[go: up one dir, main page]

CN119112787B - A kind of refenacin soft mist and preparation method thereof - Google Patents

A kind of refenacin soft mist and preparation method thereof Download PDF

Info

Publication number
CN119112787B
CN119112787B CN202411631399.3A CN202411631399A CN119112787B CN 119112787 B CN119112787 B CN 119112787B CN 202411631399 A CN202411631399 A CN 202411631399A CN 119112787 B CN119112787 B CN 119112787B
Authority
CN
China
Prior art keywords
refenacin
stabilizer
solvent
soft
lei
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CN202411631399.3A
Other languages
Chinese (zh)
Other versions
CN119112787A (en
Inventor
辜玉瑶
杨光
刘青锋
施斌
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Zezheng Pharmaceutical Technology Co ltd
Shandong Hi Qual Pharmatech Co ltd
Original Assignee
Shanghai Zezheng Pharmaceutical Technology Co ltd
Shandong Hi Qual Pharmatech Co ltd
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.)
Filing date
Publication date
Application filed by Shanghai Zezheng Pharmaceutical Technology Co ltd, Shandong Hi Qual Pharmatech Co ltd filed Critical Shanghai Zezheng Pharmaceutical Technology Co ltd
Priority to CN202411631399.3A priority Critical patent/CN119112787B/en
Publication of CN119112787A publication Critical patent/CN119112787A/en
Application granted granted Critical
Publication of CN119112787B publication Critical patent/CN119112787B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pulmonology (AREA)
  • Inorganic Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides a soft spray of raffinacin and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. The Lei Fen-cine soft fog agent comprises Lei Fen-cine, a pH regulator, a stabilizer and a solvent, wherein the weight ratio of Lei Fen-cine to the stabilizer is 2-4:1-5, and the stabilizer is PVP and sodium gluconate. The Lei Fen-cine soft aerosol has the advantages of good stability, high fine particle fraction, high delivery efficiency, simple preparation method and easy popularization.

Description

Rafenacin soft aerosol and preparation method thereof
Technical Field
The invention provides a soft spray of raffinacin and a preparation method thereof, belonging to the technical field of pharmaceutical preparations.
Background
Lei Fen nacin is a long-acting muscarinic antagonist useful for maintenance treatment of patients with Chronic Obstructive Pulmonary Disease (COPD). It can improve lung function, reduce clinical symptoms of COPD, and prevent further exacerbation of lesions by inhalation of a spray of solution.
Lei Fen Naxin solution for inhalation was developed by Mylan company under the trade name Yupelri and was in the specification of 3ml: 175. Mu.g. The Lei Fen-cine solution for inhalation is an atomized inhalation solution, and is inhaled for administration through an oral cavity after being atomized by a common jet atomizer on the market, and is administered once a day, and each time, the atomization is required to be carried out for 8 minutes, and the delivery efficiency is low.
Chinese patent CN117205186a discloses a spray for inhalation of raffinacin and a preparation method thereof, wherein the ratio of fine particles smaller than 5 μm formed after the spray for inhalation is atomized by a spraying device is not less than 10%, the particle size distribution of spray droplets is uniform, but the impurity content is higher in a stability test experiment.
Chinese patent CN117771222B discloses a spray for inhalation of raffinacin and a preparation method thereof, which comprises an active ingredient Lei Fen, a trihydrate or a pharmaceutically acceptable salt thereof, an osmotic pressure regulator, a pH regulator, a bacteriostatic agent, a stabilizer and a solvent, wherein when the bacteriostatic agent is selected from trichloro-tert-butanol, the pH regulator is selected from citric acid, sodium citrate and the stabilizer is selected from PVP, the atomization time of the spray is short, but crystallization phenomenon can occur after the spray is placed for more than 10 days at 5 ℃, and besides the common stabilizer and the pH regulator of the spray, the bacteriostatic agent is added, so that the burden of lungs can be increased.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention provides a soft spray of the raffinacin and a preparation method thereof, wherein the soft spray has the advantages of good stability, high fine particle fraction, high delivery efficiency, simple preparation method and easy popularization.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
on one hand, the invention provides a soft spray of the raffinacin, which comprises Lei Fen parts of the raffinacin, a pH regulator, a stabilizer and a solvent, wherein the weight ratio of the Lei Fen parts of the raffinacin to the stabilizer is 2-4:1-5, and the stabilizer is PVP and sodium gluconate.
Specifically, the Lei Fen nacin is Lei Fen nacin or a pharmaceutically acceptable salt thereof.
Specifically, the Lei Fen-cine soft fog agent comprises, by weight, 0.2-0.7% of Lei Fen-cine, 0.8-2.5% of pH regulator, 0.5-0.65% of stabilizer and the balance of solvent.
Preferably, the Lei Fen-0.65% soft mist agent comprises, by weight, 0.3-0.6% Lei Fen-0.5% pH regulator, 0.9-1.5% stabilizer and the balance solvent.
Specifically, the weight ratio of PVP to sodium gluconate is 1-6:2.
Preferably, the weight ratio of PVP to sodium gluconate is 2-3:1.
Preferably, the weight ratio of PVP to sodium gluconate is 3:1.
Specifically, the pH regulator is one or more of disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium citrate, citric acid, sodium acetate and acetic acid.
Preferably, the pH regulator is sodium citrate and citric acid.
Specifically, the solvent is water for injection.
Specifically, the pH value of the Lei Fen nafine soft fog agent is 4-5.
Specifically, the fine particles formed upon administration by atomization have a particle diameter of 1 to 8. Mu.m.
In a second aspect, the invention provides a preparation method of a soft spray of raffinancin, which is characterized by comprising the following steps:
(1) Dissolving a stabilizer in a part of solvent to obtain a solution 1;
(2) Adding Lei Fen nacin to the solution 1 in the step (1) to obtain a solution 2;
(3) Adding a pH regulator into the solution 2 in the step (2) to regulate the pH value;
(4) Adding the rest solvent, filtering, sterilizing, and sealing.
Specifically, the filter membrane of the filtration is 0.22 μm;
Specifically, the part of solvent in the step (1) is 80-90% of solvent by volume.
Specifically, the pH value of the step (3) is 4-5.
The beneficial effects of the invention are as follows:
(1) The invention ensures that the Lei Fen narcissus soft aerosol has good stability and less total impurities in storage by adjusting the proportion of Lei Fen narcissus and the stabilizer and adjusting the type and proportion of the stabilizer.
(2) The invention ensures that the fine particle fraction of the Lei Fen soft mist agent is high and the delivery efficiency is high by adjusting the proportion of Lei Fen cine to the stabilizer and adjusting the type and proportion of the stabilizer.
Detailed Description
The invention is illustrated by the following specific examples, but is in no way limited thereto, in order to make the objects, technical solutions and advantages of the invention more apparent. The following description of the preferred embodiments of the invention is merely illustrative of the invention and should not be taken as limiting the invention, it being understood that any modifications, equivalents, and improvements made within the spirit and principles of the invention are intended to be included within the scope of the invention.
1. Examples and comparative examples
The preparation method comprises the following steps:
(1) Dissolving a stabilizer in 80% of a solvent;
(2) Adding Lei Fen nacin to the solution of step (1);
(3) Adding a pH regulator into the solution in the step (2) until the pH of the solution is 4-5;
(4) Adding the rest solvent, filtering, sterilizing, and sealing.
The compositions of examples 1-3 and comparative examples 1-5 are shown in Table 1.
TABLE 1
2. Stability test
The impurity contents of examples 1 to 3, comparative examples 1 to 5 and the purchased Yupelri Lei Fen nacin solution (hereinafter abbreviated as Yupelri) were tested by leaving them at 60℃for 10 days.
Examples 1-3, comparative examples 1-5 and Yupelri were left at 5℃for 10 days, and observed for crystallization.
The stability test results are shown in Table 2.
TABLE 2
The weight ratio of the Lei Fen-sodium and the stabilizer in comparative example 1 is not in the protection scope of the application, the stability is poor, the total impurity content is increased, and the crystallization is easy at low temperature. Comparative examples 2 to 3 used only one stabilizer, which was poor in stability, increased in total impurity content and liable to devitrification at low temperature. The weight ratio of PVP to sodium gluconate in comparative example 4 is not within the protection scope of the present application, and the stability is poor, the total impurity content is increased, and crystallization is easy at low temperature. In comparative example 5, L-fucose and gluconic acid were used as stabilizers, which had poor stability, increased total impurity content and easy crystallization at low temperature. The stability of commercially available formulation Yupelri, although superior to the comparative example, was not as good as that of inventive examples 1-3.
Examples 1-3, which are within the scope of the present invention, are stable and do not crystallize at low temperatures with less total impurities when left for 10 days at 60 ℃.
3. Atomization index detection
APSD of examples 1-3, comparative examples 1-5 and Yupelri was tested. Referring to the four parts of the chinese pharmacopoeia 2020 edition, the Fine Particle Fraction (FPF) and delivery efficiency were examined by simulating the human respiratory structure with a new generation cascade impactor (NGI) according to the inhalation formulation fine particle aerodynamic characterization method (general rule 0951), and the results are shown in table 3.
TABLE 3 Table 3
Comparative example 1 Lei Fen the weight ratio of the cine to the stabilizer is outside the scope of the present application, the fine particle fraction thereof is low and the delivery efficiency is low. Comparative examples 2-3 used only one stabilizer, which had a low fine particle fraction and low delivery efficiency. The weight ratio of PVP and sodium gluconate of comparative example 4, which is outside the scope of the present application, was low in fine particle fraction and low in delivery efficiency. Comparative example 5 uses other kinds of stabilizers in combination with sodium gluconate, but its fine particle fraction is low and delivery efficiency is low. The fine particle fraction and delivery efficiency of the commercially available formulation Yupelri were not as good as the comparative examples, and were not as good as the inventive examples 1-3.
Examples 1-3 are within the scope of the claimed invention, with high fine particle fraction and high delivery efficiency.
Finally, it should be noted that the above description is only for illustrating the technical solution of the present invention, and not for limiting the scope of the present invention, and that the simple modification and equivalent substitution of the technical solution of the present invention can be made by those skilled in the art without departing from the spirit and scope of the technical solution of the present invention.

Claims (8)

1.一种雷芬那辛软雾剂，其特征在于，包括雷芬那辛、pH调节剂、稳定剂和溶剂；1. A refenacin soft mist, characterized in that it comprises refenacin, a pH regulator, a stabilizer and a solvent; 所述雷芬那辛与稳定剂的重量比为：2-4:1-5；The weight ratio of revenacin to the stabilizer is: 2-4:1-5; 所述稳定剂为PVP和葡萄糖酸钠；The stabilizers are PVP and sodium gluconate; 所述雷芬那辛软雾剂，以重量百分比计，包括如下组分：雷芬那辛0.2%-0.7%、pH调节剂0.8%-2.5%、稳定剂0.5%-0.65%和溶剂余量；The refenacin soft mist comprises the following components by weight percentage: 0.2%-0.7% refenacin, 0.8%-2.5% pH regulator, 0.5%-0.65% stabilizer and the remainder of solvent; 所述PVP和葡萄糖酸钠的重量比为：1-6：2；The weight ratio of PVP to sodium gluconate is 1-6:2; 所述雷芬那辛软雾剂的pH值为4-5。The pH value of the refenacin soft mist is 4-5. 2.根据权利要求1所述的雷芬那辛软雾剂，其特征在于，所述雷芬那辛为雷芬那辛或其药学上可接受的盐。2. The refenacin soft spray according to claim 1, characterized in that the refenacin is refenacin or a pharmaceutically acceptable salt thereof. 3.根据权利要求1所述的雷芬那辛软雾剂，其特征在于，以重量百分比计，包括如下组分：雷芬那辛0.3%-0.6%、pH调节剂0.9%-1.5%、稳定剂0.5%-0.65%和溶剂余量。3. The refenacin soft mist according to claim 1 is characterized in that it comprises the following components by weight percentage: 0.3%-0.6% refenacin, 0.9%-1.5% pH adjuster, 0.5%-0.65% stabilizer and the remainder of solvent. 4.根据权利要求1所述的雷芬那辛软雾剂，其特征在于，所述pH调节剂为磷酸二氢钠、枸橼酸钠、枸橼酸、醋酸钠和醋酸中的一种或几种；4. The revenacin soft spray according to claim 1, characterized in that the pH regulator is one or more of sodium dihydrogen phosphate, sodium citrate, citric acid, sodium acetate and acetic acid; 所述溶剂为注射用水。The solvent is water for injection. 5.根据权利要求1所述的雷芬那辛软雾剂，其特征在于，雾化给药时形成的微细粒子粒径为1-8μm。5. The revenacin soft mist according to claim 1, characterized in that the particle size of the fine particles formed during atomization administration is 1-8 μm. 6.权利要求1-5任一项所述的雷芬那辛软雾剂的制备方法，其特征在于，包括如下步骤：6. The method for preparing the revenacin soft mist according to any one of claims 1 to 5, characterized in that it comprises the following steps: （1）取稳定剂溶于部分溶剂中，得到溶液1；(1) dissolving the stabilizer in part of the solvent to obtain solution 1; （2）向步骤（1）的溶液1中加入雷芬那辛，得到溶液2；(2) adding revenacin to the solution 1 of step (1) to obtain a solution 2; （3）向步骤（2）的溶液2中加入pH调节剂，调节pH值；(3) adding a pH adjuster to solution 2 of step (2) to adjust the pH value; （4）加入剩余量的溶剂，过滤、除菌、封口。(4) Add the remaining solvent, filter, sterilize, and seal. 7.根据权利要求6所述的制备方法，其特征在于，步骤（1）所述的部分溶剂为80%-90%体积百分比的溶剂。7. The preparation method according to claim 6, characterized in that the partial solvent in step (1) is 80%-90% by volume of the solvent. 8.根据权利要求6所述的制备方法，其特征在于，步骤（3）所述的pH值为4-5。8. The preparation method according to claim 6, characterized in that the pH value in step (3) is 4-5.
CN202411631399.3A 2024-11-15 2024-11-15 A kind of refenacin soft mist and preparation method thereof Active CN119112787B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202411631399.3A CN119112787B (en) 2024-11-15 2024-11-15 A kind of refenacin soft mist and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202411631399.3A CN119112787B (en) 2024-11-15 2024-11-15 A kind of refenacin soft mist and preparation method thereof

Publications (2)

Publication Number Publication Date
CN119112787A CN119112787A (en) 2024-12-13
CN119112787B true CN119112787B (en) 2025-01-24

Family

ID=93750160

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202411631399.3A Active CN119112787B (en) 2024-11-15 2024-11-15 A kind of refenacin soft mist and preparation method thereof

Country Status (1)

Country Link
CN (1) CN119112787B (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117205186A (en) * 2023-09-01 2023-12-12 齐鲁制药有限公司 Leifenacin inhalation spray and preparation method thereof
CN117263848A (en) * 2023-09-19 2023-12-22 山东京卫制药有限公司 Inhalation spray of raffinacin

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2009241628A1 (en) * 2008-02-26 2009-11-05 Elevation Pharmaceuticals, Inc. Method and system for the treatment of chronic obstructive pulmonary disease with nebulized anticholinergic administrations
CN117771222B (en) * 2023-12-05 2024-07-05 山东京卫制药有限公司 Leifenacin inhalation spray and preparation method thereof
CN118750472B (en) * 2024-06-13 2025-02-11 朗天药业(湖北)有限公司 A kind of revenacin inhalation solution and preparation method

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117205186A (en) * 2023-09-01 2023-12-12 齐鲁制药有限公司 Leifenacin inhalation spray and preparation method thereof
CN117263848A (en) * 2023-09-19 2023-12-22 山东京卫制药有限公司 Inhalation spray of raffinacin

Also Published As

Publication number Publication date
CN119112787A (en) 2024-12-13

Similar Documents

Publication Publication Date Title
JP5001657B2 (en) Aqueous suspension of ciclesonide for nebulization
CN1148804A (en) Medicine
CN111249260A (en) Liquid inhalation formulation comprising RPL554
CN117771222B (en) Leifenacin inhalation spray and preparation method thereof
JP2022521558A (en) Peramivir solution inhaler and its manufacturing method
WO2019119720A1 (en) Fudosteine solution preparation for aerosol inhalation, and preparation method therefor
CN119112787B (en) A kind of refenacin soft mist and preparation method thereof
CN117205186B (en) Leifenacin inhalation spray and preparation method thereof
CN118750472B (en) A kind of revenacin inhalation solution and preparation method
WO2008047149A1 (en) Pharmaceutical compositions and nasal spray incorporating anhydrous mometasone furoate
AU2021413439B2 (en) Pharmaceutical composition for inhalation
WO2019091082A1 (en) Solution preparation for aerosol inhalation of carbocisteine, and preparation method therefor
WO2022105877A1 (en) Pharmaceutical composition and preparation comprising bilobalide component and use thereof
CA3179014A1 (en) Liquid formulations of indacaterol
CN114344380A (en) Asthma-relieving aerosol inhalation solution preparation and preparation method thereof
CN115337311B (en) A composition for treating respiratory system diseases and its preparation method
CN107334754B (en) Qingkailing solution preparation for aerosol inhalation and preparation method thereof
CN114948914B (en) Moxifloxacin hydrochloride solution for aerosol inhalation and preparation method thereof
CN115463117B (en) Budesonide salbutamol compound aerosol inhalation suspension with high delivery efficiency and preparation method thereof
KR102250876B1 (en) Dry powder composition comprising tiotropium or pharmaceutically acceptable salt thereof
CN113577044A (en) An inhalant solution containing andrographolide sulfonate or its salt for treating new type coronavirus pneumonia, and its preparation method
CN108743569A (en) Salbutamol sulfate aerosol inhalation solution and preparation method thereof
CN119770463A (en) Beclomethasone dipropionate suspension for inhalation and preparation method thereof
CN118892471A (en) A stable phentolamine mesylate inhalation liquid preparation and preparation method thereof
CN116211873A (en) Pharmaceutical composition for treating respiratory diseases and preparation method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant