CN101416956B - Ambroxol hydrochloride injection - Google Patents
Ambroxol hydrochloride injection Download PDFInfo
- Publication number
- CN101416956B CN101416956B CN2007100599696A CN200710059969A CN101416956B CN 101416956 B CN101416956 B CN 101416956B CN 2007100599696 A CN2007100599696 A CN 2007100599696A CN 200710059969 A CN200710059969 A CN 200710059969A CN 101416956 B CN101416956 B CN 101416956B
- Authority
- CN
- China
- Prior art keywords
- injection
- add
- ambroxol hydrochloride
- water
- sodium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229960000985 ambroxol hydrochloride Drugs 0.000 title claims abstract description 79
- 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 78
- 239000007924 injection Substances 0.000 title claims abstract description 57
- 238000002347 injection Methods 0.000 title claims abstract description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 64
- 239000003381 stabilizer Substances 0.000 claims abstract description 25
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 13
- 239000004480 active ingredient Substances 0.000 claims abstract description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 72
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 44
- 239000008215 water for injection Substances 0.000 claims description 41
- 239000011780 sodium chloride Substances 0.000 claims description 30
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 23
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 14
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 14
- 229960000502 poloxamer Drugs 0.000 claims description 14
- 229920001983 poloxamer Polymers 0.000 claims description 14
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 14
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 12
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 12
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 12
- 229960005174 ambroxol Drugs 0.000 claims description 9
- 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 claims description 9
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 8
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 8
- 235000019800 disodium phosphate Nutrition 0.000 claims description 8
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 18
- 238000002360 preparation method Methods 0.000 abstract description 15
- 229940079593 drug Drugs 0.000 abstract description 10
- 230000003204 osmotic effect Effects 0.000 abstract description 9
- 239000000843 powder Substances 0.000 abstract description 9
- 239000000945 filler Substances 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 abstract description 4
- 230000001105 regulatory effect Effects 0.000 abstract description 3
- 238000003860 storage Methods 0.000 abstract description 3
- 239000000969 carrier Substances 0.000 abstract 3
- 239000003978 infusion fluid Substances 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 57
- 229940090044 injection Drugs 0.000 description 44
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 28
- 229910052799 carbon Inorganic materials 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000000126 substance Substances 0.000 description 27
- 239000011859 microparticle Substances 0.000 description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 14
- 238000012546 transfer Methods 0.000 description 13
- 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 12
- 229930195725 Mannitol Natural products 0.000 description 12
- 239000000594 mannitol Substances 0.000 description 12
- 235000010355 mannitol Nutrition 0.000 description 12
- 230000001954 sterilising effect Effects 0.000 description 12
- 238000004659 sterilization and disinfection Methods 0.000 description 12
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 9
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 9
- 229920002125 Sokalan® Polymers 0.000 description 9
- 229960001631 carbomer Drugs 0.000 description 9
- 238000005261 decarburization Methods 0.000 description 8
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 229920002307 Dextran Polymers 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 239000012982 microporous membrane Substances 0.000 description 6
- 238000012856 packing Methods 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000013618 particulate matter Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 206010036790 Productive cough Diseases 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- 206010062717 Increased upper airway secretion Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- 229930182830 galactose Natural products 0.000 description 3
- 239000003580 lung surfactant Substances 0.000 description 3
- 210000003097 mucus Anatomy 0.000 description 3
- 208000026435 phlegm Diseases 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940093181 glucose injection Drugs 0.000 description 2
- 230000000420 mucociliary effect Effects 0.000 description 2
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000005696 Diammonium phosphate Substances 0.000 description 1
- 206010062530 Increased bronchial secretion Diseases 0.000 description 1
- -1 PH regulator Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000002588 alveolar type II cell Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 208000034209 congenital alveolar dysplasia Diseases 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 229910000388 diammonium phosphate Inorganic materials 0.000 description 1
- 235000019838 diammonium phosphate Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000007788 liquid 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
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a medicinal preparation, in particular to an ambroxol hydrochloride injection which is a stable medial composition taking ambroxol hydrochloride as an active ingredient to be combined with carriers acceptable in pharmacy. The carriers comprise a water-soluble filling agent, a pH regulating agent, a stabilizing agent, water used for injection or an osmotic pressure regulating agent and the like. As the carriers are adopted to carry out scientific preparation, the drug quality and medication safety of freeze-dried powder injections, small-needle injections and small infusion solutions are ensured, and the stability of the preparations during storage is improved.
Description
Technical field:
The present invention relates to pharmaceutical preparation, more particularly, is a kind of expectorant-ambroxol hydrochloride injection.
Background technology:
The ambroxol hydrochloride chemistry is by name: methyl-amino trans 4-[(2-amino-3,5 two bromo-phenyl)] Hexalin, its structure is as follows:
Ambroxol hydrochloride is a respiratory mucus regulator of new generation, has the superior usefulness of eliminating the phlegm, and the synthetic of alveolar surfactant had significant facilitation with secretion.Ambroxol hydrochloride can stimulate the bronchorrhea glandular secretion to be easier to mobile mucus, makes the sputum dilution, and toughness reduces, and can increase the generation and the secretion of pulmonary surfactant, thereby reduce airway resistance, reduce mucous adhesive force, activate mucociliary blanket function, promote the mucociliary transhipment.Compare with the first generation and second filial generation expelling phlegm drugs, ambroxol hydrochloride is except that having powerful mucolysis effect, and its maximum characteristics are that it can stimulate alveolar type II cells, promotes the synthetic and secretion of alveolar surfactant, thereby effectively strengthen mucus transport, promote expectoration.
Ambroxol hydrochloride is to act on one of the strongest expectorant at present clinically, be applicable to that acute/chronic bronchitis, asthmatic bronchitis, bronchial asthma and chronic pneumonia thick sputum are difficult for the patient of expectoration or dry cough without phlegm, also can be used for congenital alveolar dysplasia, clinical efficacy is very sure, and ambroxol hydrochloride is safe in utilization, better tolerance is reused no drug accumulation effect.
At present, the ambroxol hydrochloride oral preparation that has gone on the market has tablet, capsule, syrup, slow releasing capsule etc.; Injection has little needle injection, lyophilized preparation etc.
Because under oxidation or alkali condition, there is free ambroxol in ambroxol hydrochloride in the molecule, so related substance can increase in storage process, influence the quality and the safety of medicine.The pH value of control solution and adding stabilizing agent can solve above-mentioned problem of unstable.The present invention filters out reasonable stabilizing agent through great deal of experimental, guarantees that room temperature placed 3 years, and not only related substance does not increase, and every indexs such as outward appearance, clarity, particulate matter do not present significant change yet.This method is easy and simple to handle, does not need special installation, is highly suitable for increasing in the large-scale industrial production stability of medicine, improves the quality of medicine, guarantees the safety of medication.
Of the present invention through system test research screening ambroxol hydrochloride injection that determine, that contain the best stabilized key element, not seeing as yet so far has relevant report.
The objective of the invention is to, a kind of stable ambroxol hydrochloride injection Pharmaceutical composition is provided, the quality to guarantee that it increases stability and improves medicine in storage process guarantees the safety of medication.
Summary of the invention:
An object of the present invention is overcoming the shortcoming and defect of above-mentioned prior art, provide a kind of good stability, drug quality height, the ambroxol hydrochloride injection of drug safety.
Another object of the present invention provides the preparation method that contains the active ingredient hydrochloric acid ambroxol injection.
A further object of the present invention provides the stable pharmaceutical composition that contains active ingredient hydrochloric acid ambroxol administrated by injection, is made up of active ingredient hydrochloric acid ambroxol and water-soluble filler, PH regulator, stabilizing agent, water for injection or osmotic pressure regulator.
Injection provided by the present invention is meant, is active component with the ambroxol hydrochloride, with the stable type pharmaceutical composition of pharmaceutically acceptable carrier composition.Particularly, be exactly to form by active ingredient hydrochloric acid ambroxol and water-soluble filler, pH regulator agent, stabilizing agent, water for injection or osmotic pressure regulator etc.Preparation of the present invention is meant the freeze-dried powder, small injection and the primary infusion that contain ambroxol hydrochloride.Described preparation (freeze-dried powder, small injection and primary infusion) is under aqueous solution state, and its pH value is 3-5.
The water-soluble filler of preparation of the present invention is to be selected from: mannitol, low molecular dextran, sorbitol, Polyethylene Glycol, glucose, lactose or galactose; The pH regulator agent is to be selected from: organic or inorganic acid, alkali and salt such as nonvolatile acid such as citric acid, phosphoric acid, hydrochloric acid and potassium hydroxide, sodium hydroxide or potassium or ammonium, sodium carbonate or potassium or ammonium salt, sodium bicarbonate or potassium or ammonium salt, sodium hydrogen phosphate, sodium dihydrogen phosphate; Stabilizing agent is to be selected from: one or both combinations of poloxamer, carbomer, sodium lauryl sulphate or dodecyl sodium sulfate; Osmotic pressure regulator is to be selected from: the combination of one or both of sodium chloride, potassium chloride.The wherein preferred mannitol of filler, low molecular dextran, glucose; PH regulator agent preferably citric acid, hydrochloric acid, phosphoric acid, sodium hydroxide, sodium hydrogen phosphate, biphosphate; The preferred poloxamer of stabilizing agent, sodium lauryl sulphate.
The medicine of preparation of the present invention/adjuvant weight ratio or drug level are respectively:
A. the percentage by weight of lyophilized preparation Chinese medicine composition and other pharmaceutic adjuvant is 0.1-50%;
B. the concentration of small injection Chinese medicine is 20mg/ml-0.1mg/ml;
C. the concentration of primary infusion Chinese medicine is 5mg/ml-0.01mg/ml.
The primary infusion of pharmaceutical composition of the present invention is meant, the compound injection of one or more compositions of active component and sodium chloride, glucose or low molecular dextran.
The preparation method of preparation of the present invention may further comprise the steps:
(1) lyophilized preparation
Prescription is formed: ambroxol hydrochloride 0.1%-50%, water-soluble filler 50%-90%, PH regulator 0.01%-10%, stabilizing agent 0.001%-2%, osmotic pressure regulator 0.9%;
Method step: get ambroxol hydrochloride and water-soluble filler, stabilizing agent, osmotic pressure agent etc., it is an amount of to add water for injection, regulates pH value and makes its dissolving to 3-5, adds water to full dose, add the 0.1-0.5% active carbon, stirred 10-60 minute down at 20-50 ℃, the filtering with microporous membrane degerming is adopted in decarburization, filtrate is carried out packing, adopt freeze-drying, make the white loose block, seal promptly;
(2) small injection:
Prescription is formed: ambroxol hydrochloride 2.0%-0.05%, PH regulator 0.01%-10%, stabilizing agent 0.001%-2%, water for injection 88%-98%;
Method step: get ambroxol hydrochloride and stabilizing agent, osmotic pressure agent etc., it is an amount of to add water for injection, regulates pH value and makes its dissolving to 3-5, adds water to full dose, adds the 0.1-0.5% active carbon, stirs 10-60 minute decarburization, fine straining, embedding, sterilization down at 20-50 ℃;
(3) primary infusion
Prescription is formed: ambroxol hydrochloride 0.1%-0.002%, pH regulator agent 0.01%-10%, stabilizing agent 0.001%-2%, osmotic pressure regulator 0.9%, water for injection 88%-98%;
Method step: get ambroxol hydrochloride and stabilizing agent, osmotic pressure agent etc., it is an amount of about 20% to add water for injection, regulates pH value and makes its dissolving to 3-5, add the 0.1-0.5% active carbon, stirred decarburization 10-60 minute down at 20-50 ℃, add water to full dose, fine straining, embedding, sterilization.
Ambroxol hydrochloride injection stable type Pharmaceutical composition with the inventive method preparation, with the prescription of following embodiment, the result who placed 36 months in room temperature with the ambroxol hydrochloride injection related substance that does not add stabilizing agent, particulate matter, visible foreign matters compares.
Chromatographic condition:
0.01mol/L diammonium phosphate (regulating pH=7.0): acetonitrile=40: 60;
ODSC
18Chromatographic column;
1 minute/L of flow velocity;
30 ℃ of column temperatures.
Measurement result sees Table 1, table 2, table 3.
Specific embodiments:
Below listed embodiment only be indicative explanation, purpose is to help those skilled in the art to understand the present invention better, but does not limit the present invention in any way.
＜embodiment 1〉1000 components
Prescription:
Ambroxol hydrochloride 15.0g,
Citric acid 2.0g,
Sodium dihydrogen phosphate 6.0g,
Sodium chloride 18.0g,
Add the injection water to 2000ml.
Technology:
Add 1000ml water for injection earlier in container, add citric acid, sodium dihydrogen phosphate, sodium chloride successively, stirring at room was dissolved about 30 minutes, added 1mol/L hydrochloric acid or 1mol/L sodium hydroxide and transferred pH to 3-5, added ambroxol hydrochloride and fully stirred and make it to dissolve fully.Add active carbon 0.1%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 2ml embedding, sterilization, promptly gets the ambroxol hydrochloride injection.
＜embodiment 2〉1000 components
Prescription:
Ambroxol hydrochloride 30.0g,
Phosphatase 11 .0g,
Mannitol 40.0g,
Sorbitol 25.0g,
Sodium chloride 9.0g,
Add the injection water to 1000ml.
Technology:
In container, add 800ml water for injection earlier, add mannitol, sorbitol, sodium chloride stirring at room successively and dissolved about 30 minutes, add 0.1mol/L phosphoric acid or potassium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add remaining water for injection and supply full dose, add active carbon 0.2%, stirring at room 20 minutes, decarburization, adopt the filtering with microporous membrane degerming, filtrate is carried out packing by every 1ml, and pre-freeze is after 3 hours, freezing drying under reduced pressure down 15 hours, to sample temperature after room temperature, dry 5 hours again, make the white loose block, seal and promptly get ambroxol hydrochloride freeze-dried powder injection.
＜embodiment 3〉100 components
Prescription:
Ambroxol hydrochloride 15.0g,
Hydrochloric acid 2.0g,
Sodium bicarbonate 6.0g,
Sodium chloride 90.0g,
Add the injection water to 10000ml.
Technology:
In container, add 8000ml water for injection earlier, add sodium bicarbonate successively, the sodium chloride stirring at room was dissolved about 30 minutes, add 1mol/L hydrochloric acid or 1mol/L ammonium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add active carbon 0.1%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 100ml embedding, sterilization, promptly gets the ambroxol hydrochloride sodium chloride injection.
＜embodiment 4〉1000 components
Prescription:
Ambroxol hydrochloride 60.0g,
Citric acid 4.0g,
Poloxamer 1.0g,
Sodium dihydrogen phosphate 12.0g,
Sodium chloride 36.0g,
Add the injection water to 4000ml.
Technology:
In container, add 3000ml water for injection, add stabilizing agent poloxamer stirring and dissolving earlier, add citric acid, sodium dihydrogen phosphate, sodium chloride stirring at room again and dissolved about 30 minutes, add 1mol/L hydrochloric acid or 1mol/L sodium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add active carbon 0.1%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 4ml embedding, sterilization, promptly gets the ambroxol hydrochloride injection.
＜embodiment 5〉1000 components
Prescription:
Ambroxol hydrochloride 30.0g,
Citric acid 2.0g,
Mannitol 40.0g,
Lactose 20.0g,
Sodium lauryl sulphate 1.0g,
Sodium chloride 18.0g,
Add the injection water to 2000ml.
Technology:
In container, add 1600ml water for injection, add sodium lauryl sulphate, citric acid stirring and dissolving earlier, add mannitol, lactose, sodium chloride stirring at room again and dissolved about 30 minutes, add 0.1mol/L hydrochloric acid or potassium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add remaining water for injection and supply full dose, add active carbon 0.2%, stirring at room 20 minutes, decarburization, adopt the filtering with microporous membrane degerming, filtrate is carried out packing by every 2ml, and pre-freeze is after 3 hours, freezing drying under reduced pressure down 15 hours, after reaching room temperature to sample temperature, dry 5 hours again, make the white loose block, seal and promptly get ambroxol hydrochloride freeze-dried powder injection.
＜embodiment 6〉100 components
Prescription:
Ambroxol hydrochloride 25.0g,
Phosphoric acid 2.0g,
Sodium hydrogen phosphate 5.0g,
Dodecyl sodium sulfate 0.5g,
Glucose 500.0g,
Add the injection water to 5000ml.
Technology:
In container, add 4000ml water for injection, add the dodecyl sodium sulfate stirring and dissolving earlier, add sodium hydrogen phosphate again, the glucose stirring at room was dissolved about 30 minutes, added 1mol/L phosphoric acid or 1mol/L sodium hydroxide and transferred pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add active carbon 0.2%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 50ml embedding, sterilization, promptly gets the ambroxol hydrochloride glucose injection.
＜embodiment 7〉1000 components
Prescription:
Ambroxol hydrochloride 15.0g,
Citric acid 2.0g,
Sodium lauryl sulphate 1.0g,
Sodium hydrogen phosphate 4.0g,
Sodium chloride 18.0g,
Add the injection water to 2000ml.
Technology:
In container, add 1000ml water for injection, add stabilizing agent sodium lauryl sulphate stirring and dissolving earlier, adding citric acid, sodium hydrogen phosphate, sodium chloride stirring at room again dissolved about 30 minutes, add 1mol/L hydrochloric acid or 1mol/L sodium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add active carbon 0.2%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 2ml embedding, sterilization, promptly gets the ambroxol hydrochloride injection.
＜embodiment 8〉1000 components
Prescription:
Ambroxol hydrochloride 60.0g,
Mannitol 40.0g,
Galactose 40.0g,
Dodecyl sodium sulfate 0.1g,
Sodium chloride 18.0g,
Add the injection water to 2000ml.
Technology:
In container, add 1600ml water for injection, add the dodecyl sodium sulfate stirring and dissolving earlier, dissolved about 30 minutes with mannitol, galactose, sodium chloride stirring at room again, add 0.1mol/L phosphoric acid or sodium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add remaining water for injection and supply full dose, add active carbon 0.2%, stirring at room 20 minutes, decarburization, adopt the filtering with microporous membrane degerming, filtrate is carried out packing by every 2ml, and pre-freeze is after 3 hours, freezing drying under reduced pressure down 15 hours, to sample temperature after room temperature, dry 5 hours again, make the white loose block, seal and promptly get ambroxol hydrochloride freeze-dried powder injection.
＜embodiment 9〉100 components
Prescription:
Ambroxol hydrochloride 15.0g,
Citric acid 1.0g,
Sodium carbonate 5.0g,
Poloxamer 1.0g,
Low molecular dextran 500.0g,
Add the injection water to 5000ml.
Technology:
In container, add 4000ml water for injection, add stabilizing agent poloxamer stirring and dissolving earlier, add citric acid, sodium carbonate, low molecular dextran again, stirring at room was dissolved about 30 minutes, add 1mol/L hydrochloric acid or 1mol/L ammonium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add active carbon 0.15%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 50ml embedding, sterilization, promptly gets ambroxol hydrochloride low molecular dextran injection.
＜embodiment 10〉1000 components
Prescription:
Ambroxol hydrochloride 75.0g,
Citric acid 8.0g,
Sodium lauryl sulphate 1.0g,
Poloxamer 1.0g,
Potassium bicarbonate 8.0g,
Sodium chloride 90.0g,
Add the injection water to 10000ml.
Technology:
In container, add 8000ml water for injection, add stabilizing agent sodium lauryl sulphate, poloxamer stirring and dissolving earlier, add citric acid, potassium bicarbonate, sodium chloride again, stirring at room was dissolved about 30 minutes, add 1mol/L hydrochloric acid or 1mol/L sodium hydroxide, transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add active carbon 0.15%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 10ml embedding, sterilization, promptly gets the ambroxol hydrochloride injection.
＜embodiment 11〉1000 components
Prescription:
Ambroxol hydrochloride 60.0g,
Mannitol 50.0g,
Lactose 20.0g,
Dodecyl sodium sulfate 0.1g,
Carbomer 0.1g,
Sodium chloride 18.0g,
Add the injection water to 2000ml.
Technology:
In container, add 1600ml water for injection, add dodecyl sodium sulfate, carbomer stirring and dissolving earlier, dissolved about 30 minutes with mannitol, lactose, sodium chloride stirring at room again, add 0.1mol/L hydrochloric acid or sodium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add remaining water for injection and supply full dose, add active carbon 0.2%, stirring at room 20 minutes, decarburization, adopt the filtering with microporous membrane degerming, filtrate is carried out packing by every 2ml, and pre-freeze is after 3 hours, freezing drying under reduced pressure down 15 hours, after reaching room temperature to sample temperature, dry 5 hours again, make the white loose block, seal and promptly get ambroxol hydrochloride freeze-dried powder injection.
＜embodiment 12〉100 components
Prescription:
Ambroxol hydrochloride 5.0g,
Citric acid 1.0g,
Sodium dihydrogen phosphate 5.0g,
Poloxamer 1.0g,
Carbomer 1.0g,
Glucose 500.0g,
Add the injection water to 5000ml.
Technology:
In container, add 4000ml water for injection, add stabilizing agent poloxamer, carbomer stirring and dissolving earlier, add citric acid, sodium dihydrogen phosphate, glucose again, stirring at room was dissolved about 30 minutes, add 1mol/L hydrochloric acid or 1mol/L potassium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride, fully stirring makes it to dissolve fully.Add active carbon 0.2%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 50ml embedding, sterilization, promptly gets the ambroxol hydrochloride glucose injection.
＜embodiment 13〉1000 components
Prescription:
Ambroxol hydrochloride 30.0g,
Citric acid 2.0g,
Sodium lauryl sulphate 1.0g,
Carbomer 1.0g,
Sodium dihydrogen phosphate 4.0g,
Sodium chloride 36.0g,
Add the injection water to 4000ml.
Technology:
In container, add 3000ml water for injection, add stabilizing agent sodium lauryl sulphate, carbomer stirring and dissolving earlier, add citric acid, sodium hydrogen phosphate, sodium chloride again, stirring at room was dissolved about 30 minutes, add 1mol/L phosphoric acid or 1mol/L potassium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add active carbon 0.2%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 4ml embedding, sterilization, promptly gets the ambroxol hydrochloride injection.
＜embodiment 14〉1000 components
Prescription:
Ambroxol hydrochloride 75.0g,
Mannitol 50.0g,
Macrogol 4000 20.0g,
Carbomer 1.0g,
Dodecyl sodium sulfate 1.0g,
Sodium chloride 18.0g,
Add the injection water to 2000ml.
Technology:
In container, add 1600ml water for injection, add dodecyl sodium sulfate, carbomer stirring and dissolving earlier, again with mannitol, Macrogol 4000, sodium chloride, stirring at room was dissolved about 30 minutes, add 0.1mol/L hydrochloric acid or potassium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add remaining water for injection and supply full dose, add active carbon 0.2%, stirring at room 20 minutes, decarburization, adopt the filtering with microporous membrane degerming, filtrate is carried out packing by every 2ml, and pre-freeze is after 3 hours, freezing drying under reduced pressure down 15 hours, after reaching room temperature to sample temperature, dry 5 hours again, make the white loose block, seal and promptly get ambroxol hydrochloride freeze-dried powder injection.
＜embodiment 15〉100 components
Prescription:
Ambroxol hydrochloride 30g,
Citric acid 3.0g,
Sodium dihydrogen phosphate 5.0g,
Poloxamer 1.0g,
Sodium lauryl sulphate 1.0g,
Sodium chloride 45.0g,
Add the injection water to 5000ml.
Technology:
In container, add 4000ml water for injection, add stabilizing agent poloxamer, sodium lauryl sulphate stirring and dissolving earlier, add citric acid, sodium dihydrogen phosphate, sodium chloride again, stirring at room was dissolved about 30 minutes, add 1mol/L hydrochloric acid or 1mol/L ammonium hydroxide and transfer pH to 3-5, add ambroxol hydrochloride and fully stir and make it to dissolve fully.Add active carbon 0.2%, stirring at room 20 minutes is filtered carbon removal, adds remaining water for injection and supplies full dose, measures intermediate content, and fine straining with every 50ml embedding, sterilization, promptly gets the ambroxol hydrochloride sodium chloride injection.
Table 1, different embodiment stability result be (little liquid drugs injection) relatively
| Condition | Project | Embodiment 1 | Embodiment 4 | Embodiment 7 | Embodiment 10 | Embodiment 13 |
| Room temperature 0 month | Related substance | 0.18 | 0.12 | 0.15 | 0.17 | 0.14 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Particulate matter | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 3.98 | 4.02 | 4.08 | 4.10 | 4.02 | |
| Room temperature 3 months | Related substance | 0.20 | 0.14 | 0.13 | 0.15 | 0.16 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.05 | 4.07 | 4.03 | 4.08 | 4.06 | |
| Room temperature 6 months | Related substance | 0.23 | 0.15 | 0.16 | 0.14 | 0.15 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.15 | 4.10 | 4.05 | 4.05 | 4.07 | |
| Room temperature 9 months | Related substance | 0.29 | 0.20 | 0.18 | 0.19 | 0.16 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.20 | 4.12 | 4.09 | 4.07 | 4.06 | |
| Room temperature 12 months | Related substance | 0.32 | 0.21 | 0.20 | 0.18 | 0.19 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.28 | 4.10 | 4.07 | 4.10 | 4.08 | |
| Room temperature 18 months | Related substance | 0.35 | 0.22 | 0.21 | 0.23 | 0.20 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.50 | 4.15 | 4.10 | 4.13 | 4.15 | |
| Room temperature 24 months | Related substance | 0.35 | 0.22 | 0.21 | 0.23 | 0.20 |
| Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.85 | 4.18 | 4.16 | 4.15 | 4.18 | |
| Room temperature 36 months | Related substance | 0.42 | 0.24 | 0.25 | 0.27 | 0.22 |
| Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 5.02 | 4.18 | 4.16 | 4.15 | 4.18 |
Table 2, different embodiment stability result be (freeze-dried powder) relatively
| Condition | Project | Embodiment 2 | Embodiment 5 | Embodiment 8 | Embodiment 11 | Embodiment 14 |
| Room temperature 0 month | Related substance | 0.16 | 0.14 | 0.13 | 0.12 | 0.13 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Particulate matter | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.03 | 4.06 | 4.07 | 4.11 | 4.06 | |
| Room temperature 3 months | Related substance | 0.23 | 0.15 | 0.14 | 0.15 | 0.16 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.02 | 4.04 | 4.02 | 4.07 | 4.05 | |
| Room temperature 6 months | Related substance | 0.23 | 0.15 | 0.16 | 0.14 | 0.15 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.21 | 4.05 | 4.04 | 4.06 | 4.08 | |
| Room temperature 9 months | Related substance | 0.30 | 0.16 | 0.17 | 0.18 | 0.19 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.22 | 4.06 | 4.08 | 4.04 | 4.09 | |
| Room temperature 12 months | Related substance | 0.31 | 0.17 | 0.21 | 0.19 | 0.18 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.30 | 4.12 | 4.10 | 4.12 | 4.09 | |
| Room temperature 18 months | Related substance | 0.34 | 0.19 | 0.20 | 0.21 | 0.25 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.57 | 4.13 | 4.12 | 4.14 | 4.17 | |
| Room temperature 24 months | Related substance | 0.38 | 0.21 | 0.20 | 0.21 | 0.23 |
| Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.89 | 4.11 | 4.17 | 4.17 | 4.20 | |
| Room temperature 36 months | Related substance | 0.41 | 0.20 | 0.21 | 0.28 | 0.23 |
| Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 5.10 | 4.10 | 4.14 | 4.12 | 4.19 |
Table 3, different embodiment stability result be (primary infusion) relatively
| Condition | Project | Embodiment 3 | Embodiment 6 | Embodiment 9 | Embodiment 12 | Embodiment 15 |
| Room temperature 0 month | Related substance | 0.14 | 0.11 | 0.14 | 0.18 | 0.16 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Particulate matter | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.05 | 4.01 | 4.05 | 4.17 | 4.12 | |
| Room temperature 3 months | Related substance | 0.24 | 0.18 | 0.16 | 0.17 | 0.14 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
| PH value | 4.08 | 4.04 | 4.08 | 4.07 | 4.06 | |
| Room temperature 6 months | Related substance | 0.28 | 0.16 | 0.18 | 0.16 | 0.15 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.15 | 4.10 | 4.05 | 4.05 | 4.07 | |
| Room temperature 9 months | Related substance | 0.29 | 0.20 | 0.18 | 0.19 | 0.16 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.28 | 4.11 | 4.10 | 4.09 | 4.08 | |
| Room temperature 12 months | Related substance | 0.35 | 0.20 | 0.24 | 0.23 | 0.21 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.28 | 4.10 | 4.07 | 4.10 | 4.08 | |
| Room temperature 18 months | Related substance | 0.35 | 0.22 | 0.21 | 0.23 | 0.20 |
| Visible foreign matters | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.61 | 4.12 | 4.10 | 4.15 | 4.11 | |
| Room temperature 24 months | Related substance | 0.39 | 0.21 | 0.26 | 0.28 | 0.23 |
| Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 4.91 | 4.14 | 4.18 | 4.16 | 4.14 | |
| Room temperature 36 months | Related substance | 0.45 | 0.23 | 0.27 | 0.26 | 0.25 |
| Visible foreign matters | Foreign body is arranged | Up to specification | Up to specification | Up to specification | Up to specification | |
| Insoluble microparticle | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| PH value | 5.32 | 4.17 | 4.18 | 4.17 | 4.15 |
Claims (4)
1. ambroxol hydrochloride injection, it presses regulator to form by active ingredient hydrochloric acid ambroxol, pH regulator agent, stabilizing agent, water for injection, Seepage thoroughly; Its feature is composed as follows:
1000 components
Ambroxol hydrochloride 15.0g,
Citric acid 2.0g,
Sodium dihydrogen phosphate 6.0g,
Sodium chloride 18.0g,
Add the injection water to 2000ml.
2. ambroxol hydrochloride injection, it presses regulator to form by active ingredient hydrochloric acid ambroxol, pH regulator agent, stabilizing agent, water for injection, Seepage thoroughly; Its feature is composed as follows:
1000 components
Ambroxol hydrochloride 60.0g,
Citric acid 4.0g,
Poloxamer 1.0g,
Sodium dihydrogen phosphate 12.0g,
Sodium chloride 36.0g,
Add the injection water to 4000ml.
3. ambroxol hydrochloride injection, it presses regulator to form by active ingredient hydrochloric acid ambroxol, pH regulator agent, stabilizing agent, water for injection, Seepage thoroughly; Its feature is composed as follows:
1000 components
Ambroxol hydrochloride 15.0g,
Citric acid 2.0g,
Sodium lauryl sulphate 1.0g,
Sodium hydrogen phosphate 4.0g,
Sodium chloride 18.0g,
Add the injection water to 2000ml.
4. ambroxol hydrochloride injection, it presses regulator to form by active ingredient hydrochloric acid ambroxol, pH regulator agent, stabilizing agent, water for injection, Seepage thoroughly; Its feature is composed as follows:
1000 components
Ambroxol hydrochloride 75.0g,
Citric acid 8.0g,
Sodium lauryl sulphate 1.0g,
Poloxamer 1.0g,
Potassium bicarbonate 8.0g,
Sodium chloride 90.0g,
Add the injection water to 10000ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100599696A CN101416956B (en) | 2007-10-22 | 2007-10-22 | Ambroxol hydrochloride injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100599696A CN101416956B (en) | 2007-10-22 | 2007-10-22 | Ambroxol hydrochloride injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101416956A CN101416956A (en) | 2009-04-29 |
| CN101416956B true CN101416956B (en) | 2011-03-16 |
Family
ID=40628082
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100599696A Active CN101416956B (en) | 2007-10-22 | 2007-10-22 | Ambroxol hydrochloride injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101416956B (en) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101627967B (en) * | 2009-08-03 | 2011-12-28 | 上海华源药业（宁夏）沙赛制药有限公司 | Ambroxol hydrochloride liquid preparation and preparation method thereof |
| CN101836952B (en) * | 2010-06-09 | 2012-03-14 | 云南龙海天然植物药业有限公司 | Ambroxol injection and preparation method thereof |
| CN101836953B (en) * | 2010-06-12 | 2011-08-17 | 山东罗欣药业股份有限公司 | Ambroxol hydrochloride composition injection |
| CN102552119B (en) * | 2010-12-28 | 2013-08-07 | 四川科伦药物研究有限公司 | Ambroxol hydrochloride glucose injection and preparation method thereof |
| CN102153482B (en) * | 2011-02-28 | 2013-04-03 | 天津市铭泰医药科技有限公司 | Method for refining injection-level ambroxol hydrochloride, product and injection thereof |
| CN102225049B (en) * | 2011-06-17 | 2012-11-21 | 成都百裕科技制药有限公司 | Preparation method of ambroxol hydrochloride injection with stable pH value |
| CN103006548B (en) * | 2011-09-28 | 2015-10-07 | 四川科伦药物研究有限公司 | Ambroxol hydrochloride glucose injection and preparation method thereof |
| CN102429879B (en) * | 2011-11-29 | 2013-05-29 | 海南灵康制药有限公司 | Ambroxol hydrochloride liposome injection |
| CN102872462B (en) * | 2012-10-26 | 2013-04-17 | 山东罗欣药业股份有限公司 | Ambroxol hydrochloride composition and preparation thereof |
| 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 |
| CN103393593B (en) * | 2013-08-02 | 2014-09-10 | 海南灵康制药有限公司 | Pharmaceutical composition containing ambroxol hydrochloride and fructose |
| CN103505423B (en) * | 2013-09-10 | 2016-01-20 | 马鞍山丰原制药有限公司 | Bisolvon lyophilized injectable powder 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 |
| 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 |
| CN105326804B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | Ambroxol salbutamol dripping pill |
| CN105326815B (en) * | 2015-12-08 | 2018-06-01 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol salbutamol controlled release capsule |
| CN105456221B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol salbutamol enteric coated particles |
| CN105326789B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | Ambroxol albuterol solution agent |
| CN105326805B (en) * | 2015-12-08 | 2018-06-12 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol salbutamol dripping pill |
| CN105326790B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol albuterol solution agent |
| CN105434412A (en) * | 2015-12-08 | 2016-03-30 | 青岛正大海尔制药有限公司 | Ambroxol and salbutamol controlled release capsule |
| CN105456201B (en) * | 2015-12-08 | 2018-06-01 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol salbutamol pellet |
| CN105326796B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | Ambroxol salbutamol powder |
| CN106074373A (en) * | 2016-08-18 | 2016-11-09 | 黑龙江中桂制药有限公司 | A kind of preparation method of Ambroxol Hydrochloride Glucose Injection |
| CN106667902B (en) * | 2016-12-31 | 2020-06-02 | 辰欣药业股份有限公司 | Stable ambroxol hydrochloride injection and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1954808A (en) * | 2005-10-27 | 2007-05-02 | 常州市第四制药厂有限公司 | High dose Ambroxol hydrochloride freeze-dried preparation and preparation method |
-
2007
- 2007-10-22 CN CN2007100599696A patent/CN101416956B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1954808A (en) * | 2005-10-27 | 2007-05-02 | 常州市第四制药厂有限公司 | High dose Ambroxol hydrochloride freeze-dried preparation and preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101416956A (en) | 2009-04-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101416956B (en) | Ambroxol hydrochloride injection | |
| CN100372534C (en) | Torasemide freeze-drying preparation and prepn. method | |
| CN101935099A (en) | Composition for purifying water quality and preparation method thereof | |
| CN102860980A (en) | Method for preparing rocuronium bromide injection | |
| CN101088492B (en) | Stable supersaturated gemcitabine hydrochloride solution and its preparation process | |
| CN102872462B (en) | Ambroxol hydrochloride composition and preparation thereof | |
| CN108261398A (en) | A kind of injection pharmaceutical preparation containing Levosimendan and preparation method thereof | |
| CN100389767C (en) | Injectable stable pharmaceutical composition containing active ingredient silibinin and its salt | |
| CN102349893A (en) | Edaravone pharmaceutical composition | |
| CN101554370B (en) | Syringin for injection, preparation method and application thereof | |
| CN101450051B (en) | Monomer salvianolic acid B injection and preparation method thereof | |
| CN101822822A (en) | Drug composition of pramlintide and preparation method thereof | |
| CN103006550A (en) | Citicoline sodium injection and preparation method thereof | |
| CN102871961B (en) | Injection containing tirofiban | |
| CN103536551A (en) | Fluorouracil composition freeze-dried powder for injection | |
| CN102138925B (en) | Tigecycline composition and preparation method thereof | |
| CN101129329A (en) | Injection containing huperzine for sulci venosi and method of preparing the same | |
| CN103393685B (en) | Pharmaceutical composition containing oxaliplatin and fluorouracil | |
| CN101697973B (en) | Cefathiamidine preparation for injection and preparation method thereof | |
| CN1537530A (en) | Unit dosage type compound cantharis acid powder-injection, and its prepn. method | |
| CN1813744A (en) | Method for preparing levogatifloxacin formulation for intravenous injection and formulation using same | |
| CN104645334A (en) | N-acetylcysteine and activated carbon composition as well as preparation method and application thereof | |
| CN1843504B (en) | Albumin nanosphere medicine composition and its preparation method and application method | |
| CN1836654A (en) | Pharmaceutical composition for stabilizing ambroxol hydrochloride granula | |
| CN101444478A (en) | Injection preparation containing active constituent adefovir dipivoxil and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: TIANJIN PRECEDE MEDICAL TRADE CO., LTD. Free format text: FORMER OWNER: KANGHONG MEDICINE TECH DEVELOPMENT CO., LTD., TIANJIN Effective date: 20110727 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 300193 NANKAI, TIANJIN TO: 300574 BINHAI NEW DISTRICT, TIANJIN |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20110727 Address after: 300574 building 3, No. 66 Dongting Road, Tianjin Development Zone, 406 Patentee after: Tianjin Purisen Medicine Trade Co.,Ltd. Address before: 300193 Tianjin City, Nankai District Anshan West Road No. 308 Patentee before: Tianjin Kanghong Pharmaceutical Science and Technology Development Co.,Ltd. |
|
| C56 | Change in the name or address of the patentee |
Owner name: TIANJIN KANGZHE PHARMACEUTICAL TECHNOLOGY DEVELOPM Free format text: FORMER NAME: TIANJIN PRECEDE MEDICAL TRADE CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 300574 building 3, No. 66 Dongting Road, Tianjin Development Zone, 406 Patentee after: Tianjin wisdom pharmaceutical science and Technology Development Co.,Ltd. Address before: 300574 building 3, No. 66 Dongting Road, Tianjin Development Zone, 406 Patentee before: Tianjin Purisen Medicine Trade Co.,Ltd. |
|
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20090429 Assignee: TIANJIN INSTITUTE OF PHARMACEUTICAL RESEARCH PHARMACEUTICAL RESPONSIBLE CO.,LTD. Assignor: Tianjin wisdom pharmaceutical science and Technology Development Co.,Ltd. Contract record no.: 2012990000894 Denomination of invention: Ambroxol hydrochloride injection Granted publication date: 20110316 License type: Exclusive License Record date: 20121218 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: Room 215-218, Floor 2, Building D, Comprehensive Service Area, Nangang Industrial Zone, 300000 Binhai New Area Development Zone, Tianjin Patentee after: Tianjin Kangzheweisheng Pharmaceutical Technology Development Co.,Ltd. Address before: 300574 406, Building 3, No. 66, Dongting Road, Tianjin Development Zone Patentee before: Tianjin wisdom pharmaceutical science and Technology Development Co.,Ltd. |