CN105496993A - Preparing method of ambroxol salbutamol controlled release granule - Google Patents
Preparing method of ambroxol salbutamol controlled release granule Download PDFInfo
- Publication number
- CN105496993A CN105496993A CN201510902610.5A CN201510902610A CN105496993A CN 105496993 A CN105496993 A CN 105496993A CN 201510902610 A CN201510902610 A CN 201510902610A CN 105496993 A CN105496993 A CN 105496993A
- Authority
- CN
- China
- Prior art keywords
- ambroxol
- controlled release
- release granule
- particle
- salbutamol sulfate
- 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.)
- Pending
Links
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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to an ambroxol salbutamol controlled release granule and a preparing method thereof, belonging to the field of medicinal preparations. The controlled release granule takes a saccharose particle of about 40 meshes as a core, and contains ambroxol hydrochloride, salbutamol sulfate and sodium bicarbonate, a coating solution contains Eudragit RS30D, talcum powder and tributyl citrate ester and glycerol, and the granule is stable in quality, obvious in effect and capable of effectively treating diseases of the respiratory system such as acute and chronic bronchitis and asthma.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of ambroxol albuterol controlled release granule and preparation method thereof.
Background technology
Respiratory system disease is a kind of commonly encountered diseases, frequently-occurring disease, and major lesions is in trachea-bronchial epithelial cell, pulmonary and thoracic cavity, and the many coughs of pathological changes the lighter, chest pain, breathing are influenced, severe one dyspnea, anoxia, even respiratory failure and lethal.Account for the 3rd at the mortality rate in city, then account for first place in rural area.What more should pay attention to is, due to atmospheric pollution, smoking, aged tendency of population and other factors, chronic obstructive pulmonary disease both domestic and external is made (to be called for short chronic obstructive pulmonary disease, comprise chronic bronchitis, emphysema, pulmonary heart disease), bronchial asthma, pulmonary carcinoma, pulmonary's dispersivity interstitial fibrosis, and the sickness rate of the disease such as pulmonary infection, mortality rate are growing on and on.
According to the statistical number of national urbans in 2006 and the rural area top ten principal disease cause of death, respiratory system disease (not comprising pulmonary carcinoma) accounts for the 4th (13.1%) in the Death causes in city, accounts for the 3rd (16.4%) in rural area.The physical and chemical factor caused due to atmospheric pollution, smoking, Industrial Economic Development, biotic factor inhale people and the factor such as population ages is aging, the sickness rate of respiratory system disease as pulmonary carcinoma, bronchial asthma in recent years is obviously increased, and chronic obstructive pulmonary disease remains high (more than 8% in more than 40 years old crowd).Though pulmonary tuberculosis rate controls to some extent, in recent years have again and increase trend.Pulmonary thromboembolism has constituted important health care problem, and pulmonary hypertension also receives publicity in recent years day by day.The disease incidences such as pulmonary Diffuse interstitial fibrosis and immunocompromised pulmonary infection day by day increase.The major causes of death of acquired immune deficiency syndrome (AIDS) is pulmonary infection, particularly pneumocystis carinii pneumonia.Since the end of the year 2002, severe acute respiratory syndrome (the severe acute respiratory syndrome broken out in China and world wide, SARS) epidemic situation, the young and the middle aged is born in due to multiple, its infectiousness is strong, and case fatality rate is high, lacks again medicine targetedly, thus cause the fear of the masses, bring about great losses to national economy simultaneously.The current human and bird fluenza case fatality rate occurred in multiple country is more than 60%.And bird flu virus to invade target organ main in human body be also lung.It is very large that this is just illustrating that respiratory system disease is still our people's health hazard, and it prevents and treats arduous task.
Ambroxol hydrochloride (AmbroxolHydrochloride) is also known as AMB, chemistry trans-4-[(2-amino 3 by name, 5-dibromo-benzyl) amino] cyclohexanol hydrochloridumi, it is active metabolite (the N-demethyl of expectorant bromhexine, trans hydroxyl is introduced in cyclohexyl para-position), toxicity is lower than bromhexine, and activity is higher than bromhexine.Ambroxol hydrochloride is the mucolytic researched and developed by German Boehringer Ingelheim company, first this medicine went on the market in Germany in early 1980s, in succession go on the market in many countries such as France, Italy, Japan, Spain subsequently, it is the glutinous expectorant lytic agent of a new generation, can expectoration be improved, and there is the effect promoting pulmonary surfactant and Airway secretion and ciliary movement.Ambroxol hydrochloride can regulate mucus to secrete with glutinous slurry clinically, and activation fibre swing is easy to dilute sputum, and strengthening mucus outwards transports, and be easy to discharge, it also can promote that pulmonary surfactant synthesizes, and to maintain alveolar tension, ensures lung functions index; Promote that antibiotic is to tissue infiltration, to improve concentration, strengthen bactericidal action; Antioxidation, reduces inflammatory mediator release, with the reaction that reduces inflammation; Work in coordination with bronchus spasmolysis material, to improve the curative effect of spasmolytic medicine.Therefore, this medicine can be widely used in the acute and chronic respiratory tract disease with respiratory tract abnormal secretion clinically, the particularly treatment of eliminating the phlegm of chronic bronchitis, the auxiliary treatment of transient respiratory distress of the newborn disease and pulmonary surgery, have that toxicity is low, determined curative effect can with antibiotic and with producing the advantages such as good synergy, be one of the most frequently used expectorant.In recent years in the emphasis hospital administration rank of China main cities, it ranked forefront always.Existing dosage form has oral liquid, tablet, capsule, micropill etc.
Salbutamol sulfate (SalbutamolSulfate) has another name called salbutamol, its main component is albuterol, chemistry 1-(4-hydroxyl-3-hydroxymethyl phenyl)-2-(tert-butylamine base) ethanol by name, a kind of β-adrenoreceptor analeptic of exciting bronchial smooth muscle of high selectivity, bronchial smooth muscle is relaxed, thus removes bronchial muscular spasm.Comparatively strong to bronchiectatic activity, and more weak to the β1-receptor effect of heart, be anti-asthmatic safer, the most frequently used at present.Be applicable to prevent and treat bronchial asthma, the bronchospasm of asthmatic bronchitis and emphysematic patients, the symptoms such as the dyspnea that alleviation causes because of airway obstructive diseases such as bronchial asthma, chronic bronchitis and emphysema, its advantage is rapid-action, patient symptom can be improved rapidly, spasmolytic, relieving asthma, eliminate the phlegm, shortcoming acts on lasting, only plays the effect alleviating patient's symptoms of asthma; Long period application can cause beta-receptor to regulate downwards, makes patient occur losing quick to beta receptor agonist, even invalid to treating asthma drug resistance phenomenon.Present existing dosage form has tablet, controlled release tablet, aerosol etc.
There is the dosage form such as solution and granule containing ambroxol hydrochloride and salbutamol sulfate in prior art, but had no the report of controlled release granule.
Summary of the invention
Namely object of the present invention is to provide a kind of safe and effective, steady quality, and patient adaptability is strong, and Be very effective, effectively can treat the ambroxol albuterol controlled release granule of the respiratory system disease such as acute/chronic bronchitis and asthma.
The technical scheme that the present invention solves this technical problem is:
A kind of ambroxol albuterol controlled release granule, is prepared from by the following method:
(1) ambroxol hydrochloride 10-20g, salbutamol sulfate 10-20g and sodium hydrogen carbonate powder 5-10g are pulverized 120 mesh sieves, mix homogeneously, obtain medicinal mixture;
(2) EudragitRS30D20-30g, Pulvis Talci 10-15g and tributyl citrate 5-10g are dissolved in 100g purified water, obtain coating solution;
(3) with the sucrose particle about 40 orders as core, as in centrifugal fluidization granulation machine, using appropriate water-ethanol (2:1) solution containing sucrose as binding agent, medicinal mixture is added under rolling, make sucrose particle superscribe the coating of ambroxol-hydrochloride-containing and salbutamol sulfate, form core particle;
(4) by core particle as in fluidized-bed coating machine, spray into coating solution, be blown into 60 DEG C of thermal current dryings simultaneously, obtain final product.
Wherein, described medicinal mixture preferably pulverized 120 mesh sieves by ambroxol hydrochloride 15g, salbutamol sulfate 15g and sodium bicarbonate 8g, and mix homogeneously forms.
Described coating solution is preferably dissolved in 100g purified water by EudragitRS30D25g, Pulvis Talci 12g and tributyl citrate 8 and forms.
The invention has the beneficial effects as follows described ambroxol albuterol controlled release granule steady quality, Be very effective, can effectively treat the respiratory system disease such as acute/chronic bronchitis and asthma.
Detailed description of the invention
Below in conjunction with specific embodiment, set forth the present invention further.Should be understood that these embodiments are only not used in for illustration of the present invention to limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, the usually conveniently conditioned disjunction condition of advising according to manufacturer.Unless otherwise indicated, otherwise all percent, ratio, ratio or number by weight.
Unless otherwise defined, all specialties used in literary composition and scientific words and one skilled in the art the same meaning be familiar with.In addition, any method similar or impartial to described content and material all can be applicable in the inventive method.The use that better implementation method described in literary composition and material only present a demonstration.
Embodiment 1
Ambroxol hydrochloride 10g, salbutamol sulfate 10g and sodium bicarbonate 5g are pulverized 120 mesh sieves, mix homogeneously, obtains medicinal mixture; EudragitRS30D20g, Pulvis Talci 10g and tributyl citrate 5g are dissolved in 100g purified water, obtain coating solution; With the sucrose particle about 40 orders as core, as in centrifugal fluidization granulation machine, using appropriate water-ethanol (2:1) solution containing sucrose as binding agent, medicinal mixture is added under rolling, make sucrose particle superscribe the coating of ambroxol-hydrochloride-containing and salbutamol sulfate, form core particle; By core particle as in fluidized-bed coating machine, spray into coating solution, be blown into 60 DEG C of thermal current dryings simultaneously, obtain final product.
Embodiment 2
Ambroxol hydrochloride 15g, salbutamol sulfate 15g and sodium bicarbonate 8g are pulverized 120 mesh sieves, mix homogeneously, obtains medicinal mixture; EudragitRS30D25g, Pulvis Talci 12g and tributyl citrate 8g are dissolved in 100g purified water, obtain coating solution; With the sucrose particle about 40 orders as core, as in centrifugal fluidization granulation machine, using appropriate water-ethanol (2:1) solution containing sucrose as binding agent, medicinal mixture is added under rolling, make sucrose particle superscribe the coating of ambroxol-hydrochloride-containing and salbutamol sulfate, form core particle; By core particle as in fluidized-bed coating machine, spray into coating solution, be blown into 60 DEG C of thermal current dryings simultaneously, obtain final product.
Embodiment 3
Ambroxol hydrochloride 20g, salbutamol sulfate 20g and sodium bicarbonate 10g are pulverized 120 mesh sieves, mix homogeneously, obtains medicinal mixture; EudragitRS30D30g, Pulvis Talci 15g and tributyl citrate 10g are dissolved in 100g purified water, obtain coating solution; With the sucrose particle about 40 orders as core, as in centrifugal fluidization granulation machine, using appropriate water-ethanol (2:1) solution containing sucrose as binding agent, medicinal mixture is added under rolling, make sucrose particle superscribe the coating of ambroxol-hydrochloride-containing and salbutamol sulfate, form core particle; By core particle as in fluidized-bed coating machine, spray into coating solution, be blown into 60 DEG C of thermal current dryings simultaneously, obtain final product.
Embodiment 4 stability test
1. accelerated stability test
Embodiment 2 gained ambroxol albuterol controlled release granule is set low lower 10 days of temperature (4 DEG C), high light (4500lx), high temperature (60 DEG C) and high humidity (RH75%) condition respectively, respectively at sampling in the 0th, 5,10 day, detect every quality index such as character, content, related substance, the results are shown in Table 1.
Table 1 ambroxol albuterol controlled release granule influence factor result of the test
Result shows: ambroxol albuterol controlled release granule is placed 10 days respectively under high temperature (60 DEG C), low temperature (4 DEG C), high light (4500lx), high humidity (RH75%) condition, detect every quality index, compared with 0 day, except high temperature (60 DEG C) related substance slightly increases and the content of ambroxol hydrochloride and salbutamol sulfate declines to some extent, other every quality index have no significant change.
2. accelerated test
Embodiment 2 gained ambroxol albuterol controlled release granule is placed in 40 DEG C, the constant temperature of RH20%, constant humidity cabinet 6 months, respectively at the 0th, sampling in 1,2,3,6 month, measure every quality index such as character, content, related substance, the results are shown in Table 2.
Table 2 ambroxol albuterol controlled release granule accelerated test result
Result shows: ambroxol albuterol controlled release granule 40 DEG C, place 6 months under the condition of RH20%, compared with 0 month, except related substance slightly increases, other every quality index have no significant change, and steady quality is reliable, conforms with the regulations.
3. long term test
Embodiment 2 gained ambroxol albuterol controlled release granule is placed in 25 DEG C, the environment of RH60%, respectively at the 0th, sampling in 3,6,9,12,18,24 months, check character, pH value, every quality index such as content, related substance, the results are shown in Table 3.
Table 3 ambroxol albuterol controlled release granule long-term test results
Result shows: ambroxol albuterol controlled release granule 25 DEG C, place 36 months in RH60% environment, except the granule moisture absorption, indices compared with 0 month and has no significant change, and steady quality reliably, conforms with the regulations.
The phenol red secretory volume pharmacological testing of embodiment 5 mice trachea
After phenol red to mouse peritoneal injection indicator, the latter can partly discharge from trachea secretion.Ambroxol hydrochloride and salbutamol sulfate can strengthen the secretory function of respiratory tract, thus the excretion amount that corresponding increase is phenol red.After sodium bicarbonate solution lavation trachea, irrigating solution is developed the color, detect OD value with spectrophotometer, check in phenol red excretion amount, thus the phlegm-dispelling functions of medicine can be checked.
Experimental technique: get 60 mices and be divided into 6 groups at random, be respectively blank group, ambroxol hydrochloride group, salbutamol sulfate group, basic, normal, high three the dosage groups of embodiment 2 compositions, weigh, labelling, dosage is as shown in table 4, blank group gives normal saline, and administering mode is gavage.After 30min, lumbar injection phenol red solution 0.1mL/10g respectively, after 30min, put to death animal, polish No. 7 syringe needles are inserted trachea and are about 0.3cm by anatomical isolation trachea under larynx, after fixing with silk thread ligation, sodium bicarbonate solution 0.5mL is extracted with 1mL syringe, by syringe needle lavation respiratory tract 3 times back and forth, last 1 time irrigating solution is extracted out in injecting tube, continuous 3 times of aforesaid operations, rinse 9 times altogether, take out irrigating solution is about 1.2-1.5mL, be placed in test tube, centrifugal, with 721 type spectrophotometers, wavelength 546nm, read trap OD value.Standard curve is checked corresponding phenol red concentration, respectively organizes the difference of trachea section phenols contents.Result is as shown in table 4.
The phenol red secretory volume result of the test of table 4 mice trachea
| Group | Dosage (mg/kg) | Phenol red amount (μ g/mL) | Recruitment (%) |
| Blank group | -- | 0.61±0.21 | -- |
| Ambroxol hydrochloride group | 20 | 0.78±0.41 | 27.87 |
| Salbutamol sulfate group | 20 | 0.77±0.33 | 26.23 |
| Compositions low dose group | 20 | 0.84±0.43 | 37.70 |
| Dosage group in compositions | 40 | 0.92±0.28 | 50.82 |
| Compositions high dose group | 60 | 1.34±0.31 | 119.68 |
Experimental result: result shows that each administration group obviously can both increase the phenol red secretory volume of Respiratory Tract of Mice, wherein basic, normal, high three the dosage groups of compositions of the present invention act on and strengthening compared with alone ambroxol hydrochloride group or salbutamol sulfate group, significant difference, and action effect is relevant with the dosage of each compositions, effect of high dosage is best.
The foregoing is only preferred embodiment of the present invention, and be not used to limit substantial technological context of the present invention, substantial technological content of the present invention is broadly defined in the right of application, any technology entities that other people complete or method, if with application right define identical, also or a kind of change of equivalence, be all covered by being regarded as among this right.
Claims (3)
1. a preparation method for ambroxol albuterol controlled release granule, is characterized in that, is prepared from by the following method:
(1) ambroxol hydrochloride 10-20g, salbutamol sulfate 10-20g and sodium bicarbonate 5-10g are pulverized 120 mesh sieves, mix homogeneously, obtain medicinal mixture;
(2) EudragitRS30D20-30g, Pulvis Talci 10-15g and tributyl citrate 5-10g are dissolved in 100g purified water, obtain coating solution;
(3) with the sucrose particle about 40 orders as core, as in centrifugal fluidization granulation machine, using appropriate water-ethanol (2:1) solution containing sucrose as binding agent, medicinal mixture is added under rolling, make sucrose particle superscribe the coating of ambroxol-hydrochloride-containing and salbutamol sulfate, form core particle;
(4) by core particle as in fluidized-bed coating machine, spray into coating solution, be blown into 60 DEG C of thermal current dryings simultaneously, obtain final product.
2. ambroxol albuterol controlled release granule according to claim 1, is characterized in that, described medicinal mixture pulverized 120 mesh sieves by ambroxol hydrochloride 15g, salbutamol sulfate 15g and sodium bicarbonate 8g, and mix homogeneously forms.
3. ambroxol albuterol controlled release granule according to claim 1, is characterized in that, described coating solution is dissolved in 100g purified water by EudragitRS30D25g, Pulvis Talci 12g and tributyl citrate 8g and forms.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510902610.5A CN105496993A (en) | 2015-12-08 | 2015-12-08 | Preparing method of ambroxol salbutamol controlled release granule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510902610.5A CN105496993A (en) | 2015-12-08 | 2015-12-08 | Preparing method of ambroxol salbutamol controlled release granule |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105496993A true CN105496993A (en) | 2016-04-20 |
Family
ID=55705557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510902610.5A Pending CN105496993A (en) | 2015-12-08 | 2015-12-08 | Preparing method of ambroxol salbutamol controlled release granule |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105496993A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107669636A (en) * | 2016-09-30 | 2018-02-09 | 青岛大学 | A kind of ambroxol spray |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1761453A (en) * | 2003-06-26 | 2006-04-19 | 韩国化学研究院 | Controlled release-drug delivery system for oral administration |
| CN103239432A (en) * | 2013-05-08 | 2013-08-14 | 山东罗欣药业股份有限公司 | Compound ambroxol hydrochloride composition granule and preparation method thereof |
-
2015
- 2015-12-08 CN CN201510902610.5A patent/CN105496993A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1761453A (en) * | 2003-06-26 | 2006-04-19 | 韩国化学研究院 | Controlled release-drug delivery system for oral administration |
| CN103239432A (en) * | 2013-05-08 | 2013-08-14 | 山东罗欣药业股份有限公司 | Compound ambroxol hydrochloride composition granule and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| 庄越 等: "《实用药物制剂技术》", 31 January 1999 * |
| 罗明生 等: "《中国药用辅料》", 30 April 2006 * |
| 陈卫卫 等: "《药剂学》", 31 August 2012, 西安交通大学出版社 * |
| 黄火强: "《民族药物制剂新技术》", 31 August 2011, 中央民族大学出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107669636A (en) * | 2016-09-30 | 2018-02-09 | 青岛大学 | A kind of ambroxol spray |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105496992A (en) | Ambroxol salbutamol lipid solid dispersion | |
| CN105496991A (en) | Preparing method of ambroxol salbutamol oral liquid | |
| CN105496993A (en) | Preparing method of ambroxol salbutamol controlled release granule | |
| CN105380925A (en) | Ambroxol-salbutamol control released granule | |
| CN105362226B (en) | The preparation method of ambroxol albuterol aerosol | |
| CN105456240B (en) | Ambroxol albuterol aerosol | |
| CN105412013A (en) | Preparing method for ambroxol salbutamol lipid solid dispersion | |
| CN105434411A (en) | Ambroxol and salbutamol oral liquid | |
| CN105326789B (en) | Ambroxol albuterol solution agent | |
| CN105362246A (en) | Preparation method of ambroxol salbutamol controlled release tablet | |
| CN105434390A (en) | Preparation method of ambroxol and salbutamol enteric coatel tablet | |
| CN105456201A (en) | Preparation method of ambroxol and salbutamol pellet | |
| CN105326790B (en) | The preparation method of ambroxol albuterol solution agent | |
| CN109692255A (en) | A kind of Chinese medicine composition and its preparation method and application for treating acute tracheobronchitis | |
| CN105326815A (en) | Preparation method of controlled release capsules containing ambroxol hydrochloride and salbutamol sulfate | |
| CN105362234A (en) | Ambroxol salbutamol enteric particles | |
| CN105412031A (en) | Ambroxol and salbutamol orally disintegrating tablet | |
| CN105456221A (en) | Preparation method of ambroxol and salbutamol enteric-coated granules | |
| CN105395498A (en) | Preparation method of ambroxol-salbutamol orally disintegrating tablet | |
| CN105343040B (en) | The preparation method of ambroxol salbutamol powder | |
| CN105326796B (en) | Ambroxol salbutamol powder | |
| CN105434412A (en) | Ambroxol and salbutamol controlled release capsule | |
| CN105362247A (en) | Ambroxol salbutamol controlled release tablet | |
| CN105456220A (en) | Ambroxol and salbutamol enteric-coated tablet | |
| CN105412055A (en) | Ambroxol and salbutamol tablet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160420 |