CN102671189B - Iron protein succinylate solubilizing method and oral solution preparation thereof - Google Patents
Iron protein succinylate solubilizing method and oral solution preparation thereof Download PDFInfo
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- 108010084684 iron protein succinylate Proteins 0.000 title claims abstract description 58
- 229940074442 iron protein succinylate Drugs 0.000 title claims abstract description 58
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 title claims abstract description 15
- 230000003381 solubilizing effect Effects 0.000 title abstract description 6
- 229940100688 oral solution Drugs 0.000 title abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 26
- 229940079593 drug Drugs 0.000 claims abstract description 23
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims abstract description 13
- 229960000502 poloxamer Drugs 0.000 claims abstract description 13
- 229920001983 poloxamer Polymers 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 36
- 238000001914 filtration Methods 0.000 claims description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 14
- 230000001954 sterilising effect Effects 0.000 claims description 14
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 13
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 13
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 13
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 12
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 12
- 229940085605 saccharin sodium Drugs 0.000 claims description 12
- 239000000600 sorbitol Substances 0.000 claims description 12
- 239000012982 microporous membrane Substances 0.000 claims description 11
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 230000002421 anti-septic effect Effects 0.000 claims description 6
- 239000006184 cosolvent Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
- 239000004310 lactic acid Substances 0.000 claims description 4
- 235000014655 lactic acid Nutrition 0.000 claims description 4
- 239000001630 malic acid Substances 0.000 claims description 4
- 235000011090 malic acid Nutrition 0.000 claims description 4
- 241000167854 Bourreria succulenta Species 0.000 claims description 3
- 241000675108 Citrus tangerina Species 0.000 claims description 3
- 241001093152 Mangifera Species 0.000 claims description 3
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 3
- 235000019693 cherries Nutrition 0.000 claims description 3
- CJCPHVRHJKYIJC-UHFFFAOYSA-N methyl 2-hydroxybenzoate;sodium Chemical compound [Na].COC(=O)C1=CC=CC=C1O CJCPHVRHJKYIJC-UHFFFAOYSA-N 0.000 claims description 3
- JWYIRZRIDBKTPH-UHFFFAOYSA-N propyl 2-hydroxybenzoate;sodium Chemical compound [Na].CCCOC(=O)C1=CC=CC=C1O JWYIRZRIDBKTPH-UHFFFAOYSA-N 0.000 claims description 3
- 230000007928 solubilization Effects 0.000 claims description 3
- 238000005063 solubilization Methods 0.000 claims description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 abstract description 18
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 abstract description 14
- 229960004063 propylene glycol Drugs 0.000 abstract description 9
- 229910052742 iron Inorganic materials 0.000 abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 5
- 229920000858 Cyclodextrin Polymers 0.000 abstract 1
- 239000001116 FEMA 4028 Substances 0.000 abstract 1
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 abstract 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 abstract 1
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
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Abstract
The invention discloses an iron-protein succinylate solubilizing method and an oral solution preparation thereof, which are used for solving the problems of difficulty in dissolving iron-protein succinylate into water, unstable solution and the like. In the method, lauryl sodium sulfate or poloxamer or PEG-400 or beta-cyclodextrin is taken as a solubilizing solvent, and 1,2-propylene glycol and the like are taken as latent solvents, so that the water solubility of the iron protein succinylate are increased, and the free iron content is less than 0.1 percent. An iron protein succinylate oral solution prepared by using a process disclosed by the invention is accordant with relevant regulations in the Imported Medicine Registration Standard JX20000298 and oral liquid dosage form items in the second version of the Chinese Pharmacopeia, edition 2010.
Description
Technical field
The present invention relates to a kind of solubilizing process and oral administration solution formulation preparation method thereof of indissoluble iron protein succinylate, belong to the technical field of pharmaceutical preparation, say more specifically a kind of preparation method of solubilising and oral administration solution thereof of indissoluble iron protein succinylate.
Background technology
198 years, the general mark of Italy develops a kind of iron protein succinylate by name (iron-protein succinylate in large pharmaceutical factory, abbreviation ISP) nanometer polypeptide albuminoid iron supplement medicine, in Italy, successfully go on the market and comprise that in more than 20 country in the whole world Spain, Portugal, Greece, Argentina, Korea S, China etc. go on the market and sell successively, welcome by the various countries doctor.
By China national Department of Intellectual Property (SIPO), Derwent patent database (DII) and United States Patent (USP) trademark office (USPTO) patent retrieval, domestic for iron protein succinylate solubilizing process and oral administration solution preparation Patents report are not all arranged respectively.
Iron protein succinylate is as a kind of high molecular weight protein Complexing Iron, and it was the precipitation state at pH value less than 4 o'clock, and under alkali condition, became again solable matter.It at gastric not by pepsin digestion, but can be by trypsin hydrolyzing when pH neutral.Because it has these unique characteristics, iron protein succinylate be subjected to albuminous coat protection and not by stomach acids destroy stomach function regulating protease hydrolyzed, to gastric mucosa injury not.After entering intestinal, it dissolves again, and is digested by trypsin.After the protein protection film was digested, ferrum started to discharge in duodenum.
Studies show that, iron protein succinylate is very beneficial for being absorbed by body, does not but form high absworption peak.What pharmacokinetics studies show that it presents is a kind of constant absorption trend, at each position of body, reaches gradually the best stable state that absorbs and store, so iron protein succinylate can not produce the problem of resistance of gastrointestinal.Due to the problem of resistance of gastrointestinal, in iron protein succinylate oral administration solution preparation, contain the free iron amount and must meet import drugs registered standard JX20000298.
Summary of the invention
Technical problem:The present invention seeks to develop a kind of technique that can improve iron protein succinylate dissolubility in water, and prepare iron protein succinylate oral administration solution preparation with this technique, the problems such as slightly solubility, the solution of this medicine in water is unstable to solve, free iron too high levels, be convenient to applying of this medicine.
Technical scheme:A kind of iron protein succinylate solubilization method of the present invention, take iron protein succinylate as crude drug, adds solubilizing agent, excipient and cosolvent, adds the aqueous slkali heated and stirred and dissolves, then add acid, regulates pH to 6.5-8.0pH.
Wherein, added solubilizing agent accounts for the crude drug total weight percent and is: the PEG-400 of the sodium lauryl sulphate of 0.1-1%, the poloxamer of 0.1-2%, 0.5%-10% or the beta-schardinger dextrin-of 5-20%.
Added excipient accounts for the crude drug total weight percent: the sorbitol of 5-10%.
Added cosolvent accounts for the crude drug total weight percent: the 1,2-PD of 5-10%.
Added aqueous slkali is the NaOH of 0.1-1mol/L or the KOH solution of 0.1-1mol/L, or the combination aqueous slkali of the KOH solution of the NaOH of 0.1-1mol/L and 0.1-1mol/L.
Added acid accounts for the crude drug total weight percent: the malic acid of the citric acid of 1-10%, the lactic acid of 1-10% or 1-10%.
The iron protein succinylate oral administration solution preparation of product configuration prepared by described method is: will in the settled solution of the iron protein succinylate after solubilising, add antiseptic, correctives and sweeting agent, after filtration, sterilizing, be made into iron protein succinylate oral administration solution preparation;
Added antiseptic accounts for the said preparation total weight percent: the propyl hydroxybenzoate sodium of 0.1-0.2% and the methyl hydroxybenzoate sodium of 0.1-0.2%;
Added correctives accounts for the said preparation total weight percent: Fructus Pyracanthae essence 1%, Fructus Mangifera Indicae essence 1%, the sub-essence 1% of tangerine or cherry essence 1%; Added sweeting agent accounts for the said preparation total weight percent: saccharin sodium 0.1-0.2% or steviosin 0.1-0.2%.
The oral administration solution preparation specification of preparing is 800mg/15ml iron protein succinylate oral administration solution; The oral administration solution preparation of preparing is after 2 μ m filter, then through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and through 105～115 ℃ of sterilizing 20min of high temperature.
Beneficial effect:
1. this solubilising preparing process, improved the dissolubility of iron protein succinylate in water, the iron protein succinylate oral administration solution of developing, and it contains the free iron amount and is no more than 0.1% of total content.
2. the iron protein succinylate oral administration solution of developing, indices all can meet import drugs registered standard JX20000298, and other meet relevant every regulation under two oral solution items of Chinese Pharmacopoeia version in 2010.
3. the results of stability of iron protein succinylate oral administration solution shows, this preparation all belongs to well the stability of light and heat, tentative 2 years of the storage period under room temperature; The pharmacodynamic study result shows, this preparation can effectively be treated absolute and relative iron deficiency anemia and due to ferrum intake deficiency or malabsorption, acute or chronic blood loss and infect caused recessiveness or dominant iron deficiency anemia, gestation and anemia age of sucking.The toxicologic study result shows, this preparation toxicity, side effect is lower, and this preparation has wide market prospect.
The specific embodiment
The object of the present invention is achieved like this: take iron protein succinylate as crude drug, add solubilizing agent, and excipient, cosolvent, add the aqueous slkali heated and stirred and dissolve, and adds acid, regulates pH, is made into 800mg/15ml iron protein succinylate oral administration solution.In above-mentioned settled solution, add antiseptic, correctives and sweeting agent, after filtration, sterilizing, be made into iron protein succinylate oral administration solution preparation.
Described solubilizing agent is selected from sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-or above two or more combination in any.
Described excipient is selected from sorbitol, methylcellulose, or above two or more combination in any.
Described cosolvent is selected from 1,2-PD, glycerol, ethanol, or above two or more combination in any.
Described solvent is selected from sodium hydroxide, potassium hydroxide, or above two or more combination in any.
The pH value controlling agent is selected from citric acid, lactic acid, malic acid, or above two or more combination in any.
Antiseptic is selected from methyl hydroxybenzoate sodium, propyl hydroxybenzoate sodium, or above two or more combination in any.
Correctives is selected from Fructus Pyracanthae essence, Fructus Mangifera Indicae essence, the sub-essence of tangerine, cherry essence, or above two or more combination in any.
Sweeting agent is selected from saccharin sodium, steviosin, or above two or more combination in any.
The concrete grammar of iron protein succinylate solubilizing process of the present invention and oral administration solution preparation is as follows:
1. take 0.1-1g iron protein succinylate crude drug, add the 1,2-PD 5-10% of total formulation weight amount, stirring and evenly mixing.
2. the sorbitol 5-10% that adds the total formulation weight amount in above-mentioned solution, stirring and evenly mixing.
3. the sodium lauryl sulphate 0.1-1% or poloxamer 0.1-2% or PEG-400 0.5%-10% or the beta-schardinger dextrin-5-20% that in above-mentioned solution, add the total formulation weight amount, stirring and evenly mixing.
4. in above-mentioned solution, add the KOH solution of the NaOH of 0.1-1mol/L or 0.1-1mol/L or for the combination aqueous slkali heated and stirred of above two kinds of aqueous slkalis to dissolving.
5. the 1-10% citric acid or 1-10% lactic acid or the 1-10% malic acid that in above-mentioned solution, add the total formulation weight amount, regulate pH and put 6.5-8.0, is made into the iron protein succinylate settled solution.
6. 1% essence, the 0.1-0.2% saccharin sodium that in above-mentioned settled solution, add the total formulation weight amount, after 2 μ m filter, again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, through 105～115 ℃ of sterilizing 20min of high temperature, can be made into the iron protein succinylate oral administration solution.
Embodiment 1:
Take iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml, sorbitol 1.4g, mix, add sodium lauryl sulphate 0.2g, mix, add 1mol/L NaOH solution to dissolve standardize solution and put 15ml, add the 3g citric acid, regulate pH to 6.5-8.0, add Fructus Pyracanthae essence 1g, saccharin sodium 0.03g, namely be made into the iron protein succinylate oral administration solution, the solution of preparing is after 2 μ m filter, again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, through 115 ℃ of sterilizing 20min of high temperature, obtain.
Embodiment 2:
Take iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml, sorbitol 1.4g, mix, and adds poloxamer 0.2g to mix, add 1mol/L NaOH solution to dissolve standardize solution and put 15ml, add the 3g citric acid, regulate pH to 6.5-8.0, add Fructus Pyracanthae essence 1g, saccharin sodium 0.03g, namely be made into the iron protein succinylate oral administration solution, the solution of preparing is after 2 μ m filter, then through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, through 115 ℃ of sterilizing 20min of high temperature, obtain.
Embodiment 3:
Take iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml, sorbitol 1.4g, mix, add PEG-400 0.2g, mix, add 1mol/L NaOH solution to dissolve standardize solution and put 15ml, add the 3g citric acid, regulate pH to 6.5-8.0, add Fructus Pyracanthae essence 1g, saccharin sodium 0.03g, namely be made into the iron protein succinylate oral administration solution, the solution of preparing is after 2 μ m filter, again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, through 115 ℃ of sterilizing 20min of high temperature, obtain.
Embodiment 4:
Take iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml, sorbitol 1.4g, mix, add beta-schardinger dextrin-3g, mix, add 1mol/L NaOH solution to dissolve standardize solution and put 15ml, add the 3g citric acid, regulate pH to 6.5-8.0, add Fructus Pyracanthae essence 1g, saccharin sodium 0.03g, namely be made into the iron protein succinylate oral administration solution, the solution of preparing is after 2 μ m filter, again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, through 115 ℃ of sterilizing 20min of high temperature, obtain.
Embodiment 5:Sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-
Take iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml, sorbitol 1.4g, mix, add sodium lauryl sulphate 0.1g, poloxamer 0.1g, mix, add 1mol/L NaOH solution to dissolve standardize solution and put 15ml, add the 3g citric acid, regulate pH to 6.5-8.0, add Fructus Pyracanthae essence 1g, saccharin sodium 0.03g, namely be made into the iron protein succinylate oral administration solution, the solution of preparing is after 2 μ m filter, again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, through 115 ℃ of sterilizing 20min of high temperature, obtain.
Embodiment 6:Sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-
Take iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml, sorbitol 1.4g, mix, add sodium lauryl sulphate 0.1g, PEG-400 0.1g, mix, add 1mol/L NaOH solution to dissolve standardize solution and put 15ml, add the 3g citric acid, regulate pH to 6.5-8.0, add Fructus Pyracanthae essence 1g, saccharin sodium 0.03g, namely be made into the iron protein succinylate oral administration solution, the solution of preparing is after 2 μ m filter, again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, through 115 ℃ of sterilizing 20min of high temperature, obtain.
Embodiment 7:Sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-
take iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1, 2-propylene glycol 2ml, sorbitol 1.4g, mix, add sodium lauryl sulphate 0.1g, poloxamer 0.1, PEG-400 0.1g, mix, add 1mol/L NaOH solution to dissolve standardize solution and put 15ml, add the 3g citric acid, regulate pH to 6.5-8.0, add Fructus Pyracanthae essence 1g, saccharin sodium 0.03g, namely be made into the iron protein succinylate oral administration solution, the solution of preparing is after 2 μ m filter, again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and through 115 ℃ of sterilizing 20min of high temperature, obtain.
Embodiment 8:Sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-
take iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1, 2-propylene glycol 2ml, sorbitol 1.4g, mix, add sodium lauryl sulphate 0.1g, poloxamer 0.1, PEG-400 0.1g, beta-schardinger dextrin-1g, mix, add 1mol/L NaOH solution to dissolve standardize solution and put 15ml, add the 3g citric acid, regulate pH to 6.5-8.0, add Fructus Pyracanthae essence 1g, saccharin sodium 0.03g, namely be made into the iron protein succinylate oral administration solution, the solution of preparing is after 2 μ m filter, again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and through 115 ℃ of sterilizing 20mi of high temperature.
Claims (3)
1. an iron protein succinylate solubilization method, is characterized in that: take iron protein succinylate as crude drug, add solubilizing agent, excipient and cosolvent, add the aqueous slkali heated and stirred and dissolve, then add acid, regulate pH to 6.5-8.0pH;
Added solubilizing agent accounts for the crude drug total weight percent: the PEG-400 of the sodium lauryl sulphate of 0.1-1%, the poloxamer of 0.1-2%, 0.5%-10% or the beta-schardinger dextrin-of 5-20%;
Added excipient accounts for the crude drug total weight percent: the sorbitol of 5-10%;
Added cosolvent accounts for the crude drug total weight percent: the 1,2-PD of 5-10%;
Added aqueous slkali is the NaOH solution of 0.1-1mol/L concentration or the KOH solution of 0.1-1mol/L concentration, or is the combination aqueous slkali of the KOH solution of the NaOH solution of 0.1-1mol/L concentration and 0.1-1mol/L concentration;
Added acid accounts for the crude drug total weight percent: the malic acid of the citric acid of 1-10%, the lactic acid of 1-10% or 1-10%.
2. iron protein succinylate oral administration solution preparation that adopts product configuration prepared by the described method of claim 1, it is characterized in that in the settled solution of the iron protein succinylate after solubilising, adding antiseptic, correctives and sweeting agent, after filtration, sterilizing, be made into iron protein succinylate oral administration solution preparation;
Added antiseptic accounts for the said preparation total weight percent: the propyl hydroxybenzoate sodium of 0.1-0.2% and the methyl hydroxybenzoate sodium of 0.1-0.2%;
Added correctives accounts for the said preparation total weight percent: Fructus Pyracanthae essence 1%, Fructus Mangifera Indicae essence 1%, the sub-essence 1% of tangerine or cherry essence 1%; Added sweeting agent accounts for the said preparation total weight percent: saccharin sodium 0.1-0.2% or steviosin 0.1-0.2%.
3. iron protein succinylate oral administration solution preparation according to claim 2, is characterized in that the oral administration solution of preparing preparation specification is 800mg/15ml iron protein succinylate oral administration solution; The oral administration solution preparation of preparing is after 2 μ m filter, then through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and through 105～115 ℃ of sterilizing 20min of high temperature.
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| CN102836419B (en) * | 2012-09-25 | 2014-06-25 | 济川药业集团有限公司 | Iron protein succinylate oral solution and preparation method thereof |
| CN102838667B (en) * | 2012-09-25 | 2014-06-25 | 济川药业集团有限公司 | Preparation method of iron protein succinylate |
| CN104546695A (en) * | 2013-10-25 | 2015-04-29 | 北京韩美药品有限公司 | Oral Montelukast sodium liquid preparation and preparation method thereof |
| CN104338122B (en) * | 2014-11-07 | 2017-06-30 | 河北仁合益康药业有限公司 | A kind of iron protein succinylate oral solution and preparation method thereof |
| CN104523586B (en) * | 2014-12-29 | 2017-08-18 | 广州瑞尔医药科技有限公司 | A kind of oral liquid and preparation method thereof |
| CN105363024A (en) * | 2015-12-16 | 2016-03-02 | 浙江浙北药业有限公司 | Preparation method of iron proteinsuccinylate oral solution |
| CN107320444B (en) * | 2016-04-28 | 2021-02-26 | 成都康弘药业集团股份有限公司 | Pharmaceutical solution containing lurasidone hydrochloride and preparation method thereof |
| CN108853476A (en) * | 2017-05-11 | 2018-11-23 | 武汉先路医药科技股份有限公司 | A kind of iron protein succinylate oral solution and preparation method thereof |
| CN109221178B (en) * | 2018-10-08 | 2021-01-26 | 江苏省农业科学院 | Dissolving method and application of zinc thiazole raw medicine |
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