CN1830427A - Preparation method of sodium ferulate freeze dried powder injection - Google Patents
Preparation method of sodium ferulate freeze dried powder injection Download PDFInfo
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- CN1830427A CN1830427A CN 200510051477 CN200510051477A CN1830427A CN 1830427 A CN1830427 A CN 1830427A CN 200510051477 CN200510051477 CN 200510051477 CN 200510051477 A CN200510051477 A CN 200510051477A CN 1830427 A CN1830427 A CN 1830427A
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Abstract
A freeze-dried powder injection of sodium ferulate for treating atherosclerosis, coronary heart disease, cerebrovascular disease, glomerulus disease, pulmonary hypertension, vasculitis, etc is prepared from sodium ferulate through ultrafiltration, mixing with filtered mannitol in N2 atmosphere and dark condition, pouring in containers, freeze drying and sealing.
Description
Technical field
The present invention relates to a kind of preparation method of sodium ferulate freeze dried powder injection, specifically, relating to a kind of is the lyophilized injectable powder of main composition with sodium ferulate, after sodium ferulate is handled through hyperfiltration technique, under lucifuge, feeding condition of nitrogen gas, prepare fill with mannitol filtrate again, through after the lyophilization, roll lid pack, make the lyophilized injectable powder finished product, belong to the chemical preparation field.Through clinical trial certificate, but this product intravenous drip, but the non-peptide-like endothelin receptor of antagonism, can antagonism the vasoconstriction that causes of Endothelin, boost and vascular smooth muscle cell proliferation, alleviate vascular endothelial injury; Increase the synthetic of NO, lax vascular smooth muscle; Anticoagulant, anticoagulation, improve the hemorheology feature; Suppress the synthetic of cholesterol, blood fat reducing is removed free radical, prevents lipid peroxidation injury; Influence complement, and have certain analgesia, spasmolysis.Be mainly used in vascular disease and leukocyte and thrombocytopenia such as atherosclerosis, coronary heart disease, cerebrovascular, renal glomerular disease, pulmonary hypertension, diabetic angiopathy change, vasculitis, also can be used for the treatment of migraine, vascular headache etc.
Background technology
Sodium ferulate is the sodium salt of the effective monomer component ferulic acid that extracts from traditional blood-activating and stasis-removing Radix Angelicae Sinensis, Rhizoma Chuanxiong, its chemistry 3-methoxyl group by name-4-Hydroxycinnamic Acid monocalcium salt compound, but the non-peptide-like endothelin receptor of antagonism, can antagonism the vasoconstriction that causes of Endothelin, boost and vascular smooth muscle cell proliferation, alleviate vascular endothelial injury; Increase the synthetic of NO, lax vascular smooth muscle; Anticoagulant, anticoagulation, improve the hemorheology feature; Suppress the synthetic of cholesterol, blood fat reducing is removed free radical, prevents lipid peroxidation injury; Influence complement, and have certain analgesia, spasmolysis.
At present, sodium ferulate freeze dried powder injection on the domestic market has many enterprises to produce, all adopt traditional handicraft formulated, the constant product quality of its existence is poor, and the medicinal liquid zest is strong, poor solubility, clarity disqualification rate height, pH value descends, and content descends, color burn, problems such as curative effect instability can't solve all the time.Its main cause is sodium ferulate removal fully such as partial impurities such as protein, tannin in preparation process, and the unstability of adding sodium ferulate itself causes.The breakthrough of this sodium ferulate freeze dried powder injection technology has fundamentally solved the problems referred to above.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of sodium ferulate freeze dried powder injection.
Preparation method of the present invention comprises the steps: sodium ferulate is dissolved under logical condition of nitrogen gas, carry out hyperfiltration treatment, get ultrafiltrate, under lucifuge, feeding condition of nitrogen gas, prepare through the filtrate of decarbonization filtering with mannitol again, fill, through after the lyophilization, roll lid pack, make the sodium ferulate freeze dried powder injection finished product
Preparation method detailed process of the present invention is as follows:
A) get the fresh water for injection of amount of preparation 50～80%, be cooled to 20～40 ℃, fed nitrogen 10～30 minutes, lucifuge adds the sodium ferulate in the prescription, fully after the stirring and dissolving, is 10,000～30,000 ultrafilter membrane ultrafiltration with molecular cut off, gets ultrafiltrate.
B) preparation of mannitol filtrate: get amount of preparation 10～30% fresh water for injection, add the mannitol dissolving in the prescription, add 0.1～0.5% active carbon, heated and boiled 15～30 minutes, with 40～50 ℃ of medicinal liquid circulation coolings, 0.45 μ m filter membrane decarbonization filtering, filtrate for later use.
C) above-mentioned ultrafiltrate is added in the mannitol filtrate, mix homogeneously, standardize solution, adjust pH 6.5～7.5, intermediate products after the assay was approved, with medicinal liquid after terminal 0.22 μ m filter membrane aseptic filtration, fill the nitrogen fill under the lucifuge condition in cillin bottle, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
More preferred manufacturing procedure comprises the steps:
A) get the fresh water for injection of amount of preparation 70%, be cooled to 30 ℃, fed nitrogen 20 minutes, lucifuge adds the sodium ferulate in the prescription, fully after the stirring and dissolving, is 10,000 ultrafilter membrane ultrafiltration with molecular cut off, gets ultrafiltrate.
B) preparation of mannitol filtrate: get amount of preparation 20% fresh water for injection, add the mannitol dissolving in the prescription, add 0.2% active carbon, heated and boiled 20 minutes is with 45 ℃ of medicinal liquid circulation coolings, 0.45 μ m filter membrane decarbonization filtering, filtrate for later use.
C) above-mentioned ultrafiltrate is added in the mannitol filtrate, mix homogeneously, standardize solution, adjust pH 6.7～7.2, intermediate products after the assay was approved, with medicinal liquid after terminal 0.22 μ m filter membrane aseptic filtration, fill the nitrogen fill under the lucifuge condition in cillin bottle, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
In the above-mentioned preparation method, for making constant product quality, the temperature of used water for injection is 20～40 ℃, and the time that feeds nitrogen is 10～30 minutes, and pH value is strict controlled in 6.7～7.2.
In the above-mentioned preparation method, adopting the molecular weight that dams is 10,000 ultrafilter membrane ultrafiltration, is the controlled step of invalid components in institute's preparating liquid, and used ultrafilter membrane is the commercially available prod.Its manufacturer should be the production unit of industry approval.
In the above-mentioned preparation method, lucifuge, logical condition of nitrogen gas are the committed steps of medicinal liquid preparation, pouring process.
In the above-mentioned preparation method, the employed filter membrane of terminal aseptic filtration aperture is 0.22 μ m.For making constant product quality, filter membrane should be as far as possible by fixedly manufacturer's supply.
In the above-mentioned preparation method, the active carbon of adding is 0.1～0.5%, and the heated and boiled time is 15～30 minutes, and fluid temperature is 40～50 ℃, and the filter membrane aperture of decarbonization filtering is 0.45 μ m
During injection sodium ferulate freeze dried powder injection clinical practice of the present invention, intravenous drip, a 0.1g～0.3g, once-a-day (one time 1～3,1 time on the one), dissolving back adds quiet of glucose injection, normal saline or Dextrose and Sodium Chloride Inj. 100～500ml.Intramuscular injection, a 0.1g, 1～2 time on the one (one time one, 1～2 time on the one) is faced with preceding and is dissolved with normal saline 2～4ml.
Injection sodium ferulate freeze dried powder injection of the present invention, but the non-peptide-like endothelin receptor of antagonism, can antagonism the vasoconstriction that causes of Endothelin, boost and vascular smooth muscle cell proliferation, alleviate vascular endothelial injury; Increase the synthetic of NO, lax vascular smooth muscle; Anticoagulant, anticoagulation, improve the hemorheology feature; Suppress the synthetic of cholesterol, blood fat reducing is removed free radical, the control lipid peroxidation injury; Influence complement, and have certain analgesia, spasmolysis.Be mainly used in vascular disease and leukocyte and thrombocytopenia such as atherosclerosis, coronary heart disease, cerebrovascular, renal glomerular disease, pulmonary hypertension, diabetic angiopathy change, vasculitis, also can be used for the treatment of migraine, vascular headache etc.
Sodium ferulate is handled through hyperfiltration technique in this technical process; and lucifuge, nitrogen filled protection arranged; avoided the degraded of sodium ferulate; guaranteed that invalid components is removed fully; reduced the related substance in the preparation; make that the preparation quality made is loose, dissolubility is good, stability increases, zest reduces, clarity is improved stable curative effect.
The specific embodiment
Further describe the present invention with embodiment below, but described embodiment only is used to illustrate the present invention rather than restriction the present invention.
Embodiment 1
A) get the fresh water for injection of amount of preparation 50%, be cooled to 40 ℃, fed nitrogen 30 minutes, lucifuge adds the sodium ferulate in the prescription, fully after the stirring and dissolving, is 30,000 ultrafilter membrane ultrafiltration with molecular cut off, gets ultrafiltrate.
B) preparation of mannitol filtrate: get amount of preparation 10% fresh water for injection, add the mannitol dissolving in the prescription, add 0.5% active carbon, heated and boiled 15 minutes is with 40 ℃ of medicinal liquid circulation coolings, 0.45 μ m filter membrane decarbonization filtering, filtrate for later use.
C) above-mentioned ultrafiltrate is added in the mannitol filtrate, mix homogeneously, standardize solution, adjust pH 7.0, intermediate products after the assay was approved, with medicinal liquid after terminal 0.22 μ m filter membrane aseptic filtration, fill the nitrogen fill under the lucifuge condition in cillin bottle, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
Embodiment 2
A) get the fresh water for injection of amount of preparation 80%, be cooled to 20 ℃, fed nitrogen 10 minutes, lucifuge adds the sodium ferulate in the prescription, fully after the stirring and dissolving, is 20,000 ultrafilter membrane ultrafiltration with molecular cut off, gets ultrafiltrate.
B) preparation of mannitol filtrate: get amount of preparation 30% fresh water for injection, add the mannitol dissolving in the prescription, add 0.1% active carbon, heated and boiled 30 minutes is with 50 ℃ of medicinal liquid circulation coolings, 0.45 μ m filter membrane decarbonization filtering, filtrate for later use.
C) above-mentioned ultrafiltrate is added in the mannitol filtrate, mix homogeneously, standardize solution, adjust pH 7.2, intermediate products after the assay was approved, with medicinal liquid after terminal 0.22 μ m filter membrane aseptic filtration, fill the nitrogen fill under the lucifuge condition in cillin bottle, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
Embodiment 3
A) get the fresh water for injection of amount of preparation 60%, be cooled to 35 ℃, fed nitrogen 25 minutes, lucifuge adds the sodium ferulate in the prescription, fully after the stirring and dissolving, is 10,000 ultrafilter membrane ultrafiltration with molecular cut off, gets ultrafiltrate.
B) preparation of mannitol filtrate: get amount of preparation 15% fresh water for injection, add the mannitol dissolving in the prescription, add 0.4% active carbon, heated and boiled 25 minutes is with 46 ℃ of medicinal liquid circulation coolings, 0.45 μ m filter membrane decarbonization filtering, filtrate for later use.
C) above-mentioned ultrafiltrate is added in the mannitol filtrate, mix homogeneously, standardize solution, adjust pH 6.7, intermediate products after the assay was approved, with medicinal liquid after terminal 0.22 μ m filter membrane aseptic filtration, fill the nitrogen fill under the lucifuge condition in cillin bottle, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
Embodiment 4
A) get the fresh water for injection of amount of preparation 75%, be cooled to 25 ℃, fed nitrogen 15 minutes, lucifuge adds the sodium ferulate in the prescription, fully after the stirring and dissolving, is 30,000 ultrafilter membrane ultrafiltration with molecular cut off, gets ultrafiltrate.
B) preparation of mannitol filtrate: get amount of preparation 25% fresh water for injection, add the mannitol dissolving in the prescription, add 0.3% active carbon, heated and boiled 30 minutes is with 42 ℃ of medicinal liquid circulation coolings, 0.45 μ m filter membrane decarbonization filtering, filtrate for later use.
C) above-mentioned ultrafiltrate is added in the mannitol filtrate, mix homogeneously, standardize solution, adjust pH 7.1, intermediate products after the assay was approved, with medicinal liquid after terminal 0.22 μ m filter membrane aseptic filtration, fill the nitrogen fill under the lucifuge condition in cillin bottle, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
Embodiment 5
A) get the fresh water for injection of amount of preparation 55%, be cooled to 20 ℃, fed nitrogen 20 minutes, lucifuge adds the sodium ferulate in the prescription, fully after the stirring and dissolving, is 20,000 ultrafilter membrane ultrafiltration with molecular cut off, gets ultrafiltrate.
B) preparation of mannitol filtrate: get amount of preparation 30% fresh water for injection, add the mannitol dissolving in the prescription, add 0.2% active carbon, heated and boiled 15 minutes is with 45 ℃ of medicinal liquid circulation coolings, 0.45 μ m filter membrane decarbonization filtering, filtrate for later use.
C) above-mentioned ultrafiltrate is added in the mannitol filtrate, mix homogeneously, standardize solution, adjust pH 6.8, intermediate products after the assay was approved, with medicinal liquid after terminal 0.22 μ m filter membrane aseptic filtration, fill the nitrogen fill under the lucifuge condition in cillin bottle, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
Experimental example 1
This experimental example is the detection of every gainer relevant under the character of the prepared injection sodium ferulate freeze dried powder injection of the present invention, pH value, clarity of solution and color, moisture, dissolubility and the injection item.
Character: this product is white or off-white color crystallization or crystallinity powder, or the loose block of little yellow, off-white color, and is up to specification.
PH value: get this product, add water and make the solution that contains 50mg among every 1ml, check (two appendix VIH of Chinese Pharmacopoeia version in 2000) in accordance with the law, pH value is 6.0～8.0, and is up to specification.
The clarity of solution and color: get this product, add water and make the solution that contains 20mg among every 1ml, solution should be clarified colourless; As showing muddy, compare with No. 1 turbidity standard (two appendix IXB of Chinese Pharmacopoeia version in 2000), must not be denseer; As colour developing, compare with yellow or No. 3 standard color solutions of yellow green (two appendix IXA first methods of Chinese Pharmacopoeia version in 2000), must not be darker.Through the mensuration of three batches of injection sodium ferulate freeze dried powder injections, the clarity of solution and color are all up to specification.
Moisture: get this product, measure, contain moisture and do not surpass 5.0% according to aquametry (two appendix VIIIM first methods of Chinese Pharmacopoeia version in 2000), up to specification.
Dissolubility: get 1 bottle of this product, add 10ml water for injection, dissolving fully is up to specification in 10 minutes.
Other: meet every regulation relevant under the injection item (two appendix IB of Chinese Pharmacopoeia version in 2000).
Experimental example 2
This experimental example is the qualitative determination of the prepared injection sodium ferulate freeze dried powder injection of the present invention.
(1) get this product, add water and make the solution that contains 10 μ g among every 1ml, measure, absorption maximum is arranged, minimal absorption is arranged at the wavelength place of 254nm at the wavelength place of 287nm and 310nm according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), up to specification.
(2) aqueous solution of this product shows the identification (two appendix III of Chinese Pharmacopoeia version in 2000) of sodium salt, and is up to specification.
The prepared injection sodium ferulate freeze dried powder injection of above description of test the present invention contains definite component.
Experimental example 3
This experimental example is the assay of the prepared injection sodium ferulate freeze dried powder injection of the present invention.
Assay: lucifuge operation.Get this product, thin up becomes every 1ml to contain the solution of 10 μ g, according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), measures trap at the wavelength place of 310 ± 2nm, presses C
10H
9NaO
4Absorptance (E
1% 1cm) be 610 calculating, promptly.
Standard code: contain sodium ferulate (C
10H
9NaO
4H
2O) should be 90.0%～110.0% of labelled amount.
Assay by three batches the results are shown in following table:
| Lot number | Labelled amount (%) |
| 20040501 | 98.8 |
| 20040502 | 100.1 |
| 20040503 | 99.1 |
Experimental example 4
This experimental example is the safety indexes inspection of the prepared injection sodium ferulate freeze dried powder injection of the present invention.Pyrogen: get this product, add sterilized water for injection and make the solution that contains 5mg among every 1ml, check (two appendix XID of Chinese Pharmacopoeia version in 2000) in accordance with the law, dosage is by the every 1kg injection of rabbit body weight 1ml, and is up to specification.
Aseptic: get this product, add sterilized water for injection and make the solution that contains 20mg among every 1ml, check (two appendix XIH of Chinese Pharmacopoeia version in 2000) in accordance with the law, up to specification.
Long term toxicity is measured: successive administration was observed blood, urine index in three months, and pathologic finding there is no unusually.
Safety by the prepared injection sodium ferulate freeze dried powder injection of above description of test the present invention meets the injection requirement, does not have any toxic action, uses human body safety.
Comparative example 1
The clarity of the injection sodium ferulate freeze dried powder injection that this comparative example explanation the present invention is prepared is better than producing with conventional preparation method.
The clarity criterion:
1) finds no foreign body or only be with micro-white point person, the lattice theory of making a match.
2) every bottle contains the hair that is shorter than 0.5cm and the white point of 0.1～0.2mm, white piece or color dot sum above 5 persons, the lattice theory of making a match.
3) disqualification rate surpasses 5%, this batch product lattice theory of making a match.
Relevant notion:
White piece: mean with the inspection method of regulation, can see the whiteness that tangible plane or corner angle are arranged.
White point: can not differentiate plane or corner angle by white point.
Trace white point: in official hour, only see 3 or 3 following white point persons.
Foreign body: comprise chips of glass, fiber, color dot, color lump and other external foreign body.
Inspection method:
Get respectively and adopt prepared injection sodium ferulate freeze dried powder injection of the present invention and each 200 bottles of the products that adopts the common process preparation,, the results are shown in following table by " clarity test detailed rules and regulations and criterion " and above standard inspection.
| Group | The trace white point | White point | White piece | Foreign body | Number of non-compliances | Disqualification rate | Qualification rate | Conclusion |
| The invention group | 5 bottles | 2 bottles surpass 5 | 0 | 0 | 2 bottles | 1％ | 99％ | Qualified |
| Conventional group | 61 bottles | 2 bottles surpass 5 | 8 bottles surpass 5 | 0 | 10 bottles | 5％ | 95％ | Qualified |
Clarity by the prepared injection sodium ferulate freeze dried powder injection of above description of test the present invention obviously is better than producing with conventional preparation method.
Comparative example 2
The dissolubility of the injection sodium ferulate freeze dried powder injection that this comparative example explanation the present invention is prepared is better than producing with conventional preparation method.
Inspection method: get respectively and adopt prepared injection sodium ferulate freeze dried powder injection of the present invention and each 100 bottles of the products that adopts the common process preparation, in every bottle, add 10ml water for injection, observe and write down its dissolution time.
Criterion: with the dissolution time is standard.
Good: dissolving fully in 5 minutes;
Qualified: dissolving fully in 10 minutes;
Defective: as to surpass 10 minutes and dissolve fully.
Experimental result sees the following form:
| Group | Good number | Passing number | Number of non-compliances | Sum | Acceptance rate | Total qualification rate |
| The invention group | 97 | 3 | 0 | 100 | 97％ | 100％ |
| Conventional group | 11 | 73 | 16 | 100 | 11％ | 84％ |
Dissolubility by the prepared injection sodium ferulate freeze dried powder injection of above description of test the present invention obviously is better than producing with conventional preparation method.
Comparative example 3
This comparative example illustrates that the prepared injection sodium ferulate freeze dried powder injection zest when clinical practice of the present invention is less.
| Group | The invention group | Conventional group |
| Usage and dosage | Intravenous drip, a 0.1g～0.3g, once-a-day (one time 1～3,1 time on the one), dissolving back adds quiet of glucose injection, normal saline or Dextrose and Sodium Chloride Inj. 100～500ml.Intramuscular injection, a 0.1g, 1～2 time on the one (one time one, 1～2 time on the one), face with preceding and dissolve with normal saline 2～4ml. | Intravenous drip, a 0.1g～0.3g, once-a-day (one time 1～3,1 time on the one), dissolving back adds quiet of glucose injection, normal saline or Dextrose and Sodium Chloride Inj. 100～500ml.Intramuscular injection, a 0.1g, 1～2 time on the one (one time one, 1～2 time on the one), face with preceding and dissolve with normal saline 2～4ml. |
| Clinical practice | Treat 58 routine coronary heart disease, angina pectoris | Treat 63 routine coronary heart disease, angina pectoris |
| Zest is observed | No pain and untoward reaction phenomenon | The pain phenomenon appears in 35 routine injection sites, and the erythra reaction appears in 26 examples. |
Comparative example 4
The prepared injection sodium ferulate freeze dried powder injection of this comparative example explanation employing the present invention compares with the stability of the injection sodium ferulate freeze dried powder injection that adopts conventional preparation method to produce by six months accelerated tests, the results are shown in following table.
Standard code:
Content: this product contains sodium ferulate (C
10H
9NaO
4H
2O) should be 90.0%～110.0% of labelled amount.
PH value: should be 6.0～8.0
Clarity: qualification rate should be not less than 95%
Color: should be white or off-white color crystallization or crystallinity powder, or the loose block of little yellow, off-white color.
By above experiment as can be seen, the invention group was passed through accelerated tests after six months, significant change does not take place in its content, pH value, clarity, color, and content, the pH value of conventional group all have obvious reduction, clarity, color are all against regulation, show that the stability of the injection sodium ferulate freeze dried powder injection that the present invention is prepared obviously is better than adopting conventional preparation method to be produced.
Claims (10)
1. the preparation method of an injection sodium ferulate freeze dried powder injection, described preparation method detailed process is as follows:
A) get fresh water for injection, behind the feeding nitrogen, lucifuge adds the sodium ferulate dissolving in the prescription, and ultrafiltration gets ultrafiltrate;
B) preparation of mannitol filtrate: get fresh water for injection, add the mannitol dissolving in the prescription, add active carbon, heated and boiled, decarbonization filtering, filtrate for later use;
C) above-mentioned ultrafiltrate is added in the mannitol filtrate mix homogeneously, standardize solution, adjust pH, intermediate products after the terminal aseptic filtration, fill the nitrogen fill with medicinal liquid in cillin bottle after the assay was approved under the lucifuge condition, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
2. according to claims 1 described preparation method, it is characterized in that comprising the steps:
A) get the fresh water for injection of amount of preparation 50～80%, be cooled to 20～40 ℃, fed nitrogen 10～30 minutes, lucifuge adds the sodium ferulate in the prescription, fully after the stirring and dissolving, is 10,000～30,000 ultrafilter membrane ultrafiltration with molecular cut off, gets ultrafiltrate;
B) preparation of mannitol filtrate: get amount of preparation 10～30% fresh water for injection, add the mannitol dissolving in the prescription, add 0.1～0.5% active carbon, heated and boiled 15～30 minutes, with 40～50 ℃ of medicinal liquid circulation coolings, 0.45 μ m filter membrane decarbonization filtering, filtrate for later use;
C) above-mentioned ultrafiltrate is added in the mannitol filtrate, mix homogeneously, standardize solution, adjust pH 6.5～7.5, intermediate products after the assay was approved, with medicinal liquid after terminal 0.22 μ m filter membrane aseptic filtration, fill the nitrogen fill under the lucifuge condition in cillin bottle, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
3. according to claims 1 described preparation method, it is characterized in that comprising the steps:
A) get the fresh water for injection of amount of preparation 70%, be cooled to 30 ℃, fed nitrogen 20 minutes, lucifuge adds the sodium ferulate in the prescription, fully after the stirring and dissolving, is 10,000 ultrafilter membrane ultrafiltration with molecular cut off, gets ultrafiltrate;
B) preparation of mannitol filtrate: get amount of preparation 20% fresh water for injection, add the mannitol dissolving in the prescription, add 0.2% active carbon, heated and boiled 20 minutes is with 45 ℃ of medicinal liquid circulation coolings, 0.45 μ m filter membrane decarbonization filtering, filtrate for later use;
C) above-mentioned ultrafiltrate is added in the mannitol filtrate, mix homogeneously, standardize solution, adjust pH 6.7～7.2, intermediate products after the assay was approved, with medicinal liquid after terminal 0.22 μ m filter membrane aseptic filtration, fill the nitrogen fill under the lucifuge condition in cillin bottle, after the lyophilization, roll lid pack, promptly get the sodium ferulate freeze dried powder injection finished product.
4. according to claims 1,2 or 3 described preparation methoies, the temperature that it is characterized in that the used water for injection of formulated product is 20 ℃～40 ℃.
5. according to claims 1,2 or 3 described preparation methoies, the time that it is characterized in that feeding nitrogen is 10～30 minutes.
6. according to claims 1,2 or 3 described preparation methoies, it is characterized in that the employed ultrafilter membrane of ultrafiltration is that molecular cut off is 10,000～30,000 ultrafilter membrane.
7. according to claims 1,2 or 3 described preparation methoies, it is characterized in that preparing, the condition in the pouring process is logical nitrogen, lucifuge.
8. according to claims 1,2 or 3 described preparation methoies, it is characterized in that used pH value regulator is 10% sodium hydroxide solution or 10% hydrochloric acid solution, pH value is controlled at 6.7～7.2.
9. according to claims 1,2 or 3 described preparation methoies, it is characterized in that the employed filter membrane of terminal aseptic filtration aperture is 0.22 μ m.
10. according to claims 1,2 or 3 described preparation methoies, it is characterized in that in the preparation process of mannitol filtrate that the active carbon of adding is 0.1～0.5%, the heated and boiled time is 15～30 minutes, fluid temperature is 40～50 ℃, and the filter membrane aperture of decarbonization filtering is 0.45 μ m.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510051477 CN1830427A (en) | 2005-03-08 | 2005-03-08 | Preparation method of sodium ferulate freeze dried powder injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510051477 CN1830427A (en) | 2005-03-08 | 2005-03-08 | Preparation method of sodium ferulate freeze dried powder injection |
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|---|---|
| CN1830427A true CN1830427A (en) | 2006-09-13 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101416944B (en) * | 2008-12-11 | 2010-08-18 | 海南数尔药物研究有限公司 | Sodium ferulic acid nano micelle preparation and preparation method thereof |
| CN112472674A (en) * | 2021-01-06 | 2021-03-12 | 福安药业集团湖北人民制药有限公司 | Preparation method of sodium ferulate freeze-dried powder injection |
-
2005
- 2005-03-08 CN CN 200510051477 patent/CN1830427A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101416944B (en) * | 2008-12-11 | 2010-08-18 | 海南数尔药物研究有限公司 | Sodium ferulic acid nano micelle preparation and preparation method thereof |
| CN112472674A (en) * | 2021-01-06 | 2021-03-12 | 福安药业集团湖北人民制药有限公司 | Preparation method of sodium ferulate freeze-dried powder injection |
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