CN115154416A - Acetylcysteine pharmaceutical composition with low hydrogen sulfide content and preparation method thereof - Google Patents
Acetylcysteine pharmaceutical composition with low hydrogen sulfide content and preparation method thereof Download PDFInfo
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- CN115154416A CN115154416A CN202210935146.XA CN202210935146A CN115154416A CN 115154416 A CN115154416 A CN 115154416A CN 202210935146 A CN202210935146 A CN 202210935146A CN 115154416 A CN115154416 A CN 115154416A
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- acetylcysteine
- pharmaceutical composition
- hydrogen sulfide
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- sulfide content
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- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 title claims abstract description 86
- 229960004308 acetylcysteine Drugs 0.000 title claims abstract description 86
- 229910000037 hydrogen sulfide Inorganic materials 0.000 title claims abstract description 58
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 48
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 30
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 24
- 239000007924 injection Substances 0.000 claims abstract description 19
- 238000002347 injection Methods 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 15
- 239000011812 mixed powder Substances 0.000 claims abstract description 12
- 238000003825 pressing Methods 0.000 claims abstract description 12
- 239000000843 powder Substances 0.000 claims abstract description 11
- 238000005096 rolling process Methods 0.000 claims abstract description 10
- 238000004806 packaging method and process Methods 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000001954 sterilising effect Effects 0.000 claims abstract description 7
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 239000008215 water for injection Substances 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 29
- 239000011521 glass Substances 0.000 claims description 10
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 8
- 239000002738 chelating agent Substances 0.000 claims description 8
- 229910021645 metal ion Inorganic materials 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 4
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 2
- 239000001509 sodium citrate Substances 0.000 claims description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 229940090044 injection Drugs 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 229940093181 glucose injection Drugs 0.000 description 5
- 239000008227 sterile water for injection Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 229940021715 acetylcysteine injection Drugs 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000012535 impurity Substances 0.000 description 3
- 102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 description 2
- 108050008072 Cytochrome c oxidase subunit IV Proteins 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 206010070863 Toxicity to various agents Diseases 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000570 acute poisoning Toxicity 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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
- A61K9/08—Solutions
-
- 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
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- 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
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses an acetylcysteine pharmaceutical composition with low hydrogen sulfide content and a preparation method thereof, and relates to the technical field of acetylcysteine pharmaceutical compositions. The pharmaceutical composition comprises a combination of acetylcysteine and sodium carbonate and/or sodium bicarbonate. The preparation method comprises the following steps: (1) Evenly mixing acetylcysteine, sodium carbonate and/or sodium bicarbonate, and controlling the pH value to be 5.0-8.5 to obtain mixed powder; (2) Packaging the mixed powder into injection bottles under sterile condition, pressing plugs, and capping. Or a, subpackaging the acetylcysteine sterile powder into injection bottles under the aseptic condition, pressing plugs and rolling covers to obtain the acetylcysteine preparation; b. dissolving sodium carbonate and/or sodium bicarbonate with water for injection, filtering, bottling, and sterilizing to obtain special solvent; c. packaging the acetylcysteine preparation and 1 special solvent according to 1 bottle. The acetylcysteine pharmaceutical composition disclosed by the invention is good in stability and low in hydrogen sulfide content, and the medication safety of the product is improved.
Description
Technical Field
The invention relates to the technical field of acetylcysteine pharmaceutical compositions, in particular to an acetylcysteine pharmaceutical composition with low hydrogen sulfide content and a preparation method thereof.
Background
The acetylcysteine is unstable in chemical property, so that the acetylcysteine serving as an active ingredient can be continuously degraded in a solution to generate hydrogen sulfide after being marketed, and the content of the hydrogen sulfide serving as a product marketed abroad can be gradually increased and is close to or exceeds 100ppm; while the domestic products of the terminal sterilization process on the market exceed 100ppm, even approach 200ppm.
Hydrogen sulfide is a highly neurotoxic compound, and more than 10ppm in air can be harmful to humans. After entering human body cells from blood, hydrogen sulfide is combined with disulfide bonds in cytochrome oxidase to influence the oxidation process of cytochrome, block intracellular respiration and cause systemic hypoxia, and the central nervous system is most sensitive to hypoxia and is damaged firstly.
According to the specifications of the medicines on the market in China, the usage amount of the acetylcysteine injection is 40ml, and the amount of hydrogen sulfide entering the blood of a human body after each injection is calculated according to 100ppm; the hydrogen sulfide content of products on the market in China exceeds 100ppm, even approaches to 200ppm, so the amount entering the blood of a human body is more than 4 mg. After the research of the market, patients have toxic symptoms of the central system to different degrees after using acetylcysteine injection which is marketed at home (see table 1 for acute toxic symptoms of hydrogen sulfide). The treatment course of the acetylcysteine injection on the market at home is 45 days, the period is longer, the usage is 1 time a day, if the product with more than 100ppm of hydrogen sulfide is used, the hydrogen sulfide can continuously destroy human cytochrome oxidase after the medicine enters the blood of a human body through injection, and the hydrogen sulfide will definitely cause very adverse effects on the health of a patient using the injection, even harms the health of the patient.
In addition, hydrogen sulfide has strong odor of smelly eggs, and can cause discomfort to patients when the hydrogen sulfide is used for stimulating throat or lung and aerosol inhalation administration, and even cause bronchospasm, cough and the like.
TABLE 1 acute poisoning symptoms of hydrogen sulfide
TABLE 2 toxicity of hydrogen sulfide
Disclosure of Invention
The invention aims to solve the technical problem of providing the acetylcysteine medicinal composition with low hydrogen sulfide content and the preparation method thereof, and the acetylcysteine medicinal composition prepared by the invention has good stability and low hydrogen sulfide content; in addition, because the hydrogen sulfide is slightly soluble in water, the carbon dioxide generated by the reaction of the acetylcysteine and the sodium carbonate or the sodium bicarbonate can take away hydrogen sulfide impurities, so the hydrogen sulfide content in the preparation is further reduced, and the medication safety of the product is improved.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows: a pharmaceutical composition containing acetylcysteine with low hydrogen sulfide content comprises acetylcysteine and sodium carbonate and/or sodium bicarbonate.
A preparation method of acetylcysteine pharmaceutical composition with low hydrogen sulfide content comprises the following steps:
(1) Evenly mixing acetylcysteine, sodium carbonate and/or sodium bicarbonate, and controlling the pH value of a product to be within the range of 5.0-8.5 to obtain mixed powder;
(2) And subpackaging the mixed powder into injection glass bottles under the aseptic process condition, pressing plugs and rolling covers to obtain the acetylcysteine pharmaceutical composition with low hydrogen sulfide content.
Alternatively, a method for preparing a pharmaceutical composition of acetylcysteine with low hydrogen sulfide content comprises the following steps:
a. subpackaging the acetylcysteine sterile powder into injection glass bottles under the aseptic process condition, pressing plugs, and rolling caps to obtain an acetylcysteine preparation;
b. dissolving sodium carbonate and/or sodium bicarbonate with water for injection, filtering, bottling, and sterilizing to obtain special solvent containing sodium carbonate and/or sodium bicarbonate;
c. packaging the acetylcysteine preparation 1 bottle together with 1 special solvent.
Preferably, the mass ratio of sodium carbonate to acetylcysteine is 0.1 to 0.5 (w/w).
Preferably, the mass ratio of sodium bicarbonate to acetylcysteine is 0.1 to 0.7 (w/w).
Preferably, step (1) and step b further comprise less than 0.1% w/w of the metal ion chelating agent EDTA or a pharmaceutically acceptable salt thereof, or no metal ion chelating agent EDTA or a pharmaceutically acceptable salt thereof.
Preferably, step (1) and step b further comprise a pH adjuster, or do not comprise a pH adjuster.
The pH regulator is citric acid, sodium citrate, sodium dihydrogen phosphate or disodium hydrogen phosphate.
Specifically, the preparation method of the acetylcysteine pharmaceutical composition with low hydrogen sulfide content comprises the following steps: (1) Evenly mixing acetylcysteine, sodium carbonate and/or sodium bicarbonate, metal ion chelating agent EDTA or medicinal salt thereof and pH regulator, and controlling the pH value of the product to be within the range of 5.0-8.5 to obtain mixed powder (or not containing the metal ion chelating agent EDTA or the medicinal salt thereof and/or the pH regulator); (2) And subpackaging the mixed powder into injection glass bottles under the aseptic process condition, pressing plugs and rolling covers to obtain the acetylcysteine pharmaceutical composition with low hydrogen sulfide content. The application method of the acetylcysteine pharmaceutical composition with low hydrogen sulfide content comprises the following steps: adding the acetylcysteine pharmaceutical composition with low hydrogen sulfide content into sterilized water for injection or 0.9% sodium chloride injection to prepare a solution with the concentration of about 10% w/v, and then atomizing and inhaling the solution for use; or adding sterilized water for injection, 0.9% chlorinated injection, 5% or 10% glucose injection to obtain a solution with a content of about 10% or 20% w/v, further diluting with 0.9% chlorinated injection, 5% or 10% glucose injection, and performing intravenous injection.
Or, in particular, a method for preparing a pharmaceutical composition of acetylcysteine with low hydrogen sulfide content, comprising the steps of: a. subpackaging acetylcysteine sterile powder into injection glass bottles under the aseptic process condition, pressing plugs, and rolling covers to obtain acetylcysteine preparation; b. dissolving sodium carbonate and/or sodium bicarbonate, metal ion chelating agent EDTA or its medicinal salt, and pH regulator with water for injection, filtering, bottling, and sterilizing to obtain special solvent containing sodium carbonate and/or sodium bicarbonate (optionally not containing metal ion chelating agent EDTA or its medicinal salt and/or pH regulator); c. packaging the acetylcysteine preparation 1 bottle together with 1 special solvent. The application method of the acetylcysteine pharmaceutical composition with low hydrogen sulfide content comprises the following steps: dissolving the acetylcysteine preparation in a special solvent to prepare a solution about 10% w/v, and then atomizing and inhaling; or dissolved in a special solvent to prepare a solution of about 10% or 20% w/v, and further diluted with 0.9% chlorinated injection or 5% or 10% glucose injection for intravenous injection.
Adopt the produced beneficial effect of above-mentioned technical scheme to lie in:
(1) The improved dosage form is as follows: the invention improves the injection or solution into sterile subpackaged powder preparation, and the stability of acetylcysteine in a crystallization state is obviously superior to that of the solution state, thereby improving the stability of the product and reducing the generation of toxic degradation impurity hydrogen sulfide.
(2) The improved prescription process comprises the following steps: the invention combines acetylcysteine and sodium carbonate and/or sodium bicarbonate according to a certain prescription proportion, and is dissolved by special solvent, sterilized water for injection or infusion solution before use. Because the hydrogen sulfide is slightly soluble in water, the hydrogen sulfide impurity can be taken away by carbon dioxide generated by the reaction of acetylcysteine and sodium carbonate or sodium bicarbonate, and therefore, the content of the hydrogen sulfide in the preparation is further reduced.
(3) The quality standard is improved: on the basis of the quality standard of 'acetylcysteine injection' of 2020 edition of British pharmacopoeia, the control limit of 'hydrogen sulfide' is revised from 100ppm to 20ppm, which is favorable for improving the medication safety of products.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments.
Example 1
The preparation method of the acetylcysteine pharmaceutical composition with low hydrogen sulfide content comprises the following steps:
a. subpackaging acetylcysteine sterile powder into injection glass bottles under the aseptic process condition, pressing plugs and rolling covers to prepare acetylcysteine preparation; the amount per bottle was 0.3g (calculated as acetylcysteine).
b. Dissolving 12.0kg sodium bicarbonate and 0.20kg anhydrous disodium hydrogen phosphate in water for injection, adding to 200L, filtering, bottling at a volume of 3 ml/bottle, and sterilizing with damp heat at 121 deg.C for 12 min to obtain special solvent.
c. Packaging the acetylcysteine preparation 1 bottle together with 1 special solvent.
The using method comprises the following steps: the acetylcysteine preparation is dissolved by a special solvent to prepare a solution (pH value is about 6.8) of about 10% (w/v), and the solution is atomized and inhaled for use.
Example 2
The preparation method of the acetylcysteine pharmaceutical composition with low hydrogen sulfide content comprises the following steps:
a. subpackaging acetylcysteine sterile powder into injection glass bottles under the aseptic process condition, pressing plugs and rolling covers to prepare acetylcysteine preparation; the amount of each bottle was 5g (in acetylcysteine).
b. Dissolving 10.0kg of sodium bicarbonate and 8.0kg of sodium carbonate with 0.20kg of anhydrous disodium hydrogen phosphate in water for injection, adding the solution to 200L, filtering, filling and sealing according to 25 ml/bottle, and performing damp-heat sterilization at 121 ℃ for 12 minutes to obtain the special solvent.
c. Packaging the acetylcysteine preparation in 1 bottle together with 1 unit of special solvent.
The using method comprises the following steps: the acetylcysteine preparation is dissolved in a special solvent to prepare a solution (pH value is about 6.5) of about 20% (w/v), and the solution is diluted by 250ml of 10% glucose injection and then is subjected to intravenous drip.
Example 3
The preparation method of the acetylcysteine pharmaceutical composition with low hydrogen sulfide content comprises the following steps:
(1) Uniformly mixing 15.00kg of acetylcysteine sterile powder and 4.90kg of sodium carbonate sterile powder, wherein the pH value of the product is 7.0, and obtaining mixed powder; the mass ratio of sodium carbonate to acetylcysteine was about 0.327 (w/w).
(2) And subpackaging the mixed powder into injection glass bottles under the aseptic process condition, pressing plugs, and rolling caps to obtain the acetylcysteine pharmaceutical composition with low hydrogen sulfide content, wherein the packaging amount of each bottle is 0.3g (calculated by acetylcysteine).
The using method comprises the following steps: the acetylcysteine pharmaceutical composition with low hydrogen sulfide content is added into 3ml of sterilized water for injection to prepare about 10% (w/v) solution for atomization and inhalation.
Example 4
The preparation method of the acetylcysteine pharmaceutical composition with low hydrogen sulfide content comprises the following steps:
(1) Uniformly mixing 30.00kg of acetylcysteine sterile powder and 9.75kg of sodium carbonate sterile powder, wherein the pH value of the product is 6.4, and obtaining mixed powder; the mass ratio of sodium carbonate to acetylcysteine was about 0.325 (w/w).
(2) And subpackaging the mixed powder into injection glass bottles under the aseptic process condition, pressing plugs and capping to obtain the acetylcysteine pharmaceutical composition with low hydrogen sulfide content, wherein the packaging amount of each bottle is 8g (counted by acetylcysteine).
The using method comprises the following steps: the acetylcysteine pharmaceutical composition with low hydrogen sulfide content is dissolved in 40ml of sterilized water for injection, and then diluted with 250ml of 10% glucose injection for intravenous drip.
Examples of the experiments
The stability of the acetylcysteine pharmaceutical composition of the present invention and other commercially available acetylcysteine pharmaceutical compositions were investigated, and the results are shown in table 3.
TABLE 3 influence factor test (60 ℃) data of acetylcysteine pharmaceutical compositions
As can be seen from Table 3, the hydrogen sulfide content of the product produced by the method for preparing the acetylcysteine pharmaceutical composition with low hydrogen sulfide content is significantly lower than that of the commercial product, and the satisfactory effect is achieved.
Claims (8)
1. A pharmaceutical composition of acetylcysteine with low hydrogen sulfide content, comprising a combination of acetylcysteine and sodium carbonate and/or sodium bicarbonate.
2. A process for the preparation of a low hydrogen sulfide content acetylcysteine pharmaceutical composition as claimed in claim 1, comprising the steps of:
(1) Evenly mixing acetylcysteine, sodium carbonate and/or sodium bicarbonate, and controlling the pH value of a product to be within the range of 5.0-8.5 to obtain mixed powder;
(2) And subpackaging the mixed powder into injection glass bottles under the aseptic process condition, pressing plugs and rolling covers to obtain the acetylcysteine pharmaceutical composition with low hydrogen sulfide content.
3. A process for the preparation of a low hydrogen sulfide content acetylcysteine pharmaceutical composition as claimed in claim 1, comprising the steps of:
a. subpackaging the acetylcysteine sterile powder into injection glass bottles under the aseptic process condition, pressing plugs, and rolling caps to obtain an acetylcysteine preparation;
b. dissolving sodium carbonate and/or sodium bicarbonate with water for injection, filtering, bottling, and sterilizing to obtain special solvent containing sodium carbonate and/or sodium bicarbonate;
c. packaging the acetylcysteine preparation 1 bottle together with 1 special solvent.
4. The method for preparing acetylcysteine pharmaceutical composition with low hydrogen sulfide content according to claim 2 or 3, wherein: the mass ratio of the sodium carbonate to the acetylcysteine is 0.1-0.5 (w/w).
5. The method for preparing a low-sulfureted hydrogen content acetylcysteine pharmaceutical composition according to claim 2 or 3, characterized in that: the mass ratio of the sodium bicarbonate to the acetylcysteine is 0.1-0.7 (w/w).
6. The method for preparing acetylcysteine pharmaceutical composition with low hydrogen sulfide content according to claim 2 or 3, wherein: in step (1) and step b, further comprising less than 0.1% w/w of the metal ion chelating agent EDTA or a pharmaceutically acceptable salt thereof, or no metal ion chelating agent EDTA or a pharmaceutically acceptable salt thereof.
7. The method for preparing a low-sulfureted hydrogen content acetylcysteine pharmaceutical composition according to claim 2 or 3, characterized in that: in the step (1) and the step b, a pH regulator is also contained or not contained.
8. The method for preparing acetylcysteine pharmaceutical composition with low hydrogen sulfide content as claimed in claim 7, wherein: the pH regulator is citric acid, sodium citrate, sodium dihydrogen phosphate or disodium hydrogen phosphate.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202210935146.XA CN115154416A (en) | 2022-08-05 | 2022-08-05 | Acetylcysteine pharmaceutical composition with low hydrogen sulfide content and preparation method thereof |
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| CN202210935146.XA CN115154416A (en) | 2022-08-05 | 2022-08-05 | Acetylcysteine pharmaceutical composition with low hydrogen sulfide content and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1799537A (en) * | 2005-11-08 | 2006-07-12 | 姜建国 | Preparation method and clinical application of acetylcysteine powdered injection and acetylcysteine infusion |
| CN101028252A (en) * | 2007-02-15 | 2007-09-05 | 何晶 | Injection acetylcysteine powdery medicinal composition and its making method |
| CN101054356A (en) * | 2006-04-13 | 2007-10-17 | 邵长青 | Sodium acetylcysteine for removing phlegm and curing hepatopathy and preparation method thereof |
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2022
- 2022-08-05 CN CN202210935146.XA patent/CN115154416A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1799537A (en) * | 2005-11-08 | 2006-07-12 | 姜建国 | Preparation method and clinical application of acetylcysteine powdered injection and acetylcysteine infusion |
| CN101054356A (en) * | 2006-04-13 | 2007-10-17 | 邵长青 | Sodium acetylcysteine for removing phlegm and curing hepatopathy and preparation method thereof |
| CN101028252A (en) * | 2007-02-15 | 2007-09-05 | 何晶 | Injection acetylcysteine powdery medicinal composition and its making method |
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