CN110664738A - Calcium gluconate oral solution and preparation method thereof - Google Patents
Calcium gluconate oral solution and preparation method thereof Download PDFInfo
- Publication number
- CN110664738A CN110664738A CN201910935824.0A CN201910935824A CN110664738A CN 110664738 A CN110664738 A CN 110664738A CN 201910935824 A CN201910935824 A CN 201910935824A CN 110664738 A CN110664738 A CN 110664738A
- Authority
- CN
- China
- Prior art keywords
- calcium gluconate
- oral solution
- calcium
- sucralose
- essence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
-
- 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
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
Abstract
The invention provides a calcium gluconate oral solution preparation composition; the composition comprises the following components: every 1000ml of calcium gluconate oral solution contains 80-120 g of calcium gluconate, 1-2 g of lactic acid, 0.5-2 g of lauric acid macrogolglyceride, 0.1-0.5 g of sucralose, 0.05-0.2 g of sodium hydroxide and 0.05-0.2 g of essence. The invention also provides a preparation method of the calcium gluconate oral solution. The calcium gluconate oral solution prepared finally has higher stability and safety performance due to the synergistic effect of the components.
Description
Technical Field
The invention relates to a pharmaceutical preparation composition, in particular to a calcium gluconate oral solution preparation composition and a preparation method thereof.
Background
The calcium gluconate oral solution is a medicine which is already on the market and is used for preventing and treating calcium deficiency, such as osteoporosis, tetany, bone hypoplasia, rickets and calcium supplement for children, pregnant and lactating women, menopausal women and old people. The traditional prescription is as follows: adding calcium gluconate, sucrose, calcium hydroxide, essence, and lactic acid into 1000ml of purified water. In recent years, researches have been made to improve the prescription, and the flavoring agent in the prescription is changed to be a sweetening agent such as stevioside, glucose, aspartame, acesulfame potassium and the like, and benzoic acid or sodium benzoate is added as a preservative.
The calcium gluconate oral solution has the following defects: (1) the sucrose content is high, which can cause tooth decay of children, hyperglycemia in gestation period and senile diabetes, and the sucrose is unstable at a high temperature of more than 40 ℃ and can cause the color of the solution to change; (2) the solution viscosity is high, the filtering speed of the microporous filter membrane is slow, and the production efficiency is low; (3) the calcium gluconate is in a supersaturated state in the oral solution, is easy to separate out crystals and has poor stability.
Although the prior art has made some improvements to the above drawbacks, such as CN 108853011 discloses the formulation and/or preparation process of calcium gluconate oral solution, none of them completely solves the above problems.
The sweetness of the sucralose serving as a novel sweetener is 600-800 times that of the sucrose, the sucralose is a new-generation sweetener developed after aspartame and acesulfame, is a perfect and competitive new-generation sweetener developed by people so far, has stable sucralose property, no peculiar smell and toxic or side effect, is hardly absorbed in a human body, has zero caloric value, is an ideal sweet substitute for diabetes,
the lauric acid macrogolglyceride is an excellent surfactant, meets the quality standards of USP (United states Pharmacopeia), EP (European Pharmacopeia) and JP (Japanese Pharmacopeia), is commonly used as a solubilizer in oral preparations, and thus has good evidence of safety and stability.
The invention provides a calcium gluconate oral solution without sucrose through research, the calcium gluconate is an unbalanced unstable solution system because of the supersaturated solution, crystal nucleus is easy to form and precipitate crystals, and meanwhile, when the calcium gluconate oral solution without sucrose is prepared, a plurality of unexpected difficulties are found, particularly, the clarity and the stability of the solution are difficult to maintain.
Disclosure of Invention
The invention aims to overcome the defects and shortcomings in the background art and provide the calcium gluconate oral solution composition which does not contain sucrose, preservatives and preservatives, has high stability and simple preparation process.
The calcium gluconate oral solution composition has the following formula:
the calcium gluconate oral solution is prepared by the following method:
(1) taking 90% of pure water in total amount, and heating to boil for 10-30 minutes for later use;
(2) weighing calcium gluconate according to the prescription amount, and stirring for 10-20 minutes to completely dissolve the calcium gluconate;
(3) sequentially adding sucralose, essence and polyethylene glycol laurate glyceride as auxiliary materials according to the prescription amount, stirring for 10-30 minutes to completely dissolve the sucralose, essence and polyethylene glycol laurate, and cooling the solution to room temperature;
(4) the pH value of the solution is adjusted to 4.0-4.5 by sodium hydroxide.
(5) Diluting with purified water, and filtering with 0.20 μm microporous membrane;
(6) canning with 10ml glass bottle, and sealing;
(7) the canned and sealed sample is sterilized at 121 ℃ for 15 min.
(8) And (5) performing light inspection on the sterilized sample, and packaging.
In the invention, sucralose is used to replace sucrose, and the sweetness of steviosin is about 600-800 times of that of sucrose, so that the steviosin is not absorbed by human body and does not generate heat, thus the sugar fluctuation is not caused while the taste of the finished product is maintained,
has no related side effects on children in development period, women in pregnancy period and the elderly. In the invention, no preservative is used, and the safety of the calcium gluconate oral solution product is higher. In addition, the dosage of lactic acid is reduced, the novel surfactant lauric acid macrogol glyceride is added, the lauric acid macrogol glyceride and the novel surfactant lauric acid macrogol glyceride are cooperated to be used as a stabilizer to play a role in stabilizing the dissolution of calcium gluconate in a prescription, and the lauric acid macrogol glyceride can increase the solubility of the calcium gluconate in water.
The beneficial technical effects of the invention are as follows:
1. according to the invention, sucralose is used to replace steviosin/sucrose, so that the influence of the medicine on the blood sugar concentration of a human body is reduced while better taste is obtained, and the safety risk brought by auxiliary materials is also reduced; in addition, the invention does not contain high-concentration sucrose, so the solution viscosity is low, and the filtering speed is high when the microporous membrane is used for filtering.
2. According to the invention, the dosage of lactic acid is reduced, the lauric acid macrogol glyceride is added, the lauric acid macrogol glyceride and the lauric acid macrogol glyceride are cooperated and cooperated to be used as a stabilizer to play a role in stabilizing the dissolution of calcium gluconate in a prescription, and the lauric acid macrogol glyceride can increase the solubility of calcium gluconate in water.
3. The calcium zinc gluconate oral solution prepared finally has higher stability and safety performance due to the synergistic effect of the components.
Detailed Description
The present invention will be further described below with reference to specific experimental groups, but this should not be construed as limiting the scope of the above-described subject matter of the present invention to the following experimental groups only. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention. The auxiliary materials in the following experimental groups can be replaced by the similar pharmaceutically acceptable auxiliary materials, or reduced or increased.
According to the requirements of experimental design, the medicines of experimental groups 1, 2, 3, 4 and the like are prepared.
Preparation of experimental group 1:
1. prescription:
2. the process comprises the following steps:
(1) taking 90% of pure water in total amount, and heating to boil for 10-30 minutes for later use;
(2) weighing calcium gluconate according to the prescription amount, and stirring for 10-20 minutes to completely dissolve the calcium gluconate;
(3) sequentially adding sucralose, essence and polyethylene glycol laurate glyceride as auxiliary materials according to the prescription amount, stirring for 10-30 minutes to completely dissolve the sucralose, essence and polyethylene glycol laurate, and cooling the solution to room temperature;
(4) the pH value of the solution is adjusted to 4.0-4.5 by sodium hydroxide.
(5) Diluting with purified water, and filtering with 0.20 μm microporous membrane;
(6) canning with 10ml glass bottle, and sealing;
(7) the canned and sealed sample is sterilized at 121 ℃ for 15 min.
(8) And (5) performing light inspection on the sterilized sample, and packaging.
Preparation of experimental group 2:
1. prescription:
2. the process comprises the following steps:
(1) taking 90% of pure water in total amount, and heating to boil for 10-30 minutes for later use;
(2) weighing calcium gluconate according to the prescription amount, and stirring for 10-20 minutes to completely dissolve the calcium gluconate;
(3) sequentially adding sucralose, essence and polyethylene glycol laurate glyceride as auxiliary materials according to the prescription amount, stirring for 10-30 minutes to completely dissolve the sucralose, essence and polyethylene glycol laurate, and cooling the solution to room temperature;
(4) the pH value of the solution is adjusted to 4.0-4.5 by sodium hydroxide.
(5) Diluting with purified water, and filtering with 0.20 μm microporous membrane;
(6) canning with 10ml glass bottle, and sealing;
(7) the canned and sealed sample is sterilized at 121 ℃ for 15 min.
(8) And (5) performing light inspection on the sterilized sample, and packaging.
Preparation of experimental group 3:
1. prescription:
2. the process comprises the following steps:
(1) taking 90% of pure water in total amount, and heating to boil for 10-30 minutes for later use;
(2) weighing calcium gluconate according to the prescription amount, and stirring for 10-20 minutes to completely dissolve the calcium gluconate;
(3) sequentially adding sucralose, essence and polyethylene glycol laurate glyceride as auxiliary materials according to the prescription amount, stirring for 10-30 minutes to completely dissolve the sucralose, essence and polyethylene glycol laurate, and cooling the solution to room temperature;
(4) the pH value of the solution is adjusted to 4.0-4.5 by sodium hydroxide.
(5) Diluting with purified water, and filtering with 0.20 μm microporous membrane;
(6) canning with 10ml glass bottle, and sealing;
(7) the canned and sealed sample is sterilized at 121 ℃ for 15 min.
(8) And (5) performing light inspection on the sterilized sample, and packaging.
Preparation of experimental group 4:
1. prescription:
2. the process comprises the following steps:
(1) taking 90% of pure water in total amount, and heating to boil for 10-30 minutes for later use;
(2) weighing calcium gluconate according to the prescription amount, and stirring for 10-20 minutes to completely dissolve the calcium gluconate;
(3) sequentially adding sucralose, essence and polyethylene glycol laurate glyceride as auxiliary materials according to the prescription amount, stirring for 10-30 minutes to completely dissolve the sucralose, essence and polyethylene glycol laurate, and cooling the solution to room temperature;
(4) the pH value of the solution is adjusted to 4.0-4.5 by sodium hydroxide.
(5) Diluting with purified water, and filtering with 0.20 μm microporous membrane;
(6) canning with 10ml glass bottle, and sealing;
(7) the canned and sealed sample is sterilized at 121 ℃ for 15 min.
(8) And (5) performing light inspection on the sterilized sample, and packaging.
Influence factor research:
the calcium gluconate oral solutions prepared in experimental groups 1 to 4 were mixed with commercial product 1 (trade name:
the manufacturer: three refined drugs of hayao corporation, lot number: 190304 lot) and commercial product 2 (trade name:
the manufacturer: sichuan subalpo-Tay pharmaceutical Co., Ltd, batch number: 20190401 lots) were subjected to influential tests (including high temperature tests and freeze-thaw tests):
high-temperature test: placing the sample and the commercial product at a high temperature of 60 ℃, and respectively inspecting for 15 days, 30 days and 60 days;
freeze-thaw test: samples and commercial products were subjected to a first stage: the temperature is 40 ℃ for 3 days, the low temperature is-10 ℃ to-20 ℃ for 3 days, and the second stage is as follows: 3 days at 40 ℃, 3 days at-10 ℃ to-20 ℃, 3 days at the third stage, 3 days at 40 ℃ and 3 days at-10 ℃ to-20 ℃;
the results of the examination are shown in table 1:
TABLE 1 high temperature 60 ℃ stability test results
Remarking: "-" indicates that the appearance was changed, and the quality standard was not met, and thus was not detected.
TABLE 2 Freeze thaw test results
Remarking: "-" indicates that the appearance was changed, and the quality standard was not met, and thus was not detected.
Through high-temperature investigation and freeze-thaw test investigation, data show that the product prepared by adopting the prescription process has stable quality and higher safety, wherein each index of the experimental group 3 is the most excellent.
Claims (3)
1. The calcium zinc gluconate oral solution is characterized by comprising the following components in parts by weight: every 1000ml of calcium gluconate oral solution contains 80-120 g of calcium gluconate, 1-2 g of lactic acid, 0.5-2 g of lauric acid macrogolglyceride, 0.1-0.5 g of sucralose, 0.05-0.2 g of sodium hydroxide, 0.05-0.2 g of essence and pure water which is added to 1000 ml.
2. The calcium zinc gluconate oral solution is characterized by comprising the following components in parts by weight: each 1000ml of the calcium gluconate oral solution contains 100g of calcium gluconate, 1.5g of lactic acid, 1.5g of lauric acid macrogol glyceride, 0.4g of sucralose, 0.2g of sodium hydroxide, 0.05g of essence and pure water which are complemented to 1000 ml.
3. A process for the preparation of an oral solution of calcium zinc gluconate according to claim 1 or 2, characterized in that it comprises the following steps:
1) taking 90% of pure water in total amount, and heating to boil for 10-30 minutes for later use;
2) weighing calcium gluconate according to the prescription amount, and stirring for 10-20 minutes to completely dissolve the calcium gluconate;
3) sequentially adding sucralose, essence and polyethylene glycol laurate glyceride as auxiliary materials according to the prescription amount, stirring for 10-30 minutes to completely dissolve the sucralose, essence and polyethylene glycol laurate, and cooling the solution to room temperature;
4) adjusting the pH value of the solution to 4.0-4.5 by using sodium hydroxide;
5) diluting with purified water, and filtering with 0.20 μm microporous membrane;
6) canning with 10ml glass bottle, and sealing;
7) sterilizing the canned and sealed sample at 121 deg.C for 15 min;
8) and (5) performing light inspection on the sterilized sample, and packaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910935824.0A CN110664738A (en) | 2019-09-29 | 2019-09-29 | Calcium gluconate oral solution and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910935824.0A CN110664738A (en) | 2019-09-29 | 2019-09-29 | Calcium gluconate oral solution and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110664738A true CN110664738A (en) | 2020-01-10 |
Family
ID=69080476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910935824.0A Pending CN110664738A (en) | 2019-09-29 | 2019-09-29 | Calcium gluconate oral solution and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110664738A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112545987A (en) * | 2021-01-08 | 2021-03-26 | 广西方略药业集团有限公司 | 5% calcium gluconate oral solution and preparation method thereof |
| CN115770216A (en) * | 2022-12-26 | 2023-03-10 | 佛山市南海东方澳龙制药有限公司 | Calcium gluconate oral solution for animals and preparation method thereof |
-
2019
- 2019-09-29 CN CN201910935824.0A patent/CN110664738A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112545987A (en) * | 2021-01-08 | 2021-03-26 | 广西方略药业集团有限公司 | 5% calcium gluconate oral solution and preparation method thereof |
| CN115770216A (en) * | 2022-12-26 | 2023-03-10 | 佛山市南海东方澳龙制药有限公司 | Calcium gluconate oral solution for animals and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112190575A (en) | Calcium zinc gluconate oral solution and preparation method thereof | |
| CN110664738A (en) | Calcium gluconate oral solution and preparation method thereof | |
| CN112891335A (en) | Calcium zinc gluconate oral solution and preparation method thereof | |
| CN113876700A (en) | Compound calcium gluconate oral solution and preparation method thereof | |
| CN104800199B (en) | A kind of Zinc calcium gluconate oral solution composition and preparation method thereof | |
| CN109528644A (en) | A kind of Zinc calcium gluconate oral solution and preparation method thereof | |
| EP1391202B1 (en) | Liquid drug preparations | |
| CN112494573A (en) | Sugar-free pharynx-soothing mixture and preparation method thereof | |
| CN111955632A (en) | Sialic acid-containing beverage and preparation method thereof | |
| JP2011148778A (en) | Liquid preparation composition | |
| CN110327293B (en) | Dextromethorphan guaifenesin oral liquid preparation | |
| KR100825572B1 (en) | Liquid Formulation Containing Calcium, Magnesium and Vitamin, and Preparing Method Thereof | |
| KR100254107B1 (en) | Stable liquid preparation of complex vitamin for internal use | |
| JP2001131070A (en) | Riboflavin-formulated liquid composition | |
| KR20200111138A (en) | Dexibupropen syrup formulation with improved solubility and stability | |
| CN110711172A (en) | Loratadine syrup composition | |
| CN110151688A (en) | A kind of ambroxol hydrochloride injection composition and preparation method thereof | |
| KR20190093999A (en) | Dexibupropen syrup formulation with improved solubility and stability | |
| CN117243936B (en) | Compound calcium preparation composition and preparation method thereof | |
| JPH08231403A (en) | Stable aqueous solution containing arginine vasopressin antagonist | |
| CN110840833A (en) | Sugar-free desloratadine oral solution and preparation process thereof | |
| CN111494309B (en) | Glucosamine liquid preparation and preparation method thereof | |
| CN107898809A (en) | A kind of Zinc calcium gluconate oral solution and preparation method thereof | |
| RU2313350C1 (en) | Method for increasing calcium succinate, calcium malate and calcium citrate solubility for child's medicinal formulations | |
| CN116803376B (en) | Preparation method of compound guaiacol potassium sulfonate oral solution |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200110 |
|
| WD01 | Invention patent application deemed withdrawn after publication |