CN110870854B - Ambroxol solution preparation for inhalation and preparation method and application thereof - Google Patents
Ambroxol solution preparation for inhalation and preparation method and application thereof Download PDFInfo
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- CN110870854B CN110870854B CN201811001328.XA CN201811001328A CN110870854B CN 110870854 B CN110870854 B CN 110870854B CN 201811001328 A CN201811001328 A CN 201811001328A CN 110870854 B CN110870854 B CN 110870854B
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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
- A61K9/08—Solutions
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- 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
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- 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
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
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- 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
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- 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
- A61P11/12—Mucolytics
Abstract
The invention belongs to the field of pharmaceutics, and particularly relates to an ambroxol solution preparation for inhalation, and a preparation method and application thereof. The invention provides an ambroxol solution preparation for inhalation, which comprises an ambroxol hydrochloride solution and a packaging material, wherein the ambroxol hydrochloride solution is placed in the packaging material, and the invention also provides a preparation method of the ambroxol solution preparation for inhalation. Compared with the prior art, the ambroxol solution preparation for inhalation provided by the invention has the advantages of good compatibility of the inhalation solution and the packing material, high stability, reliable quality, good safety and long storage time, and the preparation method is simple and easy to operate, low in production cost and easy for industrial production.
Description
Technical Field
The invention belongs to the field of pharmaceutics, and particularly relates to an ambroxol solution preparation for inhalation as well as a preparation method and application thereof.
Background
Ambroxol (chemical name is trans-4- [ (2-amino 3.5-dibromo benzyl) amino]Cyclohexanol, C 13 H 18 Br 2 N 2 O, CAS:18683-91-5, whose CAS is 23828-92-4 for its hydrochloride) was discovered in 1965 by Boringer Invitrogen, germany, when studying the bromhexine metabolite. Later researches show that the ambroxol hydrochloride can be used as a mucolytic agent, has stronger action than bromhexine, can increase the secretion of respiratory mucosa serous glands, reduce the secretion of the mucous glands, reduce and break mucopolysaccharide fibers in sputum, reduce the viscosity of the sputum, thin the sputum and be easy to expectorate. Ambroxol hydrochloride can also activate alveolar epithelium II type cells to synthesize surface active substances, reduce adhesive force of mucus, improve the transport of mucus in cilium and nonciliary areas in respiratory tracts, facilitate the discharge of sputum, achieve the effect of clearing respiratory tract mucosa and directly protect lung functions.
The ambroxol hydrochloride solution for inhalation is sold in Germany in the earliest time in 1978, the dosage forms in the domestic market include tablets, injections and the like, the inhalation solution is not sold in the market, and the ambroxol hydrochloride solution is possibly related to the technical barriers that the ambroxol hydrochloride is extremely unstable to light, is easily degraded when meeting light and the like. Although the stability of the ambroxol hydrochloride inhalation solution is improved by changing the prescription of the ambroxol hydrochloride inhalation solution, the stability of the inhalation solution is improved by adding a preservative (application number: 201310363444.7, the name of the invention: an ambroxol hydrochloride solution for inhalation) or a metal ion chelate stabilizer (application number: 201810117660.6, the name of the invention: an ambroxol hydrochloride solution for stable inhalation and a preparation method thereof) into the ambroxol hydrochloride inhalation solution. However, the problem of the stability of the ambroxol hydrochloride inhalation solution preparation is rarely studied from the overall angle of the preparation formed by the compatibility of packing materials and the like.
Disclosure of Invention
In order to solve the technical problems, the invention provides an ambroxol solution preparation for inhalation and a preparation method thereof. The inhalation solution preparation has excellent light stability and thermal stability, and has more reliable quality, higher safety and longer storage time.
Therefore, the first object of the present invention is to provide an ambroxol solution preparation for inhalation, which is realized by the following technical scheme:
an ambroxol solution preparation for inhalation comprises an ambroxol hydrochloride solution and a packaging material, wherein the ambroxol hydrochloride solution is placed in the packaging material.
In the above ambroxol solution formulation for inhalation, the ambroxol hydrochloride solution comprises: 1-20mg/mL (e.g., 1.2mg/mL, 1.5mg/mL, 2mg/mL, 3mg/mL, 4mg/mL, 5mg/mL, 6mg/mL, 7mg/mL, 7.5mg/mL, 8mg/mL, 9mg/mL, 11mg/mL, 13mg/mL, 15mg/mL, 17mg/mL, 19 mg/mL) ambroxol hydrochloride, an isotonicity agent, a pH adjusting agent, and a solvent.
In the above-mentioned formulation of ambroxol solution for inhalation, as a preferred embodiment, the ambroxol hydrochloride solution comprises 2 to 15mg/mL ambroxol hydrochloride, preferably 5 to 10mg/mL ambroxol hydrochloride.
In the above ambroxol solution formulation for inhalation, as a preferred embodiment, the mass ratio of the isotonic agent to the ambroxol hydrochloride is from 1; preferably, the isotonic agent is selected from one or more of sodium chloride, magnesium chloride, potassium chloride, calcium chloride, glucose, xylitol, sorbic acid.
In the ambroxol solution preparation for inhalation, as a preferable embodiment, the pH adjuster is any one of citric acid-disodium hydrogen phosphate, hydrochloric acid-sodium hydroxide, citric acid-sodium citrate, potassium dihydrogen phosphate-disodium hydrogen phosphate, and citric acid-sodium hydroxide; preferably, the pH regulator is added in an amount to make the pH value of the ambroxol hydrochloride solution be 3-8, preferably 4.5-5.5.
In the above-mentioned ambroxol solution preparation for inhalation, as a preferred embodiment, the solvent is water or a mixed solvent composed of water and an appropriate amount of a co-solvent; the water is preferably water for injection.
In the above-mentioned ambroxol solution preparation for inhalation, as a preferred embodiment, the packaging material is selected from any one of borosilicate glass ampoule bottles, aluminosilicate glass ampoule bottles, calcium borosilicate glass ampoule bottles, barium borosilicate glass ampoule bottles, zinc borosilicate glass ampoule bottles, and zirconium borosilicate glass ampoule bottles; preferably a borosilicate glass ampoule.
In the above ambroxol solution preparation for inhalation, as a preferred embodiment, the mass fraction of ferric oxide in the borosilicate glass ampoule bottle is not more than 1.0%, and the mass fraction of titanium dioxide is not more than 2.2%; preferably, the mass fraction of ferric oxide in the borosilicate glass ampoule is 0.2-0.8% (such as 0.21%, 0.25%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.75%), the mass fraction of titanium dioxide is 0.5-2.0% (such as 0.55%, 0.6%, 0.8%, 1.0%, 1.2%, 1.5%, 1.7%, 1.9%); more preferably, the mass fraction of the ferric oxide and the mass fraction of the titanium dioxide in the borosilicate glass ampoule bottle are respectively 0.2-0.4% and 0.5-1.2%.
The second purpose of the invention is to provide a preparation method of an ambroxol solution preparation for inhalation, which sequentially comprises the following steps:
(1) Weighing the ambroxol hydrochloride and the pH regulator according to the prescription amount, adding the ambroxol hydrochloride and the pH regulator into a solvent, and stirring to completely dissolve the ambroxol hydrochloride to obtain a pre-inhalation solution;
(2) Adding the isotonic agent into the pre-imbibed solution prepared in the step (1), stirring to dissolve the isotonic agent, and fixing the volume to obtain the ambroxol hydrochloride solution;
(3) And (3) filling the ambroxol hydrochloride solution obtained in the step (2) into the packaging material, sealing by fusing, and sterilizing to obtain the ambroxol hydrochloride solution preparation for inhalation.
In the above production method, as a preferred embodiment, in the step (1), the temperature of the solvent is 25 to 100 ℃, preferably 25 to 80 ℃; too low temperature of the solvent can lead to too long dissolution time of the ambroxol hydrochloride, and too high temperature can increase the content of impurities in the ambroxol hydrochloride solution.
In the above preparation method, the inventors have surprisingly found that when the isotonic agent is added to the solvent first and then the ambroxol hydrochloride is added, the ambroxol hydrochloride is hardly dissolved, and even when the mixture is stirred vigorously under heating, the ambroxol hydrochloride is hardly dissolved completely.
In the above preparation method, as a preferred embodiment, in the step (3), the temperature of the sterilization is 120 to 125 ℃ and the time is 10 to 15min; preferably, the temperature is 121 ℃ and the time is 12min.
The third purpose of the invention is to provide the application of the ambroxol solution preparation for inhalation in the preparation of medicines for treating acute and chronic respiratory diseases accompanied by abnormal sputum secretion and bad sputum excretion function, postoperative pulmonary complications and the like.
Compared with the prior art, the invention has the following technical effects:
1. the ambroxol solution preparation for inhalation provided by the invention has the advantages of good compatibility of the inhalation solution and the packaging material, high stability, reliable quality, good safety and long storage time.
2. The preparation method is simple and easy to operate, low in production cost and easy for industrial production.
Detailed Description
The preparation process and the materials used in the preparation or the dosage of the materials used in the preparation in the following examples of the pharmaceutical preparation are not limited to the words, and all methods containing the pharmaceutical preparation provided by the present invention are within the protection scope of the present invention.
The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially. The used glass ampoule bottles are purchased from the market, wherein a part of the ampoule bottles are customized by the applicant from manufacturers, and the part of the ampoule bottles are prepared according to a conventional ampoule bottle preparation method.
Example 1
(1) Weighing 7.5g of ambroxol hydrochloride and 0.1g of disodium hydrogen phosphate, adding into a proper amount of water for injection at 50 ℃, and stirring to completely dissolve the ambroxol hydrochloride to obtain a pre-inhalation solution;
(2) Adding 7g of sodium chloride into the pre-imbibed solution prepared in the step (1), stirring to dissolve the sodium chloride, fixing the volume to 1000ml, adding a proper amount of citric acid to adjust the pH value to be =5.05, and obtaining an ambroxol hydrochloride solution;
(3) And (3) filling the ambroxol hydrochloride solution obtained in the step (2) into a 2ml borosilicate glass ampoule bottle, sealing by melting, and sterilizing to obtain the ambroxol solution preparation for inhalation.
Wherein, borosilicate glass ampoule has 6 specifications, specifically:
the mass fraction of ferric oxide and the mass fraction of titanium dioxide in the borosilicate glass ampoule bottle with the label 1 are respectively 1.0wt% and 2.2wt%;
the mass fraction of ferric oxide and the mass fraction of titanium dioxide in the borosilicate glass ampoule bottle of the label 2 are respectively 0.8wt% and 2.0wt%;
the mass fraction of ferric oxide and the mass fraction of titanium dioxide in the borosilicate glass ampoule bottle of the label 3 are respectively 0.4wt% and 1.2wt%;
the mass fraction of ferric oxide and the mass fraction of titanium dioxide in the borosilicate glass ampoule bottle of the label 4 are respectively 0.2wt% and 0.5wt%;
the mass fraction of ferric oxide and the mass fraction of titanium dioxide in the borosilicate glass ampoule bottle of the label 5 are respectively 1.2wt% and 2.5wt%;
the borosilicate glass ampoule bottle of the label 6 contains 0.05wt% of ferric oxide and 0.3wt% of titanium dioxide.
And (3) stability test:
2 bottles of the ambroxol solution preparation for inhalation with the labels 1-6 in the example 1 are taken; the reference numerals 11 and 12 of reference numeral 1, the reference numerals 21 and 22 of reference numeral 2, the reference numerals 31 and 32 of reference numeral 3, the reference numerals 41 and 42 of reference numeral 4, the reference numerals 51 and 52 of reference numeral 5, and the reference numerals 61 and 62 of reference numeral 6; wherein the ambroxol solution preparation for inhalation with the reference number 11, the reference number 21, the reference number 31, the reference number 41, the reference number 51 and the reference number 61 is placed for 10 days at the temperature of 60 ℃; the inhaled ambroxol solution formulation, reference numeral 12, reference numeral 22, reference numeral 32, reference numeral 42, reference numeral 52, reference numeral 62, was irradiated for 10 days at an illumination intensity of 4500lx ± 500 lx.
HPLC is adopted to test the content of the ambroxol in the ambroxol hydrochloride solution (measured before filling in an ampoule bottle) in the example 1 and the content of the ambroxol in the ambroxol solution preparation for inhalation with the label number of 11-62; detection conditions are as follows: a chromatographic column: agilent ZORBAX extended-C18.6 x 250mm 3.5 μm; mobile phase: water (diammonium hydrogen phosphate 1.0 g/L): acetonitrile = 52; flow rate: 1.0ml/min; column temperature: 40 ℃; detection wavelength: 248nm; the detection results are shown in table 1; the change in the pH was measured and observed.
TABLE 1 ambroxol content and Property Change in the solution formulation of ambroxol for inhalation
Through the experiment, the compatibility problem of the ambroxol hydrochloride solution and the packing material is researched, when the content of ferric oxide and the content of titanium dioxide in the packing material are too high or too low, the stability of the ambroxol hydrochloride solution is influenced, the thermal stability of the ambroxol hydrochloride solution is influenced when the content of ferric oxide is too high, and the light stability of the ambroxol hydrochloride solution is influenced when the content of titanium dioxide is too high, and specific results are shown in table 1.
Example 2
(1) Weighing ambroxol hydrochloride and disodium hydrogen phosphate according to the prescription amount, adding the ambroxol hydrochloride and the disodium hydrogen phosphate into a proper amount of water for injection at 40 ℃, and stirring to completely dissolve the ambroxol hydrochloride to obtain a pre-inhalation solution;
(2) Adding a prescribed amount of sodium chloride into the pre-inhalation solution prepared in the step (1), stirring to dissolve the sodium chloride, fixing the volume to 1000ml, adding a proper amount of citric acid to adjust the pH value to be =5.50, and obtaining an ambroxol hydrochloride solution;
(3) And (3) filling the ambroxol hydrochloride solution obtained in the step (2) into a 2ml borosilicate glass ampoule bottle (the mass fraction of ferric oxide is 0.3wt%, and the mass fraction of titanium dioxide is 0.7 wt%), sealing by melting, and sterilizing to obtain the ambroxol hydrochloride solution preparation for inhalation.
Example 3
(1) Weighing ambroxol hydrochloride and disodium hydrogen phosphate according to the prescription amount, adding the ambroxol hydrochloride and the disodium hydrogen phosphate into a proper amount of water for injection at 50 ℃, and stirring to completely dissolve the ambroxol hydrochloride to obtain a pre-imbibed solution;
(2) Adding a prescribed amount of sodium chloride into the pre-inhalation solution prepared in the step (1), stirring to dissolve the sodium chloride, fixing the volume to 1000ml, adding a proper amount of citric acid to adjust the pH value to be =5.25, and obtaining an ambroxol hydrochloride solution;
(3) And (3) filling the ambroxol hydrochloride solution obtained in the step (2) into a 2ml borosilicate glass ampoule bottle (the mass fraction of ferric oxide is 0.35wt%, and the mass fraction of titanium dioxide is 0.8 wt%), sealing by melting, and sterilizing to obtain the ambroxol solution preparation for inhalation.
Example 4
(1) Weighing ambroxol hydrochloride and disodium hydrogen phosphate according to the prescription amount, adding the ambroxol hydrochloride and the disodium hydrogen phosphate into a proper amount of water for injection at 60 ℃, and stirring to completely dissolve the ambroxol hydrochloride to obtain a pre-inhalation solution;
(2) Adding a prescribed amount of sodium chloride into the pre-inhalation solution prepared in the step (1), stirring to dissolve the sodium chloride, fixing the volume to 1000ml, adding a proper amount of citric acid to adjust the pH value to be =4.74, and obtaining an ambroxol hydrochloride solution;
(3) And (3) filling the ambroxol hydrochloride solution obtained in the step (2) into a 2ml borosilicate glass ampoule bottle (the mass fraction of ferric oxide is 0.4wt%, and the mass fraction of titanium dioxide is 1.0 wt%), sealing by melting, and sterilizing to obtain the ambroxol solution preparation for inhalation.
Example 5
(1) Weighing ambroxol hydrochloride and sodium citrate according to the prescription amount, adding the ambroxol hydrochloride and the sodium citrate into a proper amount of water for injection at 50 ℃, and stirring to completely dissolve the ambroxol hydrochloride to obtain a pre-inhalation solution;
(2) Adding a prescription amount of sodium chloride into the pre-inhalation solution prepared in the step (1), stirring to dissolve the sodium chloride, fixing the volume to 1000ml, adding a proper amount of citric acid to adjust the pH value to be =5.00, and obtaining an ambroxol hydrochloride solution;
(3) And (3) filling the ambroxol hydrochloride solution obtained in the step (2) into a 2ml borosilicate glass ampoule bottle (the mass fraction of ferric oxide is 0.4wt%, and the mass fraction of titanium dioxide is 0.8 wt%), sealing by melting, and sterilizing to obtain the ambroxol solution preparation for inhalation.
Example 6
(1) Weighing ambroxol hydrochloride and disodium hydrogen phosphate according to the prescription amount, adding the ambroxol hydrochloride and the disodium hydrogen phosphate into a proper amount of water for injection at 100 ℃, and stirring to completely dissolve the ambroxol hydrochloride to obtain a pre-imbibed solution;
(2) Adding a prescribed amount of sodium chloride into the pre-inhalation solution prepared in the step (1), stirring to dissolve the sodium chloride, fixing the volume to 1000ml, adding a proper amount of citric acid to adjust the pH value to be =5.17, and obtaining an ambroxol hydrochloride solution;
(3) And (3) filling the ambroxol hydrochloride solution obtained in the step (2) into a 2ml borosilicate glass ampoule bottle (the mass fraction of ferric oxide is 0.4wt%, and the mass fraction of titanium dioxide is 1.2 wt%), sealing by melting, and sterilizing to obtain the ambroxol solution preparation for inhalation.
And (3) stability test:
2 bottles of the ambroxol solution preparation for inhalation prepared in examples 2-6 were taken; the labels of the embodiment 2 are 21 st group and 22 nd group, the labels of the embodiment 3 are 31 st group and 32 nd group, the labels of the embodiment 4 are 41 st group and 42 th group, the labels of the embodiment 5 are 51 st group and 52 th group, and the labels of the embodiment 6 are 61 st group and 62 th group; wherein the ambroxol solution preparation for inhalation of the 21 st, 31 st, 41 st, 51 st and 61 st groups is left standing at 60 ℃ for 10 days; the formulations of ambroxol solution for inhalation of groups 22, 32, 42, 52, 62 were illuminated at an illumination intensity of 4500lx ± 500lx for 10 days.
The content of ambroxol in the ambroxol hydrochloride solutions of examples 2-6 (determined before filling in ampoules), the content of ambroxol in the ambroxol solution formulations for inhalation of groups 21-62 were tested by HPLC; detection conditions are as follows: and (3) chromatographic column: agilent ZORBAX extended-C18.6 x 250mm 3.5 μm; mobile phase: water (diammonium phosphate 1.0 g/L) -acetonitrile: acetonitrile = 52; flow rate: 1.0ml/min; column temperature: 40 ℃; detection wavelength: 248nm; the detection results are shown in Table 2; the change in the pH value was measured and the change in the property was observed.
TABLE 2 ambroxol content and Property Change in the solution formulation of ambroxol for inhalation
As is clear from Table 2, the ambroxol solution formulations for inhalation within the scope of the present invention are not only good in light stability but also good in heat stability.
Claims (7)
1. An ambroxol solution preparation for inhalation, which is characterized by comprising an ambroxol hydrochloride solution and a packaging material, wherein the ambroxol hydrochloride solution is placed in the packaging material; the ambroxol hydrochloride solution comprises the following components: 1-10mg/mL ambroxol hydrochloride, an isotonic agent, a pH regulator and a solvent; the mass ratio of the isotonic agent to the ambroxol hydrochloride is 1; the isotonic agent is sodium chloride; the pH regulator is citric acid-disodium hydrogen phosphate and citric acid-sodium citrate; the addition amount of the pH regulator is to ensure that the pH value of the ambroxol hydrochloride solution is 4.5-5.5; the solvent is water for injection; the packaging material is a borosilicate glass ampoule bottle; the mass fraction of ferric oxide and the mass fraction of titanium dioxide in the borosilicate glass ampoule bottle are respectively 0.2-0.4% and 0.5-1.2%.
2. A process for the preparation of an ambroxol solution formulation for inhalation according to claim 1, comprising the following steps in sequence:
(1) Weighing the ambroxol hydrochloride and the pH regulator according to the prescription amount, adding the ambroxol hydrochloride and the pH regulator into a solvent, and stirring to completely dissolve the ambroxol hydrochloride to obtain a pre-inhalation solution;
(2) Adding the isotonic agent into the pre-imbibed solution prepared in the step (1), stirring to dissolve the isotonic agent, and fixing the volume to obtain the ambroxol hydrochloride solution;
(3) And (3) filling the ambroxol hydrochloride solution obtained in the step (2) into the packaging material, sealing by fusing, and sterilizing to obtain the ambroxol solution preparation for inhalation.
3. The method according to claim 2, wherein the temperature of the solvent in the step (1) is 25 to 100 ℃.
4. The method according to claim 3, wherein the temperature of the solvent in the step (1) is 25 to 80 ℃.
5. The method according to claim 2, wherein in the step (3), the sterilization is performed at a temperature of 120 to 125 ℃ for 10 to 15min.
6. The method according to claim 5, wherein in the step (3), the sterilization temperature is 121 ℃ and the time is 12min.
7. Use of the ambroxol solution formulation for inhalation according to claim 1 for the preparation of a medicament for the treatment of acute and chronic respiratory diseases, postoperative pulmonary complications accompanied by abnormal secretion of sputum and dysfunction in expectoration.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103126978A (en) * | 2013-02-05 | 2013-06-05 | 浙江华海药业股份有限公司 | Preparing method for ambroxol hydrochloride injection |
| CN106727321A (en) * | 2017-02-14 | 2017-05-31 | 杭州百诚医药科技股份有限公司 | A kind of suction ambroxol hydrochloride solution |
| RU2657764C1 (en) * | 2017-02-20 | 2018-06-15 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Самарский государственный медицинский университет" Министерства здравоохранения Российской Федерации | Pharmaceutical form of ambroxol hydrochloride and method of its delivery to respiratory tract |
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| CN103126978A (en) * | 2013-02-05 | 2013-06-05 | 浙江华海药业股份有限公司 | Preparing method for ambroxol hydrochloride injection |
| CN106727321A (en) * | 2017-02-14 | 2017-05-31 | 杭州百诚医药科技股份有限公司 | A kind of suction ambroxol hydrochloride solution |
| RU2657764C1 (en) * | 2017-02-20 | 2018-06-15 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Самарский государственный медицинский университет" Министерства здравоохранения Российской Федерации | Pharmaceutical form of ambroxol hydrochloride and method of its delivery to respiratory tract |
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