CN102430112B - Atomization inhalant prepared from interferon alpha and salbutamol sulfate - Google Patents
Atomization inhalant prepared from interferon alpha and salbutamol sulfate Download PDFInfo
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- CN102430112B CN102430112B CN 201110407386 CN201110407386A CN102430112B CN 102430112 B CN102430112 B CN 102430112B CN 201110407386 CN201110407386 CN 201110407386 CN 201110407386 A CN201110407386 A CN 201110407386A CN 102430112 B CN102430112 B CN 102430112B
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Abstract
The invention belongs to the field of composites of antiviral medications, which relates to an atomization inhalant prepared from interferon alpha and salbutamol sulfate. The atomization inhalant comprises the interferon alpha with a curative effective dose, the salbutamol sulfate and a pharmaceutically acceptable adjuvant with sufficient quantity. Preferentially, the single dose comprises 2.5-30mug of the interferon alpha, 0.048-0.192mug of the salbutamol sulfate and the pharmaceutically acceptable adjuvant with the sufficient quantity, and more preferentially, the single dose comprises 10-20mug of the interferon alpha, 0.096-0.144mug of the salbutamol sulfate and the pharmaceutically acceptable adjuvant with the sufficient quantity. Compared with treating viral pneumonia by singly using the interferon alpha or the salbutamol sulfate, the curative effect can be obviously improved on treating the viral pneumonia by using the atomization inhalant prepared from the interferon alpha and the salbutamol sulfate.
Description
Technical field
The present invention relates to 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, 1-6 month visible heavier case.Infant can reach 7% because the death of infecting viral pneumonia and causing is 0.5%-2.0% in developed country in developing country, at China's first cause of Infant and child deaths especially.In addition, the infectiousness of viral pneumonia and infectivity is very strong again has report to show and can occur between the kinsfolk in succession to infect, infected infant in 10 years again infection rate up to 65%.
The virus that causes viral pneumonia mainly is adenovirus (adenovirus, ADV) and respiratory syncytial virus (respiratory syncytial virus, RSV), next is influenza virus (influenza virus, IFV) and parainfluenza virus (parainfluenza virus, PIV), cytomegalovirus (cytomegalovirus again, CMV), herpes simplex virus (herpes simplex virus, HSV), enterovirus (enterovirus, EV), human metapneumovirus (hMPV) etc.Because these viruses very easily morph, bring out easily further antibacterial behind viral infection infects 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 for the treatment of at present viral pneumonia, and reason is that clinical service time is the longest, can remove rapidly and infect virus; 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 produces easily drug resistance in the life-time service process.The chemicals for the treatment of clinically viral pneumonia at present mainly contains ribavirin, ganciclovir, Oseltamivir, vidarabine, amantadine etc.For example US Patent No. 5,290, and 540 disclose the method that ribavirin is used for the treatment of 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 for the treatment of by Chinese herbs also is a problem that can not be ignored in addition.The Chinese medicine that has at present the report clinical research to be used for the viral pneumonia treatment 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 for the treatment of infantile viral pneumonia, and it is comprised 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 for the treatment of infantile viral pneumonia, and it is comprised of 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 a herbs.
Be accompanied by the fast development of biotech drug, in recent years increasing research is paid close attention to biotech drug to the treatment of viral pneumonia, use therein biotech drug comprises interferon, interleukin, human γ-globulin, 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, and effect is lasting, 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 nebula for the treatment of viral pneumonia, and it is equipped with suitable protective agent, mucosa absorption promoter, antibacterial etc. by recombinant human interferon-alpha stock solution and makes, and pH value is at 5.0-8.0.
But because aforementioned infant further brings out bacterial infection easily after infecting viral pneumonia, thereby cause mixed infection and complication to infant, therefore the clinical effectiveness that is used alone the Drug therapy Infant Viral Pneumonia is unsatisfactory, and the pharmaceutical composition that has produced drug combination or two or more effective ingredients is used for the treatment of viral pneumonia.For example the curative effect of interferon plus ribavirin therapy infantile viral pneumonia reported in " the practical medicine of China " article " interferon plus ribavirin therapy infantile viral pneumonia 30 routine observation of curative effect " that March in 2009, the 4th volume the 9th phase 144-145 page or leaf was delivered, show that drug combination group treated effect is 96.7%, and the effective percentage that uses separately the matched group of ribavirin only has 76.6%, and both have significant difference statistically.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 unsuitable for is clinically used.
Aspect the drug delivery system for the treatment of viral pneumonia, atomized inhalation is a kind of new form of administration that grows up clinically in recent years.So-called atomized inhalation refers to medicinal liquid is become the medicine mist through atomizing, reaches the dosage form that the respiratory system target site plays therapeutical effect through suction.The administration of atomized inhalation must by certain nebulization equipment, comprise compression atomizing device, ultrasound atomizer etc.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 for the treatment of clinically infantile viral pneumonia gradually.
In addition, salbutamol sulfate is a kind of Common drugs for the treatment of clinically pulmonary disease, existing lot of documents report salbutamol sulfate is used for the infantile pneumonia treatment, for example the curative effect of salbutamol sulfate associating ketotifen treatment children's bronchopneumonia reported in " Shanxi Medicine magazine " December the 35th volume in 2006 the 12nd phase 1108 pages of articles of delivering " salbutamol sulfate and ketotifen therapeutic alliance bronchopneumonia observation of curative effect ", and effective percentage can reach 65%.
Summary of the invention
Primary and foremost purpose of the present invention provides the atomized inhalation of a kind of interferon-ALPHA and salbutamol sulfate, 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 salbutamol sulfate contains the pharmaceutically acceptable auxiliaries of interferon-ALPHA, salbutamol sulfate and the Sq for the treatment of 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 salbutamol sulfate of stability, the especially interferon-ALPHA of interferon-ALPHA and salbutamol sulfate.
For example, should contain in the adjuvant and be conducive to the stable buffer solution system of interferon-ALPHA and salbutamol sulfate, 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 phosphate buffered solution 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 in addition osmotic pressure regulator 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, salbutamol sulfate and other adjuvants precipitation 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 first with after the more suitable method dissolving again and the interferon-ALPHA that has dissolved, salbutamol sulfate and other adjuvants mix.Answer rapid mixing in the preparation process, note avoiding the rapid variation of pH, temperature etc., thereby cause bioinactivation and/or the chemical degradation of active constituents of medicine interferon-ALPHA, salbutamol sulfate.
Because after active constituents of medicine interferon-ALPHA, salbutamol sulfate 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 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 to carry out to the atomized inhalation that is mixed to get necessary detection, not exist or seldom exist to confirm such bioinactivation and/or chemical degradation.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 salbutamol sulfate and adjuvant mix, the appearance of gas and/or the generation of precipitation), 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 salbutamol sulfate content detection, salbutamol sulfate purity detecting etc.Preferably carry out the active detection of interferon-ALPHA, interferon-ALPHA molecular weight detection, salbutamol sulfate 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, because mass spectrography can detect (the several amino acid whose degradeds or replace the variation that will cause the interferon-ALPHA molecular weight on the interferon-ALPHA sequence of 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.
Salbutamol sulfate 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 salbutamol sulfate, salbutamol sulfate can fully be separated in detection with adjuvant, thereby prevent that adjuvant is on the impact of salbutamol sulfate content detection.For the chromatographic peak of determining a certain retention time is salbutamol sulfate catabolite peak or solubility adjunct ingredient peak, can be under the identical chromatographic condition each solubility adjuvant reference substance, determine by the retention time comparison.
According to general knowledge as well known to those skilled in the art, when adopting the HPLC method that salbutamol sulfate is carried out content detection, need on the HPLC filled column, go up respectively with the salbutamol sulfate reference substance of volume variable concentrations or with the salbutamol sulfate reference substance of concentration different volumes with the drawing curve.
In above-mentioned various detections, if need to carry out dissolution process, but should adopt gentle condition to prevent interferon-ALPHA in the course of dissolution, salbutamol sulfate bioinactivation and/or chemical degradation; In order to eliminate the impact of precipitate on detecting that may exist, need to filter or centrifugal treating precipitate; In order to eliminate the macromole interferon-ALPHA to the impact of micromolecule salbutamol sulfate purity/content detection, can remove interferon-ALPHA in the solution with ultrafiltration; The impact that interferon-ALPHA is detected in order to eliminate the micromolecule solable matter can be removed small-molecule substance in the solution with methods such as ultrafiltration, dialysis.
In a kind of preferred embodiment, contain the interferon-ALPHA of 2.5-30 μ g and the salbutamol sulfate of 0.048-0.192mg in the atomized inhalation single-dose dosage of interferon-ALPHA of the present invention and salbutamol sulfate, and the pharmaceutically acceptable auxiliaries of Sq.
In a kind of preferred embodiment, contain the interferon-ALPHA of 10-20 μ g and the salbutamol sulfate of 0.096-0.144mg in the atomized inhalation single-dose dosage of interferon-ALPHA of the present invention and salbutamol sulfate, and the pharmaceutically acceptable auxiliaries of Sq.
In a kind of preferred embodiment, the interferon-ALPHA in the atomized inhalation of interferon-ALPHA of the present invention and salbutamol sulfate be a kind of among interferon-ALPHA 2a, interferon alpha-2 b and the Interferon α1 b or with arbitrary proportion mix several.
In a kind of preferred embodiment, the interferon-ALPHA in the atomized inhalation of interferon-ALPHA of the present invention and salbutamol sulfate is Interferon α1 b.
Another object of the present invention provides the application of atomized inhalation in preparation treatment viral pneumonia medicine of interferon-ALPHA and salbutamol sulfate.Utilize atomized inhalation treatment viral pneumonia of the present invention, can use more separately interferon-ALPHA or salbutamol sulfate treatment viral pneumonia to obtain obviously better therapeutic effect.
Description of drawings
Fig. 1 is the (chromatogram that obtains after 4.6 * 250mm) of DIKMA Platisil C18 Reversed Phase High Performance on the salbutamol sulfate reference substance.
The specific embodiment
By following embodiment enforcement of the present invention is described further, but embodiments of the present invention are not limited to following embodiment.
Embodiment 1: the preparation of the atomized inhalation of interferon-ALPHA and salbutamol sulfate
The atomized inhalation for preparing interferon-ALPHA and salbutamol sulfate by the method such as following table 1.Wherein " Recombinant Interferon α-2b " (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 α-2a " (trade name) is the recombinant human interferon alpha-2 injection that 50 μ g/ml/ prop up for the specification that Shenyang Sansheng Pharmaceutical Co., Ltd. produces; " fortune moral element " (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, " salbutamol sulfate injection " is forever large pharmaceutcal corporation, Ltd production of Jiangsu, and specification is that 0.48mg/2ml/ props up; " 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 subsequent embodiment as without particularly pointing out, implication is identical with implication in the present embodiment.
The preparation of the atomized inhalation of table 1 interferon-ALPHA and salbutamol sulfate
Embodiment 2: the mixed salbutamol sulfate purity detecting of interferon-ALPHA and salbutamol sulfate
Each interferon-ALPHA that will prepare by the method for embodiment 1 and the atomized inhalation of salbutamol sulfate are that the Millipore ultra-filtration centrifuge tube of 3000Da carries out hyperfiltration treatment with molecular cut off respectively after placing the default time, filtered solution is diluted to identical rear (the 5 μ m packing material sizes of DIKMAPlatisil C18 Reversed Phase High Performance on the 20 μ l of getting respectively with the centrifugal front volume of ultrafiltration with deionized water, column dimension 4.6 * 250mm), under 25 ℃ of column temperatures, carry out chromatographic run, mobile phase 0.08mol/L sodium dihydrogen phosphate (phosphoric acid is regulated pH value to 3.1 ± 0.05)-methanol (85: 15) eluting, flow velocity 1.0ml/min detects wavelength 276nm.Measurement result is as shown in table 2 below.
The mixed salbutamol sulfate purity detecting of table 2 interferon-ALPHA and salbutamol sulfate result
| Numbering | Mixed |
Mixed rear 12 hours | Mixed rear 24 hours | Mixed rear 48 hours |
| Atomized inhalation 1 | 98.5％ | 98.4％ | 98.4％ | 98.5％ |
| Atomized inhalation 2 | 98.4％ | 98.3％ | 98.2％ | 98.3％ |
| Atomized inhalation 3 | 98.3％ | 98.3％ | 98.4％ | 98.4％ |
| Atomized inhalation 4 | 98.5％ | 98.4％ | 98.3％ | 98.4％ |
| |
98.3％ | 98.5％ | 99.4％ | 99.3％ |
| Atomized inhalation 6 | 98.4％ | 98.2％ | 98.3％ | 98.3％ |
| Atomized inhalation 7 | 98.2％ | 98.3％ | 98.1％ | 98.2％ |
| Atomized inhalation 8 | 98.2％ | 98.4％ | 98.4％ | 98.3％ |
| Atomized inhalation 9 | 98.3％ | 98.2％ | 98.1％ | 98.1％ |
As seen, the purity on salbutamol sulfate after interferon-ALPHA mixes with salbutamol sulfate does not affect.
Embodiment 3: the mixed salbutamol sulfate content detection of interferon-ALPHA and salbutamol sulfate
With salbutamol sulfate reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute preparation, lot number 100328-200502) water respectively dissolved dilution to concentration be 0.06,0.12,0.24,0.48, behind the 0.72mg/ml by the high-efficient liquid phase chromatogram condition of embodiment 2 respectively loading measure the main peak peak area.With peak area (y) concentration (x) is carried out linear regression and get working curve, equation is y=6900000x+5158, and regression coefficient is r=0.9999.
Each interferon-ALPHA that will prepare by the method for embodiment 1 and the atomized inhalation of salbutamol sulfate carry out the ultrafiltration centrifugal treating by the method for embodiment 2 respectively after placing the default time, filtered solution is diluted to identical rear high-efficient liquid phase chromatogram condition loading by embodiment 2 with the centrifugal front volume of ultrafiltration with deionized water respectively and measures the main peak peak area.The peak area substitution working curve equation that each mensuration is obtained just can obtain the concentration of salbutamol sulfate in each atomized inhalation.Measurement result is as shown in table 3 below.
The mixed salbutamol sulfate content detection of table 3 interferon-ALPHA and salbutamol sulfate result
As seen, the content on salbutamol sulfate after interferon-ALPHA mixes with salbutamol sulfate does not affect.The testing result of salbutamol sulfate purity after comprehensive embodiment 2 interferon-ALPHA mix with salbutamol sulfate illustrates that interferon-ALPHA mixes rear salbutamol sulfate chemical degradation does not occur with salbutamol sulfate.
Embodiment 4: the mixed interferon-ALPHA molecular weight detection of interferon-ALPHA and salbutamol sulfate
Each interferon-ALPHA that will prepare by the method for embodiment 1 and the atomized inhalation of salbutamol sulfate respectively to the deionized water of 100 times of volumes dialyse (the bag filter molecular cut off is 7000Da) process, during change deionized water once.Dialysis solution is carried out respectively MALDI-TOF mass spectrum molecular weight detection, 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 salbutamol sulfate mixing.
The mixed interferon-ALPHA molecular weight detection of table 4 interferon-ALPHA and salbutamol sulfate result
Embodiment 5: the mixed interferon-ALPHA of interferon-ALPHA and salbutamol sulfate is active to be detected
Each interferon-ALPHA that will prepare by the method for embodiment 1 and the atomized inhalation of salbutamol sulfate are surveyed the activity that interferon-ALPHA is wherein measured respectively in the standard method of living by the interferon-ALPHA of " Chinese Pharmacopoeia 2010 editions (three ones) " regulation.Measurement result is as shown in table 5 below.
The active testing result of the mixed interferon-ALPHA of table 5 interferon-ALPHA and salbutamol sulfate
Activity on interferon-ALPHA after above-mentioned testing result explanation interferon-ALPHA mixes with salbutamol sulfate does not affect.
The testing result of comprehensive embodiment 4 and embodiment 5 illustrates that interferon-ALPHA mixes rear interferon-ALPHA bioinactivation and chemical degradation do not occur with salbutamol sulfate.
Embodiment 6: the animal experiment of interferon-ALPHA and salbutamol sulfate 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, virus liquid is frozen in liquid nitrogen, and the time spent is in 37 ℃ of thawings, centrifugal 10 minutes of 1000rpm, it is for 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, showed the success of rsv infection Establishment of mouse model.
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 respectively to group 9; Organizing ultrasonic atomizatio suction injection 10 every days specification is " the fortune moral element " that 30 μ g/ml/ prop up, and organizing ultrasonic atomizatio suction 11 every days specification is " the salbutamol sulfate injection " 0.5 that 0.48mg/2ml/ props up; Organize ultrasonic atomizatio suction 12 every days normal saline 1ml.Every average daily the ultrasonic atomizatio of all each groups sucks 1 time, and ultrasonic atomizatio sucks 5 times (5 days) altogether.Get Mouse 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 (8)
1. the atomized inhalation of interferon-ALPHA and salbutamol sulfate, it is characterized in that described atomized inhalation is comprised of the pharmaceutically acceptable auxiliaries of interferon-ALPHA, salbutamol sulfate and Sq, the interferon-ALPHA that contains 2.5-30 μ g among the single-dose dosage 1ml, the salbutamol sulfate of 0.048-0.192mg.
2. atomized inhalation according to claim 1 is characterized in that containing among the single-dose dosage 1ml interferon-ALPHA of 10-20 μ g, the salbutamol sulfate of 0.096-0.144mg.
3. 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.
4. 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.
5. 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.
6. atomized inhalation according to claim 1, it is characterized in that described interferon-ALPHA be a kind of among interferon-ALPHA 2a, interferon alpha 2 b and the Interferon α1 b or with arbitrary proportion mix several.
7. atomized inhalation according to claim 2 is characterized in that described interferon-ALPHA is Interferon α1 b.
8. one of according to claim 1-7 application of described atomized inhalation in preparation treatment viral pneumonia medicine.
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| CN1569225A (en) * | 2003-07-24 | 2005-01-26 | 长春生物制品研究所 | Recombinant human interferon alpha nebula |
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| CN1569225A (en) * | 2003-07-24 | 2005-01-26 | 长春生物制品研究所 | Recombinant human interferon alpha nebula |
Non-Patent Citations (2)
| Title |
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| 张亚萍.雾化吸入沙丁胺醇与干扰素治疗婴幼儿重症肺炎的疗效观察.《实用医技杂志》.2006,第13卷(第13期), * |
| 韦昆成.干扰素联合沙丁胺醇、布地奈德雾化吸入佐治毛细支气管炎疗效观察.《儿科药学杂志》.2008,第14卷(第4期), * |
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Effective date of registration: 20120329 Address after: 102600, Beijing, Daxing District, North Village, Beijing biological engineering and pharmaceutical industry base, nine Fu Tian street, Beijing three yuan Gene Engineering Co., Ltd. Applicant after: Beijing Sanyuan Gene Engineering Co., Ltd. Address before: 102600, Beijing, Daxing District, North Village, Beijing biological engineering and pharmaceutical industry base, nine Fu Tian street, Beijing three yuan Gene Engineering Co., Ltd. Applicant before: Beijing Sanyuan Gene Engineering Co., Ltd. Co-applicant before: Beijing Bio-Tech Development Co., Ltd. |
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Address after: 102600 Beijing Jinyuan Industrial Development Zone Daxing District Road No. 1 Building No. 4 Patentee after: BEIJING TRI-PRIME GENE PHARMACEUTICAL CO., LTD. Address before: 102600, Beijing, Daxing District, North Village, Beijing biological engineering and pharmaceutical industry base, nine Fu Tian street, Beijing three yuan Gene Engineering Co., Ltd. Patentee before: Beijing Sanyuan Gene Engineering Co., Ltd. |