CN103860461B - A kind of pharmaceutical composition containing active ingredient hydrochloric acid ambroxol - Google Patents
A kind of pharmaceutical composition containing active ingredient hydrochloric acid ambroxol Download PDFInfo
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- CN103860461B CN103860461B CN201210543936.XA CN201210543936A CN103860461B CN 103860461 B CN103860461 B CN 103860461B CN 201210543936 A CN201210543936 A CN 201210543936A CN 103860461 B CN103860461 B CN 103860461B
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- ambroxol hydrochloride
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims abstract description 8
- 229960005174 ambroxol Drugs 0.000 title claims abstract description 5
- 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 title claims abstract description 5
- 239000004480 active ingredient Substances 0.000 title claims abstract description 4
- 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 claims abstract description 69
- 229960000985 ambroxol hydrochloride Drugs 0.000 claims abstract description 69
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 54
- 238000002347 injection Methods 0.000 claims abstract description 39
- 239000007924 injection Substances 0.000 claims abstract description 39
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000004471 Glycine Substances 0.000 claims abstract description 18
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims abstract description 17
- 229910000397 disodium phosphate Inorganic materials 0.000 claims abstract description 17
- 235000019800 disodium phosphate Nutrition 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims description 34
- 239000000243 solution Substances 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 239000008215 water for injection Substances 0.000 claims description 12
- 238000010521 absorption reaction Methods 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 238000004140 cleaning Methods 0.000 claims description 11
- 238000005261 decarburization Methods 0.000 claims description 11
- 238000001914 filtration Methods 0.000 claims description 11
- 239000012982 microporous membrane Substances 0.000 claims description 11
- 230000001105 regulatory effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000000203 mixture Substances 0.000 abstract description 5
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 230000033228 biological regulation Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 206010036790 Productive cough Diseases 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 210000003097 mucus Anatomy 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 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 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000000420 mucociliary effect Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 206010062530 Increased bronchial secretion Diseases 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 208000018569 Respiratory Tract disease Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 description 1
- 229960003174 lansoprazole Drugs 0.000 description 1
- 239000003580 lung surfactant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- VWDWKYIASSYTQR-YTBWXGASSA-N sodium;dioxido(oxo)azanium Chemical compound [Na+].[O-][15N+]([O-])=O VWDWKYIASSYTQR-YTBWXGASSA-N 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention belongs to medical art, the invention provides a kind of pharmaceutical composition containing active ingredient hydrochloric acid ambroxol; Ambroxol hydrochloride, citric acid, sodium hydrogen phosphate and glycine is comprised in this pharmaceutical composition; The injection pH that compositions of the present invention obtains is 5 ~ 6.2; The injection obtained by said composition is easy to use, is beneficial to storing, and its preparation method is simple, be easy to suitability for industrialized production, and production cost is low.
Description
Technical field
The invention belongs to medical art, be specifically related to the pharmaceutical composition containing ambroxol hydrochloride and preparation thereof.
Background technology
Ambroxol hydrochloride (lansoprazole), chemical name is: trans 4-[(amino-3, the 5-dibromo-phenyl of 2-) Methyl-amino] Hexalin.
Ambroxol hydrochloride is respiratory mucus regulator of new generation, there is outstanding ability of eliminating the phlegm, it can stimulate bronchorrhea to secrete the mucus being easy to flowing, sputum is diluted, and toughness reduces, and has significant facilitation to the synthesis of alveolar surfactant and secretion, thus reduction airway resistance, reduce the adhesive force of mucus, activate mucociliary blanket function, promote mucociliary transport.
Ambroxol hydrochloride is widely used in thick sputum, the dys-expectoration that various acute and chronic respiratory tract disease causes clinically.At present, the preparation type of domestic ambroxol hydrochloride has tablet, capsule, oral liquid slow releasing capsule, and these dosage form bioavailability are poor, and onset is slow, and gastrointestinal side effect is comparatively common.For the patient of oral inconvenience, or the state of an illness is relatively more serious or acute patient, often uses ambroxol hydrochloride injection.
Because ambroxol hydrochloride character is unstable, having under oxygen existence or decomposing under alkaline environment, and the ambroxol that dissociates, and related substance increases, and have impact on the curative effect of medicine, reduces safety, therefore, the normal pH by ambroxol hydrochloride controls in the lower stability improving ambroxol hydrochloride injection at present, but lower pH can bring discomfort to human body, increases pain pipe.
Chinese patent application CN1954808A discloses a kind of ambroxol hydrochloride injection, comprise ambroxol hydrochloride, lyophilized powder proppant and pH adjusting agent, but, the ambroxol hydrochloride injection buffer capacity adopting the method to prepare is poor, easily precipitation is produced, poor stability after redissolution, and owing to not using activated carbon adsorption in preparation process, therefore, thermal source pollution probability is high.
Chinese patent application CN10416956A also discloses a kind of ambroxol hydrochloride injection, containing ambroxol hydrochloride, sodium dihydrogen phosphate and citric acid, but adopting ambroxol hydrochloride injection poor stability prepared by the method, after long-term placement, related substance significantly increases.
Summary of the invention
For solving problem existing in above-mentioned prior art, We conducted a large amount of experimental explorations, find in ambroxol hydrochloride injection, add the pH that appropriate glycine can improve injection, and the satisfactory ambroxol hydrochloride injection of stability can be obtained.The invention provides a kind of pharmaceutical composition.
Specifically, the invention provides:
A kind of pharmaceutical composition, comprises ambroxol hydrochloride, citric acid, sodium hydrogen phosphate, glycine.
A kind of pharmaceutical composition, comprises ambroxol hydrochloride, citric acid, sodium hydrogen phosphate, glycine that weight ratio is 1:0.1 ~ 0.15:0.4 ~ 0.6:0.1 ~ 0.2.
A kind of pharmaceutical composition, preferred weight ratio is ambroxol hydrochloride, citric acid, sodium hydrogen phosphate, the glycine of 1:0.13:0.5:0.15.
Aforementioned pharmaceutical compositions also comprises sodium chloride.
The method preparing injection of pharmaceutical composition, it is characterized in that, the method comprises the following steps:
A citric acid, sodium hydrogen phosphate are dissolved in water for injection by ();
B () adds ambroxol hydrochloride in the solution of step (a), adjust ph is 5.0 ~ 6.2;
C () adds glycine in the solution of step (b), stirring and dissolving;
D () carries out removal thermal source and sterilizing, obtain ambroxol hydrochloride injection.
Pharmaceutical composition of the present invention also can contain various additives conventional on materia medica, as long as this additive does not hinder the function of ambroxol hydrochloride.Representational additive includes, but are not limited to: caffolding agent, antioxidant etc.
The present invention compared with prior art has the following advantages and good effect:
1, the injection pH obtained by said composition is 5 ~ 6.2;
2, the injection good stability obtained by said composition;
3, the injection obtained by said composition is easy to use, is beneficial to storing, and its preparation method is simple, be easy to suitability for industrialized production, and production cost is low.
Detailed description of the invention
Below by way of the description of detailed description of the invention, the invention will be further described, but this is not limitation of the present invention, those skilled in the art are according to basic thought of the present invention, various amendment or improvement can be made, but only otherwise depart from basic thought of the present invention, all within the scope of the present invention.
Ambroxol hydrochloride injection test example
1, instrument and medicine
High performance liquid chromatograph (HP1100 type, hewlette-packard), DAD detector, AgilentChemstation chromatographic work station: YB-2 type clarity test instrument (Precision Instrument Factory, Tianjin Univ.); DU640 type UV detector (Beckman company of the U.S.); PHS-3C type digital ph (Shanghai Lei Ci instrument plant); WS/08-0l type temperature and humidity regulator (blue sky, Hangzhou instrument production company limited); METYLER.AE200 type analysis balance (Switzerland); Ambroxol hydrochloride injection (three batch samples of preparation according to embodiment 5, lot number 100305,100307,100309).
2, method
2.1 chromatographic conditions and system suitability octadecylsilane chemically bonded silica are filler; With 0.01mol/L ammonium dibasic phosphate solution (by phosphoric acid adjust ph to 7.0)-acetonitrile (50:50) for mobile phase; Determined wavelength is 248nm.The separating degree at ambroxol hydrochloride peak and catabolite (impurity B) peak should be greater than 4.0, and number of theoretical plate calculates should be not less than 3000 by ambroxol hydrochloride peak.
2.2 investigate project and method
2.2.1 acidity: get ambroxol hydrochloride injection sample, adopts acidometer directly to measure.Result pH value is 5 ~ 6.2.
2.2.2 the clarity of solution and color: get ambroxol hydrochloride injection 5, according to solution colour inspection technique, 3 batch sample solution are all clarified, colourless.
2.2.3 clarity: get ambroxol hydrochloride injection 5, according to Chinese Pharmacopoeia inspection, all conform with the regulations.
2.2.4 related substance: get this product, add mobile phase dilution and make the solution containing 1mg in every 1ml, shake up, as need testing solution, precision measures need testing solution 1ml, puts in 100ml volumetric flask, adds mobile phase and is diluted to scale, shake up, in contrast solution.According to the chromatographic condition operation under assay item, get contrast solution 20ul, injection liquid chromatography, regulate detector sensitivity, make that main peak is high is about 20% of full scale; Precision measures need testing solution 20ul again, injection liquid chromatography, record chromatogram is to 3 times of main peak retention time, as there is the chromatographic peak (impurity B) consistent with system suitability solution in need testing solution chromatogram, then its peak area is multiplied by the 1/2(0.5% that 1.47 should cross contrast solution main peak area); The peak area of other single impurity should cross the 1/2(0.5% of contrast solution main peak area); Each impurity peak area (deduction blank auxiliary peak) and contrast solution main peak area (1.0%) must not be greater than, (need testing solution should face with newly joining).
2.2.5 assay: get this product in right amount, accurately weighed, add mobile phase dilution and make the solution about containing 0.15mg in every 1ml, precision measures 20ul, injection liquid chromatography, record chromatogram; Separately get ambroxol hydrochloride reference substance appropriate, add mobile phase and dissolve and dilute the solution making ambroxol-hydrochloride-containing 0.15mg in every 1ml, be measured in the same method.By external standard method with calculated by peak area, to obtain final product.
2.3 influence factor's experiments
Under marketed products terms of packing, sample is investigated under high temperature (60 DEG C), high light (45001x) condition 5,10d, to its character, acidity, impurity, content and etc. index investigate, indices all conforms with the regulations.Measurement result is in table 1.
Table 1 influence factor result of the test
2.4 Acceleration study
Under marketed products terms of packing, sample (lot number is 100305,100307,100309) is deposited under temperature (40 ± 2) DEG C, native 5% condition of relative humidity 75%, respectively at 0,1,2,3,6 sampling at the end of month, measure indices.Conform with the regulations, clarity of solution and color, clarity all conform with the regulations.Acidity, impurity and assay the results are shown in Table 2.
2.5 long-term experiment
Under marketed products terms of packing, sample (lot number is 100305,100307,100309) is deposited under temperature (25 ± 2) DEG C, relative humidity 60% ± 10% condition, respectively at 0,3,6,12,18,24 sampling at the end of month, measure indices.Each batch sample character conforms with the regulations, and clarity of solution and color, clarity conform with the regulations, and acidity, related substances and assay the results are shown in Table 2.
Table 2 accelerated test and long term test investigate result
A, B, C represent the sample that lot number is 100305,100307,100309.
Conclusion: influence factor's test, the display of accelerated test result, the every testing index of ambroxol hydrochloride injection, without significant change, has good stability; Place ambroxol hydrochloride injection 24 months every quality index under long-term room-temperature condition without significant change, product stability is good.
Preparation example
Embodiment 1
Under the condition of cleaning, 1.5g citric acid, 6g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, regulate pH to be 5.0, drop into 1.5g glycine and dissolve, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
Embodiment 2
Under the condition of cleaning, 1.8g citric acid, 6.6g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, regulate pH to be 5.2, drop into 1.7g glycine and dissolve, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
Embodiment 3
Under the condition of cleaning, 1.7g citric acid, 6.9g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, regulate pH to be 5.3, drop into 1.8g glycine and dissolve, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
Embodiment 4
Under the condition of cleaning, 2.0g citric acid, 7.8g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, regulate pH to be 5.5, drop into 2.1g glycine and dissolve, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
Embodiment 5
Under the condition of cleaning, 2.1g citric acid, 8.3g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, regulate pH to be 5.7, drop into 2.7g glycine and dissolve, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
Embodiment 6
Under the condition of cleaning, 2.25g citric acid, 8.7g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, regulate pH6.0 to be drop into 2.75g glycine and dissolve, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.。
Embodiment 7
Under the condition of cleaning, 2.1g citric acid, 9g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, regulate pH to be 6.2, drop into 3g glycine, 24g sodium chloride dissolves, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
Embodiment 8
Under the condition of cleaning, 1.6g citric acid, 7.35g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, be adjusted to pH5.1, drop into 2.3g glycine and dissolve, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
Embodiment 9
Under the condition of cleaning, 2.21g citric acid, 7.8g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, be adjusted to pH5.7, drop into 2.7g glycine, 14g sodium chloride dissolves, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
Embodiment 10
Under the condition of cleaning, 2g citric acid, 7.6g sodium hydrogen phosphate are dropped in dosing utensil, adds stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stir about 30min and make it entirely molten, regulate pH to be 5.1, drop into 1.73g glycine, 7.85g sodium chloride dissolves, add 0.3% pin carbon and to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution.Be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
Claims (1)
1. the pharmaceutical composition containing active ingredient hydrochloric acid ambroxol, it is characterized in that comprising ambroxol hydrochloride, citric acid, sodium hydrogen phosphate and glycine in pharmaceutical composition, pharmaceutical composition is prepared into injection, and wherein the preparation method of injection is:
Under the condition of cleaning, 2.1g citric acid, 8.3g sodium hydrogen phosphate are dropped in dosing utensil, add stirring and dissolving in water for injection 1200ml, be cooled to room temperature, add 15g ambroxol hydrochloride stirring 30min and make it entirely molten, pH is regulated to be 5.7, drop into 2.7g glycine to dissolve, add 0.3% pin carbon to stir absorption thermal source, filter decarburization, add water to 2000ml, through 0.22 μm of filtering with microporous membrane, obtain 7.5mg/ml ambroxol hydrochloride solution, be sub-packed in ampere bottle, obtain ambroxol hydrochloride injection.
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| CN103860461B true CN103860461B (en) | 2016-04-13 |
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| CN104316482A (en) * | 2014-08-15 | 2015-01-28 | 河北菲尼斯生物技术有限公司 | A quality control method for ambroxol hydrochloride particles |
| CN104840417A (en) * | 2015-04-30 | 2015-08-19 | 济南康和医药科技有限公司 | Ambroxol hydrochloride injection and preparation method thereof |
| CN105193712B (en) * | 2015-09-28 | 2018-07-31 | 成都天台山制药有限公司 | Ambroxol hydrochloride injection and preparation method |
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| CN101756948A (en) * | 2008-11-20 | 2010-06-30 | 海南四环医药有限公司 | Composition of ambroxol hydrochloride and arginine and preparation method thereof |
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| 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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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101756948A (en) * | 2008-11-20 | 2010-06-30 | 海南四环医药有限公司 | Composition of ambroxol hydrochloride and arginine and preparation method thereof |
| CN101756949A (en) * | 2008-11-20 | 2010-06-30 | 海南四环医药有限公司 | Composition of ambroxol hydrochloride and cysteine 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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| CN103860461A (en) | 2014-06-18 |
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Address after: 130012, 672, pioneering street, hi tech Zone, Jilin, Changchun Patentee after: CHANGCHUN HAIYUE PHARMACEUTICAL Co.,Ltd. Address before: 130012, 672, pioneering street, hi tech Zone, Jilin, Changchun Patentee before: Changchun Haiyue Pharmaceutical Co.,Ltd. |
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Denomination of invention: A pharmaceutical composition containing the active ingredient ambroxol hydrochloride Effective date of registration: 20231226 Granted publication date: 20160413 Pledgee: China Construction Bank Co.,Ltd. Changchun Science and Technology Sub branch Pledgor: CHANGCHUN HAIYUE PHARMACEUTICAL Co.,Ltd. Registration number: Y2023220000146 |
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