CN115040475A - N-acetylcysteine oral solution - Google Patents
N-acetylcysteine oral solution Download PDFInfo
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- CN115040475A CN115040475A CN202210719551.8A CN202210719551A CN115040475A CN 115040475 A CN115040475 A CN 115040475A CN 202210719551 A CN202210719551 A CN 202210719551A CN 115040475 A CN115040475 A CN 115040475A
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- Prior art keywords
- acetylcysteine
- parts
- agent
- oral solution
- sodium
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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 46
- 229960004308 acetylcysteine Drugs 0.000 title claims abstract description 46
- 229940100688 oral solution Drugs 0.000 title claims abstract description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000002360 preparation method Methods 0.000 claims abstract description 21
- 239000011261 inert gas Substances 0.000 claims abstract description 14
- 239000000126 substance Substances 0.000 claims abstract description 10
- 239000000796 flavoring agent Substances 0.000 claims abstract description 9
- 239000007788 liquid Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 239000000022 bacteriostatic agent Substances 0.000 claims abstract description 7
- 239000002738 chelating agent Substances 0.000 claims abstract description 7
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 7
- 235000003599 food sweetener Nutrition 0.000 claims abstract description 7
- 239000003765 sweetening agent Substances 0.000 claims abstract description 7
- 239000002562 thickening agent Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 88
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 14
- 229910052786 argon Inorganic materials 0.000 claims description 10
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 7
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 7
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 7
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 6
- 235000010234 sodium benzoate Nutrition 0.000 claims description 6
- 239000004299 sodium benzoate Substances 0.000 claims description 6
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 5
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 5
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 5
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 5
- 235000011034 Rubus glaucus Nutrition 0.000 claims description 5
- 244000235659 Rubus idaeus Species 0.000 claims description 5
- 235000009122 Rubus idaeus Nutrition 0.000 claims description 5
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 5
- 239000008215 water for injection Substances 0.000 claims description 5
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 4
- 239000008213 purified water Substances 0.000 claims description 4
- 229940085605 saccharin sodium Drugs 0.000 claims description 4
- QYNMSPKSYXPZHG-UHFFFAOYSA-M sodium;4-ethoxycarbonylphenolate Chemical compound [Na+].CCOC(=O)C1=CC=C([O-])C=C1 QYNMSPKSYXPZHG-UHFFFAOYSA-M 0.000 claims description 4
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 3
- 240000009088 Fragaria x ananassa Species 0.000 claims description 3
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 3
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 3
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 3
- PESXGULMKCKJCC-UHFFFAOYSA-M sodium;4-methoxycarbonylphenolate Chemical compound [Na+].COC(=O)C1=CC=C([O-])C=C1 PESXGULMKCKJCC-UHFFFAOYSA-M 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 claims description 2
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 235000019634 flavors Nutrition 0.000 claims 2
- 229940109275 cyclamate Drugs 0.000 claims 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims 1
- 239000007968 orange flavor Substances 0.000 claims 1
- 238000011049 filling Methods 0.000 abstract description 16
- 238000007789 sealing Methods 0.000 abstract description 12
- 238000001816 cooling Methods 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 7
- 238000010438 heat treatment Methods 0.000 abstract description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 4
- 239000001301 oxygen Substances 0.000 abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000002156 mixing Methods 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 25
- 238000004806 packaging method and process Methods 0.000 description 11
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 239000011521 glass Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 206010011224 Cough Diseases 0.000 description 6
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 6
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229920000728 polyester Polymers 0.000 description 6
- 229960001462 sodium cyclamate Drugs 0.000 description 6
- 230000001954 sterilising effect Effects 0.000 description 6
- 206010062717 Increased upper airway secretion Diseases 0.000 description 5
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 5
- 229910052782 aluminium Inorganic materials 0.000 description 5
- 239000003963 antioxidant agent Substances 0.000 description 5
- 230000003078 antioxidant effect Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000011888 foil Substances 0.000 description 5
- 229960003180 glutathione Drugs 0.000 description 5
- 208000026435 phlegm Diseases 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 4
- 230000007794 irritation Effects 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- VEUACKUBDLVUAC-UHFFFAOYSA-N [Na].[Ca] Chemical compound [Na].[Ca] VEUACKUBDLVUAC-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940124274 edetate disodium Drugs 0.000 description 2
- 229960001484 edetic acid Drugs 0.000 description 2
- 239000003172 expectorant agent Substances 0.000 description 2
- 230000003419 expectorant effect Effects 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 210000003456 pulmonary alveoli Anatomy 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
- 229940122858 Elastase inhibitor Drugs 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- -1 Hydroxy phenyl methyl Chemical group 0.000 description 1
- URNSECGXFRDEDC-UHFFFAOYSA-N N-acetyl-1,4-benzoquinone imine Chemical compound CC(=O)N=C1C=CC(=O)C=C1 URNSECGXFRDEDC-UHFFFAOYSA-N 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010044302 Tracheitis Diseases 0.000 description 1
- 241000289690 Xenarthra Species 0.000 description 1
- RXDLGFMMQFNVLI-UHFFFAOYSA-N [Na].[Na].[Ca] Chemical compound [Na].[Na].[Ca] RXDLGFMMQFNVLI-UHFFFAOYSA-N 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110515 cough out Drugs 0.000 description 1
- 150000001944 cysteine derivatives Chemical class 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000003602 elastase inhibitor Substances 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 229940066493 expectorants Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000003453 lung abscess Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000010268 sodium methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
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
- A61K31/195—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/12—Mucolytics
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to the technical field of medicines, in particular to an N-acetylcysteine oral solution which comprises the following raw materials in parts by weight: 100 parts of acetylcysteine, 0-30 parts of thickening agent, 0-30 parts of pH regulator, 0-10 parts of chelating agent, 0-15 parts of bacteriostatic agent, 0-5 parts of sweetening agent, 0-20 parts of flavoring agent and the balance of solvent; the content of the product is 95-105%, the pH value is 5.5-7.0, and the content of related substances is not more than 5%. The preparation process comprises inert gas protection, and specifically comprises the following steps: introducing inert gas into the container, and adding a proper amount of non-oxygen water; adding thickener, heating to 60-80 deg.C, dissolving, and mixing; cooling to 25-40 ℃, sequentially adding a pH regulator, a chelating agent, a bacteriostatic agent and acetylcysteine, fully dissolving, regulating the pH value to 5.5-7.0, adding a sweetening agent and a flavoring agent, fully dissolving, adding oxygen-free water to full dose, filling under the protection of inert gas, and sealing bottles. The invention is a liquid medicament, is more beneficial to the absorption of human body and enhances the curative effect.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to an N-acetylcysteine oral solution.
Background
Harmful gas seriously threatens the respiratory tract health of people, and can also induce the attack and development of other potential diseases, such as pneumonia, chronic pharyngitis, chronic bronchitis, lung abscess and the like, at the moment, besides the symptomatic treatment of respiratory diseases, antitussive and expectorant also needs to be properly applied to relieve cough.
The cough-relieving medicine is only used for relieving symptoms at present, and the most basic cough-relieving medicine is to treat the cough caused by the cough. Most of the cough is caused by excessive release of inflammatory mediators such as tracheitis, asthma, pneumonia, lung tumor, etc., so expectorants should be used properly for the condition of the disease.
Acetylcysteine is a cysteine derivative, belongs to a phlegm dissolving medicine, and is mainly used for breaking a disulfide bond (-S-S) of acidic glycoprotein polypeptide in phlegm through sulfydryl in molecules, so that the viscosity of the phlegm is reduced, and the phlegm is easy to cough out.
Acetylcysteine is an antioxidant, has a strong effect of scavenging free radicals, effectively protects al-antitrypsin (an elastase inhibitor) from oxidative inactivation by hypochlorous acid induced by smoke and dust, prevents lung elastin and neutrophils from being damaged, and can increase pulmonary alveoli epithelium II type cells to secrete surfactant, thereby increasing pulmonary alveoli elasticity, and thus has a definite therapeutic effect on emphysema.
Acetylcysteine is a process for reducing GSH, which plays an important role in maintaining the proper level of Glutathione (GSH) in cells, and GSH is necessary for maintaining the integrity of cell functions and cell morphology, and can prevent cells from being damaged by oxygen free radicals and various cytotoxins in vitro and in vivo, so acetylcysteine has a strong detoxifying effect. Can promote the regeneration of exhausted reducing GSH in cells of a patient, or can be used as a substrate to be directly combined with a metabolite N-acetyl-p-benzoquinone imine of acetaminophen to eliminate the toxicity of toxic metabolite products on liver cells, thereby protecting the functions of the liver cells.
The acetylcysteine preparation is widely applied clinically, and the dosage forms of the acetylcysteine preparation on the market at home and abroad at present mainly comprise tablets, granules, powder injection, inhalants and the like, and are mainly used for eliminating phlegm. The acidic aqueous solution of the product is unstable at room temperature, can be decomposed after being placed for a long time, has large irritation to human body and bad oral taste, and thus, the acetamide cystine oral solution is not seen on the market in China.
Disclosure of Invention
The invention aims to provide an N-acetylcysteine oral solution for solving the defects that an acidic acetylcysteine solution has high irritation, a neutral acetylcysteine solution is unstable and difficult to clinically apply and cannot be injected for administration in the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
designing an N-acetylcysteine oral solution, which comprises the following raw materials in parts by weight:
100 parts of acetylcysteine, 0-30 parts of thickening agent, 0-30 parts of pH regulator, 0-10 parts of chelating agent, 0-15 parts of bacteriostatic agent, 0-5 parts of sweetening agent, 0-20 parts of flavoring agent and the balance of solvent; the content of the product is 95-105%, the pH value is 5.5-7.0, and the content of related substances is not more than 5%.
Further preferably, the solvent is oxygen-free water, and the source of the oxygen-free water is purified water subjected to non-oxidation treatment by a physical means or water for injection.
Further preferably, the thickener is one or more of hydroxyethyl cellulose and sodium carboxymethyl cellulose.
More preferably, the chelating agent is one or more of calcium disodium edetate and disodium edetate.
Further preferably, the bacteriostatic agent is one or more of methyl hydroxybenzoate, ethyl hydroxybenzoate, sodium methyl hydroxybenzoate, sodium ethyl hydroxybenzoate, benzoic acid and sodium benzoate.
Further preferably, the sweetener is one or more of saccharin sodium and sodium cyclamate.
Further preferably, the flavoring agent is one or more of orange essence, raspberry essence and strawberry essence.
Further preferably, the pH regulator is one or more of sodium hydroxide and potassium hydroxide.
The steps for preparing the acetylcysteine oral solution are as follows:
introducing inert gas into a preparation container, weighing a proper amount of non-oxygen water according to the dosage, adding a specified amount of thickening agent, heating to dissolve and uniformly mix, cooling to 25-40 ℃, adding a specified amount of solid pH regulator, chelating agent, bacteriostatic agent and acetylcysteine, dissolving and uniformly mixing, adjusting the pH value to 5.5-7.0 by using a liquid pH regulator, adding a specified amount of sweetening agent and flavoring agent, adding the non-oxygen water to the full amount, filtering and sterilizing under the protection of the inert gas, filling, bottle sealing, leak detecting, packaging and warehousing the finished product under the protection of the inert gas.
Further preferably, an inert gas is used for protection during the preparation process, specifically one or more of nitrogen and argon.
Further preferably, the pH adjusting agent adjusts the pH of the solution in a solid state or a liquid state according to different preparation methods, wherein the concentration of the pH adjusting agent is one or more of 1%, 2.5%, 5%, 10% and 20% when the liquid state is adopted.
The inert gas protection technology used by the invention runs through the whole process of preparing and feeding the oral solution, filling, sealing the bottle and the like, inert gas is used for protection in the whole process, and before the oxygen-free water is fed, the inert gas is used for driving away the air in the preparation container.
The inert gas protection technology used in the invention refers to inert gas protection in the preparation process of the preparation, and the preparation container needs to be communicated with inert gas for a proper time before oxygen-free water is fed, so as to drive away the air in the container, and then the subsequent steps are executed.
The N-acetylcysteine oral solution provided by the invention has the beneficial effects that: the N-acetylcysteine oral solution adopts special antioxidant and antioxidant technology, and is added with pH regulator, so that the acetylcysteine oral solution is stable, has a pH value close to neutral, has no irritation to human body, and is suitable for oral administration; the invention is a liquid medicament, is more beneficial to the absorption of human body and enhances the curative effect.
Drawings
FIG. 1 is a schematic diagram showing the influence of nitrogen protection of an N-acetylcysteine oral solution on substances related to an acetylcysteine solution according to the present invention.
FIG. 2 is a schematic diagram showing the effect of a coating material-solvent of an N-acetylcysteine oral solution on substances related to an acetylcysteine solution according to the present invention.
FIG. 3 is a flow chart of an N-acetylcysteine oral solution according to the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.
Referring to fig. 1 to 3, the method for preparing oxygen-free water according to the present invention: proper amount of purified water, boiling for 30min, introducing nitrogen, and cooling.
The liquid preparation stirrer comprises: a desk type stirrer with the brand of IKA and the model of EUROSTAR and the equipment parameter of 300-.
Example 1
Table 1: example 1 prescription Table
| Prescription | Mass g |
| Hydroxyethyl cellulose | 800 |
| Sodium hydroxide | 2000 |
| Edetic acid calcium sodium salt | 420 |
| Sodium ethylparaben | 500 |
| Benzoic acid | 700 |
| Sodium cyclamate | 100 |
| Acetylcysteine | 10000 |
| pH regulator | 5.5 |
| Orange essence | 1000 |
| Quantification of | 500L |
The preparation method comprises the following steps:
1. introducing nitrogen into a container, adding a proper amount of oxygen-free water, adding hydroxyethyl cellulose according to the prescription amount while stirring, and heating to 60-80 ℃;
2. under the protection of nitrogen, cooling to 40 ℃, adding the sodium hydroxide with the formula amount, and stirring for dissolving;
3. under the protection of nitrogen, adding the calcium disodium edentate, the sodium ethylparaben and the benzoic acid in the prescribed amount, stirring and dissolving;
4. adding acetylcysteine according to the prescription amount under the protection of nitrogen, stirring for dissolving, and adjusting the pH value to 5.5 by using a pH regulator (1% sodium hydroxide solution);
5. under the protection of nitrogen, adding the sodium cyclamate and the orange essence in the formula amount, and stirring for dissolving;
6. under the protection of nitrogen, the oxygen-free water is fixed to the full volume and is uniformly mixed;
7. filtering, sterilizing, and aseptically packaging under nitrogen protection;
8. filling: respectively filling polyester bottles and glass bottles under the protection of nitrogen;
9. sealing the bottle: heat sealing the cover containing the aluminum foil gasket;
10. and (6) detecting leakage, packaging and warehousing finished products.
Example 2
Table 2: example 2 prescription Table
The preparation method comprises the following steps:
1. introducing argon into a container, adding a proper amount of oxygen-free water, adding sodium carboxymethylcellulose according to the prescription amount while stirring, and heating to 60-80 ℃;
2. under the protection of argon, cooling to 30 ℃, adding potassium hydroxide according to the prescription amount, and stirring for dissolving;
3. under the protection of argon, adding the calcium disodium edetate and sodium methylparaben in the prescribed amount, stirring and dissolving;
4. adding acetylcysteine according to the prescription amount under the protection of argon, stirring and dissolving, and adjusting the pH value to 6.4 by using a pH regulator (2.5% potassium hydroxide solution);
5. under the protection of argon, adding the prescribed amount of sodium cyclamate and strawberry essence, stirring and dissolving;
6. under the protection of argon, the oxygen-free water is fixed to the full volume and is uniformly mixed;
7. filtering, sterilizing, and aseptically packaging under the protection of argon;
8. filling: respectively filling polyester bottles and glass bottles under the protection of argon;
9. heat sealing the cover containing the aluminum foil gasket;
10. and (6) detecting leakage, packaging and warehousing finished products.
Example 3
Table 3: example 3 prescription Table
The preparation method comprises the following steps:
1. introducing nitrogen into a container, adding a proper amount of oxygen-free water, adding hydroxyethyl cellulose according to the prescription amount while stirring, and heating to 60-80 ℃;
2. adding a proper amount of cooled oxygen-free water under the protection of nitrogen, cooling to 35 ℃, adding a prescribed amount of sodium hydroxide, and stirring for dissolving;
3. under the protection of nitrogen, adding ethylparaben and disodium edetate according to the prescription amount, stirring and dissolving;
4. adding acetylcysteine according to the prescription amount under the protection of nitrogen, stirring for dissolving, and adjusting the pH value to 7.0 by using a pH regulator (10% potassium hydroxide solution);
5. under the protection of nitrogen, adding the saccharin sodium and the raspberry essence according to the prescription amount, stirring and dissolving;
6. under the protection of nitrogen, the oxygen-free water is fixed to the full volume and is uniformly mixed;
7. filtering, sterilizing, and aseptically packaging under nitrogen protection;
8. filling: respectively filling polyester bottles and glass bottles under the protection of nitrogen;
9. sealing the bottle: heat sealing the cover containing the aluminum foil gasket;
10. and (6) detecting leakage, packaging and warehousing finished products.
Example 4
Table 4: example 4 prescription Table
| Prescription | Mass g |
| Sodium carboxymethylcellulose | 1600 |
| Potassium hydroxide | 2400 |
| Edetic acid calcium sodium salt | 420 |
| Sodium benzoate | 1500 |
| Sodium cyclamate | 200 |
| Acetylcysteine | 10000 |
| pH regulator | 6.7 |
| Orange essence | 1000 |
| Quantification of | 500L |
The preparation method comprises the following steps:
1. introducing nitrogen into a container, adding a proper amount of water for injection, adding the sodium carboxymethylcellulose according to the prescription amount while stirring, and heating to 60-80 ℃;
2. under the protection of nitrogen, cooling to 30 ℃, adding the sodium hydroxide with the prescription amount, and stirring for dissolving;
3. under the protection of nitrogen, adding the calcium disodium edetate and the sodium benzoate according to the prescription amount, stirring and dissolving;
4. adding acetylcysteine according to the prescription amount under the protection of nitrogen, stirring for dissolving, and adjusting the pH value to 6.7 by using a pH regulator (10% sodium hydroxide solution);
5. under the protection of nitrogen, adding the sodium cyclamate and the orange essence in the formula amount, and stirring for dissolving;
6. under the protection of nitrogen, the water for injection is fixed to the full volume and is mixed evenly;
7. filtering, sterilizing, and aseptically packaging under nitrogen protection;
8. filling: respectively filling polyester bottles and glass bottles under the protection of nitrogen;
9. sealing the bottle: heat sealing the cover containing the aluminum foil gasket;
10. and (6) detecting leakage, packaging and warehousing finished products.
Example 5
Table 5: example 5 prescription Table
| Prescription | Mass g |
| Sodium carboxymethylcellulose | 1600 |
| Sodium hydroxide | 2300 |
| Hydroxy phenyl methyl ester | 500 |
| Edetate disodium | 420 |
| Sodium benzoate | 750 |
| Saccharin sodium salt | 190 |
| Acetylcysteine | 10000 |
| pH adjustment | 6.5 |
| Raspberry essence | 1000 |
| Quantification of | 500L |
The preparation method comprises the following steps:
1. introducing nitrogen into a container, adding a proper amount of oxygen-free water, adding sodium carboxymethylcellulose according to the prescription amount while stirring, and heating to 60-80 ℃;
2. adding a proper amount of cooled oxygen-free water under the protection of nitrogen, cooling to 40 ℃, adding a prescribed amount of sodium hydroxide, and stirring for dissolving;
3. under the protection of nitrogen, adding the prescribed amount of methylparaben, edetate disodium and sodium benzoate, stirring and dissolving;
4. adding acetylcysteine according to the prescription amount under the protection of nitrogen, stirring for dissolving, and adjusting the pH value to 6.3 by using a pH regulator (2.5% sodium hydroxide solution);
5. sequentially adding saccharin sodium and raspberry essence according to the prescription amount under the protection of nitrogen, stirring and dissolving;
6. under the protection of nitrogen, the oxygen-free water is fixed to the full volume and is uniformly mixed;
7. filtering, sterilizing, and aseptically packaging under nitrogen protection;
8. filling: respectively filling polyester bottles and glass bottles under the protection of nitrogen;
9. sealing the bottle: heat sealing the cover containing the aluminum foil gasket;
10. and (6) detecting leakage, packaging and warehousing finished products.
According to the process, researches are carried out on the conditions of no nitrogen protection, only nitrogen filling protection and whole nitrogen protection, and the influence of the nitrogen protection on related substances is inspected.
After the preparation is subjected to high-temperature treatment for 30 days, the amount of related substances is detected, and the results are as follows:
1. during the preparation process of the preparation, nitrogen protection is adopted in the whole process, and nitrogen protection is adopted only for filling, so that the related quality can be controlled within 5 percent, wherein the nitrogen protection in the whole process is optimal, and the nitrogen protection only for filling is suboptimal, and the detailed formula is shown in figure 1.
2. The solvent adopts water for injection, the packing material adopts polyester bottles, the glass bottles and the glass bottles can control related substances within 5 percent, and the related substances are respectively optimal and suboptimal; the solvent is oxygen-free water (purified water boiled for 30min), the packing material is glass bottle, and related substances can be controlled within 5%, such as second best, as shown in figure 2.
By adopting the technical scheme, the invention has the following effects: by adopting special antioxidant and antioxidant technology and adding pH regulator, the acetylcysteine oral solution is stable, has pH value close to neutral, has no irritation to human body, and can be orally taken; the invention is a liquid medicament, is more beneficial to the absorption of human body and enhances the curative effect.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (10)
1. The N-acetylcysteine oral solution is characterized by comprising the following raw materials in parts by weight:
100 parts of acetylcysteine, 0-30 parts of thickening agent, 0-30 parts of pH regulator, 0-10 parts of chelating agent, 0-15 parts of bacteriostatic agent, 0-5 parts of sweetening agent, 0-20 parts of flavoring agent and the balance of solvent; the content of the product is 95-105%, the pH value is 5.5-7.0, and the content of related substances is not more than 5%.
2. The N-acetylcysteine oral solution according to claim 1, wherein the inert gas is used for protection during the preparation process, in particular one or more of nitrogen and argon.
3. The N-acetylcysteine oral solution according to claim 1, wherein the solvent is oxygen-free water, and the source thereof is purified water without oxidation treatment by physical means or water for injection.
4. The N-acetylcysteine oral solution as claimed in claim 2, wherein said thickening agent is one or more of hydroxyethyl cellulose and sodium carboxymethyl cellulose.
5. The N-acetylcysteine oral solution according to claim 1, wherein the chelating agent is one or more of calcium disodium edetate and disodium edetate.
6. The oral solution of claim 1, wherein the bacteriostatic agent is one or more selected from methyl hydroxybenzoate, ethyl hydroxybenzoate, sodium methyl hydroxybenzoate, sodium ethyl hydroxybenzoate, benzoic acid, and sodium benzoate.
7. The N-acetylcysteine oral solution of claim 1, wherein the sweetener is one or more of saccharin sodium and cyclamate.
8. The N-acetylcysteine oral solution of claim 1, wherein the flavoring agent is one or more of orange flavor, raspberry flavor, and strawberry flavor.
9. The N-acetylcysteine oral solution according to claim 1, wherein the pH regulator is one or more of sodium hydroxide and potassium hydroxide.
10. The N-acetylcysteine oral solution according to claim 1, wherein the pH regulator is used for adjusting the pH value, depending on the preparation method, in a solid state or a liquid state, wherein the concentration is one or more of 1%, 2.5%, 5%, 10%, and 20% when the liquid state is used.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1711998A (en) * | 2005-03-30 | 2005-12-28 | 杭州华科生物医药技术有限公司 | Multi-dimensional acetylcysteine solution with stabilized pH near to neutrality and production thereof |
| CN102266316A (en) * | 2005-08-24 | 2011-12-07 | 坎伯兰医药品股份有限公司 | Acetylcysteine composition and uses therefor |
| CN103038356A (en) * | 2010-07-21 | 2013-04-10 | 坎伯兰医药品股份有限公司 | Acetycysteine compositions and methods of use thereof |
| CN109875959A (en) * | 2018-12-17 | 2019-06-14 | 武汉兴华智慧医药科技有限公司 | A kind of sucking acetylcysteine solution and preparation method thereof |
| CN110719773A (en) * | 2017-04-20 | 2020-01-21 | 海罗利斯发展公司 | Process for preparing a composition having a low dissolved oxygen content comprising paracetamol and optionally one or more NSAIDs and the composition obtained thereby |
-
2022
- 2022-06-23 CN CN202210719551.8A patent/CN115040475A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1711998A (en) * | 2005-03-30 | 2005-12-28 | 杭州华科生物医药技术有限公司 | Multi-dimensional acetylcysteine solution with stabilized pH near to neutrality and production thereof |
| CN102266316A (en) * | 2005-08-24 | 2011-12-07 | 坎伯兰医药品股份有限公司 | Acetylcysteine composition and uses therefor |
| CN103038356A (en) * | 2010-07-21 | 2013-04-10 | 坎伯兰医药品股份有限公司 | Acetycysteine compositions and methods of use thereof |
| CN110719773A (en) * | 2017-04-20 | 2020-01-21 | 海罗利斯发展公司 | Process for preparing a composition having a low dissolved oxygen content comprising paracetamol and optionally one or more NSAIDs and the composition obtained thereby |
| CN109875959A (en) * | 2018-12-17 | 2019-06-14 | 武汉兴华智慧医药科技有限公司 | A kind of sucking acetylcysteine solution and preparation method thereof |
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Application publication date: 20220913 |