5 ± 0.5 with 1M hydrochloric acid or sodium hydroxide;
(2) active carbon of adding recipe quantity, after the excellent coarse filtration of sand, by microporous filter membrane fine straining with 0.45um, the clarity of check medicinal liquid;
(3) medicinal liquid is sub-packed in the ampoule, the 1ml/ bottle;
(4) 115 ℃ of circulation steam sterilizations 30 minutes.
Embodiment 5 left-handed sulpiride injection safety testings
With 2 preparations of prescription among the embodiment 1 left-handed sulpiride injection (25mg/2ml) be test sample, carry out that rabbit blood vessel, muscle irritation are tested, Cavia porcellus sensitivity test and external hemolytic test, method and result are as follows:
(1) blood vessel irritation test
Method: every day is with aseptic manipulation rabbit left side ear edge outside intravenous injection test sample 5.75mg/kg, injection volume 0.46ml/kg, and 1min has injected.Auris dextra edge outside intravenous injection equal-volume normal saline is as blank, and successive administration three days is put to death rabbit behind the last injection 24h, observes blood vessel and has or not pathological changes, gets the auris dextra outside and injection point downstream, left ear outside 1cm blood vessel respectively, makes the pathology sections observation.
The result: during intravenous injection and injection back rabbit does not have uncomfortable reaction, and toleration is good, and the perusal of ear vein blood vessel is no abnormal.Pathological section microscopy result shows that each animal venous blood tube wall is complete, does not see endothelial injury, thrombosis and tissue edema, and the vein blood vessel structure is normal, does not see obvious tissue degeneratiaon, necrosis.
(2) muscle irritation test
Method: two healthy rabbits respectively about two lower limb quadriceps femoris each injects and is tried thing 1ml with aseptic manipulation, injection back 48h puts to death animal, dissects and takes out quadriceps femoris, vertically cuts, and observes the injection site irritant reaction, converses corresponding order of reaction by table 2.Calculate the summation of four quadriceps femoris order of reactions then, greater than 2 o'clock, should get 2 rabbit in addition and test again as the difference of the highest and minimum group of each quadriceps femoris order of reaction.Less than 10 o'clock, think then that the local excitation test of test sample is up to specification in four quadriceps femoris order of reactions of 2 rabbit sum of preliminary examination or retry.
Table 2
| Order of reaction | Irritant reaction |
| 0 1 2 3 4 5 | No significant change mild hyperaemia, its scope is in the following moderate hyperemia of 0.5 * 1.0cm, its scope is in the above severe hyperemia of 0.5 * 1.0cm, necrosis occurs with myodegeneration, have the brown degeneration popularity necrosis to occur |
The result: as shown in table 3, the difference that four quadriceps femoris order of reactions are the highest and minimum group is 1, assert that the local excitation test of test sample is up to specification.
Table 3
| Quadriceps femoris | Irritant reaction | Order of reaction |
| 1 2 3 4 | The no significant change below 0.5 * 1.0cm of no significant change mild hyperaemia, its scope does not have significant change | 0 1 0 0 |
(3) drug administration by injection hypersensitive test
Method: 12 Cavia porcelluss, be divided into two groups, six every group, tried six Cavia porcelluss of the left-handed sulpiride group of thing respectively at the left-handed sulpiride injection of lumbar injection on the the 1st, 3,5, each 0.5ml/ only injects three times altogether.Got female 2 male 1 three Cavia porcelluss on 14th, jugular vein is only injected left-handed sulpiride injection 1ml/, in back 15 minutes of injection, observe Cavia porcellus and anaphylaxis whether occurs, if any two or more person in perpendicular hair, dyspnea, sneeze, retch or the phenomenon such as cough 3, or one of rale, tic, collapse or phenomena of mortality person is arranged, be judged to the positive.Got three of the residues Cavia porcelluss of the left-handed sulpiride injection of lumbar injection (male 1 female 2) on the 21st day in injection back, jugular vein is only injected left-handed sulpiride injection 1ml/, in back 15 minutes of injection, observes Cavia porcellus and anaphylaxis whether occurs, and observation caliber is the same.All the other six positive matched groups of Cavia porcellus, respectively at lumbar injection injection Chymotrypsin (4000 μ/prop up) on the the 1st, 3,5, each 1000 μ/0.5ml/ only injected three times altogether.Got female 2 male 1 three Cavia porcelluss on 14th, 2000 μ/ml/ only for jugular vein injection Chymotrypsin, in back 15 minutes of injection, observe Cavia porcellus and anaphylaxis whether occurs, got three of residues in the injection back on the 21st day and injected the Cavia porcellus of Chymotrypsin (male 1 female 2), jugular vein is only injected Chymotrypsin 2000 μ/ml/, in back 15 minutes of injection, observe Cavia porcellus and anaphylaxis whether occurs, observation caliber is the same.
Result: as shown in table 4, left-handed sulpiride group Cavia porcellus is after 0.5ml/ sensitization of the left-handed sulpiride injection of lumbar injection on the the 1st, 3,5, only inject left-handed sulpiride injection 1ml/ respectively at jugular vein on the the 14th and 21, the results are shown in Table 2, individual animal has perpendicular hair phenomenon.The positive controls Cavia porcellus respectively at jugular vein injection Chymotrypsin 2000 μ/ml/ on the the 14th and 21 only, the results are shown in following table after 0.5ml/ sensitization of lumbar injection Chymotrypsin on the the 1st, 3,5, severe allergic reaction all appears in six animals.It is negative that judgement is tried the thing anaphylaxis.
Table 4
| Tried thing | Number of animals (only) | Firing time (d) | Symptoms of allergic |
| The left-handed Sulpiride parenteral solution of left-handed Sulpiride parenteral solution injection chymotrypsin injection chymotrypsin | 3 3 3 3 | 14th 21th 14th 21th | 1 only has perpendicular hair phenomenon 2 to only have three animals of perpendicular hair phenomenon all to occur perpendicular hair in the 2-5min after injection; Perpendicular hair, sneeze or rale all appear in three animals of sneeze or rale in the 5-6min after injection |
(4) hemolytic test:
Method: the rabbit auricular vein is got blood 2ml, stirs with glass rod and removes Fibrinogen, adds the normal saline of 10 times of amounts, shakes up, and is centrifugal, removes supernatant.Erythrocyte till the apparent redness of supernatant, is abandoned supernatant with normal saline washing 2-3 time, adds normal saline by the blood cell volume and is made into 2% red blood cell suspension.Add red blood cell suspension and normal saline in ratio shown in the table 5, shake up the back and place 0.5h in 37 ℃, what add different volumes then is tried the thing medicinal liquid, and in the rearmounted 37 ℃ of calorstats of mixing, every 15min observes once, per hour observes once behind the 1h, observes 4h altogether.
Table 5
| The test tube numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| 2% erythrocyte suspension (ml) normal saline (ml) medicinal liquid (ml) | 2.5 2.0 0.5 | 2.5 2.1 0.4 | 2.5 2.2 0.3 | 2.5 2.3 0.2 | 2.5 2.4 0.1 | 2.5 2.5 | 2.5 2.5 (distilled water) |
The result is as shown in table 6, and in 4h rule were examined continuously, erythrocyte evenly sank in the 1-6 test tube, and upper solution is colourless, and the R-RBC crack-free illustrates that no haemolysis occurs; Lower floor's erythrocyte does not evenly have flocculent deposit, is uniform liquid behind the jog, and no red blood cell condensation is described.7 manage at the middle and upper levels, and solution takes on a red color, and R-RBC breaks, and illustrates that distilled water causes erythrocyte hemolysis.
Table 6
| Observing time | Tried property management | ||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | |
| 15min 30min 45min 1h 2h 3h 4h | - - - - - - - | - - - - - - - | - - - - - - - | - - - - - - - | - - - - - - - | - - - - - - - | + + + + + + + |
Annotate: "-" expression erythrocyte is haemolysis not, does not assemble; "+" expression erythrocyte hemolysis.
Conclusion: rabbit blood vessel irritation test shows after intravenous injection of left-handed sulpiride injection and the intramuscular injection blood vessel and muscle nonirritant.Left-handed sulpiride injection is through Cavia porcellus intraperitoneal administration sensitization, and the intravenous administration test judges that anaphylaxis is negative.External hemolytic test result shows that left-handed sulpiride injection does not produce haemolysis or aggregation to blood.
Embodiment 6 left-handed sulpiride injection accelerated stability tests
Prescription 2 preparation injection and embodiment 2 preparation transfusions are through 6 months test of accelerated stability among the embodiment 1, experimental enviroment: 40 ℃ of humidity 75% temperature, through test ratings such as related substance, content, pH and 0 time ratio, variation that there are no significant.Table 7 and table 8 as a result.
The accelerated stability test result of the left-handed sulpiride injection of table 7 25mg/2ml
| Lot number | Time (moon) | Appearance luster | Clarity | PH value | Related substance (%) | Content (%) |
| 991218 991219 991220 | 0 1 2 3 6 0 1 2 3 6 0 1 2 3 6 | Colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid colourless clear liquid | Clarification clarification clarification clarification clarification clarification clarification clarification clarification clarification clarification clarification clarification clarification clarification | 4.19 4.18 4.19 4.19 4.21 4.15 4.14 4.13 4.16 4.16 4.20 4.21 4.22 4.19 4.19 | 0.13 0.13 0.13 0.13 0.17 0.13 0.13 0.13 0.13 0.17 0.13 0.13 0.16 0.20 0.26 | 101.2 101.2 101.4 101.6 100.8 101.6 100.7 101.8 101.0 100.9 102.2 101.6 102.7 101.3 102.5 |
The left-handed sulpiride sodium chloride injection of table 8 (25mg/100ml glass bottle packaging) accelerated stability test result
| Lot number | Time (moon) | Outward appearance | Clarity and color | PH value | Related substance (%) | Content (%) | |
| Lsp | NaCl | ||||||
| 020701 020702 020703 | 0 1 2 3 6 0 1 2 3 6 0 1 2 3 6 | Clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid clear liquid | Clear and bright achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity achromatism and clarity is colourless | 4.15 4.16 4.10 4.16 4.18 4.25 4.29 4.24 4.21 4.26 4.29 4.35 4.27 4.30 4.28 | 0.19 0.19 0.18 0.17 0.17 0.19 0.17 0.23 0.17 0.18 0.23 0.19 0.18 0.16 0.19 | 99.95 99.67 99.56 100.0 99.18 101.0 100.8 101.1 101.8 101.2 101.7 101.3 101.8 101.6 102.1 | 100.8 99.6 100.4 100.6 100.1 99.8 100.6 99.6 99.4 100.4 100.4 99.8 100.2 101.0 100.6 |
Claims (4)
1, a kind of preparation method of Levogyration sulpiride injection and its, said injection is aqueous injection or lyophilized injectable powder, comprise the steps: to dissolve left-handed sulpiride, regulate pH, add activated carbon filtration, use the microporous filter membrane fine straining, resulting injection is made aqueous injection or is made injectable powder through lyophilization through the packing sterilization, it is characterized in that left-handed sulpiride is dissolved in the water for injection that contains pharmaceutically acceptable acid, said pharmaceutically acceptable acid is hydrochloric acid or sulphuric acid or benzenesulfonic acid or citric acid, in mole, the consumption of pharmaceutically acceptable acid and left-handed sulpiride equates; Regulate pH to 4.0-6.0.
2, the preparation method of Levogyration sulpiride injection and its according to claim 1 is characterized in that said aqueous injection is injection with small volume or low capacity sodium chloride injection or high capacity sodium chloride injection or high capacity glucose injection.
3, the preparation method of Levogyration sulpiride injection and its according to claim 1 is characterized in that regulating pH to 4.0-5.0.
4, the preparation method of Levogyration sulpiride injection and its according to claim 1 is characterized in that pharmaceutically acceptable acid is a hydrochloric acid.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102871978A (en) * | 2012-10-19 | 2013-01-16 | 石家庄开发区博欣医药科技开发有限公司 | Levosulpiride tablets and preparation method thereof |
| CN103405400A (en) * | 2013-08-30 | 2013-11-27 | 孙威 | Levosulpiride injection and preparation method thereof |
| CN117180189A (en) * | 2023-09-20 | 2023-12-08 | 海南卓泰制药有限公司 | Shubianli injection and preparation method and application thereof |
-
2006
- 2006-04-27 CN CNB200610026137XA patent/CN100560068C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102871978A (en) * | 2012-10-19 | 2013-01-16 | 石家庄开发区博欣医药科技开发有限公司 | Levosulpiride tablets and preparation method thereof |
| CN102871978B (en) * | 2012-10-19 | 2014-04-09 | 河北仁合益康药业有限公司 | Levosulpiride tablets and preparation method thereof |
| CN103405400A (en) * | 2013-08-30 | 2013-11-27 | 孙威 | Levosulpiride injection and preparation method thereof |
| CN117180189A (en) * | 2023-09-20 | 2023-12-08 | 海南卓泰制药有限公司 | Shubianli injection and preparation method and application thereof |
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Assignee: Hainan Hotmed Tianya Pharmaceutical Co., Ltd. Assignor: Shanghai Hechen Pharma Engineering Co., Ltd. Contract record no.: 2010310000229 Denomination of invention: Levogyration sulpiride injection and its preparation method Granted publication date: 20091118 License type: Exclusive License Open date: 20060927 Record date: 20101231 |
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