CN102416167A - Aerosol inhalant containing interferon alpha and terbutaline sulfate - Google Patents
Aerosol inhalant containing interferon alpha and terbutaline sulfate Download PDFInfo
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Abstract
The invention belongs to the field of medicinal compositions for resisting virus, and relates to an aerosol inhalant containing interferon alpha and terbutaline sulfate. The aerosol inhalant contains a therapeutically effective amount of interferon alpha, a therapeutically effective amount of terbutaline sulfate and an appropriate amount of pharmaceutic auxiliary materials; preferably, single dose of the aerosol inhalant contains 2.5 to 30 mu g of interferon alpha, 0.5 to 2 mg of terbutaline sulfate, and an appropriate amount of pharmaceutic auxiliary materials; and more preferably, single dose of the aerosol inhalant contains 10 to 20 mu g of interferon alpha, 1 to 1.5mg of terbutaline sulfate and an appropriate amount of pharmaceutic auxiliary materials. Compared with the interferon alpha or the terbutaline sulfate, the aerosol inhalant containing the interferon alpha and the terbutaline sulfate has the advantages that the effect of treating viral pneumonia can be improved obviously.
Description
Technical field
The present invention relates to the compositions and the application in preparation treatment viral pneumonia medicine thereof of antiviral drugs.
Background technology
Viral pneumonia is a kind of infant commonly encountered diseases in period, the life and health of serious harm infant.According to incompletely statistics, the infant above 90% infected viral pneumonia in the past at 2 years old, and wherein 80% above case is in 1 years old, and the onset peak age is 2-6 month, and 1-6 month visible than the severe disease example.Infant can reach 7% because of the death that infective virus property pneumonia causes is 0.5%-2.0% in developed country in developing country, at China's dead first cause of infant especially.In addition, the infectiousness of viral pneumonia and infectivity is very strong again has report to show and can take place between the kinsfolk to infect in succession, infected infant in 10 years again infection rate up to 65%.
The virus that causes viral pneumonia mainly be adenovirus (adenovirus, ADV) and respiratory syncytial virus (respiratory syncytial virus, RSV); Next be influenza virus (influenza virus, IFV) and parainfluenza virus (parainfluenzavirus, PIV); Be cytomegalovirus (cytomegalovirus once more; CMV), herpes simplex virus (herpes simplex virus, HSV), enterovirus (enterovirus, EV), human metapneumovirus (hMPV) etc.Because these viruses very easily morph; Behind viral infection, bring out further bacterial infection easily in addition; Thereby cause mixed infection and complication to infant, so the comprehensive special control of the very difficult realization of infant viral pneumonia, effective Drug therapy lacked clinically.
Chemicals is the main medicine of treating viral pneumonia at present, and reason is that clinical service time is the longest, can remove infective virus rapidly; But the shortcoming of chemotherapy viral pneumonia is that the state of an illness rebounds easily after the drug withdrawal, can not regulate and improve children patient immunity antagonism virus, and in the life-time service process, be easy to generate drug resistance.The chemicals of treating viral pneumonia at present clinically mainly contains ribavirin, ganciclovir, Oseltamivir, vidarabine, amantadine etc.For example U.S. Pat 5,290, and 540 disclose the method that ribavirin is used to treat viral pneumonia.
Chinese medicine uses increasingly extensive in research in recent years to the treatment of viral pneumonia, this comes from the gentle lasting of herbal nature, and has immunoregulation effect concurrently.But the treatment by Chinese herbs viral pneumonia cycle is long, and Chinese medicine to a great extent and be unwell to infant and use.The long-term safety problem of treatment by Chinese herbs also is a problem that can not be ignored in addition.The Chinese medicine that has the report clinical research to be used for the viral pneumonia treatment at present mainly contains Folium Isatidis, Radix Isatidis, Flos Lonicerae, Fructus Forsythiae, Rhizoma Belamcandae, Radix Scutellariae, Rhizoma Coptidis, Herba Ephedrae, Semen Armeniacae Amarum etc.For example Chinese patent CN 03131642.5 discloses a kind of oral liquid for clearing away lung-heat preparation of treating infantile viral pneumonia, and it is made up of Chinese herbal medicine such as Herba Ephedrae, Gypsum Fibrosum, Semen Armeniacae Amarum, Semen Lepidii (Semen Descurainiae), Cortex Mori, Radix Peucedani, Bombyx Batryticatus, Radix Salviae Miltiorrhizae, Rhizoma Polygoni Cuspidati, Rhizoma Bistortaes.And for example Chinese patent CN 02138175.5 discloses a kind of pharmaceutical composition of treating infantile viral pneumonia, its by Herba Ephedrae, Semen Armeniacae Amarum, Gypsum Fibrosum, Radix Glycyrrhizae, Radix Peucedani, Bombyx Batryticatus, Radix Salviae Miltiorrhizae, Rhizoma Polygoni Cuspidati, Rhizoma Bistortae, Semen Lepidii (Semen Descurainiae), Cortex Mori ten simply Chinese medicine form.
Be accompanied by the fast development of biotech drug; The treatment of biotech drug to viral pneumonia paid close attention in increasing in recent years research; Use therein biotech drug comprises interferon, interleukin, human, thymosin, specific antiviral antibody etc., and the report that especially uses with interferon is maximum.Biotech drug, especially interferon are used for the treatment of viral pneumonia, persistent, and scalable and raising children patient immunity antagonism virus are difficult for producing drug resistance, and safety is higher.For example Chinese patent CN03147580.9 discloses a kind of recombinant human interferon-alpha spray of treating viral pneumonia, and it is equipped with adequate protective agent, mucosa absorption promoter, antibacterial etc. by recombinant human interferon-alpha stock solution and processes, and pH value is at 5.0-8.0.
But because aforementioned infant further brings out bacterial infection easily after infective virus property pneumonia; Thereby cause mixed infection and complication to infant; Therefore use a kind of clinical effectiveness of Drug therapy infant viral pneumonia unsatisfactory separately, the pharmaceutical composition that has produced drug combination or two or more effective ingredients is used for the treatment of viral pneumonia.The curative effect of interferon associating ribavirin therapy infantile viral pneumonia reported in the article " interferon associating ribavirin therapy infantile viral pneumonia 30 routine observation of curative effect " that for example " the practical medicine of China " March in 2009, the 4th volume the 9th phase 144-145 page or leaf was delivered; Show that drug combination group treatment effective percentage is 96.7%; And the effective percentage that uses the matched group of ribavirin separately has only 76.6%, and both have the significant difference on the statistics.But the research that drug combination or compositions medication are used for viral pneumonia is system not enough at present, and the research kind is also less, so the large-scale promotion that achievement in research also is inappropriate for is clinically used.
Aspect the drug delivery system of treatment viral pneumonia, atomized inhalation is a kind of new form of administration that grows up clinically in recent years.So-called atomized inhalation is meant medicinal liquid is become the medicine mist through atomizing, reaches the dosage form that the respiratory system target site plays therapeutical effect through sucking.The administration of atomized inhalation must comprise compression atomizing device, ultrasound atomizer etc. by certain atomizing suction apparatus.Owing to can directly act on the respiratory disease position without absorbing after the atomized inhalation administration; Thereby compare other dosage forms obviously higher bioavailability and drug effect arranged, so atomized inhalation becomes the first-selected dosage form of treating infantile viral pneumonia clinically gradually.
In addition; Terbutaline sulphate is a kind of common medicine of treating pulmonary disease clinically; Existing bibliographical information terbutaline sulphate and antiviral chemicals are united and are used for the infantile pneumonia treatment; For example the curative effect of terbutaline sulphate associating budesonide treatment infantile pneumonia reported in the article delivered of " Chinese Medicine guide " 2010 the 8th volume the 24th phase 53-54 page or leaf " budesonide with terbutaline sulphate atomizing suck assistant control the bronchopneumonic clinical observation of panting property of infant ", and the treatment group all has obvious minimizing than matched group breathing heavily to suppress to alleviate on natural law, cough alleviation natural law, the indexs such as sound disappearance natural law, average hospital days of stridulating.
But not seeing in the prior art has interferon-ALPHA and terbutaline sulphate to unite the report that uses the treatment viral pneumonia.
Summary of the invention
Primary and foremost purpose of the present invention provides the atomized inhalation of a kind of interferon-ALPHA and terbutaline sulphate, to be used for the treatment of infant viral pneumonia, further improves therapeutic effect.
In the embodiment on basis, the atomized inhalation of interferon-ALPHA of the present invention and terbutaline sulphate contains the pharmaceutically acceptable auxiliaries of interferon-ALPHA, terbutaline sulphate and the Sq of treating effective dose.
The preparation of atomized inhalation can select well known to a person skilled in the art method, or even with the similar method of injection.But the composition of atomized inhalation no matter, or the preparation of atomized inhalation all will take into full account the chemical stability of heat stability, pH stability and the terbutaline sulphate of stability, the especially interferon-ALPHA of interferon-ALPHA and terbutaline sulphate.
For example; Should contain in the adjuvant and help interferon-ALPHA and the stable buffer solution system of terbutaline sulphate; The pH of such buffer solution system should be between 5.0-8.0, and such buffer solution system is including, but not limited to PBS system, citrate buffer solution system; Should contain the interferon-ALPHA activity protecting agent; To prevent that the interferon-ALPHA activity from reducing or lose in the long term storage process; Such protective agent is including, but not limited to each seed amino acid, albumin and polyalcohols material, for example albumin, mannitol, trehalose, dextran.Also preferably contain osmotic pressure regulator in addition in the adjuvant, with the osmotic pressure with solution be adjusted to health in basic the grade ooze, such osmotic pressure regulator is including, but not limited to NaCl, mannitol; Preferably contain the chaotropic agent that prevents interferon-ALPHA, terbutaline sulphate and other adjuvants deposition and absorption, such chaotropic agent is including, but not limited to tween 80; Preferably contain the antiseptic that prevents the pharmaceutical preparation microbiological contamination, such antiseptic is including, but not limited to benzalkonium chloride, Nipagin ester, benzyl alcohol etc.
In the preparation process of atomized inhalation, preferably with the slightly solubility adjuvant earlier with after the suitable more method dissolving again and dissolved interferon-ALPHA, terbutaline sulphate and other adjuvants mix.Answer rapid mixing in the preparation process, note avoiding the rapid variation of pH, temperature etc., thereby cause the bioinactivation and/or the chemical degradation of active constituents of medicine interferon-ALPHA, terbutaline sulphate.
Because after active constituents of medicine interferon-ALPHA, terbutaline sulphate and adjuvant mix; Between the active constituents of medicine; Between the adjuvant, and might interact between each active constituents of medicine and the adjuvant, cause the bioinactivation and/or the chemical degradation of active constituents of medicine; Thereby reduce the clinical result of use of atomized inhalation; Even bring safety issue for the clinical use of atomized inhalation, so need carry out necessary detection, do not exist or seldom exist to confirm such bioinactivation and/or chemical degradation to the atomized inhalation that mixing obtains.The detection means of necessity of described atomized inhalation detects including, but not limited to outward appearance and (observes interferon-ALPHA; Whether coloured variation after terbutaline sulphate and adjuvant mix; The appearance of gas and/or sedimentary generation); PH detects; The interferon-ALPHA biological activity assay; The interferon-ALPHA content detection; The interferon-ALPHA molecular weight detection; Interferon-ALPHA N-terminal Sequence Detection; Interferon-ALPHA C-terminal Sequence Detection; The interferon-ALPHA amino acid composition analysis detects; The terbutaline sulphate content detection; Terbutaline sulphate purity detecting etc.Preferably carry out the active detection of interferon-ALPHA, interferon-ALPHA molecular weight detection, terbutaline sulphate purity and content detection.
Interferon-ALPHA is active to detect preferred employing the " Chinese Pharmacopoeia 2010 editions (three ones) " specified standard method.
The interferon-ALPHA molecular weight detection should adopt mass spectrography rather than electrophoresis method; (degraded of several amino acid or replacement will cause the interferon-ALPHA change of molecular weight on the interferon-ALPHA sequence because mass spectrography can detect minor variations on the interferon-ALPHA aminoacid sequence; Thereby can be detected by Mass Spectrometer Method), the sensitivity of electrophoresis method does not then reach.
Terbutaline sulphate purity/content detection preferably adopts " Chinese Pharmacopoeia 2010 editions (two ones) " specified standard rp-hplc method; Because such method can guarantee to detect the possible catabolite of terbutaline sulphate; Terbutaline sulphate can fully be separated in detection with adjuvant, thereby prevent the influence of adjuvant the terbutaline sulphate content detection.For the chromatographic peak of confirming a certain retention time is terbutaline sulphate catabolite peak or solubility adjunct ingredient peak, can be on identical chromatographic condition under each solubility adjuvant reference substance, compare through retention time and to confirm.
According to general knowledge as well known to those skilled in the art; When adopting the HPLC method that terbutaline sulphate is carried out content detection, need on the HPLC filled column, go up respectively with the terbutaline sulphate reference substance of volume variable concentrations or with the terbutaline sulphate reference substance of concentration different volumes with the drawing curve.
In above-mentioned various detections, carry out dissolution process if desired, but should adopt gentle condition to prevent interferon-ALPHA in the course of dissolution, terbutaline sulphate bioinactivation and/or chemical degradation; In order to eliminate the influence of precipitate to detecting that possibly exist, need filter or centrifugal treating precipitate; In order to eliminate of the influence of macromole interferon-ALPHA, can remove the interferon-ALPHA in the solution with ultrafiltration to micromolecule terbutaline sulphate purity/content detection; In order to eliminate the micromolecule solable matter, can remove the small-molecule substance in the solution with methods such as ultrafiltration, dialysis to the influence that interferon-ALPHA detects.
In a kind of embodiment preferred, contain the interferon-ALPHA of 2.5-30 μ g and the terbutaline sulphate of 0.5-2mg in the atomized inhalation single-dose dosage of interferon-ALPHA of the present invention and terbutaline sulphate, and the pharmaceutically acceptable auxiliaries of Sq.
In a kind of embodiment preferred, contain the interferon-ALPHA of 10-20 μ g and the terbutaline sulphate of 1-1.5mg in the atomized inhalation single-dose dosage of interferon-ALPHA of the present invention and terbutaline sulphate, and the pharmaceutically acceptable auxiliaries of Sq.
In a kind of embodiment preferred, the interferon-ALPHA in the atomized inhalation of interferon-ALPHA of the present invention and terbutaline sulphate is a kind of among interferon-ALPHA 2a, interferon alpha-2 b and the interferon-ALPHA 1b or with arbitrary proportion blended several kinds.
In a kind of embodiment preferred, the interferon-ALPHA in the atomized inhalation of interferon-ALPHA of the present invention and terbutaline sulphate is interferon-ALPHA 1b.
Another object of the present invention provides the application of atomized inhalation in preparation treatment viral pneumonia medicine of interferon-ALPHA and terbutaline sulphate.Utilize atomized inhalation treatment viral pneumonia of the present invention, can use interferon-ALPHA or terbutaline sulphate treatment viral pneumonia to obtain obviously better therapeutic effect more separately.
Description of drawings
Fig. 1 is DIKMA Platisil C on the terbutaline sulphate reference substance
18Reversed-phase high-performance liquid chromatography post (the chromatogram that 4.6 * 250mm) backs obtain.
The specific embodiment
Through following embodiment enforcement of the present invention is described further, but embodiment of the present invention is not limited to following embodiment.
Embodiment 1: the preparation of the atomized inhalation of interferon-ALPHA and terbutaline sulphate
The atomized inhalation for preparing interferon-ALPHA and terbutaline sulphate by method like following table 1.Wherein " Recombinant Interferon " (trade name) is the recombinant human interferon alpha 2 b injection that 50 μ g/ml/ prop up for the specification that Tianjin Hualida Biological Engineering Co., Ltd. produces; " Recomvinated Interferon " (trade name) is the recombinant human interferon-alpha 2 α injection that 50 μ g/ml/ prop up for the specification that Shenyang Sansheng Pharmaceutical Co., Ltd. produces; " the fortune moral is plain " (trade name) is the recombinant human interferon alpha 1 b injection that 50 μ g/ml/ prop up for the specification that Beijing Sanyuan Gene Engineering Co. Ltd. produces, and " terbutaline " (trade name) is the terbutaline sulphate atomized liquid that 5mg/2ml/ props up for the specification of AstraZeneca production; " PBS " is for containing 25mmol/L sodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution (pH7.0) of 0.15mol/L NaCl.More than each trade name in the subsequent implementation example as do not have and not particularly point out, implication is identical with implication in the present embodiment.
The preparation of the atomized inhalation of table 1 interferon-ALPHA and terbutaline sulphate
Embodiment 2: the mixed terbutaline sulphate purity detecting of interferon-ALPHA and terbutaline sulphate
Each interferon-ALPHA that will prepare by the method for embodiment 1 and the atomized inhalation of terbutaline sulphate use molecular cut off to carry out hyperfiltration treatment as the Millipore ultra-filtration centrifuge tube of 3000Da respectively after placing the preset time, and filtered solution is diluted to deionized water and gets DIKMA Platisil C on the 20 μ l respectively after identical with the centrifugal front volume of ultrafiltration
18Reversed-phase high-performance liquid chromatography post (5 μ tm packing material sizes; Column dimension 4.6 * 250mm); Under 25 ℃ of column temperatures, carry out chromatographic run; Mobile phase (acetonitrile-0.0065mol/L perfluoroetane sulfonic acid sodium solution (23: 77) is also regulated the solution of pH value to 3.4 ± 0.2 with acetic acid) eluting, flow velocity 1.0ml/min detects wavelength 280nm.Mensuration result is as shown in table 2 below.
The mixed terbutaline sulphate purity detecting of table 2 interferon-ALPHA and terbutaline sulphate result
| Numbering | Mixed back 0 hour | Mixed back 12 hours | Mixed back 24 hours | Mixed back 48 hours |
| Atomized inhalation 1 | 98.7％ | 98.7％ | 98.7％ | 98.8％ |
| Atomized inhalation 2 | 98.7％ | 98.9％ | 98.8％ | 98.8％ |
| Atomized inhalation 3 | 98.9％ | 98.8％ | 98.8％ | 98.9％ |
| Atomized inhalation 4 | 98.7％ | 98.5％ | 98.6％ | 98.7％ |
| Atomized inhalation 5 | 98.8％ | 98.7％ | 98.7％ | 98.7％ |
| Atomized inhalation 6 | 98.7％ | 98.9％ | 98.8％ | 98.9％ |
| Atomized inhalation 7 | 99.0％ | 98.8％ | 98.8％ | 99.0％ |
| Atomized inhalation 8 | 98.8％ | 99.0％ | 99.0％ | 99.0％ |
| Atomized inhalation 9 | 98.6％ | 98.7％ | 98.8％ | 98.7％ |
It is thus clear that interferon-ALPHA mixes the purity not influence of back to terbutaline sulphate with terbutaline sulphate.
Embodiment 3: the mixed terbutaline sulphate content detection of interferon-ALPHA and terbutaline sulphate
With terbutaline sulphate reference substance (Nat'l Pharmaceutical & Biological Products Control Institute preparation, lot number 100273-199701) water respectively dissolved dilution to concentration be 0.075,0.150,0.300,0.600, go up an appearance mensuration main peak peak area respectively by the high-efficient liquid phase chromatogram condition of embodiment 2 behind the 0.900mg/ml.With peak area (y) concentration (x) is carried out linear regression and get working curve, equation is y=8.2 * 10
6X+187.68, regression coefficient is r=0.9999.
Each interferon-ALPHA that will prepare by the method for embodiment 1 and the atomized inhalation of terbutaline sulphate carry out the ultrafiltration centrifugal treating by the method for embodiment 2 respectively after placing the preset time; Filtered solution respectively with deionized water be diluted to be diluted to terbutaline sulphate wherein with deionized water respectively again after identical with the centrifugal front volume of ultrafiltration theoretical content in the concentration range that above-mentioned working curve covers, press appearance mensuration main peak peak area on the high-efficient liquid phase chromatogram condition of embodiment 2 then respectively.The peak area substitution working curve equation that each mensuration is obtained just can obtain the concentration of terbutaline sulphate in the atomized inhalation after each dilution, multiply by the concentration that extension rate just can obtain terbutaline sulphate in each atomized inhalation again.Mensuration result is as shown in table 3 below.
The mixed terbutaline sulphate content detection of table 3 interferon-ALPHA and terbutaline sulphate result
It is thus clear that interferon-ALPHA mixes the content not influence of back to terbutaline sulphate with terbutaline sulphate.Comprehensive embodiment 2 interferon-ALPHA mix the testing result of back terbutaline sulphate purity with terbutaline sulphate, explain that interferon-ALPHA mixes the back terbutaline sulphate chemical degradation does not take place with terbutaline sulphate.Embodiment 4: the mixed interferon-ALPHA molecular weight detection of interferon-ALPHA and terbutaline sulphate
Each interferon-ALPHA that will prepare and the atomized inhalation of terbutaline sulphate by the method for embodiment 1 respectively to the deionized water of 100 times of volumes dialyse (the bag filter molecular cut off is 7000Da) handle, during change deionized water once.Dialysis solution is carried out MALDI-TOF mass spectrum molecular weight detection respectively, and the testing result below the record molecular weight 25000Da is as shown in table 4.In each time testing result, all only detect a values for molecular weight, the interferon-ALPHA catabolite do not occur after interferon-ALPHA being described and terbutaline sulphate being mixed.
The mixed interferon-ALPHA molecular weight detection of table 4 interferon-ALPHA and terbutaline sulphate result
Embodiment 5: the mixed interferon-ALPHA of interferon-ALPHA and terbutaline sulphate is active to be detected
Each interferon-ALPHA that will prepare by the method for embodiment 1 and the atomized inhalation of terbutaline sulphate are surveyed the activity that interferon-ALPHA is wherein measured in the standard method of living respectively by the interferon-ALPHA of " Chinese Pharmacopoeia 2010 editions (three ones) " regulation.Mensuration result is as shown in table 5 below.
The active testing result of the mixed interferon-ALPHA of table 5 interferon-ALPHA and terbutaline sulphate
Above-mentioned testing result explanation interferon-ALPHA mixes the activity not influence of back to interferon-ALPHA with terbutaline sulphate.
The testing result of comprehensive embodiment 4 and embodiment 5 explains that interferon-ALPHA mixes the back interferon-ALPHA bioinactivation and chemical degradation do not take place with terbutaline sulphate.
Embodiment 6: the animal experiment of interferon-ALPHA and terbutaline sulphate atomized inhalation treatment viral pneumonia
1) RSV Virus culture
Respiratory syncytial virus type strain RSV-Long (drawing from institute of pediatrics, Beijing) is inoculated on the Hep-2 cell; Treat that cytopathy reaches 80% above time results, viral liquid is frozen in liquid nitrogen, and the time spent is in 37 ℃ of thawings; Centrifugal 10 minutes of 1000rpm, it is subsequent use to get supernatant.
2) foundation of RSV mouse infection model
Get 96 mices all with behind the etherization, via intranasal application splashes into 10
6PFU/ml RSV virus liquid 0.1ml drips virus every day 1 time, drips altogether 2 times, and perpendicular hair, dysphoria, rapid breathing, abdominal muscle tic positive reaction appearred in mice in the 3rd day, shows that the rsv infection mouse model sets up successfully.
3) grouping and administration
Above-mentioned 96 mices that infected RSV virus are divided into 12 groups, 8 every group at random.Every day, ultrasonic atomizatio sucked the described atomized inhalation 1 of previous embodiment to atomized inhalation 9 each 1ml to group 1 to group 9 respectively; Organizing ultrasonic atomizatio suction injection 10 every days specification is " the fortune moral is plain " that 30 μ g/ml/ prop up, and organizing ultrasonic atomizatio suction 11 every days specification is " terbutaline " 0.5 that 5mg/2ml/ props up; Organize ultrasonic atomizatio suction 12 every days normal saline 1ml.All respectively organize every day all ultrasonic atomizatio suck 1 time, ultrasonic atomizatio sucks 5 times (5 days) altogether.Get mice blood after 5 days and carry out the BALF numeration of leukocyte, the result is as shown in table 6 below.
Table 6BALF numeration of leukocyte result
Claims (9)
1. the atomized inhalation of interferon-ALPHA and terbutaline sulphate is characterized in that described atomized inhalation contains the pharmaceutically acceptable auxiliaries of interferon-ALPHA, terbutaline sulphate and the Sq of treating effective dose.
2. atomized inhalation according to claim 1 is characterized in that containing in the single-dose dosage interferon-ALPHA of 2.5-30 μ g, the terbutaline sulphate of 0.5-2mg, and the pharmaceutically acceptable auxiliaries of Sq.
3. atomized inhalation according to claim 2 is characterized in that containing in the single-dose dosage interferon-ALPHA of 10-20 μ g, the terbutaline sulphate of 1-1.5mg, and the pharmaceutically acceptable auxiliaries of Sq.
4. atomized inhalation according to claim 1 is characterized in that described pharmaceutically acceptable auxiliaries comprises the interferon-ALPHA activity protecting agent, is selected from one or more the combination in albumin, mannitol, trehalose, the dextran.
5. atomized inhalation according to claim 1 is characterized in that described pharmaceutically acceptable auxiliaries comprises osmotic pressure regulator, is selected from one or both the combination in NaCl, the mannitol.
6. atomized inhalation according to claim 1 is characterized in that described pharmaceutically acceptable auxiliaries comprises antiseptic, is selected from one or more the combination in benzalkonium chloride, Nipagin ester, the benzyl alcohol.
7. atomized inhalation according to claim 1 is characterized in that described interferon-ALPHA is a kind of among interferon-ALPHA 2a, interferon alpha-2 b and the interferon-ALPHA 1b or with arbitrary proportion blended several kinds.
8. atomized inhalation according to claim 7 is characterized in that described interferon-ALPHA is interferon-ALPHA 1b.
9. according to the application of the described atomized inhalation of one of claim 1-8 in preparation treatment viral pneumonia medicine.
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| CN110693861A (en) * | 2018-07-09 | 2020-01-17 | 北京盈科瑞创新药物研究有限公司 | Terbutaline sulfate solution preparation for aerosol inhalation and preparation method thereof |
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