CN106109421A - A kind of Bisolvon granule and preparation technology thereof - Google Patents
A kind of Bisolvon granule and preparation technology thereof Download PDFInfo
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- 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
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- 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
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- C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C211/44—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring
- C07C211/52—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
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Abstract
The invention belongs to pharmaceutical technology field, more particularly to a kind of Bisolvon granule, described Bisolvon granule is prepared from by following composition: Bisolvon 1～8mg, lactose 145～165mg, sorbitol 280～330mg, silicon dioxide 2～6mg, essence 0.2～1mg, water is appropriate.The medicine of described Bisolvon granule divides that stable content, dissolution are high, is not likely to produce impurity, preparation technology simply, easily stores, and is particularly well-suited to the patient with dysphagia or infant, and general applicability is good.
Description
Technical field
The invention belongs to pharmaceutical technology field, be specifically related to a kind of Bisolvon granule and preparation technology thereof.
Background technology
Bisolvon, its chemical name is: N-methyl-N-cyclohexyl-2-amino-3,5-dibromobenzene methylamine hydrochloride,
For white or the crystalline powder of off-white color；Odorless, tasteless.Bisolvon is the most molten in ethanol or chloroform, atomic in water
Dissolve.Can be done directly on bronchus body of gland, promote the lysosome of mucous secreting cell to disengage, make the viscous sugared fiber of apoplexy due to phlegm divide
Change cracking；May also suppress the synthesis of acidoglycoprotein in mucous gland and goblet cell, be allowed to secrete the little molecule that viscosity is relatively low
Glycoprotein, so that the viscosity of sputum reduces, it is easy to expectoration.Additionally, cause respiratory tract with also can stimulating gastric mucosa reflexive
Glandular secretion increases, and makes sputum dilute.Since the sixties in 20th century, Bisolvon is i.e. that a kind of wide variety of mucus is molten
Solving agent, it also has character and the antibacterial activity in vitro removing free radical.The openest Bisolvon used generally note
Penetrate agent or injection lyophilized powder or oral liquid or tablet or capsule.
Bisolvon solvability in water is the most weak, although dissolubility is preferable in acid condition, but less stable,
Being easily generated impurity, European Pharmacopoeia 7.0 editions has recorded 5 kinds of impurity (A, B, C, D, E), wherein most commonly seen with impurity E.In order to ensure
The quality of medicine and stability, also need predissolve before preparing the injection of Bisolvon or oral liquid or using
Freeze dried injection, it usually needs add more adjuvant to improve stability and more harsh to preparation technology requirement.As
This, necessarily cause the increase of cost of drugs, and selling price is high.It is known that the disease such as chronic bronchitis and asthma belongs to week
The chronic disease that phase is longer, is difficult to the symptom of expectoration to dispel the most adjoint mucus, it is necessary to take larger amount of eliminating the phlegm
Medicine, therefore drug price is high, is unfavorable for the utilization and extention of medicine, it is impossible to meet the basic healthy need of general public well
Ask.It addition, this type of Bisolvon has higher requirement to storage and traffic condition.And for injection, patient also needs to
The assistance of special medical professional, uses inconvenience and needs to increase extra-pay.
The tablet of Bisolvon or capsule need patient to swallow, and suffer with chronic bronchitis and asthma etc.
The patient of disease generally entails excessive phlegm symptom, dysphagia, makes troubles to patient, and therefore compliance is poor.It addition, infant
Patient generally takes tablet or capsule, therefore lacks general applicability.And tablet and capsule are in preparation, it is difficult to precisely
Controlling the content of effective ingredient, each batch medicine divides stable content to be difficult to ensure that.
Summary of the invention
It is an object of the invention to overcome above-described defect, it is provided that a kind of taking convenience, medicament contg is stable, be difficult to
Produce impurity, preparation technology storage simple, easy, the Bisolvon granule of transport.It addition, hydrochloric acid bromine prepared by the present invention is own
New granule is easy to carry, and dissolution is high, and medicine bioavailability is high, and compliance is good, and mouthfeel is good, has been especially suitable for dysphagia
Patient or infant patient, universal adaptability is good.
The primary and foremost purpose of the present invention is to provide a kind of Bisolvon granule, described Bisolvon granule
Component and content are as follows:
Described essence is that one or more in edible essence combine.
On the basis of solving technical problem of the present invention, in order to optimize Bisolvon granule further
Stability, reduces the content producing impurity as much as possible, and the present inventor has carried out again substantial amounts of test, it is thus achieved that more excellent
Bisolvon granule prescription.
Preferably, the Bisolvon used in described Bisolvon granule is that a kind of new Bisolvon is brilliant
Body compound, use Cu-K alpha ray to measure X-ray powder diagram that this crystal obtains is as shown in Figure 1.It spreads out with 2 θ ± 0.2
The X-ray powder diagram that firing angle represents 6.3 °, 9.7 °, 10.2 °, 11.5 °, 13.6 °, 17.8 °, 20.1 °, 21.2 °,
21.7 °, 22.8 °, 23.1 °, 25.0 °, show characteristic peak at 26.5 °.
Described Bisolvon crystalline compounds is prepared by following method:
(1) Bisolvon crude product is ground, crosses 200～300 mesh sieves, be then added to acetic acid: ethyl acetate body
Long-pending ratio is in the mixed solution of 3～5:1, stirring and dissolving；
(2) methanol is added while stirring: water volume ratio is the mixed solution of 1:3～4, is warming up to 40～45 DEG C simultaneously；
(3), after mixed solution adds, stand, be cooled to 5～10 DEG C, growing the grain 8～10 hours, washing, it is dried, obtains hydrochloric acid
Bromhexine crystal.
Use the new crystalline compounds of above-described Bisolvon as crude drug, hydrochloric acid bromine can be effectively improved own
The stability of new granule, the impurity content of generation is few.
Preferably, described Bisolvon granule is prepared from by following composition:
It is highly preferred that described Bisolvon granule is prepared from by following composition:
It is highly preferred that described Bisolvon granule is prepared from by following composition:
Another free-revving engine of the present invention is to provide a kind of technique preparing described Bisolvon granule, including under
Row step: Bisolvon crude drug, lactose, sorbitol, silicon dioxide are crossed 80 mesh sieves by (1) respectively, standby；
(2) Bisolvon of recipe quantity and lactose are pressed the method mix homogeneously of equal increments, adds recipe quantity
Sorbitol mix homogeneously, obtains mixed powder；
(3) when mixed powder is stirred continuously, with water for wetting agent soft material, cross 16 mesh sieves and pelletize；
(4) being dried by prepared wet granular, less loss weight must not cross 1.5%, crosses 10 mesh sieve granulate；
(5) granule after granulate adds silicon dioxide and the essence of recipe quantity, mix homogeneously；
(6) investigate particle appearance uniform, measure the actual content of Bisolvon in granule；
(7) according to the actual content measurement result of Bisolvon, calculate sample-loading amount, granule is loaded in film bag, rapidly
Seal bag mouth.
Further, the uniformity of the described mixed powder in step (2) reaches following standard: A+2.2s≤10.
Further, described step (7) also includes revealing sampling observation, every sampling observation in 30 minutes once.Prepared by the present invention
Bisolvon granule good stability, the impurity content of generation is low, takes compliance good, be especially suitable for dysphagia or
The patient of inconvenience.It addition, its preparation technology is simple, need not storage and the traffic condition of harshness, reduce cost.
Accompanying drawing explanation
The X-ray powder diffraction pattern of the Bisolvon crystalline compounds of Fig. 1 embodiment of the present invention 1 preparation.
Detailed description of the invention
The preparation of embodiment 1 Bisolvon crystal
(1) Bisolvon crude product is ground, crosses 200～300 mesh sieves, be then added to acetic acid: ethyl acetate body
Long-pending than in the mixed solution of 3:1, stirring and dissolving；
(2) methanol is added while stirring: water volume ratio is the mixed solution of 1:3, is warming up to 40 DEG C simultaneously；
(3), after mixed solution adds, stand, be cooled to 5 DEG C, growing the grain 8 hours, washing, it is dried, obtains Bisolvon brilliant
Body.
Prepare the X-ray powder diffraction spectrum of gained as shown in Figure 1.
The preparation of embodiment 2 Bisolvon crystal
(1) Bisolvon crude product is ground, crosses 300 mesh sieves, be then added to acetic acid: ethyl acetate volume ratio is
In the mixed solution of 5:1, stirring and dissolving；
(2) methanol is added while stirring: water volume ratio is the mixed solution of 1:4, is warming up to 45 DEG C simultaneously；
(3), after mixed solution adds, stand, be cooled to 10 DEG C, growing the grain 10 hours, washing, it is dried, obtains Bisolvon
Crystal.
Prepare the X-ray powder diffraction spectrum of gained as shown in Figure 1.
The preparation of embodiment 3 Bisolvon crystal
(1) Bisolvon crude product is ground, crosses 250 mesh sieves, be then added to acetic acid: ethyl acetate volume ratio is
In the mixed solution of 4:1, stirring and dissolving；
(2) methanol is added while stirring: water volume ratio is the mixed solution of 1:3, is warming up to 42 DEG C simultaneously；
(3), after mixed solution adds, stand, be cooled to 7 DEG C, growing the grain 9 hours, washing, it is dried, obtains Bisolvon brilliant
Body.
Prepare the X-ray powder diffraction spectrum of gained as shown in Figure 1.
The preparation of embodiment 4 Bisolvon granule
Prescription:
Preparation method:
(1) Bisolvon crude drug, lactose, sorbitol, silicon dioxide are crossed respectively 80 mesh sieves, standby；
(2) Bisolvon of recipe quantity and lactose are pressed the method mix homogeneously of equal increments, adds recipe quantity
Sorbitol mix homogeneously, obtains mixed powder；
(3) when mixed powder is stirred continuously, with water for wetting agent soft material, cross 16 mesh sieves and pelletize；
(4) being dried by prepared wet granular, less loss weight must not cross 1.5%, crosses 10 mesh sieve granulate；
(5) granule after granulate adds silicon dioxide and the essence of recipe quantity, mix homogeneously；
(6) investigate particle appearance uniform, measure the actual content of Bisolvon in granule；
(7) according to the actual content measurement result of Bisolvon, calculate sample-loading amount, granule is loaded in film bag, rapidly
Seal bag mouth.
The preparation of embodiment 5 Bisolvon granule
Prescription:
Preparation method:
(1) Bisolvon crude drug, lactose, sorbitol, silicon dioxide are crossed respectively 80 mesh sieves, standby；
(2) Bisolvon of recipe quantity and lactose are pressed the method mix homogeneously of equal increments, adds recipe quantity
Sorbitol mix homogeneously, obtains mixed powder；
(3) when mixed powder is stirred continuously, with water for wetting agent soft material, cross 16 mesh sieves and pelletize；
(4) prepared wet granular is dried, less loss weight 1%, crosses 10 mesh sieve granulate；
(5) adding silicon dioxide and the essence of recipe quantity in the granule after granulate, mix homogeneously, the uniformity reaches A+2.2s
≤10；
(6) investigate particle appearance uniform, measure the actual content of Bisolvon in granule；
(7) according to the actual content measurement result of Bisolvon, calculate sample-loading amount, granule is loaded in film bag, rapidly
Seal bag mouth, reveal sampling observation once every 30 minutes.
The preparation of embodiment 6 Bisolvon granule
Prescription:
Preparation method:
(1) Bisolvon crude drug, lactose, sorbitol, silicon dioxide are crossed respectively 80 mesh sieves, standby；
(2) Bisolvon of recipe quantity and lactose are pressed the method mix homogeneously of equal increments, adds recipe quantity
Sorbitol mix homogeneously, obtains mixed powder；
(3) when mixed powder is stirred continuously, with water for wetting agent soft material, cross 16 mesh sieves and pelletize；
(4) prepared wet granular is dried, less loss weight 0.5%, crosses 10 mesh sieve granulate；
(5) adding silicon dioxide and the essence of recipe quantity in the granule after granulate, mix homogeneously, the uniformity reaches A+2.2s
≤10；
(6) investigate particle appearance uniform, measure the actual content of Bisolvon in granule；
(7) according to the actual content measurement result of Bisolvon, calculate sample-loading amount, granule is loaded in film bag, rapidly
Seal bag mouth, reveal sampling observation once every 30 minutes.
The preparation of embodiment 7 Bisolvon granule
Prescription:
Preparation method:
(1) Bisolvon crude drug, lactose, sorbitol, silicon dioxide are crossed respectively 80 mesh sieves, standby；
(2) Bisolvon of recipe quantity and lactose are pressed the method mix homogeneously of equal increments, adds recipe quantity
Sorbitol mix homogeneously, obtains mixed powder；
(3) when mixed powder is stirred continuously, with water for wetting agent soft material, cross 16 mesh sieves and pelletize；
(4) prepared wet granular is dried, less loss weight 0.8%, crosses 10 mesh sieve granulate；
(5) adding silicon dioxide and the essence of recipe quantity in the granule after granulate, mix homogeneously, the uniformity reaches A+2.2s
≤10；
(6) investigate particle appearance uniform, measure the actual content of Bisolvon in granule；
(7) according to the actual content measurement result of Bisolvon, calculate sample-loading amount, granule is loaded in film bag, rapidly
Seal bag mouth, reveal sampling observation once every 30 minutes.
The preparation of embodiment 8 Bisolvon granule
Prescription:
Preparation method:
(1) Bisolvon crude drug, lactose, sorbitol, silicon dioxide are crossed respectively 80 mesh sieves, standby；
(2) Bisolvon of recipe quantity and lactose are pressed the method mix homogeneously of equal increments, adds recipe quantity
Sorbitol mix homogeneously, obtains mixed powder；
(3) when mixed powder is stirred continuously, with water for wetting agent soft material, cross 16 mesh sieves and pelletize；
(4) prepared wet granular is dried, less loss weight 0.4%, crosses 10 mesh sieve granulate；
(5) adding silicon dioxide and the essence of recipe quantity in the granule after granulate, mix homogeneously, the uniformity reaches A+2.2s
≤10；
(6) investigate particle appearance uniform, measure the actual content of Bisolvon in granule；
(7) according to the actual content measurement result of Bisolvon, calculate sample-loading amount, granule is loaded in film bag, rapidly
Seal bag mouth, reveal sampling observation once every 30 minutes.
The preparation of embodiment 9 Bisolvon granule
The prescription that this embodiment is used is identical with embodiment 4, only difference is that Bisolvon used is for this
The Bisolvon crystalline compounds with new crystal structure of invention preparation, the method for preparation is the same as in Example 4.
The preparation of embodiment 10 Bisolvon granule
The prescription that this embodiment is used is identical with embodiment 5, only difference is that Bisolvon used is for this
The Bisolvon crystalline compounds with new crystal structure of invention preparation, the method for preparation is same as in Example 5.
The preparation of embodiment 11 Bisolvon granule
The prescription that this embodiment is used is identical with embodiment 6, only difference is that Bisolvon used is for this
The Bisolvon crystalline compounds with new crystal structure of invention preparation, the method for preparation is same as in Example 6.
The preparation of embodiment 12 Bisolvon granule
The prescription that this embodiment is used is identical with embodiment 7, only difference is that Bisolvon used is for this
The Bisolvon crystalline compounds with new crystal structure of invention preparation, the method for preparation is same as in Example 7.
The preparation of embodiment 13 Bisolvon granule
The prescription that this embodiment is used is identical with embodiment 8, only difference is that Bisolvon used is for this
The Bisolvon crystalline compounds with new crystal structure of invention preparation, the method for preparation is the same as in Example 8.
Test example 1 content uniformity test
The purpose of this test is to investigate the drug content uniformity of Bisolvon prepared by the present invention.Measure is concrete
Method is with reference to the detection method of the granule uniformity described in 2015 editions four general rules 0941 of Chinese Pharmacopoeia.
The sample of the mixed powder different parts of preparation process (2) in Example 4, precision weighs 12.5mg (with Bisolvon
Content meter), be placed in 25ml measuring bottle, add methanol appropriate, ultrasonic make Bisolvon dissolve and with methanol dilution to scale, shake
Even, filter, take filtrate as need testing solution；Separately take Bisolvon standard reference material appropriate, accurately weighed, add methanol molten
Solve and be quantitatively diluted in every 1ml the solution containing about 0.5mg, as reference substance solution；Precision measures reference substance solution and for examination
The each 10 μ l of product solution, inject chromatograph of liquid, record chromatogram, by external standard method with Bisolvon in calculated by peak area powder
Content.
Bisolvon is prepared each batch sample of embodiment and is all tested by this test, the uniformity result of gained
It is satisfied by A+2.2s≤10, the good evenness of Bisolvon granule, meets pharmacopeia 2015 editions about granule uniformity
Requirement.
Test example 2 dissolution is tested
The method of testing that this test example is used is the method described in 2015 editions two annex XC of pharmacopeia, at 50 revs/min of bars
Testing under part, sample time is 5mim, 10min and 15min, every sub-sampling 10ml, and dissolution result see table.
By test result it can be seen that the Bisolvon granule prepared of the present invention in 15min in almost all molten
Going out, dissolve fast, content is high, and taking convenience is quick, good drug efficacy.
Especially, by result of the test it follows that embodiment 9-13 uses the novel Bisolvon crystal of present invention acquisition
Compound, it is more excellent than embodiment 4 that the Bisolvon granule of preparation has preferably dissolution, i.e. embodiment 9 relatively, implements
Example 10 is more excellent compared with embodiment 5, the like, embodiment 13 is more excellent compared with embodiment 8.Therefore, the novel hydrochloric acid bromine that the present invention obtains
Oneself new crystalline compounds can promote the dissolution of Bisolvon granule further.
Test example 3 accelerated test
Take Bisolvon granule prepared by embodiment of the present invention 4-13, pack by commercial standard, in temperature 40 ± 2
DEG C, be accelerated test under conditions of relative humidity 75% ± 5%, investigates 6 months, take 1 respectively, 2,3, sampling in June, test product
Raw impurity content (%), result is as shown in the table.
By test result it follows that Bisolvon granule prepared by the present invention places 6 in accelerated test condition
Month, the impurity content of generation is low, and drug quality is stable, good reliability.
It addition, by result of the test it follows that embodiment 9-13 uses the novel Bisolvon crystal of present invention acquisition
Compound, the Bisolvon granule of preparation has the most excellent stability, i.e. embodiment 9 is more excellent than embodiment 4, implements
Example 10 is more excellent compared with embodiment 5, the like, embodiment 13 is more excellent compared with embodiment 8.Therefore, the novel hydrochloric acid bromine that the present invention obtains
Oneself new crystalline compounds can improve the stability of Bisolvon granule further.
Test example 4 Bisolvon assay
Take Bisolvon granule prepared by embodiment of the present invention 4-13, pack by commercial standard, in temperature 40 ± 2
DEG C, be accelerated test under conditions of relative humidity 75% ± 5%, investigates 6 months, take 0 respectively, 2,3, sampling in June, test salt
The actual content of acid bromhexine, result is as shown in the table.
From test result, the medicine of the own granule of hydrochloric acid bromine prepared by the present invention divides content highly stable, and homogeneous,
Drug effect is reliable, is very suitable for popularization and application.It addition, prepared by the novel Bisolvon crystalline compounds using the present invention to obtain
The medicine of Bisolvon granule divides content higher, more stable, and performance is more preferably.
Claims (9)
1. a Bisolvon granule, it is characterised in that described Bisolvon granule prepared by following composition and
Become:
A kind of Bisolvon granule the most according to claim 1, it is characterised in that described Bisolvon is one
Kind of Bisolvon crystalline compounds, it utilizes X-ray powder diagram that Cu-K alpha ray measurement obtains as it is shown in figure 1, with 2
The X-ray powder diagram that θ ± 0.2 angle of diffraction represents 6.3 °, 9.7 °, 10.2 °, 11.5 °, 13.6 °, 17.8 °, 20.1 °,
21.2 °, 21.7 °, 22.8 °, 23.1 °, 25.0 °, show characteristic peak at 26.5 °.
A kind of Bisolvon granule the most according to claim 2, it is characterised in that described Bisolvon crystal
Compound is prepared through the following steps:
(1) Bisolvon crude product is ground, crosses 200～300 mesh sieves, be then added to acetic acid: ethyl acetate volume ratio
It is in the mixed solution of 3～5:1, stirring and dissolving；
(2) methanol is added while stirring: water volume ratio is the mixed solution of 1:3～4, is warming up to 40～45 DEG C simultaneously；
(3), after mixed solution adds, stand, be cooled to 5～10 DEG C, growing the grain 8～10 hours, washing, it is dried, obtains hydrochloric acid bromine own
New crystal.
4. according to a kind of Bisolvon granule described in claims 1 to 3 any one, it is characterised in that described salt
Acid bromhexine granule is prepared from by following composition:
A kind of Bisolvon granule the most according to claim 4, it is characterised in that described Bisolvon granule
Agent is prepared from by following composition:
A kind of Bisolvon granule the most according to claim 4, it is characterised in that described Bisolvon granule
Agent is prepared from by following composition:
7. the preparation technology according to the Bisolvon granule described in any one of claim 1-6, it is characterised in that bag
Include the following step:
(1) Bisolvon crude drug, lactose, sorbitol, silicon dioxide are crossed respectively 80 mesh sieves, standby；
(2) Bisolvon of recipe quantity and lactose are pressed the method mix homogeneously of equal increments, adds the Pyrusussuriensis of recipe quantity
Alcohol mix homogeneously, obtains mixed powder；
(3) when mixed powder is stirred continuously, with water for wetting agent soft material, cross 16 mesh sieves and pelletize；
(4) being dried by prepared wet granular, less loss weight must not exceed 1.5%, crosses 10 mesh sieve granulate；
(5) granule after granulate adds silicon dioxide and the essence of recipe quantity, mix homogeneously；
(6) investigate particle appearance uniformity, measure the actual content of Bisolvon in granule；
(7) according to the actual content measurement result of Bisolvon, calculate sample-loading amount, granule is loaded in film bag, seal rapidly
Bag mouth, to obtain final product.
Preparation technology the most according to claim 7, it is characterised in that the uniformity of the described mixed powder in step (2) reaches
To following standard: A+2.2s≤10.
Preparation technology the most according to claim 7, it is characterised in that described step (7) also includes revealing sampling observation, every
Sampling observation in 30 minutes is once.
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| CN101361719A (en) * | 2008-08-29 | 2009-02-11 | 南昌弘益科技有限公司 | Bromhexine hydrochloric acid orally disintegrating tablet production method |
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| CN102775316A (en) * | 2012-08-17 | 2012-11-14 | 夏智红 | Bromhexine hydrochloride compound and medicine composition thereof |
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2016
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101361719A (en) * | 2008-08-29 | 2009-02-11 | 南昌弘益科技有限公司 | Bromhexine hydrochloric acid orally disintegrating tablet production method |
| CN102525949A (en) * | 2012-01-17 | 2012-07-04 | 山东罗欣药业股份有限公司 | Cefaclor composition particles and preparation method thereof |
| CN102775316A (en) * | 2012-08-17 | 2012-11-14 | 夏智红 | Bromhexine hydrochloride compound and medicine composition thereof |
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