CN1824295A - Preparation technology of poly gelatin peptide injection liquid - Google Patents
Preparation technology of poly gelatin peptide injection liquid Download PDFInfo
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- CN1824295A CN1824295A CN 200510132242 CN200510132242A CN1824295A CN 1824295 A CN1824295 A CN 1824295A CN 200510132242 CN200510132242 CN 200510132242 CN 200510132242 A CN200510132242 A CN 200510132242A CN 1824295 A CN1824295 A CN 1824295A
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Abstract
A process for preparing the injection of polygeline includes such steps as dissolving gelatin in the water for injection, adding acid, hydrolyzing, regulating pH=6.5-7.5, adding sodium (or calcium or potassium) chloride, dissolving, adding the water for injection, adding the activated carbon for injection, adsorbing heat source and impurities, sand filtering for removing carbon, fine filtering, loading in containers, sealing, sterilizing and examining.
Description
Technical field
The invention belongs to the preparation technology of poly gelatin peptide injection, be specifically related to a kind of preparation method who produces the blood substitutes poly gelatin peptide injection take ox bone, pig bone or other gelatin as raw material.
Background technology
Polygeline is in recent years a new generation's improvement gelatin, since for after clinical, finds that it possesses desirable Artificial colloid condition, has more superiority than dextran and HES. Because Polygeline indices and blood of human body are close, electrolyte content and pH value are more near human plasma, and dextran and HES are without this characteristic; Polygeline is noiseless to blood coagulation system, and dextran and HES all have blood coagulation resisting function, and are subject to dose limiting; Polygeline is compared slightly allergic reaction with dextran with HES, and of short duration slight; Polygeline also can improve circulatory function better, show hemodilution after, cardiac output, the oxygen of body transports, cardiac index and mean arterial pressure increase, and dextran and HES function in this respect is relatively poor. Many studies show that, Polygeline has good effect to aspects such as the replenishing of acute hypovolemia, hemodilutions, so more be applied to hemodilution and autotransfusion.
Poly gelatin peptide injection is the Plasma substitutes of gelatin solution that the World Health Organization (WH0) " essential drugs guide " is recommended, and has blood pressure, the rapidly additional effect of keeping blood volume and keeping osmotic pressure of promoting. Have the not available advantage of human blood in the clinical use, need not blood group mate during such as blood transfusion, the cross infection of the diseases such as the hepatitis that can avoid transfuses blood causes, AIDS etc. are suitable for clinical emergency treatment.
But at present there is different preparation methods in poly gelatin peptide injection, is that CN1387912A and publication number are all to have used crosslinking agent glyoxal, succinic anhydride, glutaraldehyde etc. among " preparation method of poly gelatin peptide injection " of CN1586620A such as publication number. Wherein glyoxal sucks, takes in or may be harmful to human body after skin absorbs. Its steam or smog have spread effect to eyes, skin, mucous membrane and the upper respiratory tract. Belong to the moderate toxicity material, eye and schneiderian membrane are had the minimal irritation effect, can cause that animal hypermesises. Slow poisoning can cause pancreatic damage. Acute toxicity: LD502020mg/kg (rat oral); 200mg/kg (mouse peritoneal). Although glutaraldehyde is little than glyoxal to the excitant of skin and mucous membrane, tissue is had moderate toxicity can cause bronchitis and pulmonary edema. Glutaraldehyde causes allergy and does not usually betide first, through incubation period, from several minutes to 72h anaphylactoid various symptom can occur after the contact again. If the poly gelatin peptide injection that has the residual words such as glyoxal, glutaraldehyde may cause preparing in preparation process causes multiple bad reaction when clinical practice. Need not to add any crosslinking agent and prepare poly gelatin peptide injection by the inventive method, safer when clinical practice.
Summary of the invention
The object of the present invention is to provide a kind of poly gelatin peptide injection and preparation method thereof. Poly gelatin peptide injection by the inventive method preparation meets the national drug standards, has blood pressure, the rapidly additional effect of keeping blood volume and keeping osmotic pressure of promoting. And production technology is simply controlled, and easily industrialized production does not add any crosslinking agent, and the production qualification rate is high, product quality easy to control.
More particularly, main feature of the present invention is: adopt conventional method hydrolysis, make hydrolysis be easy to control, need not special installation, be easy to large production; Do not add any crosslinking agent, avoid the residual and toxic and side effect that body is produced of crosslinking agent fully; Directly the controlled hydrolysis condition makes the weight average molecular weight of the Polygeline that obtains between 35000～39000 dalton; In essence filtration journey, remove the little part Polygeline of molecular weight, make the Polygeline molecular weight distribution that obtains more concentrated; Adopt parenteral solution sterilizing methods commonly used 121 ℃ of sterilizations, the weight average molecular weight of Polygeline is reduced to about 30000～35000 dalton again, meet the scope of the weight average molecular weight 27500～39500 of national Specification.
Poly gelatin peptide injection preparation technology concrete steps of the present invention are:
1, gelatin hydrolysis:
Get gelatin and put in the appropriate vessel, it is an amount of to inject water, stirs and makes dissolving, and acid adding is hydrolyzed in right amount.
2, add pH value conditioning agent:
Being hydrolyzed an amount of pH value conditioning agent adjusting pH value of complete rear adding is 6.5～7.5.
3, add electrolyte:
Take by weighing again an amount of sodium chloride, calcium chloride, potassium chloride, electrolyte is dissolved fully, add again water for injection to recipe quantity.
4, adsorption clarification:
Add an amount of needle-use activated carbon, stirring and adsorbing pyrogen, impurity etc. take off charcoal with the middling speed sand stick. Liquid circulation 20 minutes.
5, smart filter.
6, packing is jumped a queue, and rolls lid.
7, sterilization.
8, full inspection, packing.
More specifically, method of the present invention may further comprise the steps:
1, gelatin hydrolysis:
Getting gelatin puts in the appropriate vessel, make the gelatin dissolving with 40～70 ℃ waters for injection, get hydrochloric acid, sulfuric acid or other inorganic acid, its concentration should be 0.1%～2.0% (WN), preferred concentration is 0.5%～1.0% (WN), add in the gelatin solution that has dissolved, stir, sealing, in 90～121 ℃ of Water Under solutions, preferred temperature is 90～108 ℃, and the controlled hydrolysis time is between 30 minutes～100 minutes, and the preferred time is 60 minutes～80 minutes. Finally making the weight average molecular weight that is hydrolyzed the Polygeline that obtains is good between 35000～39000 dalton.
2, add pH value conditioning agent:
Be hydrolyzed an amount of pH value conditioning agent of complete rear adding, pH value conditioning agent can be NaOH, sodium acid carbonate, sodium carbonate etc., also can be above-mentioned every mixture, and the pH value of solution is between 6.5～7.5 behind the adjusting gelatin hydrolysis.
3, add electrolyte:
Take by weighing again in the solution of an amount of sodium chloride, calcium chloride, potassium chloride adding above-mentioned steps 2 gained, add electrolytical amount and should meet the requirement of the poly gelatin peptide injection national drug standards, be to contain potassium in every 1ml parenteral solution to should be 2.0～4.0 μ mol, sodium should be 139～152 μ mol, calcium should be 0.2～2.0 μ mol, stirring is dissolved electrolyte fully, adds water for injection to recipe quantity again.
4, adsorption clarification:
The adding needle-use activated carbon is set up to be stated in the mixed solution, activated carbon dosage is 0.01～2.0% (W/V), and preferable amount is 0.05～1.0% (W/V), stirring and adsorbing pyrogen, impurity etc., mixing time is preferably 20 minutes～and 30 minutes, whipping temp is preferably 50～60 ℃. Take off charcoal with the middling speed sand stick. Liquid circulation 20 minutes.
5, the 0.45um filtering with microporous membrane is used first in smart filter, uses the 0.22um filtering with microporous membrane again.
6, packing is jumped a queue, and rolls lid.
7,121 ℃ of pressure sterilizings are generally adopted in sterilization, and sterilization time is preferably 20 minutes～and 30 minutes.
8, full inspection, packing.
The specification of the poly gelatin peptide injection of said method Production and Packaging can be that every 500ml liquid contains 3.2g nitrogen (Polygeline is in nitrogen content), also can be that the 250ml liquid contains 1.6g nitrogen (Polygeline is in nitrogen content).
The outstanding feature of poly gelatin peptide injection preparation is that the preparation method is simple among the present invention, does not add any crosslinking agent, reaction condition easy to control, and easily industrialized production, clinical practice is safer.
We are according to " the General Requirements of in two appendix of Chinese pharmacopoeia version in 2000 injection being checked, and with reference to the proper mass standard [standard No.: WS1-XG-011-2002] of Polygeline, quality research work and methodological investigation have been carried out for controlling this product quality, mainly comprise: proterties, differentiate, check (pH value, potassium, sodium, calcium, chlorine, free amine group, weight average molecular weight, heavy metal, particulate matter, pyrogen, aseptic, hypersensitive test), assay etc. The quality standard of formulating is as follows:
Poly gelatin peptide injection
Jumingjiaotai Zhusheye
Polygeline Injection
This product is the sterile water solution that healthy ox bone or Swine bone gelatin hydrolysis are made, and contains Polygeline in nitrogenous (N), should be 90.0～110.0% of labelled amount.
[proterties] this product is flaxen clear liquid, slightly is with viscosity, sometimes aobvious slight opalescence.
It is an amount of that [discriminating] gets this product, and water is made the solution that contains 2mg among every 1ml, gets 2ml and add 12.5% copper-bath 0.05ml, and mixing adds 8.5% sodium hydroxide solution 0.5ml again, and solution should show purple or aubergine.
[inspection] pH value should be 6.5～7.5 (" two appendix VIH of Chinese pharmacopoeia version in 2000).
The preparation of potassium, sodium, calcium standard solution
Standard liquid prepares the according to the form below precision and measures each ion standard liquid dilution
| Titer | The amount of taking | The measuring bottle volume | Get the standard diluent concentration |
| Potassium standard liquid (1000 μ g/ml) | 2ml | 200 | 10μg/ml |
| Sodium standard solution (1000 μ g/ml) | 5ml | 50 | 100μg/ml |
| Calcium standard solution (1000 μ g/ml) | 5ml | 50 | 100μg/ml |
According to the form below configuration standard solution series
| The standard dilution | The amount of taking I (ml) | The amount of taking II (ml) | The amount of taking III (ml) |
| Potassium 10 μ g/ml | 1 | 5 | 10 |
| Sodium 100 μ g/ml | 1 | 2 | 5 |
| Calcium 100 μ g/ml | 0.5 | 2.5 | 10 |
Take each standard dilution by upper table respectively, put in the 100ml measuring bottle and (wherein add respectively hydrochloric acid 2ml in the standard liquid series of potassium), be diluted to scale with deionized water, shake up, as standard liquid, then the concentration series of standard liquid is:
| Concentration of standard solution (μ g/ml) | |||
| Potassium | 0.1 | 0.5 | 1.0 |
| Sodium | 1.0 | 2.0 | 5.0 |
| Calcium | 0.5 | 2.5 | 10 |
The preparation precision of need testing solution is measured this product 5ml, puts in the high type quartz beaker of 50ml, adds deionized water 5ml and nitric acid-perchloric acid (4: 1) 12ml, hot digestion to solution is clarified, let cool, be diluted to scale with deionized water, as the need testing solution storing solution.
Precision is measured need testing solution storing solution 2ml, puts in the 50ml measuring bottle, is diluted to scale with deionized water, shakes up, as the need testing solution of measuring potassium. The need testing solution 10ml that precision is measured above-mentioned potassium puts in the 100ml measuring bottle, is diluted to scale with deionized water, shakes up, as the need testing solution of measuring sodium; Get storing solution as the need testing solution of measuring calcium.
Determination method is got above-mentioned reference substance solution and each need testing solution, according to atomic absorption spectrophotometry (two appendix IVD of Chinese Pharmacopoeia version in 2000 first method), respectively at 589.0nm, 766.0nm, measure the trap of sodium, potassium, calcium with the strong point of 422.7nm, calculate and contain potassium among every 1ml and should be 2.0～4.0 μ mol, sodium should be 139～152 μ mol, and calcium should be 0.2～2.0 μ mol.
The chlorine precision is measured this product 5ml, add water 50ml and 2mol/L salpeter solution 0.5ml, mixing, according to potentiometric titration (two appendix VIIA of Chinese Pharmacopoeia version in 2000), with silver nitrate titration liquid (0.1mol/L) titration, [the silver nitrate titration liquid (0.1mol/L) of every 1ml is equivalent to the chlorine of 0.1mmol], calculate. Chloride 100～140 μ mol that should be among every 1ml.
The free amine group precision is measured this product 40ml, put in the 100ml conical flask, add the hydrochloric acid solution 1.6ml of 2mol/L, stir and constant temperature to 20 ℃, being titrated to pH with NaOH titrating solution (0.2mol/L) is 6.0, and record consumes the amount (M of NaOH titrating solution1). Continuing to make the pH value with the titration of NaOH titrating solution is 9.0, add formalin (get formalin and regulate pH value to 7.0 ± 0.02 with sodium hydroxide test solution) 4.0ml, place and continue titration after about 30 seconds and make pH value to 8.5, record consumes the amount (M of NaOH titrating solution2), be calculated as follows titration value.
Titration value (every 40ml test sample consumes the milliliter number of 1mol/L NaOH titrating solution)=(M2-M
1)×F/5
In the formula, F is the correction factor of NaOH titrating solution (0.2mol/L).
Titration value should be 0.50～0.65.
Weight average molecular weight (Mw) measure according to the molecular weight and molecular weight distribution determination method (Chinese Pharmacopoeia two appendix VH in 2000) of polysaccharide. With gel chromatographic columns (TSK-G3000PWXL7.8mm * 300mm), (get potassium dihydrogen phosphate 7.0g with phosphate buffer, two hypophosphite monohydrate disodium hydrogen 16.2g, sodium azide 0.8g, add water 4000ml mixing) be mobile phase, flow velocity is per minute 0.5ml, 35 ℃ of column temperatures, differential refraction detector.
Its corresponding retention time of dextran molecule amount reference substance that takes by weighing 5 known molecular amounts is calculated regression equation. Get this product 20ml, add mobile phase to 50ml, as need testing solution, measure with method, record molecular weight distribution curve, and calculate by software. Weight average molecular weight should be 27500～39500.
The heavy metal precision is measured this product 10ml, checks in accordance with the law, (Chinese Pharmacopoeia version appendix in 2000 VIIIH, the second method), contain heavy metal must not cross 1,000,000/.
Particulate matter is got this product, checks (two appendix IXC of Chinese Pharmacopoeia version in 2000 microscopic counting) in accordance with the law, should be up to specification.
Pyrogen is got this product, checks (two appendix XID of Chinese Pharmacopoeia version in 2000) in accordance with the law, and metering should be up to specification by the every 1kg injection of rabbit body weight 10ml.
The aseptic this product of getting checks (two appendix XIH of Chinese Pharmacopoeia version in 2000 membrane-filter procedure) in accordance with the law, should be up to specification.
The hypersensitive test method is got this product as sensitization liquid and need testing solution, according to the laxative remedy inspection, and should be up to specification.
This genealogy of law is injected cavy abdominal cavity and vein with the need testing solution of doses, and the allergic reaction situation of observing animal in setting time is to judge whether a kind of method up to specification of test sample.
For examination animal health cavy, male and female all can, body weight 250～350g before the test and in the observation period of test, all should raise by normal raising condition, does the animal of this test and must not reuse.
The preparation of test solution is made need testing solution with sodium chloride injection by normal concentration under each medicine item except as otherwise herein provided.
Inspection technique is got 6 of above-mentioned cavys, every other day lumbar injection need testing solution 0.5ml, and continuous 3 times, then be divided into two groups, 3 every group, respectively at for the first time injection rear the 14th day and intravenous injection test sample 1.0ml on the 21st.
The result judges after the intravenous injection all allergic reaction must not occur in 15 minutes, if any the two or more persons in perpendicular hair, expiratory dyspnea, sneeze, retch or the phenomenon such as cough 3; Or the one of rale, tic, collapse or the phenomena of mortality should be and is judged to be the positive.
Other should meet every regulation relevant under the injection item (two appendix IB of Chinese Pharmacopoeia version in 2000) and measure.
Assay is got this product, measures according to nitrogen analysis method (two appendix VIID of Chinese Pharmacopoeia version in 2000).
The classification blood volume replenishes medicine.
Specification 500ml: 3.2g (in nitrogen content); 250ml: 1.6g (in nitrogen content).
The storage sealing, 2～25 ℃ of preservations.
Allergic reaction
By above-mentioned quality standard, poly gelatin peptide injection three batch samples of the inventive method development are carried out quality examination, the result is as follows:
Poly gelatin peptide injection three batch sample assays
| Interventions Requested | Standard | Three batches of assays | ||
| The 1st batch | The 2nd batch | The 3rd batch | ||
| Proterties | Faint yellow clear liquid slightly is with viscosity, sometimes aobvious slight opalescence | Faint yellow clear liquid slightly is with viscosity | Faint yellow clear liquid slightly is with viscosity | Faint yellow clear liquid slightly is with viscosity |
| Chemistry is differentiated | Should show purple or aubergine | Be positive reaction | Be positive reaction | Be positive reaction |
| Loading amount | Should be up to specification | Up to specification | Up to specification | Up to specification |
| Clarity test | Should be up to specification | Up to specification | Up to specification | Up to specification |
| The pH value | Should be 6.5～7.5 | 7.03 | 7.01 | 7.06 |
| Particulate matter | Should be up to specification | Up to specification | Up to specification | Up to specification |
| Potassium | Contain 2.0～4.0 μ mol among every 1ml | 3.00 | 2.98 | 2.99 |
| Sodium | Contain 139～152 μ mol among every 1ml | 145.87 | 146.96 | 147.72 |
| Calcium | Contain 0.2～2.0 μ mol among every 1ml | 1.06 | 1.13 | 1.02 |
| Chlorine | Contain 100～140 μ mol among every 1ml | 124.88 | 123.87 | 123.26 |
| Free amine group | Titration value should be 0.50～0.65 | 0.58 | 0.57 | 0.56 |
| Weight average molecular weight | Should be between 27500～39500 | 34075 | 33897 | 34000 |
| Heavy metal | Be no more than 1,000,000/ | Up to specification | Up to specification | Up to specification |
| Pyrogen | Should be up to specification | Up to specification | Up to specification | Up to specification |
| Aseptic | Should be up to specification | Up to specification | Up to specification | Up to specification |
| Hypersensitive test | Reaction should be negative | Reaction is negative | Reaction is negative | Reaction is negative |
| Assay | In nitrogenous (N), should be 90.0～110.0% of labelled amount | 100.43％ | 100.76％ | 100.60％ |
| Conclusion | Three batches of poly gelatin peptide injections are by above-mentioned drug standard draft check, and the result is up to specification. | |||
Simultaneously we are to these three batches of poly gelatin peptide injections, according to " pertinent regulations of two appendix of Chinese pharmacopoeia version in 2000 have been carried out stability study, and are specific as follows:
1, accelerated test
Get this product, press commercially available back, under temperature is 40 ℃ ± 2 ℃, the condition of relative humidity 75% ± 5%, place. At duration of test respectively at sampling at the 0th, 1,2,3,6 the end of month once, the result shows that this product placed 6 months under accelerated test investigation condition, and indices is all up to specification.
2, long term test
Get this product, press commercially available back, under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%, placed 36 months. Respectively at sampling at the 3rd, 6,9,12,18,24,36 the end of month once, the result shows that this product placed 24 months under long term test investigation condition, and indices is all up to specification.
3, pyrogen and the sterility test in acceleration and the long term test
Accelerating 6th month and long-term 6,12,18,24 months, this product has been carried out the inspection of aseptic, pyrogen and particulate matter, the result is all up to specification.
Above result of the test shows that the poly gelatin peptide injection of the inventive method development is basicly stable under accelerated test, long term test condition.
In sum, the poly gelatin peptide injection preparation process of the inventive method development is simple, is suitable for suitability for industrialized production, and the quality standard of formulating can be controlled product quality substantially.
The specific embodiment
Embodiment 1:
1, gets gelatin 180g and put in the appropriate vessel, add 70 ℃ of about 4000ml of water for injection, stir and to make the gelatin dissolving, after adding hydrochloric acid 20ml and stirring mixed solution is put 90 ℃ of constant temperature hydrolysis 70 minutes.
2, an amount of NaOH of the complete rear adding of hydrolysis is regulated pH value 7.0.
3, take by weighing again in the solution after 30g sodium chloride, 0.5g calcium chloride, 1g potassium chloride add said hydrolyzed, add water for injection to 5000ml.
4, the needle-use activated carbon that adds 1.0% (g/ml), 60 ℃ are incubated 30 minutes, take off charcoal with the middling speed sand stick. Liquid circulation 20 minutes.
5, with the smart filter of the miillpore filter of 0.45 μ m.
6, measure pH value and the content of the subsequent filtrate of above-mentioned the 5th step gained.
7, qualified rear can is jumped a queue in the 500ml infusion bottle, rolls lid.
8, pressure sterilizing 30 minutes under 115 ℃ of conditions.
9, full inspection, packing, warehouse-in.
Embodiment 2:
1, gets gelatin 200g and put in the appropriate vessel, add 50 ℃ of about 3000ml of water for injection, stir and to make the gelatin dissolving, add and after 10% sulfuric acid solution 100ml stirs mixed solution is put 100 ℃ of constant temperature hydrolysis 60 minutes.
2, an amount of sodium acid carbonate of the complete rear adding of hydrolysis is regulated pH value 6.8.
3, take by weighing again in the solution after 33g sodium chloride, 0.56g calcium chloride, 1.1g potassium chloride add said hydrolyzed, add water for injection to 5000ml.
4, enter the needle-use activated carbon of 0.5% (g/ml), 70 ℃ are incubated 20 minutes, take off charcoal with the middling speed sand stick. Liquid circulation 20 minutes.
5, with the smart filter of the miillpore filter of 0.45 μ m.
6, measure pH value and the content of the subsequent filtrate of above-mentioned the 5th step gained.
7, qualified rear can is jumped a queue in the 250ml infusion bottle, rolls lid.
8, pressure sterilizing 40 minutes under 115 ℃ of conditions.
9, full inspection, packing, warehouse-in.
Embodiment 3:
1, gets gelatin 200g and put in the appropriate vessel, add 40 ℃ of about 4200ml of water for injection, stir and to make the gelatin dissolving, after adding 5% hydrochloric acid 200ml and stirring mixed solution is put 121 ℃ of constant-temperature high-pressures hydrolysis 30 minutes.
2, an amount of NaOH and the sodium acid carbonate of the complete rear adding of hydrolysis regulated pH value 7.3.
3, take by weighing again in the solution after 33g sodium chloride, 0.56g calcium chloride, 1.1g potassium chloride add said hydrolyzed, add water for injection to 5000ml.
4, the needle-use activated carbon that adds 0.01 (g/ml), 50 ℃ are incubated 40 minutes, take off charcoal with the middling speed sand stick. Liquid circulation 20 minutes.
5, with the smart filter of the miillpore filter of 0.45 μ m.
6, measure pH value and the content of the subsequent filtrate of above-mentioned the 5th step gained.
7, qualified rear can is jumped a queue in the 500ml infusion bottle, rolls lid.
8, pressure sterilizing 35 minutes under 115 ℃ of conditions.
9, full inspection, packing, warehouse-in.
Claims (11)
1, the preparation technology of poly gelatin peptide injection, its feature process step is:
A. gelatin hydrolysis:
Get gelatin and put in the appropriate vessel, inject water an amount of (be about recipe quantity 60% to 90% between), stir and make dissolving,
Acid adding is hydrolyzed in right amount.
B. add pH value conditioning agent:
Being hydrolyzed an amount of pH value conditioning agent adjusting pH value of complete rear adding is 6.5～7.5.
C. add electrolyte:
Take by weighing again an amount of sodium chloride, calcium chloride, potassium chloride, electrolyte is dissolved fully, add again water for injection to recipe quantity.
D. adsorption clarification:
Add an amount of needle-use activated carbon, stirring and adsorbing pyrogen, impurity etc. take off charcoal with the middling speed sand stick. Liquid circulation 20 minutes.
E. smart filter.
F. packing is jumped a queue, and rolls lid.
G. sterilization.
H. entirely examine, pack.
2, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, in the steps A, the temperature of the used water for injection of dissolving gelatin is 40～70 ℃.
3, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, in the steps A, the temperature during gelatin hydrolysis is 90～121 ℃, and preferred temperature is 90～108 ℃.
4, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, in the steps A, the gelatin hydrolysis time is 30 minutes～100 minutes, and the preferred time is 60 minutes～80 minutes.
5, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, in the steps A, used acid is hydrochloric acid, sulfuric acid or other inorganic acid, and its concentration is 0.1%～2.0% (W/V), and preferred concentration is 0.5%～1.0% (W/V).
6, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, among the step B, used pH value conditioning agent can be NaOH, sodium acid carbonate, sodium carbonate etc., also can be above-mentioned every mixture.
7, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, among the step D, the consumption of used needle-use activated carbon is 0.01～2.0% (W/V), and preferable amount is 0.05～1.0% (W/V).
8, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, among the step D, mixing time is 10 minutes～70 minutes, is preferably 20 minutes～30 minutes.
9, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, among the step D, whipping temp is 20～80 ℃, is preferably 50～60 ℃.
10, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, among the step G, sterilising temp is 121 ℃.
11, the preparation method of poly gelatin peptide injection as claimed in claim 1 is characterized in that, among the step G, sterilization time is 15 minutes～50 minutes, is preferably 20 minutes～30 minutes.
Priority Applications (1)
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|---|---|---|---|
| CN 200510132242 CN1824295A (en) | 2005-12-27 | 2005-12-27 | Preparation technology of poly gelatin peptide injection liquid |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510132242 CN1824295A (en) | 2005-12-27 | 2005-12-27 | Preparation technology of poly gelatin peptide injection liquid |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103230585A (en) * | 2013-05-15 | 2013-08-07 | 湖北美林药业有限公司 | Polygeline dextran composition |
-
2005
- 2005-12-27 CN CN 200510132242 patent/CN1824295A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103230585A (en) * | 2013-05-15 | 2013-08-07 | 湖北美林药业有限公司 | Polygeline dextran composition |
| CN103230585B (en) * | 2013-05-15 | 2014-06-25 | 湖北美林药业有限公司 | Polygeline dextran composition |
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