CN100563641C - The compositions of ambroxol or its salt and anti-infectives - Google Patents
The compositions of ambroxol or its salt and anti-infectives Download PDFInfo
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- CN100563641C CN100563641C CNB2005101311210A CN200510131121A CN100563641C CN 100563641 C CN100563641 C CN 100563641C CN B2005101311210 A CNB2005101311210 A CN B2005101311210A CN 200510131121 A CN200510131121 A CN 200510131121A CN 100563641 C CN100563641 C CN 100563641C
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- compositions
- ammonia
- group
- andrographolide
- baicalin
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 140
- 229960005174 ambroxol Drugs 0.000 title claims abstract description 18
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical group NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 title claims abstract description 18
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
- 239000002552 dosage form Substances 0.000 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 abstract description 71
- IKIIZLYTISPENI-ZFORQUDYSA-N baicalin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IKIIZLYTISPENI-ZFORQUDYSA-N 0.000 abstract description 56
- 229960000985 ambroxol hydrochloride Drugs 0.000 abstract description 53
- BOJKULTULYSRAS-OTESTREVSA-N Andrographolide Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1/[C@H](O)COC1=O BOJKULTULYSRAS-OTESTREVSA-N 0.000 abstract description 51
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- ASLUCFFROXVMFL-UHFFFAOYSA-N andrographolide Natural products CC1(CO)C(O)CCC2(C)C(CC=C3/C(O)OCC3=O)C(=C)CCC12 ASLUCFFROXVMFL-UHFFFAOYSA-N 0.000 abstract description 42
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to medical technical field, a kind of pharmaceutical composition that contains ambroxol or its pharmaceutically acceptable salt and at least a anti-infectives and its production and use is disclosed, wherein anti-infectives is selected from: baicalin and/or 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt, this pharmaceutical composition can be made into various pharmaceutically acceptable dosage forms; Compositions has synergistic function in aspect diseases such as being used for thick sputum that preparation treatment causes by the microbial upper respiratory tract infection of sensitivity, chronic bronchitis, pneumonia and upper respiratory tract infection (as acute and chronic bronchitis, bronchial asthma, bronchiectasis, pulmonary tuberculosis etc.), dys-expectoration, and good stability, improve greatly than singly using with the ambroxol hydrochloride of dosage or the effect of baicalin or andrographolide, produced beyond thought effect, be with a wide range of applications.
Description
1, technical field
The present invention relates to a kind of contain ambroxol or its pharmaceutically acceptable salt and and the pharmaceutical composition of at least a anti-infectives and preparation method thereof, belong to medical technical field.
2, background technology
In China's demography, respiratory system disease is second cause of the death, mainly comprise upper respiratory tract infection, acute and chronic bronchitis, diseases such as pneumonia, its cardinal symptom has cough, expectoration and asthma etc., and respiratory system disease is mainly in winter-spring season, many elder generations are caused that by viral infection minority is by due to the antibacterial direct infection.But alternative clinically medicine is also few and onset is slower.
Ambroxol (ambroxol Amb) is the derivant of bromine hexylamine, and its chemistry is called anti--4[(2-amino-3,5-dibromobenzene methyl) amino] Hexalin, be a kind of new glutinous expectorant dissolving medicine, its expectorant effect is better than bromhexine.This medical instrument has dissolving secretion mucus and promotes the effect that mucus is got rid of, and can increase the secretion of respiratory mucosa serous gland, reduces the mucous gland secretion, thereby reduces the sputum viscosity; Can promote simultaneously the secretion of pulmonary surfactant, increase the bronchus ciliary movement, make sputum be easy to expectoration, reach remarkable expectoration, improve the effect of breath state.Be applicable to thick sputum that acute and chronic respiratory tract disease (as acute and chronic bronchitis, bronchial asthma, bronchiectasis, pulmonary tuberculosis etc.) causes, dys-expectoration etc.(ambroxol hydrochloride Amb) is the hydrochlorate of ambroxol to ambroxol hydrochloride, with it identical mechanism of action is arranged, the domestic existing listings of oral formulations such as ambroxol hydrochloride sheet, capsule at present.
Radix Scutellariae is the dry root of labiate Radix Scutellariae Scutellaria baicalensis Georgi, and property hardship, cold is returned lung, gallbladder, spleen, large intestine, small intestine meridian, effect with heat clearing and damp drying, eliminating fire and detoxication, be used for hygropyrexia, fever disease in summer vomiting and nausea uncomfortable in chest, cough due to lung-heat, diseases such as hyperpyrexia excessive thirst.Baicalin is the effective active composition that extracts in the Radix Scutellariae, be β-maltonic acid-5,6-dihydroxy 4-oxygen-2-phenyl-4H-.alpha.-5:6-benzopyran-7, recorded into the 10th 239 pages of national drug standards chemical drugs provincial standard rising national standards of National Drug Administration (Chinese Pharmacopoeia Commission's volume), wherein regulation contains baicalin (C
21H
18O
11) must not be less than 90.0% (injection); Must not be less than 83.0% (for oral use).Baicalin is an antimicrobial drug, has pharmacological actions such as antibacterial anti-inflammatory, heat-clearing and toxic substances removing, chelated metal ions, calmness, blood pressure lowering, neuroprotective, is mainly used in diseases such as infection, pneumonia, hepatitis, hypertension.Domestic existing 5 families of baicalin raw material listing at present.
Herba Andrographis is the dry aerial parts of acanthaceous plant Herba Andrographis Andrographis paniculata (Burm.f.) Ness, has heat-clearing and toxic substances removing, removing heat from blood, repercussive effect, and its main active is an andrographolide.14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is the andrographolide that extracts from Herba Andrographis, after semi-synthetic, the derivant of making that highly bioactive Herba Andrographis is arranged makes route of administration more direct, and pharmacological action is stronger, toxic and side effects is littler, has analgesic, antiinflammatory, sterilization, antiviral effect.Pharmacological research shows that its k-na salt (being andrographolide) can suppress early stage capillary permeability and increase and inflammatory exudation and edema, can excited specifically hypophysis-adrenal cortex function, and promote ACTH to discharge, increase the biosynthesis of ACTH in the antepituitary; External effect with multiple viruses such as deactivation adenovirus, influenza virus, Respiroviruses.That its potassium salt (being Andrographolide) has is analgesic, calm, increase the emergency capability of body to pathogenic infection, and influenza virus, pneumonia adenovirus, intestinal syncytial virus and respiratory syncytial virus are had deactivation.
Utilize ambroxol or its pharmaceutically acceptable salt and baicalin, 14-deshydroxy-11 at present, 12-two dehydrogenation andrographolide-3, the interaction of one or more in the 19-disuccinic acid half ester salt, composition of prescription, be used for the treatment of the medicine of aspects such as the thick sputum that causes by the microbial upper respiratory tract infection of sensitivity, chronic bronchitis, pneumonia and upper respiratory tract infection (as acute and chronic bronchitis, bronchial asthma, bronchiectasis, pulmonary tuberculosis etc.), dys-expectoration, do not appear in the newspapers as yet.
3, summary of the invention
In order to meet clinical needs, better treat respiratory system disease, improve the people ' s health level, the invention provides a kind of pharmaceutical composition and preparation method thereof, said composition contains ambroxol or its pharmaceutically acceptable salt and at least a anti-infectives of effective dose, and wherein anti-infectives is selected from: baicalin and/or 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt.
Aforementioned pharmaceutical compositions, its parts by weight are: 5～120 parts of ambroxol or its pharmaceutically acceptable salts, anti-infectives is different and different according to medicine, for baicalin is 125～2000 parts, for 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is 10～200 parts.
Aforementioned pharmaceutical compositions, its parts by weight are preferably: 10～60 parts of ambroxol or its pharmaceutically acceptable salts, anti-infectives is different and different according to medicine, for baicalin is 250～1000 parts, for 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is 20～80 parts.
Aforementioned pharmaceutical compositions, its parts by weight be more preferably: 30 parts of ambroxol or its pharmaceutically acceptable salts, anti-infectives are different and different according to medicine, for baicalin is 500 parts, for 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is 40 parts.
Aforementioned pharmaceutical compositions, its parts by weight are particularly preferred to be: the compositions that 30 parts of ambroxol or its pharmaceutically acceptable salts and baicalin are 500 parts; Perhaps be: 30 parts of ambroxol or its pharmaceutically acceptable salts and 14-deshydroxy-11,12-two dehydrogenation andrographolide-3, the compositions that 19-disuccinic acid half ester salt is 40 parts.
More than form to be by weight as proportioning, when producing, can or reduce according to the corresponding proportion increase, as large-scale production can be unit with the kilogram, or be unit with the ton, small-scale production can be unit with the gram also, weight can increase or reduce, but the constant rate of weight proportion between each composition.
More than form, as if being unit with the gram, can make the preparation of 100～10000 consumptions, as injection, can be made into 100～10000,1～10 of each consumption as tablet, can be made into 100～10000, takes 1～10 at every turn.
The ratio of above weight proportion obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
The consumption of drug component of the present invention is groped to sum up to draw through the inventor in a large number, and each amounts of components all has better curative effect in above-mentioned weight portion scope.
Pharmaceutical composition of the present invention, ambroxol pharmaceutically acceptable salt are hydrochlorate, sulfate, lactate, acetate, mesylate, tartrate, maleate, fumarate, hydrobromate, aspartate, the preferred salt hydrochlorate.
Pharmaceutical composition of the present invention, 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is monopotassium salt, single sodium salt, k-na salt, single magnesium salt, single calcium salt, single zinc salt, preferred monopotassium salt (being Andrographolide), single sodium salt or k-na salt (being andrographolide).And have at present and experiment showed, 14-deshydroxy-11,12-two dehydrogenation andrographolide-3, the variation between the different salts such as the monopotassium salt of 19-disuccinic acid half ester, single sodium salt or k-na salt does not have tangible influence to its drug action.
The present invention also provides pharmaceutical composition of the present invention in the application that is used for aspects such as thick sputum that preparation treatment causes by the microbial upper respiratory tract infection of sensitivity, chronic bronchitis, pneumonia and upper respiratory tract infection (as acute and chronic bronchitis, bronchial asthma, bronchiectasis, pulmonary tuberculosis etc.), dys-expectoration.
Pharmaceutical composition of the present invention can add one or more pharmaceutically acceptable carriers, with oral, snuffing is gone into or the mode of parenteral is applied to the patient who needs this treatment.Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, soft capsule, dispersible tablet, oral liquid, granule, chewable tablet, oral cavity disintegration tablet, drop pill, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, make liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup etc.; When being used for parenteral, can be made into solution, water or the oil-suspending agent etc. of injection, as liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion etc.The preferred dosage form of this compositions is oral formulations or injection or inhalant, as sheet, capsule, granule, powder pin, liquid drugs injection, transfusion etc.
Pharmaceutical composition of the present invention can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.
Pharmaceutical composition of the present invention is when making oral formulations, and selectable filler has: starch, Icing Sugar, calcium phosphate, calcium sulfate two water things, dextrin, microcrystalline Cellulose, lactose, pregelatinized Starch, mannitol etc.; Selectable binding agent has: sodium carboxymethyl cellulose, PVP-K30, hydroxypropyl cellulose, starch slurry, methyl fiber rope, ethyl cellulose, hypromellose, gelling starch etc.; Selectable disintegrating agent has: dried starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose etc.; Selectable lubricant has: magnesium stearate, Pulvis Talci, sodium lauryl sulphate, micropowder silica gel etc.
Pharmaceutical composition of the present invention in order to increase its dissolubility, can add solubilizing agents such as polyoxyethylene sorbitan monoleate when making injection.Can add the isoosmotic adjusting agent that is used to regulate osmotic pressure in the transfusion, for example, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.
The present composition has the following advantages:
(1) pharmaceutical composition of aspect such as the thick sputum that provides a kind of ambroxol or its pharmaceutically acceptable salt and at least a anti-infectives compatibility to be used for the treatment of upper respiratory tract infection, chronic bronchitis, pneumonia and upper respiratory tract infection (as acute and chronic bronchitis, bronchial asthma, bronchiectasis, pulmonary tuberculosis etc.) first to cause, dys-expectoration and its production and use has satisfied urgent clinical needs;
(2) first the interaction and the composition of prescription of the present composition carried out pharmacodynamic study, found that compositions has tangible breath state, antibiotic, antiviral, the refrigeration function of improving, chronic obstructive pulmonary disease (COPD) rat model lung there is remarkable protective effect, can reduce the expression of TNF-a among the COPD, airway inflammation is had inhibitory action; Can obviously increase the phenol red secretory volume in mouse breathing road; Can reduce external bacteriostatic minimal inhibitory concentration; To significant protective effect being arranged by the mice of bacterial infection; The pneumonia that virus infected mice is caused has the obvious suppression effect; Also the rabbit body temperature that vaccine is caused raises the obvious suppression effect is arranged.In above-mentioned each experimental group, compositions experimental group and ambroxol hydrochloride group or baicalin group or andrographolide group are compared, significant difference is remarkable (p＜0.05) all, it is remarkable to show that ambroxol hydrochloride and anti-infectives baicalin or andrographolide share effect, and consequently those skilled in the art institute is beyond thought;
(3) preparation technology of the present invention is simple, and drug quality is uniform and stable;
(4) stability experiment that carries out shows that the every index of pharmaceutical composition of the present invention is all more stable, has guaranteed safety of clinical administration;
(5) present composition drug combination determined curative effect, and reduced relative dosage, be with a wide range of applications.
Below routine by experiment beneficial effect of further setting forth medicine of the present invention.In the following experimental example: the compositions of ambroxol hydrochloride, baicalin hereinafter to be referred as
The yellow compositions of ammoniaThe compositions of ambroxol hydrochloride, andrographolide hereinafter to be referred as
The scorching compositions of ammonia
The yellow compositions of experimental example 1 ammonia, the scorching compositions of ammonia are to the protective effect of chronic obstructive pulmonary disease (COPD) rat model lung
Experiment material and instrument: main medicine and source: 0.9% normal saline, commercial; Ambroxol hydrochloride, commercial; The yellow compositions of ammonia (ambroxol hydrochloride+baicalin=30mg+500mg), self-control; The scorching compositions of ammonia (ambroxol hydrochloride+andrographolide=30mg+40mg), self-control; TNF-in situ hybridization test kit is available from Wuhan Boster Biological Technology Co., Ltd.;
Key instrument: OLYMPUS-CH microscope (Japanese Olympus company); OLYMPUS-BH
2Photomicrographic device (Japanese Olympus company); Lucite is smoked case (Beijing respiratory disease institute); Image analyzer (Japanese Olympus company).
Animal subject: Wistar rat, 90, Mus 12 weeks of age, body weight 240 ± 20g.
Experimental technique: 1. animal grouping and modelling
90 of healthy male Wistar rats are divided into following 9 groups at random: normal healthy controls group, COPD model group, ambroxol hydrochloride group, basic, normal, high three the dosage groups of the yellow compositions of ammonia, basic, normal, high three the dosage groups of the scorching compositions of ammonia, 10 every group.The normal healthy controls group places indoor normal nursing, irritates stomach and gives normal saline 1mL, every day 1 time.The COPD model group is used the smoked interior injection of the gas-adding pipe LPS method of inhaling of medicated cigarette and is set up the COPD model, respectively at injecting each 200 μ g (200 μ L) of LPS in the 1st, 21 day trachea, rat placed in the smoked case of airtight lucite in the 2nd～20 day, the 22nd～40 day, inject big chicken board cigarette with filter tip smog, each 10 medicated cigarettes, be total to 2h, every day 2 times.Irritate stomach on the 1st～40 day and give normal saline 1mL, every day 1 time.Each administration group except that normal healthy controls group, COPD model group is used the smoked interior injection of the gas-adding pipe LPS method of inhaling of medicated cigarette and is set up the COPD model, and gastric infusion when model begins to set up, dosage see Table 1,2,3, every day 1 time, 40d continuously.
2. animal is handled and morphological observation
After the rat abdominal cavity anesthesia, dissect the exposure common carotid artery, take arterial blood to detect arterial partial pressure of oxygen and arterial partial pressure of carbon dioxide.Rat sacrificed by exsanguination is afterwards dissected and is exposed trachea, with lung tissue exsomatize, formaldehyde fixed, conventional gradient ethanol dehydration, waxdip, embedding.The routine paraffin wax section, hematoxylin-eosin staining, om observation.Get 3 rats for every group, cut the about 2mm in cross section * 10mm LS, send that Electron Microscopy Room carries out that the back is fixing, dehydration, embedding, section, dyeing, transmission electron microscope observing.And use micro--microcomputer image processing system, measure following index: 1. average alveolar number (MAN): count the alveolar number in each visual field, divided by the area in this visual field, promptly get MAN, its numerical value can reflect alveolar density.2. the average liner of alveolar (MLI) at interval, its numerical value reflection alveolar average diameter.
3.TNF-a the detection of expressing
Adopt the situ hybridization method, light microscopic is observed down, cytoplasm the brown yellow granule the occurs positive cell of person.Get and partially slicedly replace probe, positive cell do not occur, illustrate that probe specificity is strong with 0.1mol/LPBS.With image analyzer gray scale scanning being carried out in the in situ hybridization section, is 1 with the matched group gray scale, the relative intensity that record TNF-a mRNA expresses.
4. statistical procedures
Data represent that with mean ± standard deviation application SPSS 11.0 statistical packages take statistics to learn and handle, and two sample means are relatively used the t check, and many batch totals amount data is relatively used variance analysis.
Experimental result: 1.COPD rat model outward appearance is observed
COPD rat model hair tarnishes, and is yellow puckery; The look asthenia, mobility descends; Body constitution amount and healthy rat there was no significant difference (p＞0.05).
2. PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM
Under the light microscopic, normal healthy controls group bronchus of rat mucosal epithelium structural integrity, bronchus cilium marshalling, alveolar structure is complete, no edema due to disorder of QI and inflammation, big or small uniformity.COPD model group rat has the characteristic pathological change of chronic bronchitis, obstructive emphysema.The pathological change of ambroxol hydrochloride group bronchus of rat lung tissue such as inflammatory cell infiltration, goblet cell hypertrophy, alveolar ectasia fusion, pulmonary congestion etc. all obviously alleviate than the COPD model group; But compare with the normal healthy controls group, still have the pathological characteristic of chronic bronchitis, obstructive emphysema.The pathological change of yellow basic, normal, high dosage group of compositions of ammonia and the basic, normal, high dosage group of the scorching compositions of ammonia bronchus of rat lung tissue such as inflammatory cell infiltration, goblet cell hypertrophy, alveolar ectasia fusion, pulmonary congestion etc. all extremely obviously alleviate than the COPD model group; And compare with the normal healthy controls group, the pathological characteristic of chronic bronchitis, obstructive emphysema does not have notable difference.
3. respectively organize lung tissue morphology measurement result
Table 1 lung tissue morphology measurement result (x ± s)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the normal healthy controls group;
#P＜0.05,
##P＜0.01 is compared with the COPD model group;
﹠amp;P＜0.05 is compared with the ambroxol hydrochloride group.
COPD model group MLI is greater than the normal healthy controls group, difference have utmost point significance (
*P＜0.01); MAN is less than the normal healthy controls group, have utmost point significant difference (
*P＜0.01).Ambroxol hydrochloride group MLI is less than the COPD model group, difference have significance (
#P＜0.05); MAN is more than the COPD model group, have significant difference (
#P＜0.05).Ambroxol hydrochloride group MLI, MAN and normal healthy controls group relatively, all have significant difference (
*P＜0.05).Yellow basic, normal, high dosage group of compositions of ammonia and the basic, normal, high dosage group of the scorching compositions of ammonia MLI be all less than the ambroxol hydrochloride group, have significant difference (
﹠amp;P＜0.05); MAN is more than the ambroxol hydrochloride group, have significant difference (
﹠amp;P＜0.05); MLI, MAN and COPD model group relatively, all have utmost point significant difference (
##P＜0.01); MLI, MAN and normal healthy controls group relatively all do not have significant difference (p＞0.05).See Table 1.
4. blood gas analysis result
COPD model group arterial partial pressure of oxygen is lower than the normal healthy controls group, have utmost point significant difference (
*P＜0.01); Arterial partial pressure of carbon dioxide is higher than the normal healthy controls group, have utmost point significant difference (
*P＜0.01).Ambroxol hydrochloride group arterial partial pressure of oxygen and partial pressure of carbon dioxide and normal healthy controls group more also have significant difference (
*P＜0.05); With the COPD model group more also have significant difference (
#P＜0.05).Scorching compositions basic, normal, high dosage group arterial partial pressure of oxygen of yellow basic, normal, high dosage group of compositions of ammonia and ammonia and partial pressure of carbon dioxide and COPD model group more all have utmost point significant difference (
##P＜0.01), with the ambroxol hydrochloride group more all have significant difference (
﹠amp;P＜0.05), more all there is not significant difference (p＞0.05) with the normal healthy controls group.See Table 2.
Table 2 arterial blood gas analysis result (p/kPa, x ± s)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the normal healthy controls group;
#P＜0.05,
##P＜0.01 is compared with the COPD model group;
﹠amp;P＜0.05 is compared with the ambroxol hydrochloride group.
5.TNF-amRNA express
Table 3 TNF-a mRNA is at the expression of bronchial mucosa epithelium (x ± s)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the normal healthy controls group;
#P＜0.05,
##P＜0.01 is compared with the COPD model group;
﹠amp;P＜0.05 is compared with the ambroxol hydrochloride group.
The TNF-amRNA gene has certain expression in the normal healthy controls group lung tissue, and expressing obviously in the COPD model group increases, and both comparing differences have significance (p＜0.01).Ambroxol hydrochloride group TNF-a mRNA expression intensity and normal healthy controls group comparing difference significance (
*P＜0.05); With the COPD model group more also have significant difference (
#P＜0.05).Scorching compositions basic, normal, high dosage group TNF-a mRNA expression intensity of yellow basic, normal, high dosage group of compositions of ammonia and ammonia and COPD model group more all have utmost point significant difference (
##P＜0.01), with the ambroxol hydrochloride group more all have significant difference (
﹠amp;P＜0.05), more all there is not significant difference (p＞0.05) with the normal healthy controls group.See Table 3.
In sum; yellow basic, normal, high dosage group of compositions of ammonia and the basic, normal, high dosage group of the scorching compositions of ammonia all are better than the ambroxol hydrochloride group to the protective effect of chronic obstructive pulmonary disease (COPD) rat model lung; can reduce the expression of TNF-a among the COPD; airway inflammation there is inhibitory action; can safeguard the integrity of alveolar type II epithelial cell structure, promote the synthetic and secretion of PS.Show that each compositions compatibility of the present invention has synergistic function, and action effect is relevant with the dosage of each compositions, effect of high dosage is best.
The yellow compositions of experimental example 2 ammonia, the scorching compositions of ammonia are to the influence of the phenol red secretory volume in mouse breathing road
Experiment material and instrument: main medicine and source: 0.9% normal saline, commercial; Ambroxol hydrochloride, commercial; The yellow compositions of ammonia (ambroxol hydrochloride+baicalin=30mg+500mg), self-control; The scorching compositions of ammonia (ambroxol hydrochloride+andrographolide=30mg+40mg), self-control;
Key instrument: 722 type spectrophotometers.
Animal subject: healthy Kunming mouse, body weight 24～28g, male, 80.
Experimental technique: get 80 of mices, be divided into 8 groups at random, be respectively blank group, ambroxol hydrochloride group, basic, normal, high three the dosage groups of the yellow compositions of ammonia, basic, normal, high three the dosage groups of the scorching compositions of ammonia, 10 every group.Each administration group, every day gastric infusion, dosage sees Table 4, successive administration 3 days, the blank group is irritated stomach and is given normal saline.Last administration fasting in preceding 1 day, 0.5 hour lumbar injection 5% phenol red solution 500mg/kg after the last administration.Gave excessive anesthetics after 0.5 hour and put to death animal, separate trachea, insert injection, use the 2ml normal saline flushing, flushing liquor adds 1M NAOH 0.1ml colour developing, in 546nm wavelength colorimetric, calculates phenol red content with 722 type spectrophotometers.
The yellow compositions of table 4 ammonia, the scorching compositions of ammonia are to the influence of the phenol red secretory volume in mouse breathing road (X ± SD)
Annotate:
#P＜0.05,
##P＜0.01 is compared with the blank group;
﹠amp;P＜0.05 is compared with the ambroxol hydrochloride group.
Experimental result: the results are shown in Table 4.Each administration group all obviously increase the phenol red secretory volume in mouse breathing road (
#P＜0.05 He
##P＜0.01).Wherein basic, normal, high three the dosage groups of the yellow compositions of ammonia, basic, normal, high three the dosage groups of the scorching compositions of ammonia are compared the effect enhancing with single with the ambroxol hydrochloride group, significant difference (
﹠amp;P＜0.05), and action effect is relevant with the dosage of each compositions, and effect of high dosage is best.
The yellow compositions of experimental example 3 ammonia, the outer minimum inhibitory concentration experiment of the scorching composition of ammonia
Experiment material: main medicine and source: 0.9% normal saline, commercial; Levofloxacin, commercial; Baicalin, commercial; Andrographolide, self-control; The yellow compositions of ammonia (ambroxol hydrochloride+baicalin=30mg+500mg), self-control; The scorching compositions of ammonia (ambroxol hydrochloride+andrographolide=30mg+40mg), self-control;
Strain: staphylococcus aureus, escherichia coli, bacillus subtilis, alpha streptococcus, Diplococcus pneumoniae, hemophilus influenza.
The preparation of test liquid: the normal saline group is made as negative control group, the levofloxacin group is made as positive controls, get negative control group, positive controls, baicalin group, andrographolide group, the yellow compositions group of ammonia, the scorching compositions group of ammonia, be mixed with the test liquid that concentration is 8mg/ml respectively, serial dilution is the test liquid of 4mg/ml, 2mg/ml, 1mg/ml, 0.5mg/ml, 0.25mg/ml, 0.125mg/ml.
The preparation of bacteria suspension: with above-mentioned for the examination strain with suitable slant activation after, make with sterilized water and to contain the bacterium number and be about 10
8Individual/the ml bacteria suspension.
The mensuration of minimum inhibitory concentration (MIC): preparation bacterial liquid culture medium, accurately measure 8ml by every pipe, the packing test tube, 21 of each strain packing of antibacterial, in 121.3 ℃ of warm sterilizations 20 minutes, accurately measure 8mg/ml then, 4mg/ml, 2mg/ml, 1mg/ml, 0.5mg/ml, 0.25mg/ml, 0.125mg/ml the medicine 1ml of series concentration, inject sterilized fluid medium, each concentration repeats 3 times, a kind of bacterium of each series inoculation, every test tube accurately injects the 0.1ml bacteria suspension, and antibacterial is put 37 ℃ of cultivation 1～2d in the incubator, observes the growth phenomenon.Another series is not inoculated any strain as blank.
Minimum inhibitory concentration is used the OD value representation.With the OD value of 721 type spectrophotometric determination inoculums, culture fluid OD value becomes positive correlation with the interior bacterial reproduction speed of culture fluid under the 550nm wavelength; Culture after the cultivation and blank carry out colorimetric determination on 721 spectrophotometers, identical with the two absorption, do not have the minimum inhibitory concentration of the least concentration of bacteria growing as the yellow compositions of ammonia, the scorching compositions of ammonia in the culture medium.
The yellow compositions of table 5 ammonia, the scorching compositions of ammonia are to the minimum inhibitory concentration (MIC) for the examination bacterium
Annotate: minimum inhibitory concentration is a meansigma methods in the table.
Experimental result: the results are shown in Table 5.The yellow compositions of ammonia is compared with the minimum inhibitory concentration of negative control group, positive controls, baicalin group respectively for the minimum inhibitory concentration of examination strain to each, and the former all is significantly less than the back three's to each minimum inhibitory concentration for the examination strain; The scorching compositions of ammonia is compared with the minimum inhibitory concentration of negative control group, positive controls, andrographolide group respectively for the minimum inhibitory concentration of examination strain to each, and the former also all is significantly less than the back three's to each minimum inhibitory concentration for the examination strain.The yellow compositions of ammonia, the scorching compositions of ammonia is respectively the minimum inhibitory concentration of staphylococcus aureus:＜0.125mg/ml, 0.125mg/ml, colibacillary minimum inhibitory concentration is respectively: 0.5mg/ml, 2mg/ml, minimum inhibitory concentration to bacillus subtilis is respectively: 0.25mg/ml, 0.125mg/ml, minimum inhibitory concentration to alpha streptococcus is respectively: 0.125mg/ml, 0.25mg/ml, minimum inhibitory concentration to Diplococcus pneumoniae is respectively: 0.125mg/ml, 0.125mg/ml, the minimum inhibitory concentration of hemophilus influenza is respectively: 0.25mg/ml, 1mg/ml.Show that ambroxol hydrochloride and baicalin compatibility, ambroxol hydrochloride and andrographolide compatibility all have synergistic function.
Bacteriostatic experiment in the yellow compositions of experimental example 4 ammonia, the scorching compositions mice of the ammonia body
Experiment material: main medicine and source: 0.9% normal saline, commercial; The baicalin sheet, commercial; Andrographolide, commercial; The yellow compositions of ammonia (ambroxol hydrochloride+baicalin=30mg+500mg), self-control; The scorching compositions of ammonia (ambroxol hydrochloride+andrographolide=30mg+40mg), self-control.
Animal subject: 360 of healthy mices, body weight 18～22g, male and female dual-purpose.
Bacterium liquid: with 5% gastric Mucin dilution staphylococcus aureus, Diplococcus pneumoniae suspension, bacteria containing amount is 10
10Individual/ml.
Experimental technique: get 360 of mices, be divided into 18 groups at random, be respectively blank group, baicalin group, andrographolide group, basic, normal, high three the dosage groups of the yellow compositions of ammonia, basic, normal, high three the dosage groups of the scorching compositions of ammonia, 20 every group.Every mouse peritoneal injection bacterium liquid 0.5ml infects, irritated stomach respectively in 1,6 hour behind the injection bacterium liquid and give 0.9% normal saline, baicalin, andrographolide, basic, normal, high three dosage of the yellow compositions of ammonia, basic, normal, high three dosage of the scorching compositions of ammonia, dosage sees Table 6.Infect the back and observe 24 hours animal survival numbers, judge the drug protection effect.
The yellow compositions of table 6 ammonia, the scorching compositions of ammonia are to the protective effect of infecting mouse
*: mice is in moribund condition and is condemned to death.
Experimental result: the results are shown in Table 6.In staphylococcus aureus, each treatment group of Diplococcus pneumoniae infecting mouse; basic, normal, high three the dosage groups of the yellow compositions of ammonia, basic, normal, high three the dosage groups of the scorching compositions of ammonia all obviously are better than baicalin group, andrographolide group and matched group to the protective effect of mice; and action effect is relevant with the dosage of compositions, and effect of high dosage is best.
The yellow compositions of experimental example 5 ammonia, the scorching compositions interior resisting virus experiment of ammonia
Experiment material: main medicine and source: influenza virus liquid (FM
1), self-control; 0.9% normal saline, commercial; The baicalin sheet, commercial; Andrographolide, commercial; The yellow compositions of ammonia (ambroxol hydrochloride+baicalin=30mg+500mg), self-control; The scorching compositions of ammonia (ambroxol hydrochloride+andrographolide=30mg+40mg), self-control.
Animal subject: 100 of Kunming mouses, male and female half and half, body weight 18～22g.
Experimental technique: get 100 of Kunming mouses, male and female half and half, be divided into 10 groups at random, be respectively and infect matched group, normal control group, baicalin group, andrographolide group, basic, normal, high three the dosage groups of the yellow compositions of ammonia, basic, normal, high three the dosage groups of the scorching compositions of ammonia, 10 every group.Except that normal group, mice is slightly anaesthetized with ether, with 1/5 LD
50Influenza virus liquid (FM
1) the collunarium infection.Begin gastric infusion the previous day from infecting, every day 2 times, continuous 5 days, wherein infected group and normal control group gave with the volume normal saline.Dissected after taking by weighing the mice body weight on the 6th day, win full lung and weigh, calculate the lung exponential quantity one by one, and obtain lung index suppression ratio.Formula: heavy (the g)/body weight (g) * 100 of lung index=lung, lung index suppression ratio %=(virus control group lung index average-experimental group lung index average)/virus control group lung index average * 100%.(annotate: the lung index is big, and expression lung weight is big, and pneumonopathy range degree is serious.)
The yellow compositions of table 7 ammonia, the scorching compositions of ammonia to the pulmonary inflammatory influence of influenza virus infecting mouse (x ± s, n=10)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the normal control group;
#P＜0.05,
##P＜0.01 is compared with the infection matched group;
﹠amp;P＜0.05 is compared with the baicalin group; ▲ p＜0.05 is compared with the andrographolide group.
Experimental result: the results are shown in Table 7.Infect back mouse lung exponential quantity and obviously increase, compare with the normal control group, significant difference (
*P＜0.01).Each administration group all have tangible viral infection resisting function (
#P＜0.05 He
##P＜0.01), wherein the viral infection resisting function of the yellow compositions of ammonia is compared significant difference with single with baicalin
(﹠amp; P＜0.05), the viral infection resisting function of the scorching compositions of ammonia is compared with andrographolide with single, difference also significantly (
▲P＜0.05).Show that ambroxol hydrochloride and baicalin compatibility, ambroxol hydrochloride and andrographolide compatibility all have the obvious suppression effect to the pneumonia that virus infected mice causes, the lung exponential quantity obviously reduces, the lung tissue lesion degree obviously alleviates, and action effect is relevant with the dosage of compositions, and effect is best during high dose.
The yellow compositions of experimental example 6 ammonia, the analgesic experiment of the scorching compositions of ammonia
Experiment material: main medicine and source: 0.9% normal saline, commercial; The baicalin sheet, commercial; Andrographolide, commercial; The yellow compositions of ammonia (ambroxol hydrochloride+baicalin=30mg+500mg), self-control; The scorching compositions of ammonia (ambroxol hydrochloride+andrographolide=30mg+40mg), self-control.
Pyrogen: typhoid fever, paratyphoid fever, second triple vaccine, commercial.
Animal subject: healthy white big ear rabbit, male and female dual-purpose, body weight 2.4～2.8kg.
Experimental technique: a few days ago in experiment, survey the normal rectal temperature of rabbit every day 4 times, select fluctuation anus temperature every day to be no more than 0.2 ℃ 72 of rabbit, be divided into 9 groups at random, be respectively matched group, baicalin group, andrographolide group, basic, normal, high three the dosage groups of the yellow compositions of ammonia, basic, normal, high three the dosage groups of the scorching compositions of ammonia, 8 every group.Test the basal body temperature of surveying animal morning on the same day earlier, give tame rabbit ear vein injection pyrogenicity, survey the anus temperature after half an hour respectively, and the filling stomach gives corresponding medicine with typhoid fever, paratyphoid fever, the second triple vaccine of 0.5ml/kg.Surveyed the anus temperature once in per 1 hour after the administration, totally 4 times, surveyed anus temperature and basic anus using warming therapy difference with different time, be the index of body temperature variation.
The yellow compositions of table 8 ammonia, the scorching compositions of ammonia to the refrigeration function of vaccine pyrogenicity rabbit (x ± s, n=8)
Annotate:
*P＜0.05,
*P＜0.01 is compared with matched group;
﹠amp;P＜0.05 is compared with the baicalin group;
▲P＜0.05 is compared with the andrographolide group.
Experimental result: the results are shown in Table 8.Each administration group all has tangible refrigeration function, compares with matched group, significant difference (
*P＜0.05 He
*P＜0.01).Wherein the yellow compositions of ammonia, the scorching compositions of ammonia have tangible refrigeration function to the rabbit body temperature rising that vaccine causes, and use baicalin or andrographolide longer duration more separately, medication still has after 4 hours and separates thermal effect, and action effect is relevant with the dosage of compositions, and effect is best during high dose.
The yellow compositions of experimental example 7 ammonia, the scorching composition stable experiment of ammonia
Test sample: the yellow compositions of ammonia (self-control, ambroxol hydrochloride+baicalin=30mg+500mg);
The scorching compositions of ammonia (self-control, ambroxol hydrochloride+andrographolide=30mg+40mg).
Investigation project: character, content, related substance.
Long-time stability experimental technique and result: each compositions of this product is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 6 months, 12 months, every index has no significant change, and experimental result shows that the long-term placement of pharmaceutical composition of the present invention is basicly stable.
4, the specific embodiment
The specific embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can be replaced with acceptable accessories in following examples, perhaps reduces, increases.
The preparation of the yellow compositions conventional tablet of embodiment 1 ammonia
1, prescription:
Ambroxol hydrochloride 15g
Baicalin 250g
Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 1.0g
Carboxymethylstach sodium 2.0g
Prepare 1000 altogether
2, concrete steps:
It is standby that ambroxol hydrochloride and baicalin were pulverized 100 mesh sieves.Take by weighing raw material and adjuvant according to recipe quantity, hypromellose 2% the aqueous solution made soluble in water is standby.With ambroxol hydrochloride, baicalin, starch, microcrystalline Cellulose mix homogeneously, it is an amount of to add the 2%HPMC aqueous solution, stir, make suitable soft material, cross 20 mesh sieve system granules, granule is dried under 60 ℃ condition, and dry good granule adds magnesium stearate and carboxymethylstach sodium, cross 18 mesh sieve granulate, mix homogeneously.Sampling, the semi-finished product chemical examination.According to the definite sheet weight sheet of chemical examination.Finished product is examined entirely, the packing warehouse-in.
The preparation of the scorching composition film coated tablet of embodiment 2 ammonia
1, prescription:
Ambroxol hydrochloride 30g
Andrographolide 40g
Starch 50.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Low-substituted hydroxypropyl cellulose 10.0g
Prepare 1000 altogether
2, concrete steps:
It is standby that ambroxol hydrochloride and andrographolide were pulverized 100 mesh sieves.Take by weighing raw material and adjuvant according to recipe quantity, hypromellose 2% the aqueous solution made soluble in water is standby.With ambroxol hydrochloride, andrographolide, starch, microcrystalline Cellulose mix homogeneously, it is an amount of to add the 2%HPMC aqueous solution, stir, make suitable soft material, cross 20 mesh sieve system granules, granule is dried under 60 ℃ condition, and dry good granule adds magnesium stearate and low-substituted hydroxypropyl cellulose, cross 18 mesh sieve granulate, mix homogeneously.Sampling, the semi-finished product chemical examination.According to the definite sheet weight sheet of chemical examination.The ordinary tablet that makes is done the sheet heart, film coating promptly, finished product is examined entirely, packing warehouse-in.
The preparation of the yellow compositions of embodiment 3 ammonia, the scorching composition capsule of ammonia
1, prescription:
The yellow composition prescription of ammonia
Ambroxol hydrochloride 30g
Baicalin 250g
Starch 40.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Prepare 1000 altogether
The scorching composition prescription of ammonia
Ambroxol hydrochloride 30g
Andrographolide 20g
Starch 40.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Prepare 1000 altogether
2, concrete steps:
It is standby that ambroxol hydrochloride and baicalin (or andrographolide) were pulverized 100 mesh sieves.Take by weighing raw material and adjuvant according to recipe quantity, hypromellose 2% the aqueous solution made soluble in water is standby.With ambroxol hydrochloride, baicalin (or andrographolide), starch, microcrystalline Cellulose mix homogeneously, it is an amount of to add the 2%HPMC aqueous solution, stir, make suitable soft material, cross 20 mesh sieve system granules, granule is dried under 60 ℃ condition, and dry good granule adds magnesium stearate, cross 18 mesh sieve granulate, mix homogeneously.Sampling, the semi-finished product chemical examination.The loading amount of determining according to chemical examination incapsulates.Finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow compositions of embodiment 4 ammonia, the scorching composition granule of ammonia
1, prescription:
The yellow composition prescription of ammonia
Ambroxol hydrochloride 30g
Baicalin 500g
Icing Sugar 970.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
The scorching composition prescription of ammonia
Ambroxol hydrochloride 30g
Andrographolide 40g
Icing Sugar 930.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
2, concrete steps:
It is standby that sucrose was pulverized 100 mesh sieves.With ambroxol hydrochloride, that baicalin (or andrographolide) was pulverized 100 mesh sieves was standby.Take by weighing raw material and adjuvant according to recipe quantity, the method mix homogeneously that ambroxol hydrochloride, baicalin (or andrographolide) and Icing Sugar are progressively increased with equivalent, it is an amount of to add the 2%HPMC50% alcoholic solution, stir, make suitable soft material, cross 20 mesh sieve system granules, granule is dried under 60 ℃ condition, and dried granule is crossed 18 mesh sieve granulate.Sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule.Packing, finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow compositions of embodiment 5 ammonia, the scorching composition powder injection of ammonia
1, prescription:
The yellow composition prescription of ammonia
Ambroxol hydrochloride 15g
Baicalin 500g
Polyoxyethylene sorbitan monoleate 100g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
The scorching composition prescription of ammonia
Ambroxol hydrochloride 15g
Andrographolide 40g
Polyoxyethylene sorbitan monoleate 100g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
2, concrete steps:
At first vessel that dosing is used and antibiotic glass bottle, plug etc. carry out aseptic process.Take by weighing raw material and adjuvant according to recipe quantity.Get the sterile water for injection of dosing amount 60%, ambroxol hydrochloride and baicalin (or andrographolide) are added, the polyoxyethylene sorbitan monoleate heated and stirred dissolving that adds recipe quantity is complete, add the dissolving of mannitol heated and stirred more fully, add sterile water for injection to full dose, the needle-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes is through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution,, check the clarity of solution, the semi-finished product chemical examination through the microporous filter membrane fine straining of 0.22 μ m.Be sub-packed in the antibiotic glass bottle half tamponade.Sample is put into the freeze dryer lyophilization.Pre-freeze-45 ℃ 5 hours, low-temperature vacuum drying-45 ℃～0 ℃ 20 hours was warming up to 25 ℃ of vacuum dryings 3 hours then.Lyophilizing finishes, and lid is rolled in tamponade.Finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow compositions of embodiment 6 ammonia, the scorching compositions aqueous injection of ammonia
1, prescription:
The yellow composition prescription of ammonia
Ambroxol hydrochloride 30g
Baicalin 500g
Polyoxyethylene sorbitan monoleate 100g
Water for injection adds to 5000ml
Prepare 1000 altogether
The scorching composition prescription of ammonia
Ambroxol hydrochloride 30g
Andrographolide 40g
Polyoxyethylene sorbitan monoleate 100g
Water for injection adds to 5000ml
Prepare 1000 altogether
2, concrete steps:
Carry and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.Get the water for injection of dosing amount 60%, the ambroxol hydrochloride and the baicalin (or andrographolide) that add recipe quantity, the polyoxyethylene sorbitan monoleate heated and stirred dissolving that adds recipe quantity is complete, and benefit adds to the full amount of water for injection, and adds the needle-use activated carbon of dosing amount 0.1%, heated and stirred 15 minutes, through sand filtration rod filtering decarbonization, measure the also pH value of regulator solution, through the microporous filter membrane fine straining of 0.45 μ m, check the clarity of solution, the semi-finished product chemical examination.In glass ampule, 100 ℃ of flowing steam sterilizations 30 minutes are put into sample 0.01% methylene blue solution while hot and are hunted leak with the solution sealing by fusing.Lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow compositions of embodiment 7 ammonia, the scorching compositions sodium chloride transfusion of ammonia
1, prescription:
The yellow composition prescription of ammonia
Ambroxol hydrochloride 30g
Baicalin 500g
Polyoxyethylene sorbitan monoleate 100g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
The scorching composition prescription of ammonia
Ambroxol hydrochloride 30g
Andrographolide 40g
Polyoxyethylene sorbitan monoleate 100g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
2, concrete steps:
Carry and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.The water for injection of getting dosing amount 30% adds ambroxol hydrochloride and baicalin (or andrographolide), and the polyoxyethylene sorbitan monoleate heated and stirred dissolving that adds recipe quantity is complete, and the water for injection of sodium chloride with dosing amount 40% is dissolved fully.Merge above-mentioned solution, benefit adds to the full amount of water for injection, and adds the needle-use activated carbon of dosing amount 0.1%, and heated and stirred 15 minutes is through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution,, check the clarity of solution through the microporous filter membrane fine straining of 0.45 μ m, the semi-finished product chemical examination, fill is in the infusion bottle of 100ml.115 ℃ of pressure sterilizings 30 minutes.Lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of the yellow compositions of embodiment 8 ammonia, the scorching compositions glucose infusion liquid of ammonia
1, prescription:
The yellow composition prescription of ammonia
Ambroxol hydrochloride 30g
Baicalin 500g
Polyoxyethylene sorbitan monoleate 100g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
The scorching composition prescription of ammonia
Ambroxol hydrochloride 30g
Andrographolide 40g
Polyoxyethylene sorbitan monoleate 100g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
2, concrete steps:
Carry and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.The water for injection of getting dosing amount 30% adds ambroxol hydrochloride and baicalin (or andrographolide), the polyoxyethylene sorbitan monoleate heated and stirred dissolving that adds recipe quantity is complete, glucose is complete with the water for injection dissolving of dosing amount 40%, merge above-mentioned solution, benefit adds to the full amount of water for injection, the needle-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes is through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution,, check the clarity of solution, the semi-finished product chemical examination through the microporous filter membrane fine straining of 0.45 μ m.Fill is in the infusion bottle of 100ml.115 ℃ of pressure sterilizings 30 minutes.Lamp inspection, finished product is examined entirely, the packing warehouse-in.
Claims (3)
1. a pharmaceutical composition is characterized in that, said composition is made up of the component of following parts by weight: 30 parts of ambroxol or its pharmaceutically acceptable salts, 500 parts of baicalins.
2. pharmaceutical composition as claimed in claim 1 is characterized in that described ambroxol pharmaceutically acceptable salt is a hydrochlorate.
3. pharmaceutical composition as claimed in claim 2 is characterized in that, this pharmaceutical composition and mixing acceptable accessories are made clinically any or pharmaceutically acceptable dosage form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101311210A CN100563641C (en) | 2005-12-26 | 2005-12-26 | The compositions of ambroxol or its salt and anti-infectives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101311210A CN100563641C (en) | 2005-12-26 | 2005-12-26 | The compositions of ambroxol or its salt and anti-infectives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1989953A CN1989953A (en) | 2007-07-04 |
| CN100563641C true CN100563641C (en) | 2009-12-02 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005101311210A Expired - Fee Related CN100563641C (en) | 2005-12-26 | 2005-12-26 | The compositions of ambroxol or its salt and anti-infectives |
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| Country | Link |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010110748A1 (en) * | 2009-03-24 | 2010-09-30 | National University Of Singapore | Use of andrographolide compounds for treating inflammation and airway disorders |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107648311B (en) * | 2017-08-30 | 2020-07-10 | 四川省中医药科学院 | Composition and medicine with antiviral and antiinflammatory effects |
| CN113880898B (en) * | 2020-10-30 | 2023-07-25 | 杭州拉林智能科技有限公司 | Flavonoid glycoside-organic amine antimicrobial compound salt compound and preparation method and application thereof |
| CN113662952B (en) * | 2021-08-25 | 2022-11-22 | 天津中医药大学 | Compound dry powder inhalant for treating idiopathic pulmonary fibrosis and application thereof |
| CN115671081A (en) * | 2022-10-19 | 2023-02-03 | 天津中医药大学 | Application of dry powder inhalant |
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2005
- 2005-12-26 CN CNB2005101311210A patent/CN100563641C/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| 沐舒坦治疗小儿毛细支气管炎54例. 施传娥等.江苏药学与临床研究，第11卷第6期. 2003 |
| 沐舒坦治疗小儿毛细支气管炎54例. 施传娥等.江苏药学与临床研究，第11卷第6期. 2003 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010110748A1 (en) * | 2009-03-24 | 2010-09-30 | National University Of Singapore | Use of andrographolide compounds for treating inflammation and airway disorders |
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| Publication number | Publication date |
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| CN1989953A (en) | 2007-07-04 |
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