CN102716076A - Ambroxol hydrochloride medicine combination for injection - Google Patents
Ambroxol hydrochloride medicine combination for injection Download PDFInfo
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- CN102716076A CN102716076A CN2012102319050A CN201210231905A CN102716076A CN 102716076 A CN102716076 A CN 102716076A CN 2012102319050 A CN2012102319050 A CN 2012102319050A CN 201210231905 A CN201210231905 A CN 201210231905A CN 102716076 A CN102716076 A CN 102716076A
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- Prior art keywords
- ambroxol hydrochloride
- injection
- acetic acid
- glacial acetic
- water
- Prior art date
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- QNVKOSLOVOTXKF-UHFFFAOYSA-N 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1=C(Br)C=C(Br)C=C1CNC1CCC(O)CC1 QNVKOSLOVOTXKF-UHFFFAOYSA-N 0.000 title claims abstract description 138
- 229960000985 ambroxol hydrochloride Drugs 0.000 title claims abstract description 136
- 238000002347 injection Methods 0.000 title claims abstract description 53
- 239000007924 injection Substances 0.000 title claims abstract description 53
- 239000003814 drug Substances 0.000 title abstract description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 68
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 46
- 230000001954 sterilising effect Effects 0.000 claims abstract description 40
- 239000008215 water for injection Substances 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 38
- 239000000243 solution Substances 0.000 claims abstract description 37
- 239000011780 sodium chloride Substances 0.000 claims abstract description 34
- 238000003756 stirring Methods 0.000 claims abstract description 31
- 229960000583 acetic acid Drugs 0.000 claims abstract description 29
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 29
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims abstract description 28
- 239000001632 sodium acetate Substances 0.000 claims abstract description 28
- 235000017281 sodium acetate Nutrition 0.000 claims abstract description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000007689 inspection Methods 0.000 claims abstract description 11
- 238000001914 filtration Methods 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 31
- 238000002360 preparation method Methods 0.000 claims description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 239000003610 charcoal Substances 0.000 claims description 21
- 229940105082 medicinal charcoal Drugs 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 19
- 238000004659 sterilization and disinfection Methods 0.000 claims description 18
- 239000000890 drug combination Substances 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 238000002156 mixing Methods 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 229960004249 sodium acetate Drugs 0.000 abstract 1
- 229960002668 sodium chloride Drugs 0.000 abstract 1
- 238000000967 suction filtration Methods 0.000 abstract 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
- 238000012360 testing method Methods 0.000 description 23
- 206010011224 Cough Diseases 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000003172 expectorant agent Substances 0.000 description 10
- 230000003419 expectorant effect Effects 0.000 description 10
- 206010036790 Productive cough Diseases 0.000 description 9
- 239000013618 particulate matter Substances 0.000 description 9
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 8
- 229910000397 disodium phosphate Inorganic materials 0.000 description 8
- 235000019800 disodium phosphate Nutrition 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 210000002345 respiratory system Anatomy 0.000 description 7
- 208000024794 sputum Diseases 0.000 description 7
- 210000003802 sputum Anatomy 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 229960005174 ambroxol Drugs 0.000 description 6
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000001179 sorption measurement Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
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- 150000003839 salts Chemical class 0.000 description 4
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- 206010018910 Haemolysis Diseases 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- 230000003139 buffering effect Effects 0.000 description 3
- 210000002175 goblet cell Anatomy 0.000 description 3
- 230000008588 hemolysis Effects 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
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- 239000003381 stabilizer Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 206010006458 Bronchitis chronic Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000003322 Coinfection Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010062717 Increased upper airway secretion Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000000621 bronchi Anatomy 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
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- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000007451 chronic bronchitis Diseases 0.000 description 2
- 210000004081 cilia Anatomy 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 208000026435 phlegm Diseases 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 230000009325 pulmonary function Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 210000001533 respiratory mucosa Anatomy 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- -1 2-amino 3,5-dibromo-benzyl Chemical group 0.000 description 1
- JBDGDEWWOUBZPM-UHFFFAOYSA-N 4-[(2-amino-3,5-dibromophenyl)methylamino]-1-cyclohexanol Chemical compound NC1=C(Br)C=C(Br)C=C1CNC1CCC(O)CC1 JBDGDEWWOUBZPM-UHFFFAOYSA-N 0.000 description 1
- 201000006306 Cor pulmonale Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 208000007123 Pulmonary Atelectasis Diseases 0.000 description 1
- 208000004186 Pulmonary Heart Disease Diseases 0.000 description 1
- 208000018569 Respiratory Tract disease Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 206010053692 Wound complication Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000005091 airway smooth muscle Anatomy 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 210000003123 bronchiole Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 210000000254 ciliated cell Anatomy 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- CBMPTFJVXNIWHP-UHFFFAOYSA-L disodium;hydrogen phosphate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].OP([O-])([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CBMPTFJVXNIWHP-UHFFFAOYSA-L 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
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- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses an ambroxol hydrochloride medicine combination for injection. The ambroxol hydrochloride injection is composed of ambroxol hydrochloride, sodium chloride, glacial acetic acid and sodium acetate, wherein each ambroxol hydrochloride injection is composed of 15-30mg of ambroxol hydrochloride, 18-36mg of sodium chloride, 10-20mg of glacial acetic acid and 2.52-5.1g of sodium acetate. The preparing method includes: taking 90% of water for injection as the prescription amount; adding the glacial acetic acid and the sodium acetate as the prescription amount for stirring to dissolve the glacial acetic acid and the sodium acetate at the temperature of 55-65 DEG C; adding the ambroxol hydrochloride as the prescription amount, stirring to dissolve the ambroxol hydrochloride, adding the sodium chloride as the prescription amount in the solution, and stirring to totally dissolve the sodium chloride; measuring the initial pH value, regulating the pH value to be within the range of 3.5-4.5 with 10% glacial acetic acid solution; adding 0.05% of medical carbon in the solution, stirring and standing for 30 minutes; performing suction filtration, replenishing injection water to full amount, and evenly mixing; performing fine filtering; filling; sterilizing for 15 minutes under hot pressure at the temperature of 121 DEG C; performing lamp inspection; warehousing; and obtaining the ambroxol hydrochloride injection. The ambroxol hydrochloride medicine combination is good in photo-stability and stability, improves product yield, reduces cost, achieves industrialization, can be better applied to clinical medicine and has obvious advantages.
Description
Technical field
The present invention relates to the medicine in the field of medicaments, especially relate to a kind of stablely, can not produce particulate matter, ambroxol hydrochloride pharmaceutical composition of the injection of good stability and preparation method thereof light.
Background technology
Ambroxol hydrochloride is a kind of glutinous expectorant lytic agent, has another name called the hydrochloric acid NA-872, expectorant with improve characteristics such as the pulmonary function effect is strong and be widely used in clinical.This medicine can act on secretory cell, regulates serosity and mucous secretion, and serous secretion is increased, and mucolytic is diluted, and can strengthen the swing of cilium, increases the removing ability of mucus transportation system, makes sputum be easy to discharge.Ambroxol hydrochloride also is a kind of respiratory system protective agent, has antioxidation, the release of inflammation-inhibiting medium, and lax airway smooth muscle promotes the effects such as synthetic and secretion of pulmonary surfactant.Ambroxol hydrochloride can also increase the drug level of antibiotic in air flue, thereby improves antibiotic curative effect.
Ambroxol hydrochloride
English name: Ambroxol Hydrochloride;
Chemical name: trans-4-[(2-amino 3,5-dibromo-benzyl) amino] Hexalin hydrochlorate;
Molecular formula: C
13H
18Br
2N
2OHCl;
Structural formula:
Respiratory system disease is one of disease kind of being familiar with of people, such as flu, and cough, bronchitis, mostly bronchial asthma etc. is commonly encountered diseases and frequently-occurring disease.Respiratory system disease occurs in human respiratory tract's (comprising throat, trachea, bronchus and pulmonary), and to cough, expectorant is breathed heavily, and is its common symptom.These symptoms influence patient's rest and health, if do not heal for a long time, also possibly develop into emphysema, bronchiectasis and pulmonary heart disease etc.When respiratory tract is ill, cough, expectorant and to breathe heavily can be independent appearance, but also exist simultaneously often, and can promote mutually or increase the weight of.For example, expectorant can stimulate respiratory mucosa to cause cough; When abundant expectoration blocks bronchioles, not only cause asthma, can also cause secondary infection, further damage respiratory tract, increase the weight of cough, cough up phlegm and pant.
Sputum is secreted by body of gland of trachea and bronchus (mucous gland, serous gland) and goblet cell.Under normal circumstances, body of gland and goblet cell are secreted a small amount of mucus and are covered in the respiratory mucosa surface, play protective effect, and microgranules such as the dust of suction can be sticked by mucus, are discharged by the cilium directed movement simultaneously.Under the situation of respiratory inflammation, body of gland and goblet cell hypertrophy are loose, secretions increase, and viscosity increases, ciliated cell pathological changes in addition, ciliary movement goes down, and mucus can not in time be discharged, so expectorant is arranged.But sensor and afferent nerve endings under the sputum irritates nucous membrane increase the weight of or cause cough, also can block respiratory tract, cause out of breath even suffocate.The stagnant of sputum created condition for secondary infection again, further damages respiratory tissues, and the symptom that makes cough, coughs up phlegm and pant further increases the weight of, and forms vicious cycle.So dispel sputum is the important measure of curing the disease to the ill.
The sickness rate of China's diseases of respiratory system and case fatality rate are all high in recent years, at present, have been China human mortality's the third-largest factor.Therefore, the exploitation of treatment respiratory system disease medicine also becomes a pith of drug research.Under the situation of respiratory tract infection (like respiratory tract diseases such as chronic bronchitiss); Tend to produce a large amount of sputums; Respiratory tract is stopped up in the existence of expectorant; Causing cough easily, pant, even cause dyspnea, so especially the difficulty of spitting often appears in children's and old man. the application of expectorant is very necessary.Ambroxol hydrochloride series is to act on the strongest expectorant at present clinically, and is very sure to its curative effect both at home and abroad.
The first-elected listing of Germany Boehringer Ingelheim company in 1979; To have toxicity low because of it; Expectorant with improve characteristics such as the pulmonary function effect is strong and be widely used in clinically, and successively go on the market in nearly 20 countries such as Italy, Switzerland, Argentina, Japan, France, Spain, Singapore, Thailand.China is in beginning import in 1991, mainly contains the mucosolvan etc. that German He Su reaches An Pusuo that the pharmaceutical factory produces, German Boehringer Ingelheim company.In recent years, the research focus of ambroxol turns to and is used for breast, abdominal postoperative prevention pulmonary infection, pulmonary atelectasis.Particularly before the art with the chronic bronchitis or the patient of other basic pulmonary disease, the operation back is because body fluid reduces, and stomach tube keeps, bed, reasons such as wound pain cause thick sputum to be difficult for expectoration, serious pulmonary infection even the threat to life of causing.
Application number be CN201110388637.9 disclosure of the Invention a kind of ambroxol hydrochloride lipidosome injection and method for making thereof.This lipidosome injection is processed by ambroxol hydrochloride, cholesterol, soy phosphatidylserine, soyasterol, Tween 80, trehalose and the PVP of specified weight proportioning.Introduce Tween 80 in the injection, can cause haemolysis, reliability can not effectively guarantee.
Application number is that the invention of CN201110163622.2 belongs to pharmaceutical field, is specifically related to the method for preparing of the stable ambroxol hydrochloride injection of a kind of pH value.Concrete: be to guarantee that through adding buffer system solution pH value before and after sterilization is stable; Avoid the pH value generation significant change of sterilization front and back; Reduce the generation of impurity; Select for use buffering to the pH stabilizing agent as solution, the buffering that is adopted is to being citric acid-sodium hydrogen phosphate, and is a pair of arbitrarily in citric acid-sodium citrate.And select by above-mentioned buffering to the pH scope of the buffer of preparation between 4.5 ~ 5.5.The committed step of method for preparing of the present invention is to utilize buffer salt system to guarantee the pH value of solution value stabilization, reduces or avoid ambroxol hydrochloride to degrade to generate impurity B and impurity E, helps medicine performance curative effect, and avoids having side effects because of impurity.
What application number was that the invention of CN201010615049.X relates to is ambroxol hydrochloride composition of a kind of injection and preparation method thereof; Said composition contains ambroxol hydrochloride and mannitol; Its preparation method is: 1) preparation: ambroxol hydrochloride and mannitol are put in the preparing tank for 1:1 ~ 4 by weight proportion; Add the injection water, stir and make it to dissolve fully also mix homogeneously; 2) aseptic filtration, packing, the false add plug; 3) vacuum lyophilization promptly gets.The present invention fills a prescription simply, and technology is advanced, the quality stable homogeneous, and moisture drying is thorough, and the performance of redissolving is better.
Application number is that the invention of CN201010199259.5 provides a kind of ambroxol hydrochloride composition; Said composition comprises following composition: ambroxol hydrochloride 14-16 weight portion, citric acid 2.6-3.2 weight portion, sodium hydrogen phosphate 4.8-6.0 weight portion and sodium chloride 13-16 weight portion; The resulting ambroxol hydrochloride injection of the ambroxol hydrochloride injection component that also has above-mentioned composition to process is simple; Under than higher PH (5.5-7.0) condition; The stability of active medicine ambroxol hydrochloride is more suitable for the human injection than higher, the sense of discomfort of bringing to the patient when reducing injection.
Application number is the invention of CN201010195712.5 injection that a kind of ambroxol is provided and preparation method thereof; This injection contains ambroxol or its pharmaceutically acceptable salt, sodium hydrogen phosphate and citric acid; Wherein, The weight ratio of ambroxol or its pharmaceutically acceptable salt, sodium hydrogen phosphate and citric acid is 1: 0.18-0.22: 0.12-0.16, preferably, the weight ratio of ambroxol or its pharmaceutically acceptable salt, sodium hydrogen phosphate and citric acid is 1: 0.20: 0.14.The pharmaceutically acceptable salt of ambroxol of the present invention is preferably hydrochlorate.The amount of activated that adopts in the preparation is 0.2-0.3%.
Application number be CN200910306512.X disclosure of the Invention a kind of ambroxol hydrochloride small-volume injection and preparation method thereof of high stability.Ambroxol hydrochloride low capacity intravenous injection of the present invention; Wherein the concentration expressed in percentage by weight of ambroxol hydrochloride is 0.3 ~ 4%; Wherein ambroxol hydrochloride solution comprises that also can form soda acid cushions right component, and wherein ambroxol hydrochloride solution also comprises carbon dioxide, and the segment space in the ampoule is filled with nitrogen.
Application number is a kind of ambroxol hydrochloride liquid preparation of the invention discloses of CN200910090241.9 and preparation method thereof.This method comprises the steps: ambroxol hydrochloride, stabilizing agent and osmotic pressure regulator are dissolved in the water for injection, and mixing obtains solution I, then solution I is filtered, and obtains the ambroxol hydrochloride liquid preparation.Do not introduce active carbon in the method for preparing of the present invention.
Application number is that the invention of CN200710059969.6 relates to pharmaceutical preparation; More particularly; Relate to a kind of ambroxol hydrochloride injection, it is to be active component with the ambroxol hydrochloride, with the stable type pharmaceutical composition of pharmaceutically acceptable carrier composition; These carriers comprise water-soluble filler, pH regulator agent, stabilizing agent, water for injection or osmotic pressure regulator etc.; Owing to adopt said carrier to carry out section's methodology, guaranteed the drug quality and the drug safety of freeze-dried powder of the present invention, small injection and primary infusion preparation, and can improve the stability of goods in storage process.
The ambroxol hydrochloride injection that prior art is produced all has very strict requirement to the requirement of storage, lucifuge, in use, preservation and transportation, all has inconvenience.
The inventor is through studying for a long period of time, and unexpected the discovery used special adjuvant; The ambroxol hydrochloride pharmaceutical composition of special process preparation, light resistance is good, is difficult for producing particulate matter; Good stability has not only successfully solved the problem of the poor stability of ambroxol hydrochloride, reduces production costs; Easy to implement, can realize industrialization, remarkable in economical benefits.
Summary of the invention
First purpose of the present invention is to provide a kind of ambroxol hydrochloride pharmaceutical composition of injection, and this ambroxol hydrochloride injection is stable to light, is difficult for producing particulate matter; Good stability; To improving product yield, reduce cost, realize industrialization; Better application has more remarkable advantages in clinical.
Second purpose of the present invention is to provide a kind of ambroxol hydrochloride preparation of drug combination method of injection, and this method is simple, prepared ambroxol hydrochloride pharmaceutical composition; Stable to light; Be difficult for producing particulate matter, clarity is good, good stability.
For realizing first purpose of the present invention, the present invention adopts following technical scheme:
A kind of ambroxol hydrochloride pharmaceutical composition of injection, per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 15-30g
Sodium chloride 18-36g
Glacial acetic acid 10-20g
Sodium acetate 2.52-5.1g
Water for injection adds to 2L or 4L.
Preferably, per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 15g
Sodium chloride 18g
Glacial acetic acid 10g
Sodium acetate 2.52g
Water for injection adds to 2L.
Preferably, per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 30g
Sodium chloride 36g
Glacial acetic acid 20g
Sodium acetate 5.1g
Water for injection adds to 4L.
Preferably, per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 30g
Sodium chloride 36g
Glacial acetic acid 20g
Sodium acetate 5.1g
Water for injection adds to 2L.
Ambroxol hydrochloride pharmaceutical composition of the present invention is to adopt following method preparation:
Get recipe quantity water for injection 90%, temperature adds the glacial acetic acid and the sodium acetate of recipe quantity, after the stirring and dissolving at 55-65 ℃; The ambroxol hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 3.5-4.5 with 10% acetum or 10% sodium hydroxide solution according to original ph; To adding medicinal charcoal, stir, place; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; Sterilization; Lamp inspection; Warehouse-in; Promptly get the ambroxol hydrochloride injection.
Among the present invention, the consumption of described medicinal charcoal is 0.05-0.1%.
Among the present invention, described stirring is to stir 30 minutes down at 55-65 ℃.
Among the present invention, described sterilization is at 121 ℃ of pressure sterilizing 15-20 minutes, is preferably 121 ℃ of pressure sterilizings 15 minutes.
For realizing second purpose of the present invention, the present invention adopts following technical scheme:
Ambroxol hydrochloride preparation of drug combination method of the present invention, wherein, this method comprises the steps:
Get recipe quantity water for injection 90%, temperature adds the glacial acetic acid and the sodium acetate of recipe quantity, after the stirring and dissolving at 55-65 ℃; The ambroxol hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 3.5-4.5 with 10% acetum or 10% sodium hydroxide solution according to original ph; To adding medicinal charcoal, stir, place; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; Sterilization; Lamp inspection; Warehouse-in; Promptly get the ambroxol hydrochloride injection.
According to aforesaid method for preparing, wherein, the consumption of described medicinal charcoal is 0.05-0.1%.
According to aforesaid method for preparing, wherein, described stirring is to stir 30 minutes down at 55-65 ℃.
According to aforesaid method for preparing, wherein, described sterilization is at 121 ℃ of pressure sterilizing 15-20 minutes, is preferably 121 ℃ of pressure sterilizings 15 minutes.
Below to the more detailed elaboration of the present invention:
One aspect of the present invention provides a kind of ambroxol hydrochloride pharmaceutical composition of injection, per 1000 described ambroxol hydrochloride pharmaceutical compositions, and its prescription consists of:
Ambroxol hydrochloride 15-30g
Sodium chloride 18-36g
Glacial acetic acid 10-20g
Sodium acetate 2.52-5.1g
Water for injection adds to 2L or 4L.
Traditional ambroxol hydrochloride injection, photostability is poor, is prone to degraded, separates out, and quality can't guarantee.
Among the present invention, in stability study process, find to select for use a certain amount of cysteine hydrochloride to ambroxol hydrochloride injection light; Behind the pH value of elder generation's regulator solution; Dissolve ambroxol hydrochloride again, add a certain proportion of sodium chloride, can effectively improve the stability of said preparation light; Also make it be difficult for separating out, the related substance no change.Through the screening of tens of times test recipes and the summary of test data, optimized its recipe quantity, not only solved the problem of photostability difference, and made the product clarity good, constant product quality.
The ambroxol hydrochloride pharmaceutical composition of a kind of injection according to the invention, per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 15-30g
Sodium chloride 18-36g
Glacial acetic acid 10-20g
Sodium acetate 2.52-5.1g
Water for injection adds to 2L or 4L.
Preferably, per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 15g
Sodium chloride 18g
Glacial acetic acid 10g
Sodium acetate 2.52g
Water for injection adds to 2L.
Preferably, per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 30g
Sodium chloride 36g
Glacial acetic acid 20g
Sodium acetate 5.1g
Water for injection adds to 4L.
Preferably, per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 30g
Sodium chloride 36g
Glacial acetic acid 20g
Sodium acetate 5.1g
Water for injection adds to 2L.
The inventor finds through great deal of experimental, when the ambroxol hydrochloride pharmaceutical composition of counting is above-mentioned when more apolegamy side being arranged, and described injection the best in quality, stable best.
Another aspect of the present invention provides the method for preparing of ambroxol hydrochloride injection of the present invention, and this method is simple, and prepared ambroxol hydrochloride injection is stable to light, is difficult for producing particulate matter, and clarity is good, good stability.
Method for preparing provided by the present invention comprises: get recipe quantity water for injection 90%, temperature adds the glacial acetic acid and the sodium acetate of recipe quantity, after the stirring and dissolving at 55-65 ℃; The ambroxol hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 3.5-4.5 with 10% acetum or 10% sodium hydroxide solution according to original ph; To adding medicinal charcoal, stir, place; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; Sterilization; Lamp inspection; Warehouse-in; Promptly get the ambroxol hydrochloride injection.
The ambroxol hydrochloride injection that makes according to the inventive method proves that through industrial amplification production machine study on the stability product is stable, and through pharmacology, toxicological test, solution is non-stimulated to blood vessel, does not have irritated reaction, does not also have haemolysis, and human body is not had injury.
In the method for preparing of the present invention, the consumption of described medicinal charcoal is 0.05-0.1%.
In the method for preparing of the present invention, described stirring is to stir 30 minutes down at 55-65 ℃.
Add an amount of medicinal charcoal and can improve the clarity of solution; Can adsorb thermal source, pigment again; Medicinal charcoal does not have absorption to ambroxol hydrochloride; The inventor adopts UV-VIS spectrophotometry to measure the content of ambroxol hydrochloride, investigated the influence to ambroxol hydrochloride content in the injection of medicinal charcoal, temperature, adsorption time.The result shows, the medicinal charcoal consumption is at 0.05-0.1%, and adsorption time is at 30 minutes, and adsorption temp is at 55-65 ℃, best results.
In the method for preparing of the present invention, described sterilization is at 121 ℃ of pressure sterilizing 15-20 minutes, is preferably 121 ℃ of pressure sterilizings 15 minutes.
Product of the present invention is the sterile water solution of ambroxol hydrochloride, and sterilising conditions is very crucial, should reach sterilization effect, can not destroy solution again, and the inventor investigates sterilising conditions, sees Test Example 4 for details.The result shows, at 121 ℃ of pressure sterilizing 15-20 minutes, and wherein 121 ℃ of pressure sterilizings 15 minutes, best results.
Compared with prior art, the present invention has following advantage:
1) new ambroxol hydrochloride composition provided by the present invention has thoroughly solved the stability problem of ambroxol hydrochloride to light.
2) ambroxol hydrochloride injection provided by the present invention is for the market risk of the yield that improves this product, reduction product, and better application has very big help in clinical treatment.
3) new ambroxol hydrochloride composition provided by the present invention proves constant product quality through industrialized great production and study on the stability, through pharmacology, toxicological test; Solution is non-stimulated to blood vessel; Do not have irritated reaction, do not have haemolysis yet, human body is not had injury.
4) method for preparing of new ambroxol hydrochloride composition provided by the present invention, this method is simple, and prepared ambroxol hydrochloride injection is stable to light, can not separate out, and clarity is good, good stability.
The specific embodiment
Below in conjunction with embodiment the present invention is done further explain
Embodiment 1
Per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 15g
Sodium chloride 18g
Glacial acetic acid 10g
Sodium acetate 2.52g
Water for injection adds to 2L.
Preparation technology: get recipe quantity water for injection 90%, temperature adds the glacial acetic acid and the sodium acetate of recipe quantity, after the stirring and dissolving at 55-65 ℃; The ambroxol hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 3.5-4.5 with 10% acetum or 10% sodium hydroxide solution according to original ph; To adding medicinal charcoal 0.05%, stir, placed 30 minutes; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; 121 ℃ of pressure sterilizings 15 minutes; Lamp inspection; Warehouse-in; Promptly get the ambroxol hydrochloride injection.
Embodiment 2
Per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 30g
Sodium chloride 36g
Glacial acetic acid 20g
Sodium acetate 5.1g
Water for injection adds to 4L.
Preparation technology: get recipe quantity water for injection 90%, temperature adds the glacial acetic acid and the sodium acetate of recipe quantity, after the stirring and dissolving at 55-65 ℃; The ambroxol hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 3.5-4.5 with 10% acetum or 10% sodium hydroxide solution according to original ph; To adding medicinal charcoal 0.05%, stir, placed 30 minutes; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; 121 ℃ of pressure sterilizings 15 minutes; Lamp inspection; Warehouse-in; Promptly get the ambroxol hydrochloride injection.
Embodiment 3
Per 1000 described ambroxol hydrochloride pharmaceutical compositions, its prescription consists of:
Ambroxol hydrochloride 30g
Sodium chloride 36g
Glacial acetic acid 20g
Sodium acetate 5.1g
Water for injection adds to 2L.
Preparation technology: get recipe quantity water for injection 90%, temperature adds the glacial acetic acid and the sodium acetate of recipe quantity, after the stirring and dissolving at 55-65 ℃; The ambroxol hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 3.5-4.5 with 10% acetum or 10% sodium hydroxide solution according to original ph; To adding medicinal charcoal 0.05%, stir, placed 30 minutes; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; 121 ℃ of pressure sterilizings 15 minutes; Lamp inspection; Warehouse-in; Promptly get the ambroxol hydrochloride injection.
Comparing embodiment 1
CN20101019929.5 embodiment 1
Prescription: 1000 components
Ambroxol hydrochloride 16g
Citric acid 2.8g
Sodium hydrogen phosphate 4.9g
Sodium chloride 15g
Water for injection 1800mL.
Method for preparing: recipe quantity ambroxol hydrochloride, citric acid, sodium hydrogen phosphate, sodium chloride are dissolved in the water for injection; Wherein the total amount of water for injection is 70% of a total water amount, stirs to make its dissolving record pH between 5.5, adds active carbon 0.02% then; At room temperature stir about is 10 minutes; Remove by filter active carbon, add to the full amount of water for injection then, carry out fine straining, embedding, sterilization afterwards again.
Comparing embodiment 2
CN201010195712.5
Ambroxol hydrochloride 15g
Sodium hydrogen phosphate 3.3g
Citric acid 2.4g
Sodium chloride 13.6g
Nitrogen is an amount of
Water for injection adds to 2000mL.
Method for preparing: take by weighing sodium hydrogen phosphate, citric acid, it is an amount of to add the injection water, makes dissolving; Add ambroxol hydrochloride, stirring and dissolving; Add sodium chloride, dissolving.Add 0.3% (W/V) active carbon, stirred 20 minutes, filter.The inflated with nitrogen embedding is in 2ml brown glass ampoule.(121 ℃, 15min), the visible foreign matters passed examination promptly gets in the sterilization leak detection.
Test Example 1
This Test Example is used to investigate the stability of solution of prescription and clarity, particulate matter and the sedimentary situation that influences of buffer system recipe quantity and solution.
Prescription is formed
| Prescription | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 |
| Ambroxol hydrochloride | 15g | 15g | 15g | 15g |
| Sodium chloride | 18g | 18g | 18g | 18g |
| Glacial acetic acid | —— | 40g | 20g | 10g |
| Sodium acetate | —— | 10.2g | 5.1g | 2.52g |
| Water for injection | Add to 2L | Add to 2L | Add to 2L | Add to 2L |
| Process | 1000 | 1000 | 1000 | 1000 |
The 1-that will write out a prescription prescription 4 places the illumination 72 hours of 4500LX ± 500LX, respectively at 0 day, 10 days its character, pH value and related substance is checked.The result sees the following form:
Above result of the test shows; Prescription 2-prescription 4 places the illumination 72 hours of 4500LX ± 500LX; Each item inspection all meets up to specification, and comparative example 1 and comparative example 2 place 72 hours each indexs of illumination of 4500LX ± 500LX to change not quite, but particulate matter is defective.
Test Example 2
This Test Example is to investigate the influence to ambroxol hydrochloride content in the injection of medicinal charcoal consumption, temperature, adsorption time.
The preparation of 1 ambroxol hydrochloride sample solution: according to embodiment 1 preparation 3L.
The influence that 2 different time different amounts medicinal charcoal adsorb ambroxol hydrochloride: get reserve liquid 100ml25 part respectively; Per 5 parts is one group, adds medicinal charcoal 0,0.05,0.1,0.15,0.2g respectively, in 60 ℃ of thermostat water baths, works overtime 15,20,25,30,35 minutes respectively for 5 parts in every group; Be cooled to room temperature; Get subsequent filtrate and measure trap according to containing under the quantifier, calculate content, the result sees table:
Medicinal charcoal different amounts and different influences of stirring you to ambroxol hydrochloride content
From showing and can find out, the consumption of medicinal charcoal was greater than 0.15 o'clock, and the content of ambroxol hydrochloride obviously descends, and adsorption time is long more, and content descends obvious more, and therefore the medicinal charcoal consumption is 0.05 in the preparation process, and adsorption time was at 30 minutes.
Test Example 3
This Test Example is to investigate the stability of ambroxol hydrochloride composition provided by the present invention.
The accelerated test of ambroxol hydrochloride injection
Method according to the embodiment of the invention 1 prepares three batches of ambroxol hydrochloride injection (lot number is respectively MT1001001, MT1001002, MT1001003) according to commercially available back; At 40 ℃ ± 2 ℃; The condition of RH75% ± 5% was placed 6 months; Respectively at sampling in the 1st, 2,3,6 month, detect during this time, and compare with 0 day data according to stable inspection item.
1, investigation project
High spot reviews: character, pH value, visible foreign matters, osmotic pressure molar density, related substance and content.
2, test data sees the following form
Above conclusion (of pressure testing) can be found out: these article detect index in 6 months each items of accelerated test condition held and compared no significant difference with 0 month, and stability is measured.
Test Example 4
This Test Example is to investigate under the sterilising conditions temperature to the influence of ambroxol hydrochloride injection content:
These article are the sterile water solution of ambroxol hydrochloride, and sterilising conditions is very crucial, should reach sterilization effect; Can not destroy solution again; The inventor investigates sterilising conditions, behind the ambroxol hydrochloride solution by prescription preparation certain volume, be packaged in the ampoule bottle respectively at 115 ℃ 30 minutes; 121 ℃ 20 minutes, 121 ℃ 15 minutes
,121 ℃ of sterilizations in 20 minutes, observe in the solution of sterilization back drug content following table as a result:
Sterilising conditions is to the influence of ambroxol hydrochloride injection content
| Sterilising conditions | Stock solution | 115 ℃ 30 minutes | 121 ℃ 8 minutes | 121 ℃ 15 minutes | 121 ℃ 20 minutes |
| Content (%) | 100.5 | 96.3 | 100.2 | 100.0 | 97.6 |
Can find out from above test: the sterilising temp condition is little to these article influences, select 121 ℃ 15 minutes, F0>12, reach sterilization effect, solution content is not almost had influence.
Comparative test example 1, comparative test example 2 and embodiment 1 were placed the illumination of 4500LX ± 500LX, 60 ℃ ± 2 ℃ pyritous calorstats respectively 10 days, its character, pH value, related substance, content, visible foreign matters and particulate matter are checked respectively at 0 day, 10 days.The result sees the following form:
Comparative test example 1
Can know according to result of the test; Embodiment 1 and comparative example placed 10 days in illumination and pyritous calorstat, and embodiment 1 is under different condition, and each inspection item has no significant change; The comparative example is all comparatively responsive to light, heat; Content reduces obviously, and particulate matter is defective, brings the very big factors of instability for clinical middle drug safety.
Claims (9)
1. the ambroxol hydrochloride pharmaceutical composition of an injection is characterized in that, per 1000 described ambroxol hydrochloride pharmaceutical compositions, and its prescription consists of:
Ambroxol hydrochloride 15-30g
Sodium chloride 18-36g
Glacial acetic acid 10-20g
Sodium acetate 2.52-5.1g
Water for injection adds to 2L or 4L.
2. the described ambroxol hydrochloride pharmaceutical composition of claim 1 is characterized in that, per 1000 described ambroxol hydrochloride pharmaceutical compositions, and its prescription consists of:
Ambroxol hydrochloride 15g
Sodium chloride 18g
Glacial acetic acid 10g
Sodium acetate 2.52g
Water for injection adds to 2L.
3. the described ambroxol hydrochloride pharmaceutical composition of claim 1 is characterized in that, per 1000 described ambroxol hydrochloride pharmaceutical compositions, and its prescription consists of:
Ambroxol hydrochloride 30g
Sodium chloride 36g
Glacial acetic acid 20g
Sodium acetate 5.1g
Water for injection adds to 4L.
4. the described ambroxol hydrochloride pharmaceutical composition of claim 1 is characterized in that, per 1000 described ambroxol hydrochloride pharmaceutical compositions, and its prescription consists of:
Ambroxol hydrochloride 30g
Sodium chloride 36g
Glacial acetic acid 20g
Sodium acetate 5.1g
Water for injection adds to 2L.
5. the described ambroxol hydrochloride preparation of drug combination of claim 1 method is characterized in that, this method comprises the steps:
Get recipe quantity water for injection 90%, temperature adds the glacial acetic acid and the sodium acetate of recipe quantity, after the stirring and dissolving at 55-65 ℃; The ambroxol hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 3.5-4.5 with 10% acetum or 10% sodium hydroxide solution according to original ph; To adding medicinal charcoal, stir, place; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; Sterilization; Lamp inspection; Warehouse-in; Promptly get the ambroxol hydrochloride injection.
6. method for preparing according to claim 5 is characterized in that, the consumption of described medicinal charcoal is 0.05-0.1%.
7. method for preparing according to claim 5 is characterized in that, described stirring is to stir 30 minutes down at 55-65 ℃.
8. method for preparing according to claim 5 is characterized in that, described sterilization is at 121 ℃ of pressure sterilizing 15-20 minutes.
9. method for preparing according to claim 8 is characterized in that, described sterilization is 121 ℃ of pressure sterilizings 15 minutes.
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| CN102988281A (en) * | 2012-12-11 | 2013-03-27 | 辽宁科泰生物基因制药股份有限公司 | Injection of ambroxol hydrochloride and preparation method thereof |
| CN104771358A (en) * | 2014-01-14 | 2015-07-15 | 江苏柯菲平医药股份有限公司 | Acebrophylline injection and preparation method thereof |
| CN105675523A (en) * | 2014-11-17 | 2016-06-15 | 蚌埠丰原涂山制药有限公司 | Ambroxol content UV spectrophotometric test method |
| CN107320445A (en) * | 2017-07-14 | 2017-11-07 | 峨眉山通惠制药有限公司 | A kind of ambroxol hydrochloride injection and preparation method thereof |
| CN109662943A (en) * | 2018-12-25 | 2019-04-23 | 石家庄鹏海制药股份有限公司 | The preparation method of ambroxol hydrochloride injection |
| CN113004157A (en) * | 2019-12-20 | 2021-06-22 | 康普药业股份有限公司 | Preparation method of ambroxol hydrochloride |
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| CN102225049A (en) * | 2011-06-17 | 2011-10-26 | 成都金典药物科技开发有限公司 | Preparation method of ambroxol hydrochloride injection with stable pH value |
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| CN101836952A (en) * | 2010-06-09 | 2010-09-22 | 云南龙海天然植物药业有限公司 | Ambroxol injection and preparation method thereof |
| CN101836953A (en) * | 2010-06-12 | 2010-09-22 | 山东罗欣药业股份有限公司 | Ambroxol hydrochloride composition injection |
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| CN102988281A (en) * | 2012-12-11 | 2013-03-27 | 辽宁科泰生物基因制药股份有限公司 | Injection of ambroxol hydrochloride and preparation method thereof |
| CN104771358A (en) * | 2014-01-14 | 2015-07-15 | 江苏柯菲平医药股份有限公司 | Acebrophylline injection and preparation method thereof |
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| CN107320445A (en) * | 2017-07-14 | 2017-11-07 | 峨眉山通惠制药有限公司 | A kind of ambroxol hydrochloride injection and preparation method thereof |
| CN109662943A (en) * | 2018-12-25 | 2019-04-23 | 石家庄鹏海制药股份有限公司 | The preparation method of ambroxol hydrochloride injection |
| CN113004157A (en) * | 2019-12-20 | 2021-06-22 | 康普药业股份有限公司 | Preparation method of ambroxol hydrochloride |
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