CN112898291A - Preparation method of pidotimod sodium - Google Patents
Preparation method of pidotimod sodium Download PDFInfo
- Publication number
- CN112898291A CN112898291A CN202110110635.7A CN202110110635A CN112898291A CN 112898291 A CN112898291 A CN 112898291A CN 202110110635 A CN202110110635 A CN 202110110635A CN 112898291 A CN112898291 A CN 112898291A
- Authority
- CN
- China
- Prior art keywords
- pidotimod
- sodium
- stirring
- preparing
- temperature
- 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.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of pidotimod sodium. In a solvent, carrying out a salt forming reaction on pidotimod and alkali to obtain a reaction solution; adding a cationic surfactant into the solvent to obtain a mixed solution; and dripping the reaction liquid into the mixed solution, preserving heat, carrying out gradient cooling, stirring for crystallization, filtering, leaching, and drying under reduced pressure to obtain the pidotimod sodium. The method has the advantages of simple process, easy operation, high product yield and purity, low production cost, environmental protection and suitability for industrial production.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of pidotimod sodium.
Background
It is the human immune system that safeguards health.
The human immune system is divided into two forms of non-specific immunity and specific immunity. Non-specific immunity is inherent in humans, and specific immunity refers to the specific resistance of the human body to a pathogen, which varies from person to person and is generally obtained by vaccination, illness or occult infection.
Healthy immunity is an important factor for securing the body from pathogens, and in fact, it often causes a low immunity in humans for one reason or another.
Pidotimod is an immune enhancer, which promotes non-specific and specific immunity. Pidotimod can promote the phagocytic activity of macrophages and neutrophils and improve the chemotaxis of the macrophages and the neutrophils; activating natural killer cells; promoting mitogen-induced lymphocyte proliferation and reducing helper T Cell (CD) in case of hypoimmunity4 +) And suppressive T Cells (CD)8 +) The ratio of (A) to (B) is increased and normal is recovered; the cellular immune response is promoted by stimulating interleukin-2 and interferon-gamma.
CN101423516A discloses a preparation method and medicinal application of pidotimod sodium salt, which is obtained by the steps of reacting pidotimod with sodium hydroxide in water or ethanol, concentrating and drying or freeze-drying. The method needs higher temperature for concentrating the solvent, is easy to deteriorate, and has complicated operation of the freeze drying method.
CN102101881A discloses a preparation method and application of pidotimod potassium salt, wherein pidotimod potassium salt is prepared by reacting equal moles of pidotimod and potassium hydroxide in water or other solvents or mixed solutions of a plurality of solvents. The method does not carry out sufficient heat preservation stirring, and the obtained product has low yield and low purity.
At present, only the synthesis of the pidotimod salt is studied in the literature and patents, but the yield and purity of the pidotimod salt are not studied.
Disclosure of Invention
The invention aims to provide a preparation method of pidotimod sodium, which has the advantages of simple process, easy operation and suitability for industrial production, and the prepared pidotimod sodium has good stability, good water solubility, high yield and high purity.
The preparation method of the pidotimod sodium comprises the following steps:
(1) in a solvent, carrying out a salt forming reaction on pidotimod and alkali to obtain a reaction solution;
(2) adding a cationic surfactant into the solvent to obtain a mixed solution;
(3) and dripping the reaction liquid into the mixed solution, preserving heat, carrying out gradient cooling, stirring for crystallization, filtering, leaching, and drying under reduced pressure to obtain the pidotimod sodium.
The alkali in the step (1) is one of sodium hydroxide, sodium bicarbonate or sodium carbonate, and the molar ratio of pidotimod to the alkali is 1: 0.5-1.2.
The solvent in the step (1) is water, and the mass ratio of the pidotimod to the solvent is 1: 1-7.
The salt-forming reaction temperature in the step (1) is 0-70 ℃, and the salt-forming reaction time is 1-2 h.
The cationic surfactant in the step (2) is cetyl trimethyl ammonium bromide, and the mass ratio of the pidotimod to the cationic surfactant is 1: 0.001-0.005.
The solvent in the step (2) is one of methanol, ethanol, acetone, acetonitrile, ethyl acetate, ethylene glycol, glycerol, dichloromethane, trichloromethane or straight-chain alkane, and the mass ratio of pidotimod to the solvent is 1: 5-30.
The straight-chain alkane is C7-C13 straight-chain alkane.
The dropping temperature in the step (3) is 40-60 ℃.
The heat preservation time in the step (3) is 1-4 h.
The gradient cooling in step (3) is carried out at a rate of 5 ℃ per 1 hour to 15-25 ℃.
The stirring speed in the step (3) is 30-150r/min, and the stirring time is 1-2 hours.
The temperature of the reduced pressure drying in the step (3) is 50-70 ℃.
Chemical structural formula of pidotimod sodium:
the molecular formula is as follows: c9H11N2O4SNa
Molecular weight: 266.28
The pidotimod sodium can be prepared into various dosage forms including but not limited to tablets, injections, capsules and the like by adding various auxiliary materials according to different processes.
The pidotimod sodium is used for treating repeated upper and lower respiratory tract infections (pharyngitis, tracheitis, bronchitis and tonsillitis); ② repeated infections of otorhinolaryngology (rhinitis, sinusitis, otitis); ③ urinary system infections, etc.; the composition is used for reducing the frequency of acute attack and relieving the attack degree, and can also be used as the auxiliary treatment of antibiotics during acute infection.
In the invention, the pidotimod is prepared into the pidotimod sodium, so that the stability and the water solubility of the pidotimod sodium are improved, and the yield and the purity are improved. Further research shows that after the surfactant is added, the product is changed from the previous powder state into the granular state, so that the pharmaceutical property is greatly improved.
The carboxyl is hydrophilic group and can form hydrogen bond with water, so that the lower carboxylic acid can be mutually dissolved with water in any ratio; as the relative molecular mass increases, the hydrophobic groups (hydrocarbon groups) become larger and less soluble in water. The pidotimod sodium salt is generated from the original carboxylic acid structure, so that the water solubility is improved.
The surfactant reduces the surface tension of water by adsorbing at the gas-liquid two-phase interface, and also reduces the oil-water interfacial tension by adsorbing between the liquid interfaces. Many surfactants can also aggregate into aggregates in the bulk solution. The surfactant used in the invention is a cationic surfactant, and is characterized by high water solubility, stability in acidic and alkaline solutions, and good surface activity and sterilization. The CTAB surfactant plays a role in dispersing, and a solute is uniformly dispersed in a solution, so that the yield is greatly improved. The CTAB in the invention has the advantages of small dosage, convenient operation, no toxicity and no corrosion, can be dissolved in hot water and ethanol, and can be easily dissolved in an isopropanol aqueous solution, so that excessive residues are not easy to cause.
The invention has the following beneficial effects:
1. compared with the pidotimod, the pidotimod sodium has better water solubility and improves the stability of the pidotimod; the pH value of the pidotimod sodium is 6-7, which is closer to the pH value of a human body, and the damage of acidity to the human body is reduced.
2. The pidotimod sodium can be prepared into tablets or capsules, and has better mouthfeel.
3. The method has the advantages of simple process, easy operation, high product yield and purity, low production cost, environmental protection and suitability for industrial production.
Drawings
FIG. 1 is a schematic representation of a granulated product obtained in example 1.
FIG. 2 is a liquid chromatogram of the product obtained in example 1.
FIG. 3 is a liquid chromatogram of the product obtained in comparative example 1.
Detailed Description
The present invention is further described below with reference to examples.
Example 1
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 11.35g of sodium bicarbonate in batches, adjusting the pH value to be 6.5-7.5, and stirring and reacting for 1h at 20 ℃ to obtain a reaction solution;
(2) adding 0.1g of cetyl trimethyl ammonium bromide serving as a surfactant into 180g of ethanol to obtain a mixed solution;
(3) dropping the reaction liquid into the mixed solution, controlling the temperature to be 60 ℃, after the dropping is finished, keeping the temperature and stirring for 1h, then cooling to 15 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 2h, controlling the stirring speed to be 30r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; and (3) putting the wet pidotimod sodium into a reduced-pressure oven, setting the temperature at 50 ℃, and drying to obtain 31.49g of white uniform particles, wherein the yield is 96.3%, and the purity is 99.54%. The figure of the product is shown in figure 1, the liquid chromatogram of the product is shown in figure 2, and the result of the product stability test is shown in table 2.
Example 2
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 11.35g of sodium bicarbonate in batches, adjusting the pH value to be 6.5-7.5, and stirring and reacting for 1h at 30 ℃ to obtain a reaction solution;
(2) adding 0.1g of cetyl trimethyl ammonium bromide serving as a surfactant into 300g of acetone to obtain a mixed solution;
(3) dropping the reaction liquid into the mixed solution, controlling the temperature to be 60 ℃, after the dropping is finished, keeping the temperature and stirring for 1h, then cooling to 20 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 1h, controlling the stirring speed to be 50r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; the pidotimod sodium wet product is put into a reduced-pressure oven, the temperature is set to be 60 ℃, and the drying is carried out, so that 31.58g of white uniform particles are obtained, the yield is 96.6%, the purity is 99.63%, and the product stability test results are shown in table 2.
Example 3
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 11.35g of sodium bicarbonate in batches, adjusting the pH value to be 6.5-7.5, and stirring and reacting for 1h at 25 ℃ to obtain a reaction solution;
(2) adding 0.1g of cetyl trimethyl ammonium bromide serving as a surfactant into 300g of ethyl acetate to obtain a mixed solution;
(3) dropping the reaction liquid into the mixed solution, controlling the temperature to be 60 ℃, after the dropping is finished, keeping the temperature and stirring for 1h, then cooling to 25 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 2h, controlling the stirring speed to be 60r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; the pidotimod sodium wet product is put into a reduced-pressure oven, the temperature is set to be 70 ℃, and the drying is carried out, so that 31.39g of white uniform particles are obtained, the yield is 96.0%, the purity is 99.42%, and the product stability test results are shown in table 2.
Example 4
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 11.35g of sodium bicarbonate in batches, adjusting the pH value to be 6.5-7.5, and stirring and reacting for 1h at 50 ℃ to obtain a reaction solution;
(2) adding 0.1g of cetyl trimethyl ammonium bromide serving as a surfactant into 180g of dichloromethane to obtain a mixed solution;
(3) dropping the reaction liquid into the mixed solution, controlling the temperature to be 60 ℃, after the dropping is finished, keeping the temperature and stirring for 1h, then cooling to 18 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 1h, controlling the stirring speed to be 150r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; the pidotimod sodium wet product is put into a reduced-pressure oven, the temperature is set to be 60 ℃, and the drying is carried out, so that 31.45g of white uniform particles are obtained, the yield is 96.2%, the purity is 99.32%, and the product stability test results are shown in table 2.
Example 5
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 7.15g of sodium carbonate in batches, adjusting the pH value to be 6.5-7.5, and stirring and reacting for 1h at 0 ℃ to obtain a reaction solution;
(2) adding 0.1g of cetyl trimethyl ammonium bromide serving as a surfactant into 180g of ethanol to obtain a mixed solution;
(3) dropping the reaction liquid into the mixed solution, controlling the temperature to be 60 ℃, after the dropping is finished, keeping the temperature and stirring for 1h, then cooling to 20 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 1h, controlling the stirring speed to be 100r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; the pidotimod sodium wet product is put into a reduced-pressure oven, the temperature is set to be 50 ℃, and the drying is carried out, so that 31.52g of white uniform particles are obtained, the yield is 96.4%, the purity is 99.44%, and the product stability test results are shown in table 2.
Example 6
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 7.15g of sodium carbonate in batches, adjusting the pH value to be 6.5-7.5, and stirring and reacting for 1h at 70 ℃ to obtain a reaction solution;
(2) adding 0.1g of cetyl trimethyl ammonium bromide serving as a surfactant into 270g of acetonitrile to obtain a mixed solution;
(3) dropping the reaction liquid into the mixed solution, controlling the temperature to be 60 ℃, after the dropping is finished, keeping the temperature and stirring for 1h, then cooling to 23 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 1.5 h, controlling the stirring speed to be 120r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; the pidotimod sodium wet product is put into a reduced pressure oven, the temperature is set to be 50 ℃, and the drying is carried out, so that 31.55g of white uniform particles are obtained, the yield is 96.5%, the purity is 99.03%, and the product stability test results are shown in table 2.
Example 7
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 4.5g of sodium hydroxide in batches, adjusting the pH value to be 6.5-7.5, and stirring and reacting for 1h at 30 ℃ to obtain a reaction solution;
(2) adding 0.1g of cetyl trimethyl ammonium bromide serving as a surfactant into 300g of methanol to obtain a mixed solution;
(3) dropping the reaction liquid into the mixed solution, controlling the temperature to be 60 ℃, after the dropping is finished, keeping the temperature and stirring for 1h, then cooling to 20 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 2h, controlling the stirring speed to be 30r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; the pidotimod sodium wet product is put into a reduced-pressure oven, the temperature is set to be 50 ℃, and the drying is carried out, so that 31.49g of white uniform particles are obtained, the yield is 96.3%, the purity is 99.73%, and the product stability test results are shown in table 2.
Example 8
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 4.5g of sodium hydroxide in batches, adjusting the pH value to 6.5-7.5, and stirring and reacting for 1h at 60 ℃ to obtain a reaction solution;
(2) adding 0.1g of cetyl trimethyl ammonium bromide serving as a surfactant into 180g of ethanol to obtain a mixed solution;
(3) dropping the reaction liquid into the mixed solution, controlling the temperature to be 60 ℃, after the dropping is finished, keeping the temperature and stirring for 1h, then cooling to 25 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 1h, controlling the stirring speed to be 30r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; the pidotimod sodium wet product is put into a reduced-pressure oven, the temperature is set to be 60 ℃, and the drying is carried out, so that 31.45g of white uniform particles are obtained, the yield is 96.2%, the purity is 99.66%, and the product stability test results are shown in table 2.
Comparative example 1
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 4.5g of sodium hydroxide in batches, adjusting the pH value to be 6.5-7.5, and stirring and reacting for 1h at 30 ℃ to obtain a reaction solution;
(2) dripping the reaction liquid into 300g of methanol, controlling the temperature to be 60 ℃, keeping the temperature and stirring for 1h after dripping is finished, then cooling to 20 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 2h, controlling the stirring speed to be 30r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; and (3) putting the wet pidotimod sodium into a reduced-pressure oven, setting the temperature to be 50 ℃, and drying to obtain 30.58g of white powdery solid, wherein the yield is 93.4%, the purity is 93.99%, the liquid chromatogram of the product is shown in figure 3, and the product stability test result is shown in table 2.
Comparative example 2
(1) Adding 30ml of purified water and 30g of pidotimod into a 500ml four-mouth bottle in sequence, stirring and dissolving for 0.5h, adding 4.5g of sodium hydroxide in batches, adjusting the pH value to 6.5-7.5, and stirring and reacting for 1h at 60 ℃ to obtain a reaction solution;
(2) dropping the reaction solution into 180g of ethanol, controlling the temperature to be 60 ℃, keeping the temperature and stirring for 1h after the dropping is finished, then cooling to 25 ℃ at the speed of 5 ℃ per 1h, keeping the temperature and stirring for 1h, controlling the stirring speed to be 30r/min, then performing suction filtration, and leaching with ethanol to obtain a pidotimod sodium wet product; and (3) putting the wet pidotimod sodium into a reduced-pressure oven, setting the temperature to be 60 ℃, and drying to obtain 30.24g of white powdery solid, wherein the yield is 92.5%, the purity is 94.12%, and the product stability test result is shown in table 2.
TABLE 1 results of product yield and purity for examples 1-8 and comparative examples 1-2
| Name (R) | Amount of finished product | Yield of | Purity of |
| Example 1 | 31.49g | 96.3％ | 99.54％ |
| Example 2 | 31.58g | 96.6％ | 99.63％ |
| Example 3 | 31.39g | 96.0％ | 99.42％ |
| Example 4 | 31.45g | 96.2％ | 99.32％ |
| Example 5 | 31.52g | 96.4％ | 99.44％ |
| Example 6 | 31.55g | 96.5％ | 99.03 |
| Practice ofExample | |||
| 7 | 31.49g | 96.3％ | 99.73％ |
| Example 8 | 31.45g | 96.2％ | 99.66％ |
| Comparative example 1 | 30.58g | 93.4％ | 93.99％ |
| Comparative example 2 | 30.24g | 92.5％ | 94.12％ |
TABLE 2 product stability test results of examples 1-8 and comparative examples 1-2
As can be seen from table 2, the maximum purity of the example was 0.06% in six months, while the maximum purity of the comparative example was 0.59% in six months, and the smaller the purity change was in the same time, the better the stability was, and thus it can be seen that the product stability of the example was higher than that of the comparative example.
Claims (10)
1. A preparation method of pidotimod sodium is characterized by comprising the following steps:
(1) in a solvent, carrying out a salt forming reaction on pidotimod and alkali to obtain a reaction solution;
(2) adding a cationic surfactant into the solvent to obtain a mixed solution;
(3) and dripping the reaction liquid into the mixed solution, preserving heat, carrying out gradient cooling, stirring for crystallization, filtering, leaching, and drying under reduced pressure to obtain the pidotimod sodium.
2. The method for preparing pidotimod sodium according to claim 1, wherein the base in step (1) is one of sodium hydroxide, sodium bicarbonate or sodium carbonate, and the molar ratio of pidotimod to base is 1: 0.5-1.2.
3. The method for preparing pidotimod sodium according to claim 1, wherein the solvent in step (1) is water, and the mass ratio of pidotimod to the solvent is 1: 1-7.
4. The method for preparing pidotimod sodium according to claim 1, wherein the salt-forming reaction temperature in step (1) is 0-70 ℃, and the salt-forming reaction time is 1-2 h.
5. The method for preparing pidotimod sodium according to claim 1, wherein the cationic surfactant in step (2) is cetyltrimethylammonium bromide, and the mass ratio of pidotimod to cationic surfactant is 1: 0.001-0.005.
6. The method for preparing pidotimod sodium according to claim 1, wherein the solvent in step (2) is one of methanol, ethanol, acetone, acetonitrile, ethyl acetate, ethylene glycol, glycerol, dichloromethane, trichloromethane or straight-chain alkane, and the mass ratio of pidotimod to the solvent is 1: 5-30.
7. The method for preparing pidotimod sodium according to claim 1, characterized in that the dropping temperature in step (3) is 40-60 ℃, and the holding time is 1-4 h.
8. The method for preparing pidotimod sodium according to claim 1, wherein said gradient decreasing temperature in step (3) is decreasing to 15-25 ℃ at a rate of 5 ℃ per 1 hour.
9. The method for preparing pidotimod sodium according to claim 1, wherein the stirring rate in step (3) is 30-150r/min, and the stirring time is 1-2 hours.
10. The method for preparing pidotimod sodium according to claim 1, wherein the reduced pressure drying temperature in step (3) is 50-70 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110110635.7A CN112898291B (en) | 2021-01-27 | 2021-01-27 | Preparation method of pidotimod sodium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110110635.7A CN112898291B (en) | 2021-01-27 | 2021-01-27 | Preparation method of pidotimod sodium |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112898291A true CN112898291A (en) | 2021-06-04 |
| CN112898291B CN112898291B (en) | 2022-05-03 |
Family
ID=76118860
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110110635.7A Active CN112898291B (en) | 2021-01-27 | 2021-01-27 | Preparation method of pidotimod sodium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112898291B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101411684A (en) * | 2008-12-03 | 2009-04-22 | 北京琥珀光华医药科技开发有限公司 | Injection containing pidotimod sodium salt |
| CN101422428A (en) * | 2008-01-16 | 2009-05-06 | 北京琥珀光华医药科技开发有限公司 | Injection containing sodium pidotimod |
| CN101423516A (en) * | 2008-01-16 | 2009-05-06 | 北京琥珀光华医药科技开发有限公司 | Preparation of pidotimod sodium and medicinal use thereof |
| CN101766603A (en) * | 2008-12-26 | 2010-07-07 | 北京琥珀光华医药科技开发有限公司 | Intramuscular injection solution for enhancing immunity |
| CN102100664A (en) * | 2009-12-16 | 2011-06-22 | 青岛康地恩药业有限公司 | Injection containing pidotimod potassium salt and preparation method thereof |
| CN102101881A (en) * | 2009-12-16 | 2011-06-22 | 青岛康地恩药业有限公司 | Preparation and application of pidotimod potassium salt |
-
2021
- 2021-01-27 CN CN202110110635.7A patent/CN112898291B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101422428A (en) * | 2008-01-16 | 2009-05-06 | 北京琥珀光华医药科技开发有限公司 | Injection containing sodium pidotimod |
| CN101423516A (en) * | 2008-01-16 | 2009-05-06 | 北京琥珀光华医药科技开发有限公司 | Preparation of pidotimod sodium and medicinal use thereof |
| CN101411684A (en) * | 2008-12-03 | 2009-04-22 | 北京琥珀光华医药科技开发有限公司 | Injection containing pidotimod sodium salt |
| CN101766603A (en) * | 2008-12-26 | 2010-07-07 | 北京琥珀光华医药科技开发有限公司 | Intramuscular injection solution for enhancing immunity |
| CN102100664A (en) * | 2009-12-16 | 2011-06-22 | 青岛康地恩药业有限公司 | Injection containing pidotimod potassium salt and preparation method thereof |
| CN102101881A (en) * | 2009-12-16 | 2011-06-22 | 青岛康地恩药业有限公司 | Preparation and application of pidotimod potassium salt |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112898291B (en) | 2022-05-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105330609B (en) | A kind of method for preparing LCZ696 | |
| CN112939799B (en) | Synthesis method of N-methylol acrylamide | |
| CN110642955B (en) | Esterified selenium polysaccharide and preparation method and application thereof | |
| CN110041261A (en) | A kind of preparation method of naphcon | |
| CN112898291B (en) | Preparation method of pidotimod sodium | |
| KR101577488B1 (en) | Cefdinir acid double salt and its preparation | |
| CA2861891C (en) | Crystal form of (6s)-5-methyltetrahydrofolate salt and method for preparing same | |
| CN107400069B (en) | Preparation method of lauroyl arginine ethyl ester hydrochloride | |
| CN113651798A (en) | Preparation method of Voranolan fumarate | |
| CN114957236A (en) | Preparation method of 2-acylaminothiazole compound | |
| CN109096129B (en) | Preparation method of L-carnitine tartrate | |
| CN104151249B (en) | Medetomidine industrialization method for splitting | |
| CN114651898B (en) | Triazole feed additive for improving immunity as well as preparation method and application thereof | |
| CN101185642B (en) | Glucosamine lysine selenium salt and production process | |
| CN106187818B (en) | A kind of method for preparing cancer therapy drug Vorinostat | |
| CN111377949B (en) | Preparation method of tetramisole free base | |
| CN114957109A (en) | Method for preparing agglomerated large-particle-size high-fluidity nicotinic acid crystal | |
| CN1283624A (en) | Process for preparing 'Xidinafei' medicine | |
| CN108752399B (en) | Synthesis method of isopropyl-beta-D-thiogalactoside | |
| CN109369757B (en) | Method for preparing Sofosbuvir crystal form 6 | |
| CN113354647A (en) | Ganciclovir sodium synthesis process | |
| CN111961056A (en) | Method for simultaneously synthesizing hypoxanthine and tetraacetyl ribose by utilizing inosine | |
| CN111471027A (en) | Synthesis process of ribavirin intermediate and intermediate | |
| CN107892692A (en) | The preparation method and applications of (6S) 5 methyl tetrahydrofolate zinc salt | |
| CN106008267B (en) | A kind of preparation method of cancer therapy drug Vorinostat |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |