CN112603888A - Preparation method of mixed sugar electrolyte injection and prepared mixed sugar electrolyte injection - Google Patents
Preparation method of mixed sugar electrolyte injection and prepared mixed sugar electrolyte injection Download PDFInfo
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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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
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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
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
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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
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
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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
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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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
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
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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
- A61K33/42—Phosphorus; Compounds thereof
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
Abstract
The invention provides a preparation method of a mixed sugar electrolyte injection and the prepared mixed sugar electrolyte injection, and relates to the technical field of medical injections. The preparation method takes mixed sugar, electrolyte components, water and pH regulator as raw materials to prepare the solution; firstly, dissolving mixed sugar and electrolyte components in partial water to obtain a solution A; adding a pH regulator into the solution A, adding the balance of water, and uniformly mixing to obtain a solution B; and then sequentially carrying out fine filtration, filling and sterilization on the solution B to obtain the mixed sugar electrolyte injection. According to the preparation method, the high-purity nitrogen subjected to sterilization and filtration is introduced in the solution preparation process, and the residual oxygen content of the solution in the preparation process is controlled to be 0.01-0.2 mg/L, so that the residual oxygen content of the solution is effectively reduced, the degradation of related substances in the prepared solution is greatly reduced, the product is purer, and the product quality is improved.
Description
Technical Field
The invention relates to the technical field of medical injection, in particular to a preparation method of mixed sugar electrolyte injection and the prepared mixed sugar electrolyte injection.
Background
Under various pathogenic bacteria attacks and in operation periods, the human body needs to be supplemented not only with water and electrolytes, but also with a nutrient heat source mainly comprising sugar, so that a plurality of nutrient infusion preparations are developed. Because of wide sources and low price of glucose, the sugar electrolyte injection used in domestic clinic at present is mainly glucose sodium chloride injection, however, the energy supplement and the electrolyte supplement are monotonous, and the clinical requirement cannot be met. Meanwhile, for the diabetic, the metabolic load is large after glucose injection due to the abnormal glucose tolerance of the diabetic, and the glucose cannot be effectively utilized. In addition, only glucose is used as a substrate, and there is a possibility that a diabetes-like change occurs in liver enzyme activity after injection, and inhibition of glucose 6 phosphate dehydrogenase remains even when insulin is used.
Some preparation schemes of mixed sugar electrolyte injection are also disclosed in the prior art, but the residual oxygen of the solution in the existing preparation method is high, so that anhydrous glucose and fructose can be degraded to generate 5-hydroxymethylfurfural; needle-type activated carbon is usually adopted as an adsorbent for adsorption, but other impurities are introduced into the activated carbon; therefore, the quality of the mixed sugar electrolyte injection prepared by the existing scheme is poor.
Therefore, research and development of a novel preparation process of the mixed sugar electrolyte injection reduces impurities in a prepared solution, and makes a product purer, which is necessary and urgent.
In view of the above, the present invention is particularly proposed.
Disclosure of Invention
The first purpose of the invention is to provide a preparation method of a mixed sugar electrolyte injection, wherein the preparation method controls the residual oxygen amount of the solution to be less than 0.2mg/L in the preparation process by introducing high-purity nitrogen subjected to sterilization and filtration in the solution preparation process, so that the residual oxygen content in the solution is effectively reduced, the degradation of related substances in the prepared solution is reduced, and the product is purer.
The second purpose of the invention is to provide a mixed sugar electrolyte injection which is mainly prepared by the preparation method of the mixed sugar electrolyte injection.
In order to achieve the above purpose of the present invention, the following technical solutions are adopted:
the invention provides a preparation method of a mixed sugar electrolyte injection, which comprises the following steps:
(a) providing a mixed sugar, an electrolyte component, water and a pH regulator as raw materials;
(b) carrying out solution blending by using the raw materials provided in the step (a);
the solution preparation comprises the following steps: firstly, mixed sugar and electrolyte component solution are put into partial water to obtain solution A; adding a pH regulator into the solution A, adding the balance of water, and uniformly mixing to obtain a solution B, thereby finishing solution blending;
introducing high-purity nitrogen subjected to sterilization and filtration in the solution blending process in the step (b), and controlling the residual oxygen amount of the solution in the blending process to be 0.01-0.2 mg/L;
(c) and (c) sequentially carrying out fine filtration, subpackaging and sterilization on the solution B prepared in the step (B) to obtain the mixed sugar electrolyte injection.
Further, the mixed sugar in the step (a) comprises anhydrous glucose, fructose and xylitol.
Further, the electrolyte component in the step (a) includes sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, calcium chloride, magnesium chloride, zinc sulfate and sodium bisulfite.
Further, the pH regulator in the step (a) is citric acid;
preferably, the water in step (a) is water for injection.
Further, the step (a) comprises the following components in parts by weight:
657-803 parts of sodium chloride, 369-451 parts of sodium acetate, 1026-1254 parts of dipotassium phosphate trihydrate, 440-510 parts of citric acid, 166-204 parts of calcium chloride, 229-281 parts of magnesium chloride, 0.56-0.77 part of zinc sulfate, 189-231 parts of sodium bisulfite, 27000-33000 parts of anhydrous glucose, 13500-16500 parts of fructose, 6750-8250 parts of xylitol and 390000-480000 parts of water for injection;
preferably, the step (a) comprises the following components in parts by mass:
730 parts of sodium chloride, 410 parts of sodium acetate, 1140 parts of dipotassium phosphate trihydrate, about 490 parts of citric acid, 185 parts of calcium chloride, 255 parts of magnesium chloride, 0.7 part of zinc sulfate, 210 parts of sodium bisulfite, 30000 parts of anhydrous glucose, 15000 parts of fructose, 7500 parts of xylitol and about 440000 parts of water for injection.
Further, the blending temperature of the solution A in the step (b) is 40-60 ℃;
preferably, the pH value of the solution B in the step (B) is 4.5-6.0;
preferably, the step (b) further comprises the step of removing residual oxygen from the partial water before preparing the solution a.
Further, the step (b) comprises the steps of:
(b1) adding 50-80% of injection water into the solution prepared by adopting a preparation tank with a stirring paddle, heating to 90-110 ℃ to remove residual oxygen in the injection water, and then cooling to 40-60 ℃;
(b2) sequentially adding sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, citric acid, calcium chloride, magnesium chloride, zinc sulfate, sodium bisulfite, anhydrous glucose, fructose and xylitol into a blending tank, and then stirring for 15-40min to fully dissolve to obtain a solution A;
introducing nitrogen subjected to sterilization and filtration in the blending process of the step (b2), and controlling the residual oxygen amount of the solution A to be 0.01-0.2 mg/L;
(b3) adding a pH regulator and the balance of water into the solution A to regulate the pH to 4.5-6.0, and then stirring for 15-40min to obtain a solution B;
and (b3) introducing nitrogen subjected to sterilization and filtration in the blending process of the step (b3), and controlling the residual oxygen amount of the solution A to be 0.01-0.2 mg/L.
Further, the pressure of the fine filtration in the step (c) is 0.1-0.5 Mpa;
preferably, the filtration precision of the fine filtration is 0.2-0.22 μm.
Further, the sterilization temperature in the step (c) is 120-123 ℃, and the sterilization pressure is 0.2-0.25 MPa.
The mixed sugar electrolyte injection prepared by the preparation method of the mixed sugar electrolyte injection provided by the invention.
Compared with the prior art, the invention has the beneficial effects that:
the preparation method of the mixed sugar electrolyte injection provided by the invention is characterized in that the mixed sugar, the electrolyte component, water and a pH regulator are used as raw materials to prepare the solution; firstly, mixed sugar and electrolyte component solution are put into partial water to obtain solution A; adding a pH regulator into the solution A, adding the balance of water, and uniformly mixing to obtain a solution B; and then, sequentially carrying out fine filtration, subpackaging and sterilization on the solution B to obtain the mixed sugar electrolyte injection. The preparation method comprises the steps of introducing high-purity nitrogen subjected to sterilization and filtration in the solution preparation process, and controlling the residual oxygen amount of the solution to be less than 0.2mg/L in the preparation process. The residual oxygen amount is controlled mainly because the molecules of the anhydrous glucose and the fructose contain aldehyde groups, which can be oxidized into carboxyl and can also be reduced into hydroxyl, thereby generating the 5-hydroxymethylfurfural. The oxygen content in the solution is reduced, and the oxidative degradation of anhydrous glucose and fructose can be avoided, so that the degradation of related substances in the prepared solution is greatly reduced, the product is purer, and the product quality is improved.
The mixed sugar electrolyte injection provided by the invention is mainly prepared by the preparation method of the mixed sugar electrolyte injection, and further has the advantages of less impurities and high clarity.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments, and it should be understood that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
According to one aspect of the present invention, a method for preparing a mixed sugar electrolyte injection solution, the method comprising the steps of:
(a) providing a mixed sugar, an electrolyte component, water and a pH regulator as raw materials;
(b) carrying out solution blending by using the raw materials provided in the step (a);
the solution preparation comprises the following steps: firstly, mixed sugar and electrolyte component solution are put into partial water to obtain solution A; adding a pH regulator into the solution A, adding the balance of water, and uniformly mixing to obtain a solution B, thereby finishing solution blending;
introducing high-purity nitrogen subjected to sterilization and filtration in the solution blending process in the step (b), and controlling the residual oxygen amount of the solution in the blending process to be 0.01-0.2 mg/L;
(c) and (c) sequentially carrying out fine filtration, subpackaging and sterilization on the solution B prepared in the step (B) to obtain the mixed sugar electrolyte injection.
The preparation method of the mixed sugar electrolyte injection provided by the invention is characterized in that the mixed sugar, the electrolyte component, water and a pH regulator are used as raw materials to prepare the solution; firstly, mixed sugar and electrolyte component solution are put into partial water to obtain solution A; adding a pH regulator into the solution A, adding the balance of water, and uniformly mixing to obtain a solution B; and then, sequentially carrying out fine filtration, subpackaging and sterilization on the solution B to obtain the mixed sugar electrolyte injection. The preparation method comprises the steps of introducing high-purity nitrogen subjected to sterilization and filtration in the solution preparation process, and controlling the residual oxygen amount of the solution in the preparation process to be 0.01-0.2 mg/L. The residual oxygen amount is controlled mainly because the molecules of the anhydrous glucose and the fructose contain aldehyde groups, which can be oxidized into carboxyl and can also be reduced into hydroxyl, thereby generating the 5-hydroxymethylfurfural. The oxygen content in the solution is reduced, and the oxidative degradation of anhydrous glucose and fructose can be avoided, so that the degradation of related substances in the prepared solution is greatly reduced, the product is purer, and the product quality is improved.
In a preferred embodiment of the present invention, the mixed sugar in the step (a) comprises anhydrous glucose, fructose and xylitol.
As a preferred embodiment, the mixed sugar electrolyte injection is a solution containing 10.5% of sugar, which is prepared by mixing glucose, fructose and xylitol according to the ratio of 4: 2: 1, wherein the fructose and the xylitol supply energy to the body and support the body without depending on insulin; the fructose has high energy supply speed and small influence on blood sugar; xylitol can activate a pentose phosphate pathway, promote the synthesis of glucose-6-phosphate dehydrogenase and is beneficial to the oxidative utilization of glucose and fructose. The mixed sugar electrolyte injection also contains trace elements such as zinc, calcium, magnesium, sodium, potassium and the like, and is beneficial to supplementing electrolytes in vivo and correcting electrolyte disorder; the zinc can participate in the synthesis of various enzymes and hormones in vivo, directly influence the synthesis of insulin, nucleic acid, protein and the like, can promote the regeneration of wound tissues and wound healing, and enhance the body resistance.
Preferably, the electrolyte comprises sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, calcium chloride, magnesium chloride, zinc sulfate, and sodium bisulfite.
In a preferred embodiment of the present invention, the pH adjusting agent in step (a) is citric acid;
preferably, the water in step (a) is water for injection.
In a preferred embodiment of the present invention, the step (a) comprises the following components in parts by mass:
730 parts of sodium chloride, 410 parts of sodium acetate, 1140 parts of dipotassium phosphate trihydrate, about 490 parts of citric acid, 185 parts of calcium chloride, 255 parts of magnesium chloride, 0.7 part of zinc sulfate, 210 parts of sodium bisulfite, 30000 parts of anhydrous glucose, 15000 parts of fructose, 7500 parts of xylitol and about 440000 parts of water for injection.
In a preferred embodiment of the present invention, the solution a in step (b) is prepared at a temperature of 40 to 60 ℃;
in a preferred embodiment of the present invention, the pH of the solution B in the step (B) is 4.5 to 6.0; in a preferred embodiment, the pH of the solution B is lower than the 5-HMF value when the pH is in the range of 4.5 to 6.0.
In a preferred embodiment of the present invention, the step (b) further comprises a step of removing residual oxygen from the water portion before preparing the solution a.
In the above preferred embodiment, the step (b) includes the steps of:
(b1) adding 50-80% of injection water into the solution prepared by adopting a preparation tank with a stirring paddle, heating to 90-110 ℃ to remove residual oxygen in the injection water, and then cooling to 40-60 ℃;
(b2) sequentially adding sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, citric acid, calcium chloride, magnesium chloride, zinc sulfate, sodium bisulfite, anhydrous glucose, fructose and xylitol into a blending tank, and then stirring for 15-40min to fully dissolve to obtain a solution A;
introducing nitrogen subjected to sterilization and filtration in the blending process of the step (b2), and controlling the residual oxygen amount of the solution A to be 0.01-0.2 mg/L;
(b3) adding a pH regulator and the balance of water into the solution A to regulate the pH to 4.5-6.0, and then stirring for 15-40min to obtain a solution B;
and (b2) introducing nitrogen subjected to sterilization and filtration in the blending process of the step (b2), and controlling the residual oxygen amount of the solution A to be 0.01-0.2 mg/L.
In a preferred embodiment of the present invention, the pressure of the fine filtration in the step (c) is 0.1 to 0.5Mpa, and the temperature of the fine filtration is 30 to 50 ℃;
preferably, the filtration precision of the fine filtration is 0.2-0.22 μm.
In a preferred embodiment of the present invention, the sterilization temperature in the step (c) is 120 to 123 ℃ and the sterilization pressure is 0.2 to 0.25 MPa.
Preferably, the preparation method of the mixed sugar electrolyte injection comprises the following steps:
1) preparing the solution by adopting a preparation tank with a stirring paddle, adding 50-80% of the prepared volume of the injection water, heating and boiling to remove the residual oxygen in the injection water, and cooling to 40-60 ℃;
2) sequentially adding sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, citric acid, calcium chloride, magnesium chloride, zinc sulfate, sodium bisulfite, anhydrous glucose, fructose and xylitol into a preparation tank, stirring for 15-40 minutes after adding to completely dissolve the raw materials, adjusting the pH value of the solution to 4.5-6.0 by using a citric acid solution, adding water for injection to full dose, stirring for 15-40 minutes, sampling to detect an intermediate, introducing high-purity nitrogen subjected to sterilization and filtration into the preparation tank, and controlling the residual oxygen content of the liquid medicine to be less than 0.2 mg/L;
3) cooling the liquid medicine to about 30-50 ℃, then carrying out fine filtration operation, wherein the pressure of the fine filtration operation is 0.1-0.5 MPa, blowing off the pipeline by high-purity nitrogen before using a filter and the pipeline of the fine filtration operation, discharging about 10-30L of the liquid medicine after degerming and filtration from the back of the filter before the filtration starts, avoiding influencing the content of the liquid medicine, then carrying out visible foreign matter inspection on the liquid medicine after the fine filtration, and conveying the liquid medicine to a filling process after the liquid medicine is qualified;
4) filling the liquid medicine into a 500ml three-layer co-extrusion infusion bag by using an automatic bag making-filling-sealing machine, taking the co-extrusion films of specified varieties, specifications and batches according to production instructions, filling the co-extrusion films into equipment, setting the batch number and the production date content of the products printed on the infusion bag according to the production instructions, and checking the printing content and the position on the initially manufactured infusion bag;
5) rinsing the liquid medicine pipeline and filling equipment for 4 times before formal filling, wherein the filling quantity inspection is online inspection; meanwhile, nitrogen gas replacement is carried out before filling equipment, the high-level tank and the pipeline are used; the 500ml specification loading is 517ml plus or minus 2 ml; the filling temperature of the liquid medicine is kept between 30 and 50 ℃;
6) sterilizing the product by using a water bath type sterilization cabinet, and drying the sterilized product by using a dryer; the sterilization conditions are as follows: sterilizing at 121 ℃, unloading and drying by adopting an automatic bag unloading machine and a dryer, wherein the sterilizing pressure is 0.20-0.25 MPa, and the discharging temperature after cooling is 40-60 ℃;
7) inspecting the appearance and visible foreign matters of the product by a visual method, and removing unqualified products;
8) and (4) passing the products through a micropore inspection machine one by one, and detecting the products with micropore leakage.
According to one aspect of the invention, the mixed sugar electrolyte injection is prepared by the preparation method of the mixed sugar electrolyte injection.
The mixed sugar electrolyte injection provided by the invention is mainly prepared by the preparation method of the mixed sugar electrolyte injection, and further has the advantages of less impurities and high clarity.
The technical solution of the present invention will be further described with reference to examples and comparative examples.
Example 1
A method of preparing a mixed carbohydrate electrolyte injection, the method comprising the steps of:
1. providing a mixed sugar, an electrolyte component, water and a pH adjusting agent as raw materials;
the raw materials specifically comprise the following components: 730g of sodium chloride, 410g of acetic acid, 1140g of dipotassium phosphate trihydrate, about 490g of citric acid, 185g of calcium chloride, 255g of magnesium chloride, 0.7g of zinc sulfate, 210g of sodium bisulfite, 30000g of anhydrous glucose, 15000g of fructose, 7500g of xylitol and about 440000 parts of water for injection;
2. preparing the solution by adopting a preparation tank with a stirring paddle, adding 80% of injection water with the prepared volume, heating and boiling to remove residual oxygen in the injection water, and cooling to 40 ℃;
3. sequentially adding sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, citric acid, calcium chloride, magnesium chloride, zinc sulfate, sodium bisulfite, anhydrous glucose, fructose and xylitol into a liquid preparation tank, stirring for 15 minutes after adding to completely dissolve the raw materials, adjusting the pH value of the solution to 5.07 by using a citric acid solution, adding water for injection to full dose, sampling and detecting an intermediate after stirring for 15 minutes, introducing high-purity nitrogen subjected to sterilization and filtration into the preparation tank in the preparation process, and controlling the residual oxygen content of the liquid medicine to be less than 0.2 mg/L;
4. cooling the liquid medicine to about 30 ℃, then carrying out fine filtration operation, wherein the pressure of the fine filtration operation is 0.1MPa, blowing off the pipeline by high-purity nitrogen before using a filter and a pipeline of the fine filtration operation, discharging about 15L of the liquid medicine after degerming and filtering from the back of the filter before starting filtration, avoiding influencing the content of the liquid medicine, then carrying out visible foreign matter inspection on the liquid medicine after the fine filtration, and conveying the liquid medicine to a filling process after the liquid medicine is qualified;
5. filling the liquid medicine into a 500ml three-layer co-extrusion transfusion bag by using an automatic bag making-filling-sealing machine; sterilizing the product by using a water bath type sterilization cabinet, and drying the sterilized product by using a dryer; the sterilization conditions are as follows: sterilizing at 121 ℃, and accumulating the F0 value to 8.3; unloading and drying by using an automatic bag unloading machine and a drying machine, wherein the sterilization pressure is 0.20MPa, the cabinet discharging temperature is 55 ℃ after cooling, and drying is carried out on the sterilized product by using the drying machine.
Example 2
A method of preparing a mixed carbohydrate electrolyte injection, the method comprising the steps of:
1. the same as example 1;
2. preparing the solution by adopting a preparation tank with a stirring paddle, adding 80% of injection water with the prepared volume, heating and boiling to remove residual oxygen in the injection water, and cooling to 50 ℃;
3. sequentially adding sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, citric acid, calcium chloride, magnesium chloride, zinc sulfate, sodium bisulfite, anhydrous glucose, fructose and xylitol into a liquid preparation tank, stirring for 30 minutes after adding to completely dissolve the raw materials, adjusting the pH value of the solution to 5.06 by using a citric acid solution, adding water for injection to full dose, sampling and detecting an intermediate after stirring for 30 minutes, introducing high-purity nitrogen subjected to sterilization and filtration into the preparation tank in the preparation process, and controlling the residual oxygen content of the liquid medicine to be less than 0.2 mg/L;
4. cooling the liquid medicine to about 30 ℃, then carrying out fine filtration operation, wherein the pressure of the fine filtration operation is 0.1MPa, blowing off the pipeline by high-purity nitrogen before using a filter and a pipeline of the fine filtration operation, discharging about 15L of the liquid medicine after degerming and filtering from the back of the filter before starting filtration, avoiding influencing the content of the liquid medicine, then carrying out visible foreign matter inspection on the liquid medicine after the fine filtration, and conveying the liquid medicine to a filling process after the liquid medicine is qualified;
5. filling the liquid medicine into a 500ml three-layer co-extrusion transfusion bag by using an automatic bag making-filling-sealing machine; sterilizing the product by using a water bath type sterilization cabinet, and drying the sterilized product by using a dryer; the sterilization conditions are as follows: sterilizing at 121 ℃, and accumulating F0 value to 10.0; unloading and drying by using an automatic bag unloading machine and a drying machine, wherein the sterilization pressure is 0.20MPa, the cabinet discharging temperature is 55 ℃ after cooling, and drying is carried out on the sterilized product by using the drying machine.
Example 3
A method of preparing a mixed carbohydrate electrolyte injection, the method comprising the steps of:
1. the same as example 1;
2. preparing the solution by adopting a preparation tank with a stirring paddle, adding 80% of injection water with the prepared volume, heating and boiling to remove residual oxygen in the injection water, and cooling to 60 ℃;
3. sequentially adding sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, citric acid, calcium chloride, magnesium chloride, zinc sulfate, sodium bisulfite, anhydrous glucose, fructose and xylitol into a liquid preparation tank, stirring for 40 minutes after adding to completely dissolve the raw materials, adjusting the pH value of the solution to 5.04 by using a citric acid solution, adding water for injection to full dose, sampling and detecting an intermediate after stirring for 40 minutes, introducing high-purity nitrogen subjected to sterilization and filtration into the preparation tank in the preparation process, and controlling the residual oxygen content of the liquid medicine to be less than 0.2 mg/L;
4. cooling the liquid medicine to about 30 ℃, then carrying out fine filtration operation, wherein the pressure of the fine filtration operation is 0.1MPa, blowing off the pipeline by high-purity nitrogen before using a filter and a pipeline of the fine filtration operation, discharging about 15L of the liquid medicine after degerming and filtering from the back of the filter before starting filtration, avoiding influencing the content of the liquid medicine, then carrying out visible foreign matter inspection on the liquid medicine after the fine filtration, and conveying the liquid medicine to a filling process after the liquid medicine is qualified;
5. filling the liquid medicine into a 500ml three-layer co-extrusion transfusion bag by using an automatic bag making-filling-sealing machine; sterilizing the product by using a water bath type sterilization cabinet, and drying the sterilized product by using a dryer; the sterilization conditions are as follows: sterilizing at 121 ℃, and accumulating the F0 value to 13.7; unloading and drying by using an automatic bag unloading machine and a drying machine, wherein the sterilization pressure is 0.20MPa, the cabinet discharging temperature is 55 ℃ after cooling, and drying is carried out on the sterilized product by using the drying machine.
Comparative example 1
The comparative example except for step (3) was: sequentially adding sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, citric acid, calcium chloride, magnesium chloride, zinc sulfate, sodium bisulfite, anhydrous glucose, fructose and xylitol into a liquid preparation tank, stirring for 15 minutes after adding to completely dissolve the raw materials, adjusting the pH value of the solution to 4.96 by using a citric acid solution, adding water for injection to full dose, and sampling to detect an intermediate after stirring for 15 minutes; "otherwise, the same procedure as in example 1 was repeated.
This comparative example is different from example 1 in that nitrogen gas was not introduced during the solution formulation.
Experimental example 1
In order to show that the mixed sugar electrolyte injection prepared by the method has the advantages of less impurities and high clarity, effect experiments are carried out on the injections prepared in example 1 and comparative example 1, and specific detection results are shown in the following table:
from the above experimental data, it is understood that oxygen is a very important factor affecting the stability of the sugar electrolyte injection. The main ways oxygen enters the product are: on the one hand, oxygen has certain solubility in water; on the other hand, a certain amount of oxygen is also present in the air in the space of the drug container, and the oxygen in the air is inevitably dissolved in the drug solution during the operations of preparing and filling the drug solution. And the nitrogen is introduced to effectively remove oxygen and prevent the product from being oxidized. Therefore, in the production process of the product, nitrogen replacement must run through the whole production process, and the nitrogen is filled to effectively inhibit the generation of 5-HMF, thereby ensuring the quality of the product.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (10)
1. A preparation method of mixed sugar electrolyte injection is characterized by comprising the following steps:
(a) providing a mixed sugar, an electrolyte component, water and a pH regulator as raw materials;
(b) carrying out solution blending by using the raw materials provided in the step (a);
the solution preparation comprises the following steps: firstly, dissolving mixed sugar and electrolyte components in partial water to obtain a solution A; adding a pH regulator into the solution A, adding the balance of water, and uniformly mixing to obtain a solution B, thereby finishing solution blending;
introducing nitrogen subjected to sterilization and filtration in the solution blending process, and controlling the residual oxygen amount of the solution in the blending process to be 0.01-0.2 mg/L;
(c) and (c) sequentially carrying out fine filtration, filling and sterilization on the solution B prepared in the step (B) to obtain the mixed sugar electrolyte injection.
2. The method of claim 1, wherein the mixed sugar in step (a) comprises anhydrous glucose, fructose and xylitol.
3. The method of preparing a mixed sugar electrolyte injection as set forth in claim 1, wherein the electrolyte components in the step (a) include sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, calcium chloride, magnesium chloride, zinc sulfate and sodium bisulfite.
4. The method for preparing the mixed sugar electrolyte injection of claim 1, wherein the pH regulator in the step (a) is citric acid;
preferably, the water in step (a) is water for injection.
5. The method for preparing the mixed sugar electrolyte injection according to claim 1, wherein the step (a) comprises the following components in parts by mass:
657-803 parts of sodium chloride, 369-451 parts of sodium acetate, 1026-1254 parts of dipotassium phosphate trihydrate, 440-510 parts of citric acid, 166-204 parts of calcium chloride, 229-281 parts of magnesium chloride, 0.56-0.77 part of zinc sulfate, 189-231 parts of sodium bisulfite, 27000-33000 parts of anhydrous glucose, 13500-16500 parts of fructose, 6750-8250 parts of xylitol and 390000-480000 parts of water for injection;
preferably, the step (a) comprises the following components in parts by mass:
730 parts of sodium chloride, 410 parts of sodium acetate, 1140 parts of dipotassium phosphate trihydrate, 490 parts of citric acid, 185 parts of calcium chloride, 255 parts of magnesium chloride, 0.7 part of zinc sulfate, 210 parts of sodium bisulfite, 30000 parts of anhydrous glucose, 15000 parts of fructose, 7500 parts of xylitol and 440000 parts of water for injection.
6. The method for preparing the mixed sugar electrolyte injection of claim 1, wherein the temperature for preparing the solution A in the step (b) is 40-60 ℃;
preferably, the pH value of the solution B in the step (B) is 4.5-6.0;
preferably, the step (b) further comprises the step of removing residual oxygen from the partial water before preparing the solution a.
7. The method of claim 6, wherein the step (b) comprises the steps of:
(b1) adding 50-80% of injection water into the solution prepared by adopting a preparation tank with a stirring paddle, heating to 90-110 ℃ to remove residual oxygen in the injection water, and then cooling to 40-60 ℃;
(b2) sequentially adding sodium chloride, sodium acetate, dipotassium hydrogen phosphate trihydrate, citric acid, calcium chloride, magnesium chloride, zinc sulfate, sodium bisulfite, anhydrous glucose, fructose and xylitol into a blending tank, and then stirring for 15-40min to fully dissolve to obtain a solution A;
introducing nitrogen subjected to sterilization and filtration in the blending process of the step (b2), and controlling the residual oxygen amount of the solution A to be 0.01-0.2 mg/L;
(b3) adding a pH regulator and the balance of water into the solution A to regulate the pH to 4.5-6.0, and then stirring for 15-40min to obtain a solution B;
and (b3) introducing nitrogen subjected to sterilization and filtration in the blending process of the step (b3), and controlling the residual oxygen amount of the solution A to be 0.01-0.2 mg/L.
8. The method for preparing the mixed sugar electrolyte injection as claimed in claim 1, wherein the pressure of the fine filtration in the step (c) is 0.1 to 0.5Mpa, and the temperature of the fine filtration is 30 to 50 ℃;
preferably, the filtration precision of the fine filtration is 0.2-0.22 μm.
9. The method for preparing the mixed saccharide electrolyte injection according to claim 1, wherein the sterilization temperature in the step (c) is 120-123 ℃ and the sterilization pressure is 0.2-0.25 MPa.
10. The mixed sugar electrolyte injection prepared by the preparation method of the mixed sugar electrolyte injection according to any one of claims 1 to 9.
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| EP0510687A2 (en) * | 1991-04-26 | 1992-10-28 | The Green Cross Corporation | Infusion preparation |
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| CN103405473A (en) * | 2013-08-27 | 2013-11-27 | 山东齐都药业有限公司 | Mixed carbohydrate-electrolyte injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP0510687A2 (en) * | 1991-04-26 | 1992-10-28 | The Green Cross Corporation | Infusion preparation |
| CN101167739A (en) * | 2007-10-16 | 2008-04-30 | 中国大冢制药有限公司 | Compound fructose electrolyte injection and preparation method thereof |
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