WO2019147154A1 - Composition pharmaceutique (variantes) utilisation de la composition pharmaceutique (variantes) - Google Patents

Composition pharmaceutique (variantes) utilisation de la composition pharmaceutique (variantes) Download PDF

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Publication number
WO2019147154A1
WO2019147154A1 PCT/RU2018/000023 RU2018000023W WO2019147154A1 WO 2019147154 A1 WO2019147154 A1 WO 2019147154A1 RU 2018000023 W RU2018000023 W RU 2018000023W WO 2019147154 A1 WO2019147154 A1 WO 2019147154A1
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WIPO (PCT)
Prior art keywords
salbutamol
hemisuccinate
hydroxymethyl
phenyl
methyl
Prior art date
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PCT/RU2018/000023
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English (en)
Russian (ru)
Inventor
Александр Григорьевич ЧУЧАЛИН
Тамерлан Асланбекович БАЛАЕВ
София Яковлевна Скачилова
Ирина Борисовна БАДЮГИНА
Татьяна Николаевна МОЛОСТОВА
Юрий Тихонович КАЛИНИН
Оксана Владимировна ПРОСКУРИНА
Анастасия Николаевна ДУКЛЕР
Original Assignee
Александр Григорьевич ЧУЧАЛИН
Тамерлан Асланбекович БАЛАЕВ
София Яковлевна Скачилова
Ирина Борисовна БАДЮГИНА
Татьяна Николаевна МОЛОСТОВА
Юрий Тихонович КАЛИНИН
Оксана Владимировна ПРОСКУРИНА
Анастасия Николаевна ДУКЛЕР
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by Александр Григорьевич ЧУЧАЛИН, Тамерлан Асланбекович БАЛАЕВ, София Яковлевна Скачилова, Ирина Борисовна БАДЮГИНА, Татьяна Николаевна МОЛОСТОВА, Юрий Тихонович КАЛИНИН, Оксана Владимировна ПРОСКУРИНА, Анастасия Николаевна ДУКЛЕР filed Critical Александр Григорьевич ЧУЧАЛИН
Priority to PCT/RU2018/000023 priority Critical patent/WO2019147154A1/fr
Priority to EA202000218A priority patent/EA202000218A1/ru
Publication of WO2019147154A1 publication Critical patent/WO2019147154A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions

Definitions

  • the invention relates to medicine, the pharmaceutical industry, namely, to pharmaceutical compositions intended for the treatment of bronchopulmonary diseases such as bronchial asthma, chronic obstructive pulmonary disease, bronchitis, pneumonia.
  • bronchopulmonary diseases such as bronchial asthma, chronic obstructive pulmonary disease, bronchitis, pneumonia.
  • iodomethyl tropine ester c1,1- (2-hydroxymethyl-2-phenyl) butyric acid as a monodrug in a metered dose aerosol dosage form is used in medicine as a bronchodilator for the treatment of various bronchopulmonary diseases [1], [2].
  • tropine ester iodomethyl b, 1- (2-hydroxymethyl-2-phenyl) butyric acid has antioxidant properties, and to a much lesser extent, unlike other anticholinergics, affects the cholinergic receptors of the heart, stomach, and other organs.
  • Salbutamol hemisuccinate as a monodrug containing the active ingredient - Salbutamol - alpha1 - [[(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1,3-benzenedimethanol - as sulfate or hemisuccinate - is used in various dosage forms medicine as a bronchodilator for the treatment of various bronchopulmonary diseases and as a tokolitika in obstetrics.
  • Salbutamol hemisuccinate due to the content in the molecule of succinic acid, has a high biological activity with a minimum of side effects: improves respiration at the cellular level, eliminates the side effects associated with metabolic acidosis, minimizes cardiotoxic effects due to high selectivity (stimulation of 2 -adrenergic receptors) and metabolism
  • Derivatives of salbutamol does not lead to the desensitization of p 2 -adrenergic receptors, does not form, in contrast to salbutamol sulfate, inactive metabolites with effect of p-blockers [3].
  • Patent RU 2457832 [6] the composition in the form of an aerosol based on tropine ester iodomethyl with!, 1- (2-hydroxymethyl-2-phenyl) butyric acid, whose content is from 40 to 640 ⁇ g, are included in the aerosol also medicinal substances of various pharmacotherapeutic groups - analgesics, anti-allergic, anti-inflammatory, anti-infective, bronchodilator drugs and others. Salbutamol and its derivatives are not included.
  • Patent RU 2327450 [7] presented pharmacotherapeutic compositions containing anticholinergics, p 2 -agonists and corticosteroids.
  • the compositions do not contain iodomethyl tropinate ester b, 1- (2-hydroxymethyl-2-propyl) butyric acid, from p 2 -agonists use salbutamol base and salbutamol sulfate.
  • Patent RU 2356537 [8] describes the use of salbutamol hemisuccinate with various drugs, without tropine ester iodomethyl ⁇ 1,1- (2-hydroxymethyl-2-phenyl) butyric acid.
  • a pharmaceutical composition that includes two components: tropine ester iodomethyl acetate SC (2-hydroxymethyl-2-phenyl) butyric acid - a blocker of M-cholinergic receptors and salbutamol hemisuccinate - a stimulator of p 2 -adrenergic receptors for the treatment of such bronchopulmonary diseases as bronchial asthma, chronic obstructive pulmonary disease, bronchitis, pneumonia.
  • the technical result is the creation of a pharmaceutical composition based on the blocker of M-cholinergic iodomethyl receptor tropine ester b, 1- (2-hydroxymethyl-2-phenyl) butyric acid and selective p 2 agonist salbutamol hemisuccinate, intended for treatment of bronchopulmonary diseases such as bronchial asthma, chronic obstructive pulmonary disease, bronchitis, pneumonia, which increases the effectiveness of the drug due to blue Gizmo components, reducing the therapeutic dose as compared with monotherapy, minimizing side reactions.
  • bronchopulmonary diseases such as bronchial asthma, chronic obstructive pulmonary disease, bronchitis, pneumonia
  • the proposed pharmaceutical composition including iodomethyl tropinovogo ester SC- (2-hydroxymethyl-2-phenyl) butyric acid in the form of a single agent, alpha1 - [[(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1,3- benzoldimethanol in the form of a monodrug, including the active substance - salbutamol in the form of hemisuccinate, additionally including sodium chloride, succinic acid, water for injection, in the following ratio of ingredients, mass%:
  • the proposed pharmaceutical composition including iodomethyl tropinovogo ester SC- (2-hydroxymethyl-2-phenyl) butyric acid in the form of a single agent, alpha1 - [[(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1,3- Benzenedimethanol - as a single preparation, including the active ingredient - salbutamol in the form of hemisuccinate, additionally including sodium chloride, 0, L-hydroxyanthic acid, water for injection, with the following ratio of ingredients, mass%:
  • a pharmaceutical composition comprising iodomethyl tropine ester with 1,1- (2-hydroxymethyl-2-phenyl) butyric acid as a monodrug, alpha1 - [[(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1, 3-benzenedimethanol - in the form of a monodrug, including the active ingredient - salbutamol in the form of hemisuccinate, additionally including 3-hydroxy, 2-ethyl, 6-methyl-pyridinium butanedioate, water for injection, with the following ratio of ingredients, mass%: iodomethyl tropine ester with 1,1- (2-hydroxymethyl-2-phenyl) butyric acid 0.01 - 1 salbutamol hemisuccinate 0.01 - 1
  • the proposed pharmaceutical composition comprising tropic ester iodomethyl ⁇ 3,1- (2-hydroxymethyl-2-phenyl) butyric acid as a single agent, alpha1 - [[(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1 , 3-benzenedimethanol - in the form of a monodrug, including the active ingredient - salbutamol in the form of hemisuccinate, further comprising magnesium sulfate, succinic acid, water for injection, in the following ratio of ingredients, mass%:
  • the proposed pharmaceutical composition comprising iodomethyl tropic ester ⁇ 3,1- (2-hydroxy methyl-2-phenyl) butyric acid as a single agent, alpha 1 - [[(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1 , 3-benzenedimethanol - in the form of a monodrug, including the active ingredient - salbutamol in the form of hemisuccinate, additionally including zinc sulfate, sodium chloride, water for injection, in the following ratio of ingredients, mass%:
  • composition comprising tropine ester iodomethyl (1,1- (2-hydroxymethyl-2-phenyl) butyric acid as a single agent, alpha! - [[(1,1- Dimethylethyl) amino] methyl] -4-hydroxy-1,3-benzenedimethanol - as a monodrug, including the active ingredient - salbutamol as hemisuccinate, additionally including sodium benzoate, sodium chloride, water for injection, with the following ratio of ingredients, mass%:
  • a pharmaceutical composition including tropic ester iodomethyl, 1- (2-hydroxymethyl-2-phenyl) butyric acid, alpha! [[(1,1- Dimethylethyl) amino] methyl] -4-hydroxy-1,3-benzenedimethanol - in the form of a monodrug, including the active ingredient - salbutamol in the form of hemisuccinate, further comprising ethanol and propellant 1,1,1,2-tetrafluoroethane (R134A), with the following the ratio of ingredients, mass%:
  • compositions for the prevention and treatment of bronchospastic syndrome in bronchial asthma in case of exacerbation of bronchial asthma for relief of asthma attacks, as part of basic therapy, for the prevention and relief of bronchospasm caused by exercise or exposure to an allergen or other triggering bronchospasm factor; in chronic obstructive pulmonary disease, chronic obstructive bronchitis, pulmonary emphysema, pneumonia, as well as in catarrhal diseases as a bronchodilator as part of basic therapy, namely:
  • iodine tropine ester iodomethyl 1- (2-hydroxymethyl-2-phenyl) oily ACIDS 0.01 - 1 salbutamol hemisuccinate 0.01 - 1 sodium benzoate 0.01 - 1 sodium chloride 0.01 - 1 water for injection the rest
  • a pharmaceutical composition for the prevention and treatment of bronchospastic syndrome in bronchial asthma, chronic obstructive pulmonary disease, chronic obstructive bronchitis, pneumonia, pulmonary emphysema, including tropine ester iodomethyl, 1- (2-hydroxymethyl-2-phenyl) butyric acid, alpha1 - [[(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1,3-benzenedimethanol - in the form of a monodrug, including the active ingredient - salbutamol in the form of hemisuccinate, additionally including lactose monohydrate, with the following m ratio of ingredients, wt%:
  • a pharmaceutical composition for the prevention and treatment of bronchospastic syndrome in bronchial asthma, chronic obstructive pulmonary disease, chronic obstructive bronchitis, pneumonia, pulmonary emphysema, including tropine ester iodomethyl, 1- (2-hydroxymethyl-2-phenyl) butyric acid, alpha1 - [[(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1,3-benzenedimethanol - in the form of a monodrug, including the active ingredient - salbutamol in the form of hemisuccinate, further comprising propellant 1,1,1,2-tetrafluoroethane (R1 34A), with the following ratio of ingredients, mass%:
  • a pharmaceutical composition for the prevention and treatment of bronchospastic syndrome in bronchial asthma, chronic obstructive pulmonary disease, chronic obstructive bronchitis, pneumonia, pulmonary emphysema including c1,1- (2-hydroxymethyl-2-phenyl) butyric acid tropic ester iodomethyl, alpha1- [[(1,1-dimethylethyl) amino] methyl] -4-hydroxy-1,3-benzenedimethanol - as a single agent, including active ingredient - salbutamol in the form of hemisuccinate, additionally comprising ethanol and propellant 134A, with the following ratio of ingredients, mass%: tropic ester iodomethyl, 1- (2-hydroxymethyl-2-phenyl) oily
  • composition comprising tropic ester iodomethyl b, 1- (2-hydroxymethyl-2-phenyl) butyric acid as a monodrug, alpha1 - [[(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1, 3-benzenedimethanol in the form of a monodrug, including the active ingredient - salbutamol in the form of hemisuccinate, further comprising lactose monohydrate, with the following ratio of ingredients, mcg:
  • a pharmaceutical composition for the prevention and treatment of bronchospastic syndrome in bronchial asthma, chronic obstructive pulmonary disease, chronic obstructive bronchitis, pneumonia, pulmonary emphysema including SC c- (2-hydroxymett-2-phenyl) butyric acid iodomethyl, alpha1- [ [(1,1-Dimethylethyl) amino] methyl] -4-hydroxy-1,3-benzenedimethanol - in the form of a monodrug, including the active substance - salbutamol in the form of hemisuccinate, further comprising lactose monohydrate, with the following I eat the ratio of ingredients, mcg:
  • the samples were subjected to incandescent lamp illumination in accordance with the Pharmopoeia XI Edition for 120 hours.
  • the quality of the prototypes was studied by chromatography in a thin layer of sorbent (TLC) in various solvent systems and high performance liquid chromatography with detection by UV spectrophotometry.
  • the claimed pharmaceutical composition is presented in the form of a powder for inhalation from the calculation of the composition of ingredients per dose, where the following ingredients are included as active substances:
  • the example of the pharmaceutical composition includes:
  • lactose monohydrate 24910 ⁇ g the proposed example of the pharmaceutical composition is applicable in the form of capsules, while in one capsule there is a single dose for inhalation presented in the example.
  • Dosage form of the combined drug in the form of an inhalation solution for nebulizer therapy contains additional excipients that ensure the stability of the dosage form and its biopharmaceutical properties, as can be seen from the examples below, presented in Tables 1-6.
  • Dosage inhalation dosage form of the combined preparation in the form of a dry powder is also produced according to standard known technology using a carrier — lactose and using both a multi-dose tank inhaler — a metered-dose powder inhaler, and a single dose — using capsules or blisters, examples are presented in Table 7.
  • the dosage aerosol dosage form for inhalation based on the pharmaceutical composition is made according to known standard technology in metered dose inhalers using a hydrofluoroalkane propellant, namely, 1,1, 1,2-tetrafluoroethane (R 134A) with an appropriate dose of the combined preparation, as can be seen from Tables 8 and 9.
  • a hydrofluoroalkane propellant namely, 1,1, 1,2-tetrafluoroethane (R 134A) with an appropriate dose of the combined preparation, as can be seen from Tables 8 and 9.
  • All the proposed variants of the pharmaceutical composition exhibit synergism, thereby enhancing the bronchodilator effect, which is achieved by using variants of the proposed pharmaceutical compositions using significantly smaller doses and, accordingly, fewer side effects.
  • the technical result has been achieved by creating variants of the pharmaceutical composition based on the M-cholinergic receptor blocker iodomethyl tropine ester c.1.1- (2-hydroxymethyl-2-phenyl) butyric acid and the selective p 2 -agonist of salbutamol hemisuccinate, and options for the use of pharmaceutical compositions for treatment of such bronchopulmonary diseases, such as bronchial asthma, bronchitis, pneumonia, providing an increase in the effectiveness of the drug due to synergism, reduction of the therapeutic dose according to eniyu with monotherapy, minimizing side effects.
  • bronchopulmonary diseases such as bronchial asthma, bronchitis, pneumonia
  • the invention relates to medicine, the pharmaceutical industry, namely, to pharmaceutical compositions intended for the treatment of bronchopulmonary diseases such as bronchial asthma, chronic obstructive pulmonary disease, bronchitis, pneumonia.
  • bronchopulmonary diseases such as bronchial asthma, chronic obstructive pulmonary disease, bronchitis, pneumonia.
  • All the proposed variants of the pharmaceutical composition exhibit synergism, thereby enhancing the bronchodilator effect, which is achieved by using variants of the proposed pharmaceutical compositions using significantly smaller doses and, accordingly, fewer side effects.
  • bronchopulmonary diseases such as bronchial asthma , chronic obstructive pulmonary disease, bronchitis, pneumonia

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne la médecine humaine, l'industrie pharmaceutique et notamment les compositions pharmaceutiques destinées à soigner des maladies des bronches et poumons telles que l'asthme bronchial, la maladie chronique obstructive des poumons, les bronchites et pneumonies. Le résultat technique est obtenu par la mise au point de variantes d'une composition pharmaceutique à base d'un bloquant de récepteurs M-cholinergiques de métilate d'iode d'éther tropinique de l'acide d,l-(2-hydroxyméthyé-2-phényl)oléique et agoniste sélectif β2 salubutamol hémisuccinate, et des variantes d'utilisation d'une composition pharmaceutique pour traiter des maladies pulmonaires des bronches telles que l'asthme bronchial, la maladie obstructive chronique des poumons, les bronchites, la pneumonie, assurant une augmentation de l'efficacité de l'action de la préparation grâce à la synergie, à une baisse d'une dose thérapeutique par rapport aux mono-préparations, réduction des effets secondaires. Les inventions ont été testées dans la pratique, les compositions pharmaceutiques dans chacune des variantes proposées ont une application industrielle et pourront être largement utilisées en industrie pharmaceutique et en médecine humaine.
PCT/RU2018/000023 2018-01-23 2018-01-23 Composition pharmaceutique (variantes) utilisation de la composition pharmaceutique (variantes) WO2019147154A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/RU2018/000023 WO2019147154A1 (fr) 2018-01-23 2018-01-23 Composition pharmaceutique (variantes) utilisation de la composition pharmaceutique (variantes)
EA202000218A EA202000218A1 (ru) 2018-01-23 2018-01-23 Фармацевтическая композиция (варианты), применение фармацевтической композиции (варианты)

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PCT/RU2018/000023 WO2019147154A1 (fr) 2018-01-23 2018-01-23 Composition pharmaceutique (variantes) utilisation de la composition pharmaceutique (variantes)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113476428A (zh) * 2021-01-28 2021-10-08 朗天药业(湖北)有限公司 一种吸入用硫酸沙丁胺醇溶液及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2054932C1 (ru) * 1992-06-26 1996-02-27 Всероссийский научный центр по безопасности биологически активных веществ Ингаляционный состав для лечения бронхиальной астмы
RU2388462C2 (ru) * 2003-12-31 2010-05-10 Сайдекс, Инк. Ингаляционная композиция, содержащая сульфоалкиловый эфир циклодекстрина и кортикостероид
RU2457832C2 (ru) * 2005-09-25 2012-08-10 Сипла Лимитед Состав на основе тровентола
RU2567040C2 (ru) * 2009-12-23 2015-10-27 КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. Аэрозольная препаративная форма для лечения по поводу хронического обструктивного легочного заболевания

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2054932C1 (ru) * 1992-06-26 1996-02-27 Всероссийский научный центр по безопасности биологически активных веществ Ингаляционный состав для лечения бронхиальной астмы
RU2388462C2 (ru) * 2003-12-31 2010-05-10 Сайдекс, Инк. Ингаляционная композиция, содержащая сульфоалкиловый эфир циклодекстрина и кортикостероид
RU2457832C2 (ru) * 2005-09-25 2012-08-10 Сипла Лимитед Состав на основе тровентола
RU2567040C2 (ru) * 2009-12-23 2015-10-27 КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. Аэрозольная препаративная форма для лечения по поводу хронического обструктивного легочного заболевания

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113476428A (zh) * 2021-01-28 2021-10-08 朗天药业(湖北)有限公司 一种吸入用硫酸沙丁胺醇溶液及其制备方法
CN113476428B (zh) * 2021-01-28 2022-03-29 朗天药业(湖北)有限公司 一种吸入用硫酸沙丁胺醇溶液及其制备方法

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