CN100574757C - The compositions of acetylcysteine or its salt and anti-infectives - Google Patents
The compositions of acetylcysteine or its salt and anti-infectives Download PDFInfo
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- CN100574757C CN100574757C CN200610043586A CN200610043586A CN100574757C CN 100574757 C CN100574757 C CN 100574757C CN 200610043586 A CN200610043586 A CN 200610043586A CN 200610043586 A CN200610043586 A CN 200610043586A CN 100574757 C CN100574757 C CN 100574757C
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- Prior art keywords
- salt
- acetylcysteine
- pharmaceutically acceptable
- group
- pharmaceutical composition
- Prior art date
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to medical technical field, a kind of acetylcysteine or its pharmaceutically acceptable salt that contains effective dose disclosed, with pharmaceutical composition of at least a anti-infectives and its production and use, wherein anti-infectives is selected from: neo-houttuyninum or its pharmaceutically acceptable salt and/or 14-deshydroxy-11,12-two dehydrogenation andrographolide-3, in 19-disuccinic acid half ester salt and/or the matrine one or more, this pharmaceutical composition can be made into various pharmaceutically acceptable dosage forms, be used for the preparation treatment by the microbial pneumonia of sensitivity, bronchial asthma, aspect diseases such as chronic obstructive pulmonary disease companion pulmonary acute inflammation have synergistic function, and good stability, than improving greatly with effect with the medicine of dosage is single separately, produced beyond thought effect, be with a wide range of applications.
Description
1, technical field
The present invention relates to a kind of contain acetylcysteine or its pharmaceutically acceptable salt and and the pharmaceutical composition of at least a anti-infectives and its production and use, 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, how to cause that minority is by due to the antibacterial direct infection by viral infection.But alternative clinically medicine is also few and onset is slower.
Acetylcysteine is N-acetyl group-L-cysteine.Acetylcysteine is a mucolytic agent, has stronger phlegm dissolving effect, and contained sulfydryl in its molecule (SH) can make the disulfide bond in the apoplexy due to phlegm glycoprotein polypeptide chain (S-S-) rupture, reduce the viscosity of expectorant, and make it liquefaction.Acetylcysteine can also make the dna fiber fracture in the purulent sputum, so can not only dissolve the sticking expectorant of white and can dissolve purulent sputum.Be applicable to the dyspnea that a large amount of sticking stagnation of phlegm plugs cause, the thick sputum that causes as postoperative difficult, the acute and chronic bronchitis of coughing up phlegm, bronchiectasis, pulmonary tuberculosis, pneumonia, emphysema etc., the difficulty of coughing up phlegm, stagnation of phlegm trachea etc. still can be used for the detoxifcation of poisoning by paracetamol.The acetylcysteine structural formula is as follows:
The acetylcysteine structural formula
Anti-infectives wherein: comprise neo-houttuyninum or its pharmaceutically acceptable salt, 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt, matrine.
Herba Houttuyniae is the whole herb with root of saururaceae plant houttuynia cordata Houttuynia cordata Thunb, and acrid in the mouth, cool in nature has effects such as heat-clearing and toxic substances removing, eliminating carbuncle evacuation of pus, inducing diuresis for treating stranguria syndrome, is used for the lung abscess vomiting pus, and the expectorant dyspnea of heat type is coughed, pyretic stranguria, carbuncle sore tumefacting virus.Neo-houttuyninum (Sodium New Houttuyfonat) is the synthetics of a kind of aldehydes single active ingredient of extracting from the Herba Houttuyniae herb, chemistry sodium sulfite lauroyl acetaldehyde by name, the effect with antibiotic, anti-inflammatory and antalgic, antitumor, promotion immunity, human body immunity improving function; Diplococcus pneumoniae, Bacillus typhi, staphylococcus aureus, escherichia coli and sporothrix etc. are had obvious inhibitory action, but human body immunity improving power strengthens the leukocytic phagocytic function of patient, improve serum properdin level, improve the body non-specific immunity; Be used for all kinds of inflammation of gynecological such as adnexitis, pelvic inflammatory disease, chronic cervicitis, and can be used for upper respiratory tract infection, respiratory system infection such as chronic bronchial pneumonia, viral pneumonia.Simultaneously, neo-houttuyninum has good safety, and no obvious toxic and side effects or anaphylaxis are the substitute products of Sodium Houttuyfonate.The neo-houttuyninum structural formula is as follows:
The neo-houttuyninum structural formula
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 monopotassium 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.
Matrine is that it contains C from a kind of alkaloid of leguminous plant Herba Sophorae alopecuroidis (Sophora alopecuroidesL.) fruit or aerial parts extraction
15H
24N
2O must not be less than 98.0%, has been applied to clinical as chemicals.Matrine has antiviral, antiinflammatory, antitumor action and to multiple pharmacological effect such as central nervous system's calmness, the analgesic cooling effect of analgesia and heart tonifying, blood pressure lowering, anti-arrhythmias, the treatment of chronic hepatitis is also had good efficacy, and untoward reaction is less.The matrine structural formula is as follows:
The matrine structural formula
Utilize acetylcysteine or its pharmaceutically acceptable salt and neo-houttuyninum or its pharmaceutically acceptable salt, 14-deshydroxy-11 at present, 12-two dehydrogenation andrographolide-3, the interaction of one or more in 19-disuccinic acid half ester salt, the matrine, composition of prescription, be used for the treatment of medicine, do not appear in the newspapers as yet by aspect diseases such as the microbial pneumonia of sensitivity, bronchial asthma, chronic obstructive pulmonary disease companion pulmonary acute inflammations.
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 new pharmaceutical composition and preparation method thereof, said composition contains acetylcysteine or its pharmaceutically acceptable salt of effective dose, with at least a anti-infectives, wherein anti-infectives is selected from: neo-houttuyninum or its pharmaceutically acceptable salt and/or 14-deshydroxy-11,12-two dehydrogenation andrographolide-3, one or more in 19-disuccinic acid half ester salt and/or the matrine.
Aforementioned pharmaceutical compositions, its parts by weight are: 20～1200 parts of acetylcysteine or its pharmaceutically acceptable salts, anti-infectives is different and different according to medicine, for neo-houttuyninum or its pharmaceutically acceptable salt is 1～100 part, for 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is 10～200 parts, is 10～400 parts for matrine.
Aforementioned pharmaceutical compositions, its parts by weight are preferably: 50～600 parts of acetylcysteine or its pharmaceutically acceptable salts, anti-infectives is different and different according to medicine, for neo-houttuyninum or its pharmaceutically acceptable salt is 4～20 parts, for 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is 20～80 parts, is 40～160 parts for matrine.
Aforementioned pharmaceutical compositions, its parts by weight are more preferably: 100～300 parts of acetylcysteine or its pharmaceutically acceptable salts, anti-infectives is different and different according to medicine, for neo-houttuyninum or its pharmaceutically acceptable salt is 8 parts, for 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is 40 parts, is 80 parts for matrine.
Aforementioned pharmaceutical compositions, its parts by weight are particularly preferred to be: 8 parts of 100～300 parts of acetylcysteine or its pharmaceutically acceptable salts and neo-houttuyninum or its pharmaceutically acceptable salts; Perhaps be: 100～300 parts of acetylcysteine or its pharmaceutically acceptable salts and 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,40 parts of 19-disuccinic acid half ester salt; Perhaps be: the compositions that 100～300 parts of acetylcysteine or its pharmaceutically acceptable salts and matrine are 80 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,, can make the preparation of 100～10000 consumptions,, can be made into 100～10000,1～10 of each consumption as injection as if being unit with the gram.As tablet, can be made into 100～10000, take 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.
In the pharmaceutical composition of the present invention, the acetylcysteine pharmaceutically acceptable salt can be organic nitrogen salt, hydrochlorate, sulfate, acetate, mesylate, tartrate, maleate, fumarate, hydrobromate, aspartate.
In the pharmaceutical composition of the present invention, the neo-houttuyninum pharmaceutically acceptable salt can be sodium salt, potassium salt, calcium salt, magnesium salt, zinc salt etc., is preferably sodium salt.
In the 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).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 aforementioned pharmaceutical compositions being used to prepare the application of treatment by aspect diseases such as the microbial pneumonia of sensitivity, bronchial asthma, chronic obstructive pulmonary disease companion pulmonary acute inflammations.
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.; Also can be made into spray.The preferred dosage form of this compositions is injection or oral formulations.
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 diluent, 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 in order to increase its dissolubility, can add cosolvents such as polyoxyethylene sorbitan monoleate, polyethylene glycols, propylene glycol, glycerol 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 and glucose.Can add excipient in the powder pin, for example, mannitol, glucose, lactose, dextran, sorbitol, sucrose, glycine, sodium chloride 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, methylcellulose, 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.
The present composition has the following advantages:
(1) provide first a kind of acetylcysteine or its pharmaceutically acceptable salt and and at least a anti-infectives compatibility be used to prepare treatment by pharmaceutical composition of aspect diseases such as the microbial pneumonia of sensitivity, bronchial asthma, chronic obstructive pulmonary disease, companion pulmonary acute inflammation and its production and use, satisfied urgent clinical needs;
(2) first the interaction and the composition of prescription of pharmaceutical composition of the present invention carried out pharmacodynamic study, found that pharmaceutical composition has tangible preventive and therapeutic effect to Acute Lung Injury due to the lipopolysaccharide, made that the lung coefficient extremely significantly reduces, lung NF-
kThe relative gray scale of B obviously raises, Serum concentration of NO extremely obviously reduces, serum MDA concentration extremely obviously reduces, and can significantly increase rabbit respiratory tract sputum secretory volume, to by the mice of bacterial infection significant protective effect being arranged; 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 experiment, the pharmaceutical composition experimental group is compared with acetylcysteine group or neo-houttuyninum group or andrographolide group or matrine group with single, significant difference is remarkable (p＜0.05) all, it is remarkable to show that acetylcysteine and anti-infectives share treatment respiratory system disease 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 medicine composition injection 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 pharmaceutical composition of the present invention.In the following experimental example: the compositions of acetylcysteine, neo-houttuyninum hereinafter to be referred as
The second new compositionsThe compositions of acetylcysteine, andrographolide hereinafter to be referred as
The scorching compositions of secondThe compositions of acetylcysteine, matrine hereinafter to be referred as
The second ginseng composition
The scorching compositions of experimental example 1 second new compositions, second, second ginseng composition are to the preventive and therapeutic effect of Acute Lung Injury due to the lipopolysaccharide
Test sample: 0.9% normal saline solution, commercial; Lipopolysaccharide (LPS); Acetylcysteine (NAC) injection, specification: 20ml:4g, self-control; The second new compositions (acetylcysteine+neo-houttuyninum=100mg+8mg), self-control (preparation method is referring to embodiment 2); The scorching compositions of second (acetylcysteine+andrographolide=100mg+40mg), self-control (preparation method is referring to embodiment 2); The second ginseng composition (acetylcysteine+matrine=100mg+80mg), self-control (preparation method is referring to embodiment 2).
The laboratory animal grouping: 120 of healthy male SD rats, 180～250 of body weight are divided into 12 groups at random.Be respectively blank group, induced lung damage model group (LPS group), NAC intervention group (N﹠amp; The L group), 3 groups of (Yi Xianbanguangansuan ﹠amp of the basic, normal, high dosage of second new compositions; Xin Yuxingcaosuna ﹠amp; Lipopolysaccharide), 3 groups of (Yi Xianbanguangansuan ﹠amp of the scorching basic, normal, high dosage of compositions of second; Yan Huning ﹠amp; Lipopolysaccharide), 3 groups of (Yi Xianbanguangansuan ﹠amp of the basic, normal, high dosage of second ginseng composition; Ku Canjian ﹠amp; Lipopolysaccharide), 10 every group.
Experimental technique: Acute Lung Injury is duplicated and is adopted rat tail vein injection LPS (5mg/kg, LPS O
55: B
5, Sigma) method is set up.The preceding 1h NAC intervention group (200mg/kg) of injection LPS, second new compositions low dose group (10mg/kg), dosage group (15mg/kg), high dose group (20mg/kg), the scorching compositions low dose group (10mg/kg) of second, dosage group (15mg/kg), high dose group (20mg/kg), second ginseng composition low dose group (10mg/kg), dosage group (15mg/kg), high dose group (20mg/kg) lumbar injection respectively give relative medicine.The blank group mutually should the equivalent normal saline.
4h lumbar injection ketalar (100mg/kg) anesthesia behind each treated animal injection LPS or the normal saline, win eyeball and get blood, collection serum is put-70 ℃ of refrigerators and is preserved nitric oxide to be measured (nitric oxide, NO), malonaldehyde (malondialdehyde, NDA) (NO and NDA test kit are all built up bio-engineering research institute available from Nanjing).After getting blood, animal is put to death in the ventral aorta blood-letting fast, and speed is got lung, observes and title lung weight in wet base, calculates lung coefficient (lung coefficient: lung weight in wet base (g) ÷ rat body weight (g) * 100).Get that left lung bottom is fixed, section H-E dyeing is observed lung and is changed after the embedding, immunohistochemical method detect nuclear factor (NF)-
kThe B staining power: press SABC test kit description line ABC dyeing, one is anti-with the rabbit Mus NF-of the Chinese People's Anti-Japanese Military and Political College
kB P65 antibody, DAB develop the color (SABC, DAB test kit, the Mus NF-of the rabbit Chinese People's Anti-Japanese Military and Political College
kB P65 antibody is all available from Wuhan doctor's moral company), replace an anti-negative control of doing with PBS simultaneously.Measure with the color pathological image analytical system of multi-functional true (Video pm 32 types, Australia) then and respectively organize NF-
kAverage gray value under B SABC sheet and the corresponding negative control sheet high power field calculates relative gray scale (relative gray scale=NF-
kThe corresponding negative control sheet of B SABC sheet average gray value ÷ average gray value), gray scale is big more relatively, and staining power is more little.
Statistical analysis is handled: each is organized quantitative data and all adopts x ± s to represent, relatively checks level of significance test a=0.05, data computing application SPSS software between two groups with t.
Experimental result: (1) lung tissue pathological examination lung gross examination of skeletal muscle, blank group lung outward appearance Non Apparent Abnormality changes; LPS group lung volume increases, and the surface is dark red, and point-like under the peplos, lamellar are hemorrhage, and tangent plane is loose, has yellow or pink liquid to overflow; NAC intervention group pathological changes obviously alleviates than the LPS group, but still has marked difference than the blank group; The basic, normal, high dosage group of second new compositions, the basic, normal, high dosage group of the scorching compositions of second are compared no significant difference with the basic, normal, high dosage group of second ginseng composition with the blank group.Under the light microscopic, blank group lung tissue structure is complete, and alveolar septum does not have edema, inflammation, and alveolar space is clear; The broadening of LPS group alveolar septum is seen hemorrhagely in the part alveolar, interstitial lung is seen the volume inflammatory cell infiltration; NAC intervention group pneumonia cellular infiltration, ooze out, hemorrhagely obviously alleviate than LPS group but still have marked difference than the blank group: it is extremely remarkable that the basic, normal, high dosage group of second new compositions, the second basic, normal, high dosage group of scorching compositions and the basic, normal, high dosage group of second ginseng composition and LPS group are compared difference, relatively there were significant differences with the NAC intervention group, compares no significant difference with blank according to group.
(2) lung index variation LPS group and blank group relatively, the lung coefficient obviously increase (
*P＜0.01); NAC intervention group and LPS organize apparent in view reduction (
#P＜0.05); But with the blank group more still there were significant differences (
*P＜0.05); The basic, normal, high dosage group of second new compositions, the scorching basic, normal, high dosage group of compositions of second and the basic, normal, high dosage group of second ginseng composition and LPS organize relatively, and the lung coefficient extremely obviously reduces (
##P＜0.01), with the NAC intervention group relatively there were significant differences (
﹠amp;P＜0.05), compares there was no significant difference (p＞0.05) and with the blank group.See Table 1.
(3) lung tissue NF-
kIt is pale brown color that the B SABC detects positive staining.It is positive painted that the blank group sees that endochylema has, and karyon is painted less; LPS group karyon is obviously positive painted, and endochylema is also seen positive painted; NAC intervention group karyon is painted obviously to be reduced than the LPS group, slightly high than the blank group; The basic, normal, high dosage group of second new compositions, the scorching basic, normal, high dosage group of compositions of second and the basic, normal, high dosage group of second ginseng composition and LPS group more obviously reduce, and do not have significant difference than the blank group.LPS organizes NF-
kB dye relative gray value than the blank group obviously reduce (
*P＜0.01), expression LPS group is than blank group NF-
kThe B staining power obviously increases; The NAC intervention group than LPS group staining power obviously reduce (
#P＜0.05); But with the blank group more still there were significant differences (
*P＜0.05); The basic, normal, high dosage group of second new compositions, the scorching basic, normal, high dosage group of compositions of second and the basic, normal, high dosage group of second ginseng composition and the more obviously reduction of LPS group (
##P＜0.01), with the NAC intervention group relatively there were significant differences (
﹠amp;P＜0.05), and compare there was no significant difference (p＞0.05) with the blank group, gray value maximum during wherein with high dose, staining power is minimum.See Table 1.
(4) Serum concentration of NO changes LPS group and blank group relatively, Serum concentration of NO obviously increase (
*P＜0.01); NAC intervention group and LPS organize apparent in view reduction (
#P＜0.05); But with the blank group more still there were significant differences (
*P＜0.05); The basic, normal, high dosage group of second new compositions, the scorching basic, normal, high dosage group of compositions of second and the basic, normal, high dosage group of second ginseng composition and LPS organize relatively, and Serum concentration of NO extremely obviously reduces (
##P＜0.01), with the NAC intervention group relatively there were significant differences (
﹠amp;P＜0.05), compares there was no significant difference (p＞0.05), Serum concentration of NO minimum during wherein with high dose and with the blank group.See Table 1.
(5) serum MDA concentration change LPS group serum MDA concentration than the blank group obviously increase (
*P＜0.01); NAC intervention group and LPS organize apparent in view reduction (
#P＜0.05); But with the blank group more still there were significant differences (
*P＜0.05); The basic, normal, high dosage group of second new compositions, the scorching basic, normal, high dosage group of compositions of second and the basic, normal, high dosage group of second ginseng composition and LPS organize relatively, and serum MDA concentration extremely obviously reduces (
##P＜0.01), with the NAC intervention group relatively there were significant differences (
﹠amp;P＜0.05), compares there was no significant difference (p＞0.05), serum MDA concentration minimum during wherein with high dose and with the blank group.See Table 1.
Conclusion: experimental result shows that the scorching compositions of second new compositions, second and second ginseng composition have tangible preventive and therapeutic effect to Acute Lung Injury due to the lipopolysaccharide, makes that the lung coefficient extremely significantly reduces, lung NF-
kThe relative gray scale of B obviously raises, Serum concentration of NO extremely obviously reduces, serum MDA concentration extremely obviously reduces, with LPS group relatively have utmost point notable difference (
##P＜0.01), with the NAC intervention group relatively there were significant differences (
﹠amp;P＜0.05), compares there was no significant difference (p＞0.05) and with the blank group.
Table 1 is respectively organized induced lung coefficient, lung NF-
kThe relative gray scale of B, serum NO level, MDA concentration ratio (x ± s, n=10)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the blank group;
#P＜0.05,
##P＜0.01 is compared with the LPS group;
﹠amp;P＜0.05 is compared with the NAC intervention group.
Experimental example 2 second new compositions are to the excretory influence of rabbit sputum
Test sample and material: 0.9% normal saline solution, commercial; Acetylcysteine (NAC) injection, specification: 20ml:4g, self-control; Second new compositions injection (acetylcysteine+neo-houttuyninum=100mg+8mg), self-control (preparation method is referring to embodiment 2).
Experimental technique: with 50 of rabbit, be divided into 5 groups at random, 10 every group, be respectively blank group, acetylcysteine group, basic, normal, high three the dosage groups of second new compositions.Animal is plugged endotracheal tube with the anesthesia of urethane auricular vein, constantly provides preheating (37 ℃) to be connected with the device of constant temperature (80%) breathe air with one, at graduated cylinder that fixes of the lower end of cross tracheal intubation connection, is used to collect secretions.For preventing to produce condensed water, adopt a device that separates with Cotton Gossypii, all animals all freely breathe and guarantee the breathe air amount that it is required.Through 2 hours stable observation, will test medicine through intraperitoneal injection, dosage sees the following form.Collect 3 hours secretions after the administration immediately continuously, measure secretory volume.Calculate the excretory rate of change of sputum.Rate of change=(each experimental group sputum amount average-normal saline group sputum amount average)/normal saline group sputum amount average * 100%
(x ± s) expression, check with t by the statistical analysis of data with mean ± standard deviation for all data of statistical analysis.
Table 2 second new compositions to the excretory influence of rabbit sputum (x ± s, n=10)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the blank group;
﹠amp;P＜0.05 is compared with the acetylcysteine group.
Experimental result and conclusion: experimental result sees Table 2.Experimental result shows that each administration group all can increase rabbit respiratory tract sputum secretory volume, compare with the blank group, the secretory volume rate of change of acetylcysteine significantly (
*P＜0.05), the secretory volume rate of change of basic, normal, high three the dosage groups of second new compositions extremely significantly (
*P＜0.01), and with the acetylcysteine group relatively, difference also significantly (
﹠amp;P＜0.05), experiment shows that the second new compositions has very strong short sputum secretory action, and short sputum secretory action and the dosage of second new compositions is tangible positive correlation, acts on the strongest during high dose.
Bacteriostatic experiment in the scorching compositions mice of the experimental example 3 second body
Test sample and material: 0.9% normal saline solution, commercial; The andrographolide injection, specification: 5ml:80mg, Hainan Prov Lingkang Pharmaceutical Co., Ltd; The scorching compositions of second (acetylcysteine+andrographolide=100mg+40mg), self-control (preparation method is referring to embodiment 2).
Animal subject: 200 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 200 of mices, be divided into 10 groups at random, be respectively blank group, andrographolide group, basic, normal, high three the dosage groups of the scorching compositions of second, 20 every group.Every mouse peritoneal injection bacterium liquid 0.5ml infects, and irritates stomach respectively in 1,6 hour behind the injection bacterium liquid to give 0.9% normal saline, andrographolide, basic, normal, high three dosage of the scorching compositions of second, and dosage sees Table 3.Infect the back and observe 24 hours animal survival numbers, judge the drug protection effect.
The scorching compositions of table 3 second is to the protective effect of infecting mouse
Experimental result and conclusion: the results are shown in Table 3.In staphylococcus aureus, each treatment group of Diplococcus pneumoniae infecting mouse; basic, normal, high three the dosage groups of the scorching compositions of second all are better than andrographolide group and blank group to the protective effect of mice; experiment shows that acetylcysteine and andrographolide compatibility have very strong protective effect to staphylococcus aureus, Diplococcus pneumoniae infecting mouse; and action effect is relevant with the dosage of compositions, and effect of high dosage is best.
The experiment of experimental example 4 second ginseng composition interior resisting virus
Test sample and material: 0.9% normal saline solution, commercial; Influenza virus liquid (FM
1), commercial; Matrine injection, specification: 5ml:80mg, sky, Ningbo City weighing apparatus pharmaceutical Co. Ltd; The second ginseng composition (acetylcysteine+matrine=100mg+80mg), self-control (preparation method is referring to embodiment 2).
Animal subject: 60 of Kunming mouses, male and female half and half, body weight 18～22g.
Experimental technique: get 60 of Kunming mouses, male and female half and half are divided into 6 groups at random, are respectively to infect matched group, normal control group, matrine group, three groups of the basic, normal, high dosage of second ginseng composition, 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)
Table 4 second ginseng composition 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 matrine group.
Experimental result and conclusion: the results are shown in Table 4.Infect back mouse lung exponential quantity and obviously increase, compare with the normal control group, significant difference (
*P＜0.01).Compare with infecting matched group, each administration group all have tangible viral infection resisting function (
#P＜0.05 He
##P＜0.01), wherein the viral infection resisting function of second ginseng composition is compared with matrine with single, significant difference (
﹠amp;P＜0.05).Show that acetylcysteine and matrine 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 analgesic experiment of experimental example 5 second ginseng compositions
Test sample and material: 0.9% normal saline solution, commercial; Matrine injection, specification: 5ml:80mg, sky, Ningbo City weighing apparatus pharmaceutical Co. Ltd; The second ginseng composition (acetylcysteine+matrine=100mg+80mg), self-control (preparation method is referring to embodiment 2).
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 ℃ 40 of rabbit, be divided into 5 groups at random, be respectively matched group, matrine group, basic, normal, high three the dosage groups of second ginseng composition, 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.
Experimental result and conclusion: the results are shown in Table 5.Each administration group all has tangible refrigeration function, compares with matched group, significant difference (
*P＜0.05 He
*P＜0.01).Wherein the second ginseng composition has tangible refrigeration function to the rabbit body temperature rising that vaccine causes, and uses the matrine longer duration more separately, and 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.
Table 5 ginseng composition 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 matrine group.
Experimental example 6 second new compositions injection, the scorching composite injection of second, second ginseng composition injection stability experiment
Test sample: second new compositions injection (self-control, 5ml: acetylcysteine+neo-houttuyninum=100mg+8mg);
The scorching composite injection of second (self-control, 5ml: acetylcysteine+andrographolide=100mg+40mg);
Second ginseng composition injection (self-control, 5ml: acetylcysteine+matrine=100mg+80mg).
Investigation project: character, pH value, clarity.
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 each composite injection of this product 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 embodiment 1 present composition injectable powder
1, prescription:
Second new compositions prescription
Acetylcysteine 100g
Neo-houttuyninum 20g
Polyoxyethylene sorbitan monoleate 50g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
The scorching composition prescription of second
Acetylcysteine 100g
Andrographolide 80g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Second ginseng composition prescription
Acetylcysteine 100g
Matrine 160g
Polyoxyethylene sorbitan monoleate 50g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
2, concrete steps:
1) vessel of at first dosing being used and antibiotic glass bottle, plug etc. carry out aseptic process.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) get the sterile water for injection of dosing amount 80%, the heated and stirred dissolving fully to add mannitol and polyoxyethylene sorbitan monoleate (according to the prescription needs) again, acetylcysteine, neo-houttuyninum or andrographolide or matrine adding stirring and dissolving is complete, add sterile water for injection to full dose.
4) needle-use activated carbon of adding dosing amount 0.05% stirred 15 minutes.
5) filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.22 μ m.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) be sub-packed in the antibiotic glass bottle half tamponade.Sample is put into the freeze dryer lyophilization.Pre-freeze-40 ℃ 5 hours, low-temperature vacuum drying-40 ℃～0 ℃ 35 hours was warming up to 25 ℃ of vacuum dryings 4 hours then.
9) lyophilizing finishes, and lid is rolled in tamponade.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 2 present composition aqueous injection
1, prescription:
Second new compositions prescription
Acetylcysteine 100g
Neo-houttuyninum 8g
Polyoxyethylene sorbitan monoleate 30g
Water for injection adds to 5000ml
Prepare 1000 altogether
The scorching composition prescription of second
Acetylcysteine 100g
Andrographolide 40g
Water for injection adds to 5000ml
Prepare 1000 altogether
Second ginseng composition prescription
Acetylcysteine 100g
Matrine 80g
Ethanol 80ml
Sterile water for injection adds to 5000ml
Prepare 1000 altogether
2, concrete steps:
1) carries 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.
2) get the water for injection of dosing amount 80%, acetylcysteine, neo-houttuyninum or the andrographolide or the matrine that add recipe quantity, the polyoxyethylene sorbitan monoleate or ethanol (according to the prescription needs) the heated and stirred dissolving that add recipe quantity are complete, and benefit adds to the full amount of water for injection.
3) needle-use activated carbon of adding dosing amount 0.05% stirred 15 minutes.
4) filtering decarbonization.Measure the also pH value of regulator solution.
5) through the microporous filter membrane fine straining of 0.45 μ m.
6) clarity of inspection solution, the semi-finished product chemical examination.
7) with the solution sealing by fusing in glass ampule.
8) 100 ℃ of flowing steam sterilizations are 30 minutes.
9) while hot sample being put into 0.01% methylene blue solution hunts leak.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 3 present composition sodium chloride transfusion
1, prescription:
Second new compositions prescription
Acetylcysteine 300g
Neo-houttuyninum 4g
Polyoxyethylene sorbitan monoleate 30g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
The scorching composition prescription of second
Acetylcysteine 300g
Andrographolide 20g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Second ginseng composition prescription
Acetylcysteine 300g
Matrine 40g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
2, concrete steps:
1) handles the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) polyoxyethylene sorbitan monoleate is made into 20% solution with water for injection, acetylcysteine and neo-houttuyninum are added the heated and stirred dissolving fully, sodium chloride 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;
Perhaps be: the water for injection heated and stirred dissolving of andrographolide or matrine adding dosing amount 20% is complete, sodium chloride 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.
3) needle-use activated carbon of adding dosing amount 0.05% stirred 15 minutes.
4) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
5) through the microporous filter membrane fine straining of 0.45 μ m.
6) clarity of inspection solution, the semi-finished product chemical examination.
7) fill is in corresponding volumetrical infusion bottle.
8) 115 ℃ of pressure sterilizings are 30 minutes.
9) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 4 present composition glucose infusion liquids
1, prescription:
Second new compositions prescription
Acetylcysteine 50g
Neo-houttuyninum 8g
Polyoxyethylene sorbitan monoleate 50g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
The scorching composition prescription of second
Acetylcysteine 50g
Andrographolide 40g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Second ginseng composition prescription
Acetylcysteine 50g
Matrine 80g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
2, concrete steps:
1) carries 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.
2) polyoxyethylene sorbitan monoleate is made into 20% solution with water for injection, add the dissolving of neo-houttuyninum heated and stirred, add 40% water for injection again, add the acetylcysteine dissolving, glucose is complete with the water for injection dissolving of dosing amount 20%, merge above-mentioned solution benefit and add to the full amount of water for injection;
Perhaps be: acetylcysteine and andrographolide or matrine are added the heated and stirred dissolving fully, with the water for injection dissolving of dosing amount 40% fully with glucose.Merge above-mentioned solution, benefit adds to the full amount of water for injection.
3) needle-use activated carbon of adding dosing amount 0.05% stirred 15 minutes.
4) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
5) through the microporous filter membrane fine straining of 0.45 μ m.
6) clarity of inspection solution, the semi-finished product chemical examination.
7) fill is in corresponding volumetrical infusion bottle.
8) 115 ℃ of pressure sterilizings are 30 minutes.
9) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 5 present composition tablets
1, prescription:
Second new compositions prescription
Acetylcysteine 200g
Neo-houttuyninum 8g
Pregelatinized Starch 120.0g
Low-substituted hydroxypropyl cellulose 20g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4.0g
Carboxymethylstach sodium 16.0g
Prepare 1000 altogether
The scorching composition prescription of second
Acetylcysteine 200g
Andrographolide 40g
Pregelatinized Starch 120.0g
Low-substituted hydroxypropyl cellulose 20g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4.0g
Carboxymethylstach sodium 16.0g
Prepare 1000 altogether
Second ginseng composition prescription
Acetylcysteine 200g
Matrine 80g
Pregelatinized Starch 120.0g
Low-substituted hydroxypropyl cellulose 20g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4.0g
Carboxymethylstach sodium 16.0g
Prepare 1000 altogether
2, concrete steps:
1) it is standby acetylcysteine and neo-houttuyninum or andrographolide or matrine to be pulverized 100 mesh sieves.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with acetylcysteine, neo-houttuyninum or andrographolide or matrine, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, it is an amount of to add the 2%HPMC aqueous solution, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) the sheet weight sheet of determining according to chemical examination.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 6 present composition capsules
1, prescription:
Second new compositions prescription
Acetylcysteine 100g
Neo-houttuyninum 8g
Pregelatinized Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Micropowder silica gel 4.0g
Prepare 1000 altogether
The scorching composition prescription of second
Acetylcysteine 100g
Andrographolide 40g
Pregelatinized Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Micropowder silica gel 4.0g
Prepare 1000 altogether
Second ginseng composition prescription
Acetylcysteine 100g
Matrine 80g
Pregelatinized Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Micropowder silica gel 4.0g
Prepare 1000 altogether
2, concrete steps:
1) it is standby acetylcysteine and neo-houttuyninum or andrographolide or matrine to be pulverized 100 mesh sieves.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with acetylcysteine, neo-houttuyninum or andrographolide or matrine, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, it is an amount of to add the 2%HPMC aqueous solution, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate and micropowder silica gel, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) loading amount of determining according to chemical examination incapsulates.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 7 present composition granules
1, prescription:
Second new compositions prescription
Acetylcysteine 100g
Neo-houttuyninum 8g
Icing Sugar 2000.0g
Steviosin 10g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
The scorching composition prescription of second
Acetylcysteine 100g
Andrographolide 40g
Icing Sugar 2000.0g
Steviosin 10g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Second ginseng composition prescription
Acetylcysteine 100g
Matrine 80g
Icing Sugar 2000.0g
Steviosin 10g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
2, concrete steps:
1) it is standby sucrose to be pulverized 100 mesh sieves.It is standby that acetylcysteine and neo-houttuyninum or andrographolide or matrine were pulverized 100 mesh sieves.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) the method mix homogeneously that acetylcysteine and neo-houttuyninum or andrographolide or matrine and Icing Sugar, steviosin are progressively increased with equivalent, it is an amount of to add the 2%HPMC50% alcoholic solution, stirs, and makes suitable soft material.
4) cross 20 mesh sieve system granules.
5) granule is dried under 60 ℃ condition.
6) dried granule is crossed 18 mesh sieve granulate.
7) sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule.
8) packing, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 8 present composition sprays
1, prescription:
Second new compositions prescription
Acetylcysteine 100g
Neo-houttuyninum 8g
PEG400 100g
Sodium chloride 65g
Methyl hydroxybenzoate 0.5g
Ethyl hydroxybenzoate 0.5g
Purified water adds to 10000ml
Prepare 1000 bottles altogether
The scorching composition prescription of second
Acetylcysteine 100g
Andrographolide 40g
Sodium chloride 65g
Methyl hydroxybenzoate 0.5g
Ethyl hydroxybenzoate 0.5g
Purified water adds to 10000ml
Prepare 1000 bottles altogether
Second ginseng composition prescription
Acetylcysteine 100g
Matrine 80g
Sodium chloride 65g
Methyl hydroxybenzoate 0.5g
Ethyl hydroxybenzoate 0.5g
Purified water adds to 10000ml
Prepare 1000 bottles altogether
2, concrete steps:
1) takes by weighing raw material and adjuvant according to recipe quantity.
2) it is complete neo-houttuyninum to be added in the PEG400 of recipe quantity heating for dissolving, adds purified water while stirring, to 500ml, clear liquid;
Perhaps be: heating for dissolving in andrographolide or the matrine adding purified water is complete, to 500ml, get clear liquid.
3) acetylcysteine and sodium chloride, methyl hydroxybenzoate, ethyl hydroxybenzoate are added among the purified water 200ml, the heated and stirred dissolving is complete, with above-mentioned solution mix homogeneously.
4) measure solution and get pH value, get the sodium hydroxide solution regulator solution with 1mol/L and get pH value about 6.0.
5) replenish purified water to 10000ml, stir.
6) solution is crossed 0.8 micron filter membrane fine straining, the semi-finished product chemical examination.
7) divide in the aerosol container of packing into screw capping.
8) finished product is examined entirely, the packing warehouse-in.
Claims (7)
1. the pharmaceutical composition formed of an acetylcysteine or its pharmaceutically acceptable salt and at least a anti-infectives, it is characterized in that, described anti-infectives is selected from: neo-houttuyninum or its pharmaceutically acceptable salt and/or 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt and/or matrine, wherein the parts by weight of compositions are: 50～600 parts of acetylcysteine or its pharmaceutically acceptable salts, anti-infectives is different and different according to medicine, for neo-houttuyninum or its pharmaceutically acceptable salt is 4～20 parts, for 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is 20～80 parts, is 40～160 parts for matrine.
2. pharmaceutical composition as claimed in claim 1, the parts by weight that it is characterized in that described compositions are: 100～300 parts of acetylcysteine or its pharmaceutically acceptable salts, anti-infectives is different and different according to medicine, for neo-houttuyninum or its pharmaceutically acceptable salt is 8 parts, for 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is 40 parts, is 80 parts for matrine.
3. as each described pharmaceutical composition of claim 1～2, it is characterized in that described acetylcysteine pharmaceutically acceptable salt is hydrochlorate, sulfate, acetate, mesylate, tartrate, maleate, fumarate, hydrobromate, aspartate.
4. as each described pharmaceutical composition of claim 1～2, it is characterized in that described neo-houttuyninum pharmaceutically acceptable salt is sodium salt, potassium salt, calcium salt, magnesium salt, zinc salt.
5. as each described pharmaceutical composition of claim 1～2, it is characterized in that described 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester salt is its monopotassium salt, single sodium salt, k-na salt, single magnesium salt, single calcium salt, single zinc salt.
6. as each described pharmaceutical composition of claim 1～2, it is characterized in that described pharmaceutical composition and mixing acceptable accessories make clinically any or pharmaceutically acceptable dosage form.
7. pharmaceutical composition as claimed in claim 6 is characterized in that clinically described or pharmaceutically acceptable dosage form is injection and peroral dosage form.
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| EP2411004A4 (en) * | 2009-03-24 | 2012-08-15 | Univ Singapore | USE OF ANDROGRAPHOLIDE COMPOUNDS FOR THE TREATMENT OF INFLAMMATORY DISEASE AND RESPIRATORY DISEASES |
| CN102827039B (en) * | 2011-06-17 | 2014-09-17 | 广东东阳光药业有限公司 | Herba Houttuyniae derivative and its application in drugs |
| CN103936635B (en) * | 2011-06-17 | 2016-10-12 | 广东东阳光药业有限公司 | Herba Houttuyniae derivant and the application in medicine thereof |
| EP2589381B1 (en) * | 2011-11-04 | 2016-08-31 | Rabindra Tirouvanziam | Compositions for improving or preserving lung function in a patient with a pulmonary disorder |
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| 雾化吸入用药液组方的优选及其临床观察. 邬海桥.重庆医科大学学位论文. 2002 |
| 雾化吸入用药液组方的优选及其临床观察. 邬海桥.重庆医科大学学位论文. 2002 * |
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