CN116098860A - Calcium gluconate injection and preparation method thereof - Google Patents
Calcium gluconate injection and preparation method thereof Download PDFInfo
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- CN116098860A CN116098860A CN202211570808.4A CN202211570808A CN116098860A CN 116098860 A CN116098860 A CN 116098860A CN 202211570808 A CN202211570808 A CN 202211570808A CN 116098860 A CN116098860 A CN 116098860A
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- calcium gluconate
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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
- A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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Abstract
The invention relates to the technical field of pharmaceutical preparations, and discloses a calcium gluconate injection and a preparation method thereof, wherein the preparation method comprises the following steps: heating proper amount of water for injection to boiling, adding the prescribed amount of calcium gluconate monohydrate, stirring and keeping boiling state for 10-15min until complete dissolution; cooling the solution in the first step to room temperature, adding a proper amount of surfactant, and stirring until the surfactant is dissolved; according to the calcium gluconate injection and the preparation method thereof, the nonionic surfactant is added in the prescription process, so that the solubility of calcium gluconate monohydrate is increased, the stability of the product is improved, and the crystallization precipitation phenomenon is not easy to occur in the storage process.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a calcium gluconate injection and a preparation method thereof.
Background
The calcium gluconate injection is a common calcium supplement, has less stimulation to human tissues compared with other calcium supplementing preparations, and is safer to injection administration than calcium chloride. Calcium gluconate can also be used for antiallergic treatment, and for rescue of magnesium poisoning and fluorine poisoning.
In the prior art, the calcium gluconate injection is not a small-capacity injection product, the solubility of calcium gluconate in water is 3g/100ml (20 ℃), the solubility in boiling water is 20g/100ml, and the specification of a commercial product is 10% concentration (namely 10g/100 ml), so that the calcium gluconate injection is in a supersaturated state when stored at room temperature, and crystallization is easy to precipitate, especially at a low temperature (2-8 ℃).
Although the solution to the above problems has been proposed in the chinese patent document CN111888327B, CN109966247A, CN106619500a, the problem that precipitation crystallization occurs in calcium gluconate injection during shelf life cannot be completely avoided, and therefore, a calcium gluconate injection and a preparation method thereof are provided.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a preparation method of calcium gluconate injection, which comprises the following steps:
heating a proper amount of water for injection to boiling, adding the prescribed amount of calcium gluconate monohydrate, stirring and keeping a boiling state for 10-15min until the calcium gluconate monohydrate is completely dissolved;
step two, cooling the solution in the step one to room temperature, adding a proper amount of surfactant, and stirring until the surfactant is dissolved;
step three, regulating the liquid medicine obtained in the step two to a proper pH value in the pH range of 6.0-8.2 by hydrochloric acid or sodium hydroxide, supplementing the water for injection to the full amount, and uniformly stirring;
step four, filtering by a 0.45 micron and 0.22 micron polyether sulfone filter membrane in sequence;
filling and sealing, adding the liquid medicine, filling nitrogen until the residual oxygen content is less than 1%, and sealing in a melting way;
step six, sterilizing, wherein the sterilizing temperature is 121 ℃ and the sterilizing time is 15min.
Preferably, the surfactant in the second step comprises span, tween and sucrose ester.
Preferably, the surfactant in step two is preferably tween 80.
Preferably, the amount of Tween 80 used in the second step is 3% -5%.
Preferably, tween 80 is used in step two in an amount of preferably 3%.
Compared with the prior art, the invention has the following beneficial effects: according to the calcium gluconate injection and the preparation method thereof, the nonionic surfactant is added in the prescription process, so that the solubility of calcium gluconate monohydrate is increased, the stability of the product is improved, and the crystallization precipitation phenomenon is not easy to occur in the storage process.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
A calcium gluconate injection and a preparation method thereof, wherein the preparation method comprises the following steps:
heating a proper amount of water for injection to boiling, adding the prescribed amount of calcium gluconate monohydrate, stirring and keeping a boiling state for 10-15min until the calcium gluconate monohydrate is completely dissolved;
step two, cooling the solution in the step one to room temperature, adding a proper amount of surfactant, and stirring until the surfactant is dissolved;
step three, regulating the liquid medicine obtained in the step two to a proper pH value in the pH range of 6.0-8.2 by hydrochloric acid or sodium hydroxide, supplementing the water for injection to the full amount, and uniformly stirring;
step four, filtering by a 0.45 micron and 0.22 micron polyether sulfone filter membrane in sequence;
filling and sealing, adding the liquid medicine, filling nitrogen until the residual oxygen content is less than 1%, and sealing in a melting way;
step six, sterilizing, wherein the sterilizing temperature is 121 ℃ and the sterilizing time is 15min.
Wherein, the surfactant in the second step comprises span, tween and sucrose ester.
Wherein, the surfactant in the step II is preferably Tween 80.
Wherein, the dosage range of Tween 80 in the second step is 3-5 percent.
Wherein, the amount of Tween 80 in the second step is preferably 3%.
It should be noted that: according to the calcium gluconate injection and the preparation method thereof, the nonionic surfactant is added in the prescription process, so that the solubility of calcium gluconate monohydrate is increased, the stability of the product is improved, and the crystallization precipitation phenomenon is not easy to occur in the storage process;
what is not described in detail in this specification is prior art known to those skilled in the art.
Example 1
Adding 80% of the total amount of water for injection into a conical flask, heating and boiling, adding 104.3g of calcium gluconate monohydrate while stirring, continuously keeping a boiling state and stirring for 15min until the calcium gluconate is completely dissolved, cooling to room temperature, adding 30g of Tween (80), regulating the liquid medicine to pH 7.0 by using 1% sodium hydroxide solution, supplementing the water for injection to 1L, and filtering by using a 0.45-micrometer and 0.22-micrometer polyether sulfone filter membrane after stirring uniformly; filling the mixture into a 10ml borosilicate glass ampoule, filling nitrogen until the residual oxygen content is less than 1%, and sealing; and (5) sterilizing.
Example 2
Adding 80% of the total amount of water for injection into a conical flask, heating and boiling, adding 104.3g of calcium gluconate monohydrate while stirring, continuously keeping a boiling state and stirring for 15min until the calcium gluconate is completely dissolved, cooling to room temperature, adding 40g of Tween (80), regulating the liquid medicine to pH 7.0 by using 1% sodium hydroxide solution, supplementing the water for injection to 1L, and filtering by using a 0.45-micrometer and 0.22-micrometer polyether sulfone filter membrane after stirring uniformly; filling the mixture into a 10ml borosilicate glass ampoule, filling nitrogen until the residual oxygen content is less than 1%, and sealing; and (5) sterilizing.
Example 3
Adding 80% of the total amount of water for injection into a conical flask, heating and boiling, adding 104.3g of calcium gluconate monohydrate while stirring, continuously keeping a boiling state and stirring for 15min until the calcium gluconate is completely dissolved, cooling to room temperature, adding 50g of Tween (80), regulating the liquid medicine to pH 7.0 by using 1% sodium hydroxide solution, supplementing the water for injection to 1L, and filtering by using a 0.45-micrometer and 0.22-micrometer polyether sulfone filter membrane after stirring uniformly; filling the mixture into a 10ml borosilicate glass ampoule, filling nitrogen until the residual oxygen content is less than 1%, and sealing; and (5) sterilizing.
Comparative example 1
The preparation method of the calcium gluconate injection of the comparative example is basically the same as that of the example, except that the added stabilizer is calcium gluconate.
The calcium gluconate injection prepared in examples 1-3 and comparative example 1 were subjected to content and visible foreign matter detection, respectively, and the detection results are shown in Table 1.
TABLE 1
Examination item
Example 1
Example 2
Example 3
Comparative example 1
Calcium gluconate content
99.94%
100.23%
100.16%
100.08%
Traits (3)
Colorless clear liquid
Colorless clear liquid
Colorless clear liquid
Colorless clear liquid
The calcium gluconate injection prepared in examples 1-3 and comparative example 1 was subjected to a low-temperature freeze thawing test, and the content and the percent of pass of visible foreign matters were detected, and the detection results are shown in Table 2.
TABLE 2
Examination item
Example 1
Example 2
Example 3
Comparative example 1
Calcium gluconate content
99.94%
100.23%
100.16%
98.46%
Yield of visible foreign matter
100% (20 pieces are not separated out)
100% (20 pieces are not separated out)
100% (20 pieces are not separated out)
85% (20 pieces were detected, 3 pieces were separated out)
From the results, the stability of the calcium gluconate injection is obviously improved, and the problem that the raw material medicines are separated out and the visible foreign matters are unqualified in the storage process of the commercial products is solved. The tween (80) added in the prescription process is not beyond the daily maximum dosage published by the FDA, and the safety meets the requirements.
It is noted that relational terms such as first and second, and the like are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (5)
1. The preparation method of the calcium gluconate injection is characterized by comprising the following steps of:
heating a proper amount of water for injection to boiling, adding the prescribed amount of calcium gluconate monohydrate, stirring and keeping a boiling state for 10-15min until the calcium gluconate monohydrate is completely dissolved;
step two, cooling the solution in the step one to room temperature, adding a proper amount of surfactant, and stirring until the surfactant is dissolved;
step three, regulating the liquid medicine obtained in the step two to a proper pH value in the pH range of 6.0-8.2 by hydrochloric acid or sodium hydroxide, supplementing the water for injection to the full amount, and uniformly stirring;
step four, filtering by a 0.45 micron and 0.22 micron polyether sulfone filter membrane in sequence;
filling and sealing, adding the liquid medicine, filling nitrogen until the residual oxygen content is less than 1%, and sealing in a melting way;
step six, sterilizing, wherein the sterilizing temperature is 121 ℃ and the sterilizing time is 15min.
2. The calcium gluconate injection as set forth in claim 1, wherein: and in the second step, the surfactant comprises span, tween and sucrose ester.
3. The calcium gluconate injection as set forth in claim 1, wherein: in the step two, the surfactant is preferably Tween 80.
4. The calcium gluconate injection as set forth in claim 1, wherein: in the second step, the dosage of Tween 80 is 3-5%.
5. The calcium gluconate injection as set forth in claim 1, wherein: the amount of Tween 80 in the second step is preferably 3%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211570808.4A CN116098860A (en) | 2022-12-08 | 2022-12-08 | Calcium gluconate injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211570808.4A CN116098860A (en) | 2022-12-08 | 2022-12-08 | Calcium gluconate injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116098860A true CN116098860A (en) | 2023-05-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211570808.4A Pending CN116098860A (en) | 2022-12-08 | 2022-12-08 | Calcium gluconate injection and preparation method thereof |
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| Country | Link |
|---|---|
| CN (1) | CN116098860A (en) |
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2022
- 2022-12-08 CN CN202211570808.4A patent/CN116098860A/en active Pending
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