CN102716469A - Dry powder inhalant of interferon alpha - Google Patents
Dry powder inhalant of interferon alpha Download PDFInfo
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- CN102716469A CN102716469A CN2012102366047A CN201210236604A CN102716469A CN 102716469 A CN102716469 A CN 102716469A CN 2012102366047 A CN2012102366047 A CN 2012102366047A CN 201210236604 A CN201210236604 A CN 201210236604A CN 102716469 A CN102716469 A CN 102716469A
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- formoterol fumarate
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Abstract
The invention belongs to the field of preparations of protein drugs, and relates to a dry powder inhalant of interferon alpha. The dry powder inhalant contains consensus interferon of treatment effective dose and pharmaceutic adjuvant of the dry powder inhalant of proper dose; the interferon alpha consists of interferon alpha1b and the consensus interferon at a weight ratio of (4:6)-(6:4); and the pharmaceutic adjuvant of the dry powder inhalant comprises one or more of active protective agent, dispersive assistant, pH stability regulator, diluent and/or large-granularity carrier. In an optimized scheme, the dry powder inhalant of interferon alpha in single administration contains 1-200mu g of interferon alpha. The dry powder inhalant of interferon alpha provided by the invention has better stability and safety than the dry powder inhalant of interferon alpha of the prior art.
Description
Technical field
The inhalation dosage form that relates to interferon-ALPHA that the present invention is general, the special Foradil Aerolizer formoterol fumarate that relates to interferon-ALPHA.
Background technology
Interferon (interferon; IFN) be a kind of cytokine class medicine that produces by animal body at first with broad-spectrum disease resistance toxic action; Produce according to it that position is different with the mechanism of action can be divided into big types such as α, β, γ, λ; And every kind big type can be divided into some little hypotypes, in the same big type between different hypotype on primary structure difference very little, very approaching on the above higher structure of secondary.In several kinds big type, the α type is to use the widest a kind ofly, and this kind of interferon of clinical practice at present mainly comprises interferon-ALPHA 2a, interferon alpha 2 b, interferon-ALPHA 1b, Interferon Alfacon-1 etc.
The report that much is used for the respiration system virus disease therapeutic about interferon-ALPHA is arranged in the prior art.In diseases of respiratory system toxicity treatment of diseases, the mode administration that interferon-ALPHA generally sucks or sprays with injection, atomizing is prepared into injection, atomized inhalation and spray respectively.The curative effect of injecting recombinant human interferon alpha 1 b treatment infantile viral pneumonia reported in the article " interferon therapy viral pneumonia observation of curative effect " that for example is published on 2006 the 3rd volumes of " Chinese modern internal medicine " magazine the 6th phase 645-647 page or leaf, shows to add to compare between treatment group of treating with recombinant human interferon alpha 1 b and the matched group that adopts conventional therapy that through statistical analysis significant difference is arranged on curative effect.The article " interferon atomization inspiration treatment viral pneumonia efficacy analysis " that and for example is published on " China practical medicine " 2009 the 4th volumes the 9th phase 151-152 page or leaf has reported that atomizing sucks the curative effect of recombinant human interferon-alpha treatment infantile viral pneumonia, shows to add to compare with the matched group of employing general treatment with the treatment group of recombinant human interferon-alpha atomization inspiration treatment that through statistical analysis significant difference is arranged on curative effect.Chinese patent CN 03147580.9 discloses a kind of recombinant human interferon-alpha spray of treating viral pneumonia for another example; It is equipped with adequate protective agent, mucosa absorption promoter, antibacterial etc. by recombinant human interferon-alpha stock solution and processes; PH value is at 5.0-8.0, and the recombinant human interferon-alpha spray that the extracorporeal antivirus effect test shows above-mentioned prescription is to respiratory tract or the susceptible HSV of pulmonary
1And HSV
2Virus all has stronger inhibitory action, but to HSV
2The inhibitory action of virus is more responsive.
Though interferon-ALPHA is prepared into injection, atomized inhalation or spray and is used for diseases of respiratory system toxicity treatment of diseases clear and definite curative effect is arranged, the characteristics of general metabolism are had a greatly reduced quality the dosage of the actual performance of injection dosage form drug effect; Atomized inhalation and spray dosage form then exist effective inhalation dose low, the shortcoming that dosage can't accurately be controlled.
Interferon-ALPHA is prepared into Foradil Aerolizer formoterol fumarate, also is that atomized inhalation then can overcome these shortcomings that above injection, atomized inhalation and spray dosage form exist fully through pulmonary's inhalation from formulation characteristic.For example Chinese patent 95193669.7 discloses a kind of Foradil Aerolizer formoterol fumarate of interferon; It is prepared and is contained the interferon with the bonded treatment effective dose of medicine acceptable auxiliary by the interferon aqueous solution, this Foradil Aerolizer formoterol fumarate does not preferably contain penetration enhancer but preferably contains the adjuvant human serum albumin.And for example one Chinese patent application 200410018796.X discloses a kind of interferon powder spray; Its material by following percentage by weight is formed: interferon 0.0002%-0.8%; Diluent 70%-97.9%; Activity protecting agent 0.01%-5%, the buffer salt system of dispersibility auxiliary agent 0%-25% and maintenance pH 4-9 scopes, this powder spray does not preferably contain human albumin and absorption enhancer.
The preparation that the Foradil Aerolizer formoterol fumarate of the interferon-ALPHA of above prior art report is mainly formed from the kind and the content research optimization of C of Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries; But do not relate to the optimization of principal agent interferon-ALPHA hypotype and content basically; Therefore might be through the Foradil Aerolizer formoterol fumarate of the more excellent interferon-ALPHA of the optimization obtained performance of principal agent interferon-ALPHA hypotype and content, better to be used for the treatment of viral diseases such as viral pneumonia.
Summary of the invention
The Foradil Aerolizer formoterol fumarate that the purpose of this invention is to provide a kind of interferon-ALPHA, the Foradil Aerolizer formoterol fumarate of its more existing interferon-ALPHA has better stability and safety concurrently.
For realizing this purpose; In the embodiment on basis; The present invention provides a kind of Foradil Aerolizer formoterol fumarate of interferon-ALPHA; It contains the interferon-ALPHA of treating effective dose and the Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries of Sq; Described interferon-ALPHA is made up of interferon-ALPHA 1b and the Interferon Alfacon-1 of weight proportion 4:6 – 6:4, and described Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries is divided by function and comprised in activity protecting agent, dispersibility auxiliary agent, the agent of pH stable regulation, diluent and/or the coarsegrain carrier one or more.
Activity protecting agent play the protection interferon-ALPHA Foradil Aerolizer formoterol fumarate preparation, store with transportation in activity do not lose or the effect of less forfeiture; It can be one or more the combination in albumin, aminoacid, polyhydric alcohol, cyclodextrin, the lecithin matter; The combination of one or more in preferred albumin, lysine, 2-hydroxy propyl-Beta-cyclodextrin, the soybean lecithin, and more preferably do not comprise one or more the combination in the albuminous preferred substance.
The dispersibility auxiliary agent plays the granule of Foradil Aerolizer formoterol fumarate of the interferon-ALPHA that disperses to prepare to suitable dispersion; Prevent between the granule to reunite each other and the effect of adhesion; Can be one or more the combination in tyrosine, leucine, phenylalanine, the glycine, preferred leucine, phenylalanine.
The effect that the pH after the Foradil Aerolizer formoterol fumarate dissolving is stabilized in the physiology appropriate pH is played in the agent of pH stable regulation; Including, but not limited to PBS system, citrate buffer solution system, Ascorbate buffer solution system, require physiological safety and can and be stabilized between the 5.0-8.0 pH regulator.
Diluent plays on the basis of drug content and other pharmaceutically acceptable auxiliaries content, to fill increases the effect of Foradil Aerolizer formoterol fumarate particle weight to required loadings or suction volume; It can be one or more the combination in polyhydric alcohol, the amino acids material; The combination of one or more in preferred mannitol, xylitol, lactose, trehalose, cottonseed sugar, leucine, threonine, the glycine, and the more preferably combination of one or more in mannitol, lactose, leucine, the threonine.
The coarsegrain carrier plays help is transported to the Foradil Aerolizer formoterol fumarate granule throat from medicine-feeding part effect.When less and dispersion is higher when the Foradil Aerolizer formoterol fumarate grain graininess of the interferon-ALPHA for preparing; It is suitable for being transported to pulmonary from the throat through respiratory tract; But be not suitable for being transported to the throat from medicine-feeding part, need add the coarsegrain carrier this moment in the Foradil Aerolizer formoterol fumarate granule for preparing; Thereby though and when the Foradil Aerolizer formoterol fumarate granule of the interferon-ALPHA for preparing single less but have looser adhesion can form that (a little applied external force when granularity reached the loose aggregates of 50-100 μ m to each other; As increase ambient air stream; The Foradil Aerolizer formoterol fumarate granule of adhesion will be dispersed into each other independently Foradil Aerolizer formoterol fumarate granule), then need not in the granule of the Foradil Aerolizer formoterol fumarate of the interferon-ALPHA for preparing, to add the coarsegrain carrier.Such coarsegrain carrier can be selected one or more the combination in the materials such as lactose, mannitol, phospholipid, aminoacid, the combination of one or both in preferred lactose and the mannitol, and more preferably lactose.The particle mean size of coarsegrain carrier should be between 25-300 μ m, preferably between the 50-200 μ m, and more preferably between the 50-100 μ m.Foradil Aerolizer formoterol fumarate granule and the blended ratio of coarsegrain carrier by weight should be between 100:1-1:100, preferably between 50:1-1:50, and more preferably between 20:1-1:20.
Should be pointed out that the situation of selecting for use a kind of or one type of material to play the function of above-mentioned multiple Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries simultaneously of not getting rid of.
The Foradil Aerolizer formoterol fumarate granule of above-mentioned interferon-ALPHA can adopt preparation such as the method that well known to a person skilled in the art lyophilizing-mechanical crushing method, spray drying method, supercritical fluid method, crystallization process, preferably adopts spray drying method for preparation.When adopting the Foradil Aerolizer formoterol fumarate granule of spray drying method for preparation interferon-ALPHA, should at first prepare the solution that spray drying is used; The various compositions that also soon except that the coarsegrain carrier, constitute Foradil Aerolizer formoterol fumarate dissolve respectively afterwards to merge or unify is dissolved into solution state, then this solution is used for follow-up spray drying.Spray drying can influence the particulate performance of Foradil Aerolizer formoterol fumarate that spray-dired efficient and spray drying obtain with the solid content in the solution, should be between 0.5-10% (m/v), preferably between 1-5% (m/v), and more preferably between 1-3% (m/v) as the one of which.
In spray drying, the main preparation technology parameter of the particulate performance of Foradil Aerolizer formoterol fumarate of the interferon-ALPHA that influence prepares comprises spray drying gas feed temperature, spray gas flow, hydrojet flow etc.
Spray drying gas feed temperature is high more; Rate of drying is fast more; The material disposal ability is big more, but bioinactivation and/or chemical degradation/reaction take place in spray-drying process more easily for interferon-ALPHA and Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries, and therefore suitable inlet temperature is 80-140 ℃; Preferred 90-130 ℃, and more preferably 100-120 ℃.
The spray gas flow is high more; Rate of drying is fast more, and the material disposal ability is big more, but power consumption simultaneously is big more; Bioinactivation and/or chemical degradation/reaction take place in interferon-ALPHA and Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries more easily in spray-drying process; Therefore for the small-sized spray drying appearance as Buchi B-290, suitable gas flow is 200-1000L/h, preferred 300-800 L/h; And more preferably 500-700 L/h, the spray gas flow of the spray drying appearance of other types is capable of using to well known to a person skilled in the art that the General Principle that reaction vessel amplifies operating parameter conversion when dwindling converts.
The hydrojet flow is low more; The gas-liquid flow-rate ratio is big more, and rate of drying is fast more, and the particulate granularity of the Foradil Aerolizer formoterol fumarate that obtains is more little; But treating capacity can obviously reduce simultaneously; Processing time can obviously prolong, and the processing time longly is prone to more cause that bioinactivation and/or chemical degradation/reaction take place for interferon-ALPHA and pharmaceutically acceptable auxiliaries in spray-drying process, so for the small-sized spray drying appearance as Buchi B-290; Suitable hydrojet flow is 1-10ml/min; Preferred 2-8ml/min, and more preferably 3-5ml/min, the gas flow of the spray drying appearance of other types is capable of using to well known to a person skilled in the art that the General Principle that reaction vessel amplifies operating parameter conversion when dwindling converts.
Other spray drying condition aspects; Kind to spray drying gas does not generally have specific (special) requirements; Get final product with air, but, also can select nitrogen or noble gas as spray drying gas in order to prevent spray drying gas and interferon-ALPHA and Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries generation chemical reaction.The temperature of hydrojet is generally selected the temperature between freezing point temperature (0 ℃) to room temperature (25 ℃).
Through control to operating parameter in the above-mentioned spray-drying process; Should make in the Foradil Aerolizer formoterol fumarate granule of the interferon-ALPHA for preparing more than 50% between the particulate granularity 0.1-10 μ m; Preferred more than 70% particulate granularity between 1-5 μ m, and more preferably more than 80% particulate granularity between 2-4 μ m.
Reduce because the Foradil Aerolizer formoterol fumarate of the interferon-ALPHA that the too high meeting of moisture causes preparing is mobile; Grain graininess increases in storage process; The principal agent BA reduces, and therefore through the control of operating parameter in the above-mentioned spray-drying process, should make that moisture is controlled at below 5% in the Foradil Aerolizer formoterol fumarate granule of the interferon-ALPHA for preparing; Preferred below 3%, and most preferably below 2.5%.
The Foradil Aerolizer formoterol fumarate granule of the interferon-ALPHA that obtains through method for preparing should determine whether mix with the carrier of coarsegrain according to circumstances.
In a kind of embodiment preferred, the present invention provides a kind of Foradil Aerolizer formoterol fumarate of interferon-ALPHA, contains the interferon-ALPHA of 1-200 μ g in the single-dose dosage.
In a kind of embodiment preferred, the present invention provides a kind of Foradil Aerolizer formoterol fumarate of interferon-ALPHA, contains the interferon-ALPHA of 50-200 μ g in the single-dose dosage.
In a kind of embodiment preferred, the present invention provides a kind of Foradil Aerolizer formoterol fumarate of interferon-ALPHA, contains the activity protecting agent of 0.3-1mg among every 20mg; 0.6 the dispersibility auxiliary agent of-5mg; The pH stable regulation agent of 1-4.8mg, the diluent of 3-9mg, the coarsegrain carrier of 0-15mg.
In a kind of embodiment preferred, the present invention provides a kind of Foradil Aerolizer formoterol fumarate of interferon-ALPHA, and wherein said activity protecting agent is selected from one or more the combination in albumin, lysine, 2-HP-, the soybean lecithin.
In a kind of embodiment preferred, the present invention provides a kind of Foradil Aerolizer formoterol fumarate of interferon-ALPHA, and wherein said dispersibility auxiliary agent is selected from one or more the combination in tyrosine, leucine, phenylalanine, the glycine.
In a kind of embodiment preferred, the present invention provides a kind of Foradil Aerolizer formoterol fumarate of interferon-ALPHA, and the agent of wherein said pH stable regulation is selected from one or more the combination in PBS, citrate buffer solution, the ascorbic acid salt buffer solution.
In a kind of embodiment preferred, the present invention provides a kind of Foradil Aerolizer formoterol fumarate of interferon-ALPHA, and wherein said diluent is selected from one or more the combination in mannitol, lactose, leucine, the threonine.
In a kind of embodiment preferred, the present invention provides a kind of Foradil Aerolizer formoterol fumarate of interferon-ALPHA, and wherein said coarsegrain carrier is selected from one or both the combination in lactose and the mannitol.
The term that uses among the present invention " Foradil Aerolizer formoterol fumarate " (Dry Power Inhalation; DPI); Be also referred to as " powder spray "; Be meant micronized medicine and/or carrier and adopt special powder inhaler, initiatively or the preparation of passive suction atomization medicine to respiratory tract and even pulmonary by the patient with single dose or multiple dose depot forms.
The term that uses among the present invention " treatment effective dose " expression is when the drug administration active component is used for treatment or prevent disease, and the amount of active constituents of medicine is enough to realize treatment of diseases or prevention.The treatment effective dose will be different according to age of active constituents of medicine, disease and its seriousness and the patient that treats, body weight etc.
The term that uses among the present invention " Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries " is meant when the design of Foradil Aerolizer formoterol fumarate prescription; Be problems such as the mouldability that solves Foradil Aerolizer formoterol fumarate, effectiveness, stability, safety, join in the Foradil Aerolizer formoterol fumarate prescription except that active constituents of medicine self to other auxiliary elements of human body or animal body safety.
The term that uses among the present invention " Interferon Alfacon-1 " (consensus interferon or integrated interferon) be meant in one Chinese patent application CN02159950.5 in sequence table 3 open sequences and in description embodiment the Interferon Alfacon-1 of open method for preparing.
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 particulate preparation of the Foradil Aerolizer formoterol fumarate of interferon-ALPHA
By use solution like each spray drying of the formulated in the following table 1, and by the corresponding spray drying condition of table 2 with this solution of Buchi B-290 spray drying appearance spray drying (whole liquid sprays completion continued maintenance spray drying gas feed temperature and flow 15 minutes) thus prepare the Foradil Aerolizer formoterol fumarate granule of interferon-ALPHA.
The particulate spray drying of Foradil Aerolizer formoterol fumarate of table 1 preparation interferon-ALPHA is used solution formula
The spray drying condition of the Foradil Aerolizer formoterol fumarate of table 2 interferon-ALPHA
Embodiment 2: the particulate quality evaluation of the Foradil Aerolizer formoterol fumarate of interferon-ALPHA
Measure the activity (IU/ml) of interferon-ALPHA in the Foradil Aerolizer formoterol fumarate granule dissolving back solution of interferon-ALPHA of each prescription for preparing by the regulation of " Chinese Pharmacopoeia 2010 editions (three ones) " appendix " interferon biological activity algoscopy "; Measure the concentration (mg/ml) of interferon-ALPHA in the Foradil Aerolizer formoterol fumarate granule dissolving back solution of interferon-ALPHA of each prescription for preparing by the regulation of " Chinese Pharmacopoeia 2010 editions (three ones) " appendix " protein determination " second method Lowry method, both be divided by specific activities (IU/mg) of interferon-ALPHA in the Foradil Aerolizer formoterol fumarate granule of interferon-ALPHA of each prescription of obtaining preparing.Each spray drying of blank determination is with the specific activity of interferon-ALPHA in the solution, and the reservation of calculating spray-dried back interferon-ALPHA specific activity thus.
Measure the moisture in the Foradil Aerolizer formoterol fumarate granule of interferon-ALPHA of each prescription for preparing by the regulation of " Chinese Pharmacopoeia 2010 editions (three ones) " appendix " aquametry " first method.
Measure the particulate particle mean size of Foradil Aerolizer formoterol fumarate of each interferon-ALPHA of filling a prescription for preparing by the regulation of " Chinese Pharmacopoeia 2010 editions (two ones) " appendix " granularity and particle size distribution method " first method.
It is as shown in table 3 below that all measure the result.
The particulate quality evaluation of the Foradil Aerolizer formoterol fumarate of the interferon-ALPHA that table 3 spray drying prepares
Embodiment 3: by the Foradil Aerolizer formoterol fumarate of the Foradil Aerolizer formoterol fumarate preparation of granules interferon-ALPHA of interferon-ALPHA
The Foradil Aerolizer formoterol fumarate particulate samples of the interferon-ALPHA of the prescription 1-20 in each prescription that will obtain by the method for embodiment 1 does not mix with the coarsegrain carrier, the direct research of carrying out after the packing being used for as the Foradil Aerolizer formoterol fumarate of interferon-ALPHA embodiment 4-5 with the amount of every capsule 20mg; The Foradil Aerolizer formoterol fumarate particulate samples of the interferon-ALPHA of prescription 21-40 is with mass ratio and the commercially available coarsegrain lactose carrier granule mix homogeneously of 1:3, carries out after the packing being used for as the Foradil Aerolizer formoterol fumarate of interferon-ALPHA the research of embodiment 4-5 with the amount of every capsule 20mg.
Embodiment 4: the accelerated stability test of the Foradil Aerolizer formoterol fumarate of interferon-ALPHA
Each many of the capsules of each prescription are placed in 40 ℃; The environment of 75%RH is placed March, and the Foradil Aerolizer formoterol fumarate that sampling in every month is once measured the interferon-ALPHA of each prescription for preparing by the regulation of " Chinese Pharmacopoeia 2010 editions (three ones) " appendix " interferon biological activity algoscopy " takes out after the dissolving activity (IU/ml) of interferon-ALPHA in the solution in capsule; Measure the Foradil Aerolizer formoterol fumarate of the interferon-ALPHA of each prescription for preparing takes out interferon-ALPHA in the solution of dissolving back in capsule concentration (mg/ml) by the regulation of " Chinese Pharmacopoeia 2010 editions (three ones) " appendix " protein determination " second method Lowry method, both be divided by specific activities (IU/mg) of interferon-ALPHA in the Foradil Aerolizer formoterol fumarate of each interferon-ALPHA of filling a prescription of obtaining preparing.The specific activity that each sample of filling a prescription records with taking a sample in January, February, March respectively obtains the specific activity relative retention value of interferon-ALPHA in the accelerated stability test process divided by specific activity that sampling in corresponding 0 month records, and the result is as shown in table 4 below.
The accelerated stability test result of the Foradil Aerolizer formoterol fumarate of table 4 interferon-ALPHA
Embodiment 5: the normal human bronchial epithelial cell line toxicity test of the Foradil Aerolizer formoterol fumarate of interferon-ALPHA
Is (normal human bronchial epithelial cells by being published in the Foradil Aerolizer formoterol fumarate that article " cigarette smoke extract is to the influence of damage of human respiratory epithelial cell dna and apoptosis " 1.1-1.4 on " cancer (Chinese Journal of Cancer) " 2006 the 25th volume the 10th phase 1191-1197 page or leaf saves the interferon-ALPHA of each prescription that disclosed materials and methods research prepares to normal person's bronchial epithelial cell; NHBE) toxicity, but do following 3 changes:
1) general's " preparation of cigarette smoke extract " step wherein changes the dissolving step again of the Foradil Aerolizer formoterol fumarate of interferon-ALPHA into; Method is: each 200mg of Foradil Aerolizer formoterol fumarate (10 times of single-dose dosage) of the interferon-ALPHA of each prescription that the method by embodiment 3 that takes by weighing prepares, respectively with deionized water dissolving and dilute standardize solution to 200 μ l;
2) adding with the cigarette smoke extract CSE of each concentration in " cell culture and processing " step changes the undiluted respectively Foradil Aerolizer formoterol fumarate adding of solvent soln again (every hole adds 20 μ l) of the interferon-ALPHA of prescription of single concentration into;
3) change the Foradil Aerolizer formoterol fumarate that adds interferon-ALPHA in " MTT cytoactive mensuration " step into 6h, 12h the action time behind the solvent soln again, but still establish blank.
The result of the test that obtains according to the method described above is as shown in table 5.
The normal human bronchial epithelial cell line toxicity test result of the Foradil Aerolizer formoterol fumarate of table 5 interferon-ALPHA
Claims (9)
1. the Foradil Aerolizer formoterol fumarate of interferon-ALPHA; It is characterized in that containing the interferon-ALPHA of treating effective dose and the Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries of Sq; Described interferon-ALPHA is made up of interferon-ALPHA 1b and the Interferon Alfacon-1 of weight proportion 4:6-6:4, and described Foradil Aerolizer formoterol fumarate pharmaceutically acceptable auxiliaries is divided by function and comprised in activity protecting agent, dispersibility auxiliary agent, the agent of pH stable regulation, diluent and/or the coarsegrain carrier one or more.
2. the Foradil Aerolizer formoterol fumarate of interferon-ALPHA according to claim 1 is characterized in that containing in the single-dose dosage interferon-ALPHA of 1-200 μ g.
3. the Foradil Aerolizer formoterol fumarate of interferon-ALPHA according to claim 1 is characterized in that containing in the single-dose dosage interferon-ALPHA of 50-200 μ g.
4. according to the Foradil Aerolizer formoterol fumarate of the described interferon-ALPHA of one of claim 1-3; It is characterized in that containing in the Foradil Aerolizer formoterol fumarate of every 20mg the activity protecting agent of 0.3-1mg; 0.6 the dispersibility auxiliary agent of-5mg; The pH stable regulation agent of 1-4.8mg, the diluent of 3-9mg, the coarsegrain carrier of 0-15mg.
5. according to the Foradil Aerolizer formoterol fumarate of the described interferon-ALPHA of one of claim 1-3, it is characterized in that described activity protecting agent is selected from one or more the combination in albumin, lysine, 2-HP-, the soybean lecithin.
6. according to the Foradil Aerolizer formoterol fumarate of the described interferon-ALPHA of one of claim 1-3, it is characterized in that described dispersibility auxiliary agent is selected from one or more the combination in tyrosine, leucine, phenylalanine, the glycine.
7. according to the Foradil Aerolizer formoterol fumarate of the described interferon-ALPHA of one of claim 1-3, it is characterized in that the agent of described pH stable regulation is selected from one or more the combination in PBS, citrate buffer solution, the ascorbic acid salt buffer solution.
8. according to the Foradil Aerolizer formoterol fumarate of the described interferon-ALPHA of one of claim 1-3, it is characterized in that described diluent is selected from one or more the combination in mannitol, lactose, leucine, the threonine.
9. according to the Foradil Aerolizer formoterol fumarate of the described interferon-ALPHA of one of claim 1-3, it is characterized in that described coarsegrain carrier is selected from one or both the combination in lactose and the mannitol.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105853999A (en) * | 2016-04-22 | 2016-08-17 | 北京三元基因药业股份有限公司 | Interferon lambda-containing aerosol inhalant |
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