CN107375204A - Compound dextran 40 parenteral solution and its preparation method and application - Google Patents
Compound dextran 40 parenteral solution and its preparation method and application Download PDFInfo
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- CN107375204A CN107375204A CN201710614189.7A CN201710614189A CN107375204A CN 107375204 A CN107375204 A CN 107375204A CN 201710614189 A CN201710614189 A CN 201710614189A CN 107375204 A CN107375204 A CN 107375204A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/721—Dextrans
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Abstract
The invention belongs to pharmaceutical technology field, and in particular to a kind of compound dextran 40 parenteral solution and its preparation method and application.The preparation method of compound dextran 40 parenteral solution comprises the following steps：1) calcium chloride is dissolved with water for injection by recipe quantity, potassium chloride, sodium chloride and sodium lactate carry out it is dilute match somebody with somebody, obtain inorganic component and prepare liquid, the inorganic component prepares liquid and treats dilute match somebody with somebody；2) concentrated compounding is carried out with water for injection dissolving Dextran 40 by recipe quantity, obtains organic component and prepare liquid, the organic component prepares liquid and treats dilute match somebody with somebody；3) by the inorganic component prepare liquid and the organic component prepare liquid carry out it is dilute match somebody with somebody, and add water for injection by recipe quantity, obtain compound dextran 40 parenteral solution.Dextran 40 even molecular weight distribution, particulate and visible foreign matters are extremely low in parenteral solution, are had no adverse reaction applied to clinic, are suitable as blood volume expander.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of compound dextran 40 parenteral solution and preparation method thereof and
Using.
Background technology
Compound dextran 40 parenteral solution is compound preparation, and its component is：(40) containing dextran in per 1ml parenteral solutions
100mg, calcium chloride 0.2mg, potassium chloride 0.3mg, sodium chloride 6.0mg, sodium lactate 3.1mg.The compound preparation be primarily adapted for use in by
In wound, burn surgery hypovolemic shock caused by (boiling hot) wound and bleeding etc.；Hypovolemia during surgical operation；In vitro
Reduced during perfusion because extracorporal circulatory system produces the risk of complication.Because of electrolyte content concentration in its solution and electricity in human plasma
Matter concentration comparable is solved, to HCO3- concentration and BE without influence, be it is a kind of can effective expanding blood volume colloidal solution, to human body
The interference of interior environment is smaller, is widely used in clinic better than dextran sodium chloride and dextran glucose parenteral solution.
Great adverse reaction also easily occurs in clinical practice for said preparation simultaneously, such as shock, acute renal failure, anaphylactic shock and stomach
The Nausea and vomiting of enteron aisle and skin nettle rash etc..
Above-mentioned adverse reaction occurs in addition to the individual difference of patient, main system because the selection of Dextran 40 raw material and
Caused by the production technology difference of preparation.Dextran 40 is a kind of typical Carbohydrate drugs, is the enteral membranaceous bright beading of sucrose
A kind of macromolecule glucose polymer generated after bacterium fermentation, the existing separating and purifying technologies of are obtained using tradition through handling refined
Ethanol precipitation method be difficult to carry out the range of molecular weight distributions of dextran strict control, influence raw material impurity and contain
Amount, granularity, color and luster, dissolution velocity etc., the selection of the production technology of preparation is incorrect to will also result in formulation products unknown impuritie mistake
High, visible foreign matters and particulate are exceeded, and based on this, we have done significant improvement in terms of the selection of raw material and the production technology of preparation,
The incidence of product adverse reaction is significantly reduced, while improves product quality.
The content of the invention
To solve the deficiencies in the prior art, the invention provides a kind of compound dextran 40 parenteral solution and preparation method thereof
And application.
Technical scheme provided by the present invention is as follows：
A kind of preparation method of compound dextran 40 parenteral solution, comprises the following steps：
1) calcium chloride is dissolved with water for injection by recipe quantity, potassium chloride, sodium chloride and sodium lactate carry out it is dilute match somebody with somebody, obtain inorganic
Component prepares liquid, and the inorganic component prepares liquid and treats dilute match somebody with somebody；
2) concentrated compounding is carried out with water for injection dissolving Dextran 40 by recipe quantity, obtains organic component and prepare liquid, it is described to have
Unit commitment liquid treats dilute match somebody with somebody；
3) by the inorganic component prepare liquid and the organic component prepare liquid carry out it is dilute match somebody with somebody, and add injection by recipe quantity
With water, compound dextran 40 parenteral solution is obtained；
Wherein, the recipe quantity is：In per 1ml parenteral solutions Dextran 40 content be 100mg, calcium chloride content be
0.2mg, KCE content 0.3mg, sodium chloride content 6.0mg, lactic acid sodium content are 3.1mg
Specifically, the preparation method of compound dextran 40 parenteral solution comprises the following steps：
1) calcium chloride, potassium chloride, sodium chloride and sodium lactate are dissolved with water for injection in preparing tank by recipe quantity, obtains nothing
Unit commitment liquid, then inorganic component preparation liquid is squeezed into dilute preparing tank；
2) Dextran 40 is dissolved with water for injection in dense preparing tank by recipe quantity, obtains organic component and prepare liquid, then will
The organic component is prepared liquid and squeezed into dilute preparing tank；
3) water for injection is added in dilute preparing tank by recipe quantity, the inorganic component is prepared into liquid and the organic component is matched somebody with somebody
Liquid processed carried out in dilute preparing tank it is dilute match somebody with somebody, obtain compound dextran 40 parenteral solution；
Wherein, the recipe quantity is：In per 1ml parenteral solutions Dextran 40 content be 100mg, calcium chloride content be
0.2mg, KCE content 0.3mg, sodium chloride content 6.0mg, lactic acid sodium content are 3.1mg.
Pass through above-mentioned technical proposal, readily soluble inorganic component and less soluble organic component are matched somebody with somebody into liquid respectively, then carried out dilute
Match somebody with somebody, can improve and have that impurity separation is difficult, medical filtration is not easy in existing preparation of preparation product process, it is right in finished product preparation
The problems such as sugared molecular weight distribution of acid anhydride 40 is uneven, particulate and visible foreign matters are exceeded is revolved, while improves production efficiency and product matter
Amount, significantly reduce the incidence of formulation products adverse reaction in clinical practice.
Specifically, in step 1)：Stirring and dissolving calcium chloride, potassium chloride, sodium chloride and sodium lactate under the conditions of 75~85 DEG C.
Specifically, in step 1)：Calcium chloride, potassium chloride, sodium chloride and sodium lactate dissolving after, add w/v be 0.04~
0.06%g/ml medicinal carbon, adsorb the insoluble impurities in inorganic component solution and remove the heat in inorganic component solution
It is former.After charcoal absorption, filtered successively through 5um studs decarburization filtering and 1um polypropylene filters, by the no unit after filtering
Assignment system liquid squeezes into dilute preparing tank and treats dilute match somebody with somebody.Wherein, the general name of the elevated material of body temperature can be caused after pyrogen pointed injection.
Pass through above-mentioned technical proposal, adsorbing and removing effectively can be carried out to impurity, eliminate insoluble visible foreign matters.Specifically
, in step 1)：After charcoal absorption, filtered successively through 5um studs decarburization filtering and the decarburization of 1um polypropylene filters, decarburization
Inorganic component preparation liquid is squeezed into dilute preparing tank after filtering.
Pass through above-mentioned technical proposal, (5um) is first filtered with the stud filter of lower accuracy, effectively removed a large amount of living
Property charcoal, then filtered with the polypropylene filter (1um) of degree of precision, it is possible to reduce titanium filter is because assembling improper and fracture
And the risk of charcoal is leaked, while can effectively reduce product visible foreign matters, particulate matter, microbial load.
Specifically, in step 2)：The molecular weight of Dextran 40 is 32000~42000, can be obtained by prior art,
For example, the Dextran 40 produced by Shanghai Huamao Pharmaceutical Co.
Pass through above-mentioned technical proposal, can overcome in finished product preparation uneven Dextran 40 molecular weight distribution, particulate and
The problems such as visible foreign matters are exceeded, while production efficiency and product quality are improved, significantly reducing formulation products should in clinic
With the incidence of middle adverse reaction specifically, in step 2)：The stirring and dissolving Dextran 40 under the conditions of 75~85 DEG C；Dextrose
After acid anhydride 40 dissolves, with salt acid for adjusting pH to 4.8~5.0.
Specifically, in step 2)：100 DEG C are warming up to after having adjusted pH, adds and accounts for lysate gross mass 0.4~0.6%
G/g medicinal carbon, micro-boiling is kept to carry out charcoal absorption in 25~35 minutes.
Pass through above-mentioned technical proposal, adsorbing and removing effectively can be carried out to impurity, eliminate insoluble visible.
Specifically, filtered successively through 5um studs decarburization filtering and the decarburization of 1um polypropylene filters after charcoal absorption, mistake
Organic component preparation liquid is squeezed into dilute preparing tank after filter and treats dilute match somebody with somebody.
Pass through above-mentioned technical proposal, first filtered with the filter of lower accuracy, then entered with the filter of degree of precision
Row filtering, it is possible to reduce to the load of the filter of posterior degree of precision, so as to increase its life-span.
Specifically, in step 3)：The return stirring under the conditions of 75~85 DEG C, carry out dilute match somebody with somebody.
Specifically, in step 3)：Return stirring in a heated condition, it is 0.096~0.098g/ to Dextran 40 content
Ml, calcium chloride content are that 0.018~0.022% (g/ml) pH is 5.4~5.8, then by 0.45um polypropylene filters,
0.22um/0.22um two level polyether sulfone aseptic filtrations, obtain compound dextran 40 parenteral solution, you can squeeze into bag making, filling and sealing machine and enter
Row bag embedding.Wherein, the first order filtering accuracy of two level polyether sulfone aseptic filtration be 0.22um, second level filtering accuracy be
0.22um。
Pass through above-mentioned technical proposal, first filtered with the filter of lower accuracy, then entered with the filter of degree of precision
Row filtering, it is possible to reduce to the load of the filter of posterior degree of precision, so as to increase its life-span.
Present invention also offers be prepared into according to the preparation method of compound dextran 40 parenteral solution provided by the present invention
The compound dextran 40 parenteral solution arrived.
Dextran 40 even molecular weight distribution, particulate and visible foreign matters are extremely low in finished product preparation provided by the present invention,
Had no adverse reaction applied to clinic.
Present invention also offers according to compound dextran 40 parenteral solution provided by the invention as blood volume expander
Using.
Dextran 40 even molecular weight distribution, particulate and visible foreign matters are extremely low in finished product preparation provided by the present invention,
Had no adverse reaction applied to clinic, be suitable as blood volume expander.
Embodiment
The principles and features of the present invention are described below, and illustrated embodiment is served only for explaining the present invention, is not intended to
Limit the scope of the present invention.
Embodiment 1
The preparation method of compound dextran 40 parenteral solution 1, comprises the following steps：
1) by recipe quantity in preparing tank with stirring and dissolving calcium chloride, potassium chloride, chlorine under the conditions of 75~85 DEG C of water for injection
Change sodium and sodium lactate, after calcium chloride, potassium chloride, sodium chloride and sodium lactate dissolving, add 0.04~0.06%g/ml medicinal work
Property charcoal adsorb 15 minutes, absorption insoluble impurities and remove inorganic component solution in pyrogen, after charcoal absorption, pass through successively
The decarburization of 5um studs is filtered and 1um polypropylene filters decarburization filtering, obtains inorganic component and prepares liquid, then by the inorganic component
Liquid is prepared to squeeze into dilute preparing tank；
2) recipe quantity stirring and dissolving Dextran 40, dextrorotation under the conditions of 75~85 DEG C with water for injection in dense preparing tank is pressed
After sugared acid anhydride 40 dissolves, with salt acid for adjusting pH to 4.8~5.0,100 DEG C are warming up to after having adjusted pH, adds 0.4~0.6% (g/
G) medicinal carbon, micro-boiling is kept to carry out charcoal absorption in 30 minutes；
Filtered successively through 5um studs decarburization filtering and the decarburization of 1um polypropylene filters after charcoal absorption, obtained unit
Assignment system liquid, then organic component preparation liquid is squeezed into dilute preparing tank；
3) water for injection is added in dilute preparing tank by recipe quantity, the inorganic component is prepared into liquid and the organic component is matched somebody with somebody
Liquid processed return stirring under the conditions of 75~85 DEG C in dilute preparing tank, return stirring in a heated condition, to Dextran 40 content
For 0.096~0.098g/ml, calcium chloride content is that 0.018~0.022% (g/ml) pH is 5.4~5.8, then by 0.45um
Polypropylene filter, 0.22um/0.22um two level polyether sulfone aseptic filtrations, obtain that colourless, the slightly clear and bright compound with stickiness is right
Revolve the sugared parenteral solution 1 of acid anhydride 40.
The prescription of compound dextran 40 parenteral solution is：Dextran 40 content is 100mg, chlorination in per 1ml parenteral solutions
Calcium content is 0.2mg, KCE content 0.3mg, sodium chloride content 6.0mg, lactic acid sodium content are 3.1mg.
Embodiment 2
The preparation method of compound dextran 40 parenteral solution 2, comprises the following steps：
1) by recipe quantity in preparing tank with stirring and dissolving calcium chloride, potassium chloride, chlorine under the conditions of 75~85 DEG C of water for injection
Change sodium and sodium lactate, after calcium chloride, potassium chloride, sodium chloride and sodium lactate dissolving, add 0.04~0.06%g/ml medicinal work
Property charcoal adsorb 15 minutes, absorption insoluble impurities and remove inorganic component solution in pyrogen, after charcoal absorption, pass through successively
The decarburization of 5um studs is filtered and 1um polypropylene filters decarburization filtering, obtains inorganic component and prepares liquid, then by the inorganic component
Liquid is prepared to squeeze into dilute preparing tank；
2) recipe quantity stirring and dissolving Dextran 40, dextrorotation under the conditions of 75~85 DEG C with water for injection in dense preparing tank is pressed
After sugared acid anhydride 40 dissolves, with salt acid for adjusting pH to 4.8~5.0,100 DEG C are warming up to after having adjusted pH, adds 0.4~0.6% (g/
G) medicinal carbon, micro-boiling is kept to carry out charcoal absorption in 30 minutes；
Filtered successively through 5um studs decarburization filtering and the decarburization of 1um polypropylene filters after charcoal absorption, obtained unit
Assignment system liquid, then organic component preparation liquid is squeezed into dilute preparing tank；
3) water for injection is added in dilute preparing tank by recipe quantity, the inorganic component is prepared into liquid and the organic component is matched somebody with somebody
Liquid processed return stirring under the conditions of 75~85 DEG C in dilute preparing tank, return stirring in a heated condition, to Dextran 40 content
For 0.096~0.098g/ml, calcium chloride content is that 0.018~0.022% (g/ml) pH is 5.4~5.8, then by 0.45um
Polypropylene filter, 0.22um/0.22um two level polyether sulfone aseptic filtrations, obtain that colourless, the slightly clear and bright compound with stickiness is right
Revolve the sugared parenteral solution 2 of acid anhydride 40.
The prescription of compound dextran 40 parenteral solution is：Dextran 40 content is 100mg, chlorination in per 1ml parenteral solutions
Calcium content is 0.2mg, KCE content 0.3mg, sodium chloride content 6.0mg, lactic acid sodium content are 3.1mg.
Embodiment 3
The preparation method of compound dextran 40 parenteral solution 3, comprises the following steps：
1) by recipe quantity in preparing tank with stirring and dissolving calcium chloride, potassium chloride, chlorine under the conditions of 75~85 DEG C of water for injection
Change sodium and sodium lactate, after calcium chloride, potassium chloride, sodium chloride and sodium lactate dissolving, add 0.04~0.06%g/ml medicinal work
Property charcoal adsorb 15 minutes, absorption insoluble impurities and remove inorganic component solution in pyrogen, after charcoal absorption, pass through successively
The decarburization of 5um studs is filtered and 1um polypropylene filters decarburization filtering, obtains inorganic component and prepares liquid, then by the inorganic component
Liquid is prepared to squeeze into dilute preparing tank；
2) recipe quantity stirring and dissolving Dextran 40, dextrorotation under the conditions of 75~85 DEG C with water for injection in dense preparing tank is pressed
After sugared acid anhydride 40 dissolves, with salt acid for adjusting pH to 4.8~5.0,100 DEG C are warming up to after having adjusted pH, adds 0.4~0.6% (g/
G) medicinal carbon, micro-boiling is kept to carry out charcoal absorption in 30 minutes；
Filtered successively through 5um studs decarburization filtering and the decarburization of 1um polypropylene filters after charcoal absorption, obtained unit
Assignment system liquid, then organic component preparation liquid is squeezed into dilute preparing tank；
3) water for injection is added in dilute preparing tank by recipe quantity, the inorganic component is prepared into liquid and the organic component is matched somebody with somebody
Liquid processed return stirring under the conditions of 75~85 DEG C in dilute preparing tank, return stirring in a heated condition, to Dextran 40 content
For 0.096~0.098g/ml, calcium chloride content is that 0.018~0.022% (g/ml) pH is 5.4~5.8, then by 0.45um
Polypropylene filter, 0.22um/0.22um two level polyether sulfone aseptic filtrations, obtain that colourless, the slightly clear and bright compound with stickiness is right
Revolve the sugared parenteral solution 3 of acid anhydride 40.
The prescription of compound dextran 40 parenteral solution is：Dextran 40 content is 100mg, chlorination in per 1ml parenteral solutions
Calcium content is 0.2mg, KCE content 0.3mg, sodium chloride content 6.0mg, lactic acid sodium content are 3.1mg.
The inspection of compound dextran 40 parenteral solution, including following items：
PH value；
Heavy metal：According to《Heavy metal inspection technique standard practice instructions》(SOP-09-0306-A2) the second method inspection, with mark
Comparison liquid made of quasi- lead solution 3.0ml Same Ways compares；
Arsenic：According to《Arsenic inspection technique standard practice instructions》(SOP-09-0307-A2) the first method inspection, with standard arsenic
Standard arsenic spot compares made of solution 2.0ml Same Ways；
Particulate matter：According to《Particulate matter inspection technique standard practice instructions》(SOP-09-0313-A2) check；
It is sterile：According to《Sterility Test standard practice instructions》(SOP-09-0317-A2) membrane-filter procedure inspection；
Visible foreign matters：According to《Visible foreign matters inspection technique standard practice instructions》(SOP-09-0314-A2) check；
Molecular weight and molecular weight distribution method：According to《Molecular exclusion chromatography standard practice instructions》(SOP-09-0356-A2) survey
It is fixed；
Bacterial endotoxin：According to《Bacterial endotoxins test standard practice instructions》(SOP-09-0316-A2) check；
Total chlorine amount；
Calcium chloride；
Potassium chloride；
Sodium lactate.
The compound dextran 40 parenteral solution obtained to the present invention is tested, and monitoring result is as follows：
Compound dextran 40 parenteral solution 1
PH value：It should be 6.4；
Heavy metal：Less than 15/10000000ths；
Arsenic：Less than 0.000008%；
Particulate matter：Per in 1ml containing 10 μm and more than 10 μm of particulate less than 25, it is micro- containing 25 μm and more than 25 μm
Grain is less than 3；
It is sterile：Do not detect；
Visible foreign matters：Do not detect；
Molecular weight and molecular weight distribution：Weight average molecular weight is that 10% macromolecule fraction weight average molecular weight is less than near 38000
120000,10% small molecule part weight average molecular weight is more than 5000；
Bacterial endotoxin：
It is less than 0.50EU containing endotoxic amount in per 1ml；
Total chlorine amount：Inner quality standard：0.40%；
Calcium chloride：Inner quality standard：0.020%；
Potassium chloride：Inner quality standard：0.031%；
Sodium lactate：Inner quality standard：0.30%.
Compound dextran 40 parenteral solution 2
PH value：For 6.2；
Heavy metal：It is less than 15/10000000ths containing heavy metal；
Arsenic：Less than 0.000008%；
Particulate matter：Per in 1ml containing 10 μm and more than 10 μm of particulate less than 25, it is micro- containing 25 μm and more than 25 μm
Grain is less than 3；
It is sterile：Do not detect；
Visible foreign matters：Do not detect；
Molecular weight and molecular weight distribution：Weight average molecular weight is that 10% macromolecule fraction weight average molecular weight is less than near 35000
120000,10% small molecule part weight average molecular weight is more than 5000；
Bacterial endotoxin：It is less than 0.50EU containing endotoxic amount in per 1ml；
Total chlorine amount：Inner quality standard：0.38%；
Calcium chloride：Inner quality standard：0.019%；
Potassium chloride：Inner quality standard：0.029%；
Sodium lactate：Inner quality standard：0.32%.
Compound dextran 40 parenteral solution 3
PH value：For 5.7；
Heavy metal：It is less than 15/10000000ths containing heavy metal；
Arsenic：Less than 0.000008%；
Particulate matter：Per in 1ml containing 10 μm and more than 10 μm of particulate less than 25, it is micro- containing 25 μm and more than 25 μm
Grain is less than 3；
It is sterile：Do not detect；
Visible foreign matters：Do not detect；
Molecular weight and molecular weight distribution：Weight average molecular weight is 39000 annexes, and 10% macromolecule fraction weight average molecular weight is less than
120000,10% small molecule part weight average molecular weight is more than 5000；
Bacterial endotoxin：It is less than 0.50EU containing endotoxic amount in per 1ml；
Total chlorine amount：Inner quality standard：0.37%；
Calcium chloride：Inner quality standard：0.021%；
Potassium chloride：Inner quality standard：0.028%；
Sodium lactate：Inner quality standard：30%.
Result above analysis understands that the compound dextran 40 being prepared by preparation method provided by the present invention is noted
Penetrate hydroful foot and be better than《Compound dextran 40 parenteral solution quality standard》(TS-09-0405-A2).
The foregoing is only presently preferred embodiments of the present invention, be not intended to limit the invention, it is all the present invention spirit and
Within principle, any modification, equivalent substitution and improvements made etc., it should be included in the scope of the protection.
Claims (10)
1. a kind of preparation method of compound dextran 40 parenteral solution, it is characterised in that comprise the following steps：
1) calcium chloride is dissolved with water for injection by recipe quantity, potassium chloride, sodium chloride and sodium lactate carry out it is dilute match somebody with somebody, obtain inorganic component
Liquid is prepared, the inorganic component prepares liquid and treats dilute match somebody with somebody；
2) concentrated compounding is carried out with water for injection dissolving Dextran 40 by recipe quantity, obtains organic component and prepare liquid, it is described to have unit
Assignment system liquid treats dilute match somebody with somebody；
3) by the inorganic component prepare liquid and the organic component prepare liquid carry out it is dilute match somebody with somebody, and add injection by recipe quantity
Water, obtain compound dextran 40 parenteral solution；
Wherein, the recipe quantity is：In per 1ml parenteral solutions Dextran 40 content be 100mg, calcium chloride content 0.2mg, chlorine
Change potassium content is 0.3mg, sodium chloride content 6.0mg, lactic acid sodium content are 3.1mg.
2. the preparation method of compound dextran 40 parenteral solution according to claim 1, it is characterised in that in step 1)：
Stirring and dissolving calcium chloride, potassium chloride, sodium chloride and sodium lactate under the conditions of 75~85 DEG C.
3. the preparation method of compound dextran 40 parenteral solution according to claim 2, it is characterised in that in step 1)：
After calcium chloride, potassium chloride, sodium chloride and sodium lactate dissolving, the medicinal carbon for adding 0.04~0.06%g/ml carries out 10
The absorption of~20 minutes, for adsorbing the insoluble impurities in inorganic component solution and removing the pyrogen in inorganic component solution,
After charcoal absorption, filtered successively through 5um studs decarburization filtering and 1um polypropylene filters, by the inorganic component after filtering
Preparation liquid squeezes into dilute preparing tank and treats dilute match somebody with somebody.
4. the preparation method of compound dextran 40 parenteral solution according to claim 1, it is characterised in that in step 2)：
The weight average molecular weight of Dextran 40 is 32000~42000, and 10% macromolecule fraction weight average molecular weight is not more than 120000,
10% small molecule part weight average molecular weight is not less than 5000.
5. the preparation method of compound dextran 40 parenteral solution according to claim 4, it is characterised in that in step 2)：
The stirring and dissolving Dextran 40 under the conditions of 75~85 DEG C；After Dextran 40 dissolving, with salt acid for adjusting pH to 4.8~5.0.
6. the preparation method of compound dextran 40 parenteral solution according to claim 5, it is characterised in that in step 2)：
100 DEG C are warming up to after having adjusted pH, adds the medicinal carbon for accounting for 0.4~0.6%g/g of lysate gross mass, is kept
Micro-boiling 25~35 minutes carries out charcoal absorption, for adsorbing caused glue during the insoluble matter in raw material, dissolution of raw material
Body, protein, pyrogen and pigment；
Filtered successively through 5um studs decarburization filtering and 1um polypropylene filters after charcoal absorption, have unit by described after filtering
Assignment system liquid squeezes into dilute preparing tank and treats dilute match somebody with somebody.
7. the preparation method of compound dextran 40 parenteral solution according to claim 1, it is characterised in that in step 3)：
The return stirring under the conditions of 75~85 DEG C, carry out dilute match somebody with somebody.
8. the preparation method of compound dextran 40 parenteral solution according to claim 7, it is characterised in that in step 3)：
Return stirring in a heated condition, it is 0.096~0.098g/ml to Dextran 40 content, calcium chloride content is 0.018~
0.022%g/ml, pH is 5.4~5.8, then is removed by 0.45um polypropylene filters, 0.22um/0.22um two level polyether sulfones
Bacterium is filtered, and obtains compound dextran 40 parenteral solution.
What 9. a kind of preparation method of compound dextran 40 parenteral solution according to any one of claims 1 to 9 was prepared
Compound dextran 40 parenteral solution.
10. a kind of application of compound dextran 40 parenteral solution according to claim 9, its feature exists, as blood volume
Expand agent.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110215431A (en) * | 2019-04-08 | 2019-09-10 | 辽宁海神联盛制药有限公司 | A kind of dextran 40 glucose injection and preparation method thereof |
| CN110934888A (en) * | 2018-09-21 | 2020-03-31 | 刘力 | Novel electrolytic glycoside therapeutic pharmaceutical composition |
| CN116172949A (en) * | 2023-01-06 | 2023-05-30 | 石家庄四药有限公司 | Preparation method of compound dextran 40 injection |
Citations (3)
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| CN116172949A (en) * | 2023-01-06 | 2023-05-30 | 石家庄四药有限公司 | Preparation method of compound dextran 40 injection |
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