CN104490770A - Calcium gluconate sodium chloride injection solution and preparation method thereof - Google Patents
Calcium gluconate sodium chloride injection solution and preparation method thereof Download PDFInfo
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- CN104490770A CN104490770A CN201410755264.8A CN201410755264A CN104490770A CN 104490770 A CN104490770 A CN 104490770A CN 201410755264 A CN201410755264 A CN 201410755264A CN 104490770 A CN104490770 A CN 104490770A
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- sodium chloride
- calcium gluconate
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Abstract
The invention provides a calcium gluconate sodium chloride injection solution and a preparation method thereof. The calcium gluconate sodium chloride injection solution comprises 1% of calcium gluconate and 0.9% of sodium chloride. According to the calcium gluconate sodium chloride injection solution, sodium chloride is used as a co-solvent; a 0.9% sodium chloride solution is an isotonic solution; other components are not additionally introduced during intravenous infusion. In addition, the calcium gluconate sodium chloride injection solution is of a large-bottle preparation; the concentration of calcium gluconate is relatively low; the possibility of precipitating crystals is avoided; the calcium gluconate sodium chloride injection solution can be directly applied to intravenous infusion. The calcium gluconate sodium chloride injection solution is stable in property and easy to store, and can be stored for over 18 months under a shading and sealing condition.
Description
Technical field
The present invention relates to a kind of injection, specifically, relate to a kind of calcium gluconate sodium chloride injection.
Background technology
Calcium gluconate, chemical name is maltonic acid hydrate of calcium, and molecular formula is C
12h
22caO
14h
2o, molecular weight is 448.40, and structural formula is as follows:
Calcium gluconate is white crystalline or graininess powder, and odorless, tasteless, is soluble in boiling water, is slightly dissolved in cold water, is insoluble to the organic solvent such as ethanol or ether.
Calcium gluconate injection is calcium complement agent.Calcium can maintain nervimuscular NE, promotes teleneuron secretion acetylcholine.Serum calcium can occur that neural muscle excitability improves, and twitches when reducing, and the too high then irritability of blood calcium reduces, and occurs weakness etc.Calcium ion can improve membrane passage, increases the compactness of capillary tube, makes to ooze out minimizing, plays anti-allergic effects.Calcium ion can promote that the calcification of skeleton and tooth is formed.There is competitive antagonism between high concentration calcium ion and magnesium ion, can be used for the rescue that magnesium is poisoning.Calcium ion can generate insoluble calcium fluoride with fluoride, can be used for the rescue of fluorosis.Calcium gluconate injection is also applied when cardiac resuccitation, for hyperkalemia or low blood calcium, or the rescue of New function exception that this channel blocking causes.
In the prior art, calcium gluconate injection is small-volume injection product, and the dissolubility of calcium gluconate in water is 3.33%, and the specification of product is the concentration of 10%, is supersaturated solution.Therefore, between the storage life, easily there is crystallization.In traditional prescription, lactic acid and calcium hydroxide generate calcium lactate, though certain hydrotropy effect can be played to calcium gluconate, but calcium gluconate can only be made not occur crystallization at short notice, along with the prolongation of period of storage, especially under cryogenic, the dissolubility of calcium gluconate reduces gradually, makes saturated calcium gluconate crystallization gradually.In addition, small-volume injection in use easily causes secondary pollution owing to repeatedly puncturing, and ampoule bottle exists chips of glass hidden danger when opening simultaneously.
Summary of the invention
The object of this invention is to provide a kind of stable and safety is high, and calcium gluconate sodium chloride injection that can be directly used in intravenous drip and preparation method thereof.
A first aspect of the present invention provides a kind of calcium gluconate sodium chloride injection, and it is compound preparation, and main component is calcium gluconate and sodium chloride.
Preferably, calcium gluconate sodium chloride injection of the present invention contains the calcium gluconate of 1% and the sodium chloride of 0.9%.
Using sodium chloride as cosolvent in calcium gluconate sodium chloride injection of the present invention, not containing lactic acid and calcium hydroxide.
A second aspect of the present invention provides the preparation method of above-mentioned calcium gluconate sodium chloride injection, comprising:
(1) take 1000g calcium gluconate and 900g sodium chloride adds in 90000ml water for injection, heated and boiled lets cool after dissolving;
(2) by above-mentioned solution coarse filtration, needle-use activated carbon is added, heated and stirred;
(3) decarburization is filtered;
(4) benefit injects water to 100000ml;
(5) with 0.22 μm of microporous filter membrane fine straining;
(6) fill is to 100ml glass infusion bottle, and every bottle of 100ml, rolls lid;
(7) 121 DEG C of sterilizings 8 minutes, are reduced to room temperature in 30 minutes after sterilizing.
Preferably, needle-use activated carbon 30g is added in above-mentioned steps (2).
Preferably, in above-mentioned steps (2) at 60 DEG C heated and stirred 15min.
Preferably, 25 DEG C are cooled in above-mentioned steps (7).
Preferably, further comprising the steps of:
(8) character of calcium gluconate sodium chloride injection of preparation, discriminating, pH value, content of beary metal, osmotic pressure molar density, bacteria endotoxin content, particulate matter quantity, loading amount, visible foreign matters and calcium gluconate and sodium chloride content are detected.
Examination criteria is as follows:
[character]
This product should be colourless clear liquid;
[discriminating]
(1) get this product 10ml, add ferric chloride test solution 1, aobvious buff;
(2) calcium salt discriminating, sodium salt and muriatic identification should be shown;
[inspection]
PH value: should be 4.7 ~ 7.0;
Heavy metal: get this product 50ml, is evaporated to about 20ml, lets cool, and adds pH 3.5 acetate buffer 2ml and makes into 25ml in right amount with water, and that makes with 10 μ g/ml standard lead solution 1.5ml contrasts liquor ratio comparatively, must not exceed 3/10000000ths containing heavy metal;
Osmotic pressure molar density: osmotic pressure molar density should be 300 ~ 380mOsmol/Kg;
Bacterial endotoxin: must not more than 0.50EU containing endotoxic amount in every 1ml;
Particulate matter: must not more than 18 containing the microgranule of more than 10 μm and 10 μm in every 1ml, must not more than 2 containing the microgranules of more than 25 μm and 25 μm;
Loading amount: get this product 3 bottles, single bottled amount should be greater than 97 ml, and average loading amount should be greater than 100ml;
Visible foreign matters: get this product 20 bottles, all must not detect smoke-like microparticle column, and metal fillings, chips of glass, length or maximum particle diameter must not be detected more than the fiber of 2mm and block; Only there is 1 bottle as detected pointing object, the short fiber of below 2mm and the quantity of block, separately should get 20 bottles with method inspection, all must not detect;
[assay]
Calcium gluconate: precision measures this product 50ml, put in conical flask, thin up makes into 100ml, hydro-oxidation sodium test solution 15ml and calconum indicator 0.1g, be titrated to solution with 0.05mol/L Calcium Disodium Versenate volumetric solution and change pure blue into by purple, and titration results blank assay is corrected; Result of calculation should be 97.0% ~ 103.0% of labelled amount;
Computing formula: labelled amount %=(V × f × 22.42)/(0.5 × 1000) × 100%
Wherein, V is the milliliter number consuming Calcium Disodium Versenate volumetric solution; F is the correction factor of Calcium Disodium Versenate volumetric solution;
Sodium chloride: it is appropriate that precision measures sodium single element titer, and dilute with water makes the solution containing sodium ion 100 μ g in every 1ml, prepares reference substance stock solution; Precision measures this product 5ml, and put in 100ml measuring bottle, be diluted with water to scale, shake up, precision measures 1ml, puts in 50ml measuring bottle, is diluted with water to scale, shake up, be namely prepared into need testing solution; Precision measures reference substance stock solution 0.5ml, 1ml, 2ml, 3ml, 4ml and puts respectively in 100ml measuring bottle, is diluted with water to scale, shakes up; Get above-mentioned each solution and need testing solution, according to the light absorption value at the wavelength place of atomic absorption spectroscopy determination 589nm, be multiplied by conversion coefficient 2.542 and namely obtain Na ion concentration, according to the Na ion concentration of reference substance standard curve determination test sample, result of calculation should be 97.0% ~ 103.0% of labelled amount.
Using sodium chloride as cosolvent in calcium gluconate sodium chloride injection of the present invention, 0.9% sodium chloride solution is isosmotic solution, additionally introduces other compositions when avoiding intravenous drip.In addition, calcium gluconate sodium chloride injection of the present invention is large bottle formula, and gluconic acid calcium concentration is wherein lower, avoids the probability of crystallization, and can be directly used in intravenous drip.
Calcium gluconate sodium chloride injection stable in properties of the present invention, is easy to store, can preserves more than 18 months under shading air-tight state.
Method technique of the present invention is simple, the calcium gluconate sodium chloride injection reliable in quality of production.
Detailed description of the invention
Further illustrate the present invention below by embodiment, but the present invention is not limited.The experimental technique of unreceipted actual conditions in the following example, usually conveniently condition, or according to the condition that manufacturer advises.The percent do not indicated separately is herein quality percentage by volume, i.e. g/ml.
Embodiment 1 prepares calcium gluconate sodium chloride injection
Take 1000g calcium gluconate and 900g sodium chloride adds in 90000ml water for injection, heated and boiled lets cool after dissolving.
By above-mentioned solution coarse filtration, add 30g needle-use activated carbon, heated and stirred 15min at 60 DEG C.
Filter decarburization.
Benefit injects water to 100000ml.
With 0.22 μm of microporous filter membrane fine straining.
Fill is to 100ml glass infusion bottle, and every bottle of 100ml, rolls lid.
121 DEG C of sterilizings 8 minutes, are reduced to 25 DEG C in 30 minutes after sterilizing.
Embodiment 2 inspection methods and criteria
This product is the sterile water solution of calcium gluconate and sodium chloride.97.0% ~ 103.0% of labelled amount is all should be containing calcium gluconate and sodium chloride.Inspection methods and criteria is as follows:
[character]
This product should be colourless clear liquid.
[discriminating]
(1) get this product 10ml, add ferric chloride test solution 1, aobvious buff.
(2) get this product, check according to " general identification test ", calcium salt discriminating, sodium salt and muriatic identification should be shown.
[inspection]
PH value: check according to " pH value algoscopy ", should be 4.7 ~ 7.0.
Heavy metal: get this product 50ml, be evaporated to about 20ml, let cool, add acetate buffer (pH3.5) 2ml and make into 25ml in right amount with water, according to " heavy metal inspection technique " first method inspection, with standard lead solution 1.5ml(10 μ g/ml) make contrast liquor ratio comparatively, 3/10000000ths must not be exceeded containing heavy metal.
Osmotic pressure molar density: get this product, measure according to " osmotic pressure molar density algoscopy ", its osmotic pressure molar density should be 300 ~ 380mOsmol/Kg.
Bacterial endotoxin: get this product, checks according to " bacterial endotoxins test ", must not more than 0.50EU containing endotoxic amount in every 1ml.
Particulate matter: get this product, checks according to " in injection particulate matter inspection technique ", the microgranule containing more than 10 μm and 10 μm in every 1ml must not more than 18, must not more than 2 containing the microgranules of more than 25 μm and 25 μm.
Loading amount: get this product 3 bottles, checks according to " Minimum loading capacity examination method ", and single bottled amount should be greater than 97 ml, and average loading amount should be greater than 100ml.
Visible foreign matters: get this product 20 bottles, checks according to " visible foreign matters inspection technique ", all must not detect smoke-like microparticle column, and must not detect metal fillings, chips of glass, length or maximum particle diameter more than the obviously visible foreign matters such as the fiber of 2mm and block.Quantity as detected fine visible foreign matters (short fiber and block etc. as pointing object, below 2mm) only has 1 bottle, separately should get 20 bottles with method inspection, all must not detect.
[assay]
Calcium gluconate: precision measures this product 50ml(and is about equivalent to calcium gluconate 0.5g), put in conical flask, thin up makes into 100ml, hydro-oxidation sodium test solution 15ml and calconum indicator 0.1g, be titrated to solution with Calcium Disodium Versenate volumetric solution (0.05mol/L) and change pure blue into by purple, and titration results blank assay is corrected.Every 1ml Calcium Disodium Versenate volumetric solution (0.05mol/L) is equivalent to the calcium gluconate of 22.42mg.Result of calculation should be 97.0% ~ 103.0% of labelled amount.
Computing formula: labelled amount %=(V × f × 22.42)/(0.5 × 1000) × 100%
V: the milliliter number consuming Calcium Disodium Versenate volumetric solution (0.05mol/L);
F: the correction factor of Calcium Disodium Versenate volumetric solution.
Sodium chloride: it is appropriate that precision measures sodium single element titer, and dilute with water makes the solution containing sodium ion 100 μ g in every 1ml, prepares reference substance stock solution.Precision measures this product 5ml, and put in 100ml measuring bottle, be diluted with water to scale, shake up, precision measures 1ml, puts in 50ml measuring bottle, is diluted with water to scale, shake up, be namely prepared into need testing solution.Precision measures reference substance stock solution 0.5ml, 1ml, 2ml, 3ml, 4ml and puts respectively in 100ml measuring bottle, is diluted with water to scale, shakes up.Get above-mentioned each solution and need testing solution, according to the light absorption value at the wavelength place of atomic absorption spectroscopy determination 589nm, be multiplied by conversion coefficient 2.542 and namely obtain Na ion concentration, according to the Na ion concentration of reference substance standard curve determination test sample, result of calculation should be 97.0% ~ 103.0% of labelled amount.
The inspection of embodiment 3 calcium gluconate sodium chloride injection
Test to the calcium gluconate sodium chloride injection that embodiment 1 prepares according to the method for inspection described in embodiment 2, result is as shown in table 1.
Table 1 assay
According to the assay of table 1, according to the calcium gluconate sodium chloride injection reliable in quality that the method for embodiment 1 is produced.
Embodiment 4 medication
Intravenous drip.
Adult is used for hypocalcemia, in calcium gluconate, and a 1g(100ml), can repeat when needing.
For hypermagnesemia, in calcium gluconate, a 1 ~ 2g.
For fluorosis rescue, in calcium gluconate, a 1g, repeated after 1 hour, needed other quiet note if any twitching.
If any the damage of skin histology fluoride, every square centimeter of damaged area using glucose acid calcium 50mg.
Embodiment 5 pharmacokinetic trial
In blood plasma, about 45% calcium is combined with plasma protein, normal human serum calcium concentration 2.25 ~ 2.50mmol/L(9 ~ 11mg/100ml), parathyroid hormone, the active metabolite of calcitonin, vitamin D maintains the stability of blood calcium.Calcium mainly discharges (about 80%) from feces, and partly (about 20-30%) urinates discharge certainly.Vitamin D can promote the absorption of calcium, and calcium can be secreted into perspiration, bile, saliva, milk, urine, excrement etc.Intravenous drip this product distribution phase half-life t
1/2α is 3.1 minutes, eliminates phase half-life t
1/2β is 30.53 minutes.
Claims (9)
1. a calcium gluconate sodium chloride injection, is characterized in that the sodium chloride of calcium gluconate containing 1w/v% and 0.9w/v%.
2. calcium gluconate sodium chloride injection according to claim 1, is characterized in that not containing lactic acid and calcium hydroxide.
3. calcium gluconate sodium chloride injection according to claim 2, is characterized in that being dissolved in 100ml water for injection by 1g calcium gluconate and 0.9g sodium chloride obtains.
4. the preparation method of calcium gluconate sodium chloride injection according to claim 3, comprises the steps:
(1) take 1000g calcium gluconate and 900g sodium chloride adds in 90000ml water for injection, heated and boiled lets cool after dissolving;
(2) by the solution coarse filtration of step (1), needle-use activated carbon is added, heated and stirred;
(3) decarburization is filtered;
(4) benefit injects water to 100000ml;
(5) with 0.22 μm of microporous filter membrane fine straining;
(6) fill is to 100ml glass infusion bottle, and every bottle of 100ml, rolls lid;
(7) 121 DEG C of sterilizings 8 minutes, are reduced to room temperature in 30 minutes after sterilizing.
5. preparation method according to claim 4, wherein, step adds needle-use activated carbon 30g in (2).
6. preparation method according to claim 4, wherein, in step (2) at 60 DEG C heated and stirred 15min.
7. preparation method according to claim 4, wherein, step cools to 25 DEG C in (7).
8. the preparation method according to any one of claim 4-7, also comprises the steps:
The character of calcium gluconate sodium chloride injection of preparation, discriminating, pH value, content of beary metal, osmotic pressure molar density, bacteria endotoxin content, particulate matter quantity, loading amount, visible foreign matters and calcium gluconate and sodium chloride content are detected.
9. preparation method according to claim 8, wherein examination criteria is as follows:
[character]
This product should be colourless clear liquid;
[discriminating]
(1) get this product 10ml, add ferric chloride test solution 1, aobvious buff;
(2) calcium salt discriminating, sodium salt and muriatic identification should be shown;
[inspection]
PH value: should be 4.7 ~ 7.0;
Heavy metal: get this product 50ml, is evaporated to about 20ml, lets cool, and adds pH 3.5 acetate buffer 2ml and makes into 25ml in right amount with water, and that makes with 10 μ g/ml standard lead solution 1.5ml contrasts liquor ratio comparatively, must not exceed 3/10000000ths containing heavy metal;
Osmotic pressure molar density: osmotic pressure molar density should be 300 ~ 380mOsmol/Kg;
Bacterial endotoxin: must not more than 0.50EU containing endotoxic amount in every 1ml;
Particulate matter: must not more than 18 containing the microgranule of more than 10 μm and 10 μm in every 1ml, must not more than 2 containing the microgranules of more than 25 μm and 25 μm;
Loading amount: get this product 3 bottles, single bottled amount should be greater than 97 ml, and average loading amount should be greater than 100ml;
Visible foreign matters: get this product 20 bottles, all must not detect smoke-like microparticle column, and metal fillings, chips of glass, length or maximum particle diameter must not be detected more than the fiber of 2mm and block; Only there is 1 bottle as detected pointing object, the short fiber of below 2mm and the quantity of block, separately should get 20 bottles with method inspection, all must not detect;
[assay]
Calcium gluconate: precision measures this product 50ml, put in conical flask, thin up makes into 100ml, hydro-oxidation sodium test solution 15ml and calconum indicator 0.1g, be titrated to solution with 0.05mol/L Calcium Disodium Versenate volumetric solution and change pure blue into by purple, and titration results blank assay is corrected; Result of calculation should be 97.0% ~ 103.0% of labelled amount;
Computing formula: labelled amount %=(V × f × 22.42)/(0.5 × 1000) × 100%
Wherein, V is the milliliter number consuming Calcium Disodium Versenate volumetric solution; F is the correction factor of Calcium Disodium Versenate volumetric solution;
Sodium chloride: it is appropriate that precision measures sodium single element titer, and dilute with water makes the solution containing sodium ion 100 μ g in every 1ml, prepares reference substance stock solution; Precision measures this product 5ml, and put in 100ml measuring bottle, be diluted with water to scale, shake up, precision measures 1ml, puts in 50ml measuring bottle, is diluted with water to scale, shake up, be namely prepared into need testing solution; Precision measures reference substance stock solution 0.5ml, 1ml, 2ml, 3ml, 4ml and puts respectively in 100ml measuring bottle, is diluted with water to scale, shakes up; Get above-mentioned each solution and need testing solution, according to the light absorption value at the wavelength place of atomic absorption spectroscopy determination 589nm, be multiplied by conversion coefficient 2.542 and namely obtain Na ion concentration, according to the Na ion concentration of reference substance standard curve determination test sample, result of calculation should be 97.0% ~ 103.0% of labelled amount.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113041218A (en) * | 2021-03-23 | 2021-06-29 | 回音必集团江西东亚制药有限公司 | Calcium gluconate and sodium chloride injection and preparation method thereof |
| CN113230207A (en) * | 2021-04-16 | 2021-08-10 | 江苏意诺飞生物科技有限公司 | Preparation process of calcium gluconate and sodium chloride injection |
-
2014
- 2014-12-11 CN CN201410755264.8A patent/CN104490770A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 中华人民共和国卫生部药典委员会: "葡萄糖酸钙氯化钠注射液", 《中国药品标准》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113041218A (en) * | 2021-03-23 | 2021-06-29 | 回音必集团江西东亚制药有限公司 | Calcium gluconate and sodium chloride injection and preparation method thereof |
| CN113230207A (en) * | 2021-04-16 | 2021-08-10 | 江苏意诺飞生物科技有限公司 | Preparation process of calcium gluconate and sodium chloride injection |
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Application publication date: 20150408 |