CN102671189A - 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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- CN102671189A CN102671189A CN2012101430544A CN201210143054A CN102671189A CN 102671189 A CN102671189 A CN 102671189A CN 2012101430544 A CN2012101430544 A CN 2012101430544A CN 201210143054 A CN201210143054 A CN 201210143054A CN 102671189 A CN102671189 A CN 102671189A
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- protein succinylate
- iron protein
- iron
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- 108010084684 iron protein succinylate Proteins 0.000 title claims abstract description 63
- 229940074442 iron protein succinylate Drugs 0.000 title claims abstract description 63
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 19
- 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
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract description 23
- 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
- 238000004659 sterilization and disinfection Methods 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
- 230000007928 solubilization Effects 0.000 claims description 8
- 238000005063 solubilization Methods 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
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 abstract description 13
- 229910052742 iron Inorganic materials 0.000 abstract description 5
- 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
- 235000011175 beta-cyclodextrine Nutrition 0.000 abstract 1
- 229960004853 betadex Drugs 0.000 abstract 1
- 239000008297 liquid dosage form Substances 0.000 abstract 1
- 238000002156 mixing Methods 0.000 description 19
- 235000015165 citric acid Nutrition 0.000 description 11
- 238000005303 weighing Methods 0.000 description 9
- 238000009472 formulation Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 208000015710 Iron-Deficiency Anemia Diseases 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 241001673391 Entandrophragma candollei Species 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
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- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
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- Medicinal Preparation (AREA)
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, the method for preparing of the solubilising and the oral administration solution thereof of a kind of indissoluble iron protein succinylate of saying so more specifically.
Background technology
198 years; Italy develops a kind of iron protein succinylate by name (iron-protein succinylate in the big pharmaceutical factory of general mark; Abbreviation ISP) nanometer polypeptide albuminoid iron supplement medicine; Successfully go on the market and more than 20 country comprises that Spain, Portugal, Greece, Argentina, Korea S, China etc. go on the market successively and sell in the whole world in Italy, welcome by the various countries doctor.
Through China national Department of Intellectual Property (SIPO), Derwent patent database (DII) and United States Patent (USP) trademark office (USPTO) patent retrieval, domestic respectively for iron protein succinylate solubilizing process and oral administration solution preparation related patent U.S. Patent No. report is not all arranged.
Iron protein succinylate is as a kind of high molecular weight protein complexation ferrum, and it was the deposition state at pH value less than 4 o'clock, and under alkali condition, became solable matter again.It at gastric not by pepsin digestion, but can be when pH neutral by trypsin hydrolyzing.Because it has these unique characteristics, iron protein succinylate receives the protection of albuminous coat and not by stomach acids destroy stomach function regulating protease hydrolyzed, gastric mucosa is not caused damage.After getting into intestinal, it dissolves again, and is digested by trypsin.After the protein protection film was digested, ferrum began to discharge in duodenum.
Have research to show, iron protein succinylate is very beneficial for being absorbed by body, does not but form high absworption peak.What pharmacokinetics research showed that it appears is a kind of constant absorption trend, reaches the best stable state that absorbs and store gradually at each position of body, so iron protein succinylate can not produce the gastrointestinal problem of resistance.Because the gastrointestinal problem of resistance contains the free iron amount and must meet import drugs registered standard JX20000298 in the iron protein succinylate oral administration solution preparation.
Summary of the invention
Technical problem:The present invention seeks to develop a kind of technology that can improve iron protein succinylate dissolubility in water; And prepare iron protein succinylate oral administration solution preparation with this technology; To solve problems such as the slightly solubility of this medicine in water, solution instability, 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 is crude drug with the iron protein succinylate, adds solubilizing agent, excipient and cosolvent, adds the dissolving of aqueous slkali heated and stirred, adds acid again, 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: 1 of 5-10%, 2-propylene glycol.
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 the product preparation of said method preparation is: add antiseptic, correctives and sweeting agent in the settled solution with the iron protein succinylate behind the solubilising, through filtering, 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 being prepared is a 800mg/15ml iron protein succinylate oral administration solution; The oral administration solution preparation of being prepared is 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 sterilizations of high temperature 20min.
Beneficial effect:
1. this solubilising preparing process has 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, each item index all can meet import drugs registered standard JX20000298, and other meet each item regulation relevant 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 the room temperature; Pharmacodynamic study is the result show; This preparation can effectively be treated absolute and relative iron deficiency anemia and because ferrum intake deficiency or malabsorption, acute or chronic blood loss and infect caused recessiveness or the dominance iron deficiency anemia, gestation and anemia age of sucking.Toxicologic study result shows that this preparation toxicity, side effect is lower, and this preparation has vast market prospect.
The specific embodiment
The objective of the invention is to realize like this: with the iron protein succinylate is crude drug, adds solubilizing agent, excipient, and cosolvent adds the dissolving of aqueous slkali heated and stirred, 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 through filtering, sterilizing, are made into iron protein succinylate oral administration solution preparation.
Said solubilizing agent is selected from sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-or above two or more combination in any.
Said excipient is selected from sorbitol, methylcellulose, or above two or more combination in any.
Said cosolvent is selected from 1,2-propylene glycol, glycerol, ethanol, or above two or more combination in any.
Said 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 following:
1. take by weighing 0.1-1g iron protein succinylate crude drug, add 1 of total formulation weight amount, 2-propylene glycol 5-10%, stirring and evenly mixing.
2. the sorbitol 5-10% that in above-mentioned solution, adds the total formulation weight amount, 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 0.1-1mol/L NaOH or 0.1-1mol/L KOH solution or be that the combination aqueous slkali heated and stirred of above two kinds of aqueous slkalis is to dissolving.
5. in above-mentioned solution, add 1-10% citric acid or the 1-10% lactic acid or the 1-10% malic acid of total formulation weight amount, regulate pH and put 6.5-8.0, be 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, can be made into the iron protein succinylate oral administration solution through 105～115 ℃ of sterilizations of high temperature 20min.
Embodiment 1:
Take by weighing iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml; Sorbitol 1.4g, mixing adds sodium lauryl sulphate 0.2g, mixing; Add 1mol/L NaOH solution dissolving 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 promptly is made into the iron protein succinylate oral administration solution, and the solution of being prepared is after 2 μ m filter; Again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, promptly get through 115 ℃ of sterilizations of high temperature 20min.
Embodiment 2:
Take by weighing iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml; Sorbitol 1.4g, mixing adds poloxamer 0.2g mixing, adds 1mol/L NaOH solution dissolving standardize solution and puts 15ml; Add the 3g citric acid, regulate pH to 6.5-8.0, add Fructus Pyracanthae essence 1g; Saccharin sodium 0.03g promptly is made into the iron protein succinylate oral administration solution, and the solution of being prepared is after 2 μ m filter; Again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, promptly get through 115 ℃ of sterilizations of high temperature 20min.
Embodiment 3:
Take by weighing iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml; Sorbitol 1.4g, mixing adds PEG-400 0.2g, mixing; Add 1mol/L NaOH solution dissolving 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 promptly is made into the iron protein succinylate oral administration solution, and the solution of being prepared is after 2 μ m filter; Again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, promptly get through 115 ℃ of sterilizations of high temperature 20min.
Embodiment 4:
Take by weighing iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml; Sorbitol 1.4g, mixing adds beta-schardinger dextrin-3g, mixing; Add 1mol/L NaOH solution dissolving 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 promptly is made into the iron protein succinylate oral administration solution, and the solution of being prepared is after 2 μ m filter; Again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, promptly get through 115 ℃ of sterilizations of high temperature 20min.
Embodiment 5:Sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-
Take by weighing iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml; Sorbitol 1.4g, mixing adds sodium lauryl sulphate 0.1g, poloxamer 0.1g, mixing; Add 1mol/L NaOH solution dissolving 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 promptly is made into the iron protein succinylate oral administration solution, and the solution of being prepared is after 2 μ m filter; Again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, promptly get through 115 ℃ of sterilizations of high temperature 20min.
Embodiment 6:Sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-
Take by weighing iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml; Sorbitol 1.4g, mixing adds sodium lauryl sulphate 0.1g, PEG-400 0.1g, mixing; Add 1mol/L NaOH solution dissolving 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 promptly is made into the iron protein succinylate oral administration solution, and the solution of being prepared is after 2 μ m filter; Again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, promptly get through 115 ℃ of sterilizations of high temperature 20min.
Embodiment 7:Sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-
Take by weighing iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml; Sorbitol 1.4g, mixing adds sodium lauryl sulphate 0.1g, poloxamer 0.1, PEG-400 0.1g, mixing; Add 1mol/L NaOH solution dissolving 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 promptly is made into the iron protein succinylate oral administration solution, and the solution of being prepared is after 2 μ m filter; Again through 0.45 μ m or 0.22 μ m filtering with microporous membrane, and, promptly get through 115 ℃ of sterilizations of high temperature 20min.
Embodiment 8:Sodium lauryl sulphate, poloxamer, PEG-400, beta-schardinger dextrin-
Take by weighing iron protein succinylate crude drug 0.8g, put in the 100ml beaker, add 1,2-propylene glycol 2ml; Sorbitol 1.4g, mixing adds sodium lauryl sulphate 0.1g, poloxamer 0.1, PEG-400 0.1g, beta-schardinger dextrin-1g, mixing; Add 1mol/L NaOH solution dissolving 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 promptly is made into the iron protein succinylate oral administration solution; The solution of being prepared 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 sterilizations of high temperature 20mi.
Claims (8)
1. an iron protein succinylate solubilization method is characterized in that: be crude drug with the iron protein succinylate, add solubilizing agent, excipient and cosolvent, add the dissolving of aqueous slkali heated and stirred, add acid again, regulate pH to 6.5-8.0pH.
2. iron protein succinylate solubilization method according to claim 1 is characterized in that: 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%.
3. iron protein succinylate solubilization method according to claim 1 is characterized in that added excipient accounts for the crude drug total weight percent and is: the sorbitol of 5-10%.
4. iron protein succinylate solubilization method according to claim 1 is characterized in that added cosolvent accounts for the crude drug total weight percent and is: 1 of 5-10%, 2-propylene glycol.
5. iron protein succinylate solubilization method according to claim 1; It is characterized in that added aqueous slkali is the NaOH solution of 0.1-1mol/L concentration or the KOH solution of 0.1-1mol/L concentration, or be the combination aqueous slkali of KOH solution of NaOH solution and the 0.1-1mol/L concentration of 0.1-1mol/L concentration.
6. iron protein succinylate solubilization method according to claim 1 is characterized in that added acid accounts for the crude drug total weight percent and is: the malic acid of the citric acid of 1-10%, the lactic acid of 1-10% or 1-10%.
7. iron protein succinylate oral administration solution preparation that adopts the product preparation of the said method of claim 1 preparation; It is characterized in that adding in the settled solution with the iron protein succinylate behind the solubilising antiseptic, correctives and sweeting agent; Through filtering, 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%.
8. iron protein succinylate oral administration solution preparation according to claim 7 is characterized in that the oral administration solution preparation specification of being prepared is a 800mg/15ml iron protein succinylate oral administration solution; The oral administration solution preparation of being prepared is 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 sterilizations of high temperature 20min.
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| CN102838667A (en) * | 2012-09-25 | 2012-12-26 | 江苏济川制药有限公司 | Preparation method of iron protein succinylate |
| CN102836419A (en) * | 2012-09-25 | 2012-12-26 | 江苏济川制药有限公司 | Iron protein succinylate oral solution and preparation method thereof |
| CN104338122A (en) * | 2014-11-07 | 2015-02-11 | 石家庄开发区博欣医药科技开发有限公司 | Iron proteinsuccinylate oral solution and preparation method of iron proteinsuccinylate oral solution |
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