阅读说明：本技术 一种吸入用小儿止咳溶液制剂及其制备方法 (A kind of sucking child cough pharmaceutical solutions and preparation method thereof ) 是由 张保献 胡杰 王志华 于 2018-05-23 设计创作，主要内容包括：本发明涉及一种吸入用小儿止咳溶液制剂及其制备方法,属于制剂学领域。一种吸入用小儿止咳溶液制剂,所述溶液制剂包括：(1)甘草有效成分、桔梗有效成分、橙皮酊、氯化铵；(2)等渗剂及溶剂；其中,吸入用小儿止咳溶液制剂中的甘草有效成分由甘草流浸膏超滤得到；所述桔梗有效成分由桔梗流浸膏超滤得到。本发明提供的吸入用小儿止咳溶液制剂,通过雾化器快速形成气溶胶,起效快,不含防腐剂,可不含糖类或糖类含量显著降低,避免首过效应和胃肠道降解,且提高了病灶部位药物浓度,减少给药剂量,降低药物在其他组织中的分布,降低药物副作用,小儿使用更加安全。(The present invention relates to a kind of sucking child cough pharmaceutical solutions and preparation method thereof, belong to galenic pharmacy field.A kind of sucking child cough pharmaceutical solutions, the pharmaceutical solutions include: (1) effective liquorice, campanulaceae effective component, orange peel tincture, ammonium chloride；(2) isotonic agent and solvent；Wherein, sucking is obtained with the effective liquorice in child cough pharmaceutical solutions by liquid extract of liquorice ultrafiltration；The campanulaceae effective component is obtained by Platycodon glaucus fluidextract ultrafiltration.Sucking child cough pharmaceutical solutions provided by the invention, aerosol is quickly formed by atomizer, it is rapid-action, preservative is free of, can be free of carbohydrate or contents of saccharide significantly reduces, avoid first pass effect stomach function regulating intestinal degradation, and lesions position drug concentration is improved, dosage is reduced, distribution of the drug in its hetero-organization is reduced, drug side-effect is reduced, children's use is safer.)

1. a kind of sucking child cough pharmaceutical solutions, which is characterized in that including effective liquorice, campanulaceae effective component, orange Pi Ding, ammonium chloride, isotonic agent and solvent.

2. pharmaceutical solutions according to claim 1, which is characterized in that wherein the effective liquorice is by liquid extract of liquorice Ultrafiltration obtains, and the campanulaceae effective component is obtained by Platycodon glaucus fluidextract ultrafiltration.

3. pharmaceutical solutions according to claim 2, which is characterized in that wherein flowed in every liter of pharmaceutical solutions using Radix Glycyrrhizae Medicinal extract 37.5-187.5ml, Platycodon glaucus fluidextract 7.5-37.5ml, orange peel tincture 5-25ml, ammonium chloride 2.5-12.5g.

4. pharmaceutical solutions according to claim 2 or 3, it is characterised in that the dosage of the liquid extract of liquorice is 62- 182ml, Platycodon glaucus fluidextract dosage are 12.5-36ml, orange peel tincture dosage is 8.5-24ml, and ammonium chloride dosage is 4-12g.

5. according to the described in any item pharmaceutical solutions of claim 2-4, which is characterized in that the dosage of the liquid extract of liquorice is 94.5-175ml, Platycodon glaucus fluidextract dosage are 23.5-34.5ml, orange peel tincture dosage is 16.5-22.5ml, and ammonium chloride dosage is 8- 11g；It is furthermore preferred that the dosage of the liquid extract of liquorice is 145-165ml, Platycodon glaucus fluidextract dosage is 28-32ml, orange peel tincture is used Amount is 18.5-21.5ml, and ammonium chloride dosage is 9.5-10.5g.

6. pharmaceutical solutions according to claim 1-5, which is characterized in that the isotonic agent refers to inorganic salts etc. Penetration enhancer or carbohydrate isotonic agent, preferably inorganic salts isotonic agent.

7. according to the described in any item pharmaceutical solutions of claim 6, which is characterized in that the inorganic salts isotonic agent is chlorination One of sodium, magnesium chloride, calcium chloride are a variety of, preferably sodium chloride；The carbohydrate isotonic agent is glucose, fructose, sweet dew One of alcohol is a variety of, preferably glucose.

8. according to the described in any item pharmaceutical solutions of claim 6-7, which is characterized in that contain inorganic salts in each preparation unit The amount of isotonic agent is 0.15%-0.7%, preferably 0.2%-0.5%, more preferable 0.35%-0.5%；Contain in each preparation unit The amount of carbohydrate isotonic agent is 1%-10%, preferably 2%-8%, more preferable 2%-6.5%.

9. pharmaceutical solutions according to claim 1-8, which is characterized in that the preparation also includes cosolvent, institute It states cosolvent and is selected from ethyl alcohol, propylene glycol, glycerol, polyethylene glycol, Emulsifier EL-60, poloxamer, sapn or polysorbate One of or a variety of, preferably polysorbate or ethyl alcohol；More preferable polyoxyethylene sorbitan monoleate.

10. pharmaceutical solutions according to claim 9, which is characterized in that the dosage of the cosolvent in the formulation is 0.005-0.02%, preferably 0.01-0.02%.

11. -10 described in any item pharmaceutical solutions according to claim 1, which is characterized in that the solvent is purified water, injection With water or sterile water for injection.

12. -11 described in any item pharmaceutical solutions according to claim 1, which is characterized in that it further include pH adjusting agent, the pH Regulator is selected from hydrochloric acid, phosphoric acid, citric acid, glacial acetic acid, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium dihydrogen phosphate, phosphoric acid One of sodium dihydrogen, disodium hydrogen phosphate or dipotassium hydrogen phosphate are a variety of, preferably hydrochloric acid and sodium hydroxide.

13. -12 described in any item pharmaceutical solutions according to claim 1, which is characterized in that the pH value of the pharmaceutical solutions is preferred 3.0-7.5, more preferably 4-6, most preferably 5-6.

14. -13 described in any item pharmaceutical solutions according to claim 1, which is characterized in that preparation method the following steps are included:

(1) raw material liquid extract of liquorice, Platycodon glaucus fluidextract, orange peel tincture, ammonium chloride are weighed according to prescription ratio；

(2) extracting liquorice liquid extract adds 1-4 times of water, is stood more than for 24 hours after stirring evenly, and filtration, ultrafiltration obtains effective liquorice；

(3) Platycodon glaucus fluidextract is taken, adds 1-4 times of water, is stood after stirring evenly more than for 24 hours, is filtered, ultrafiltration obtains campanulaceae effective component；

(4) effective liquorice and campanulaceae effective component are mixed, is stood after stirring evenly more than for 24 hours, filtered, add 0.1-0.5% living Property charcoal boil 10-60min, filtered after letting cool, be added ammonium chloride, orange peel tincture, cosolvent, after stirring evenly filtration, ultrafiltration, adjust pH value 3.0-7.5 adds isotonic agent, dissolve, filtration, encapsulating to get.

15. pharmaceutical solutions according to claim 14, which is characterized in that in the step (2), add 2-3 times of water every time, often Secondary standing 48h or more；In the step (3), adds 2-3 times of water every time, stand 48h or more every time.

16. pharmaceutical solutions according to claim 14 or 15, which is characterized in that in the step (4), stand 48h every time More than, add 0.1-0.5% active carbon to boil 10-30min, adjusts the preferred 4-6 of pH value, most preferably 5-6.

17. the described in any item pharmaceutical solutions of 4-16 according to claim 1, which is characterized in that in the step (4), the orange Skin tincture is charged first to be completely dissolved in the aqueous solution containing cosolvent after, then mixed again with other ingredients.

18. effect of the described in any item pharmaceutical solutions of claim 1-17 in the drug of preparation treatment respiratory disease, institute Stating respiratory disease includes bronchitis, cough, more phlegm.

Technical field

The present invention relates to a kind of sucking child cough pharmaceutical solutions and preparation method thereof, belong to galenic pharmacy field.

Background technique

P-Cymene is a kind of classical Chinese patent drug, has the effects that eliminating the phlegm, antibechic, for cough caused by cold in children It coughs, it is on the books " Chinese Pharmacopoeia " 2015 editions.

Child cough prescription is total to four traditional Chinese medicine and is formed by liquid extract of liquorice, Platycodon glaucus fluidextract, ammonium chloride, orange peel tincture.In prescription Radix Glycyrrhizae is clearing heat and detoxicating, expelling phlegm and arresting coughing, coordinating the drug actions of a prescription；Campanulaceae promoting the dispersing function of the lung, relieving sore-throat eliminating the phlegm；Orange peel tincture strengthening the spleen and stomach, ventilating, drop are inverse Resolving sputum；Ammonium chloride resolving sputum, eliminating the phlegm.Radix Glycyrrhizae is sweet in flavor mild-natured, function expelling phlegm and arresting coughing, invigorating middle warmer and replenishing QI, is used for infantile cough, is monarch drug in a prescription； Campanulaceae is arduous flat, distributed in lung channel, and it is ministerial drug that function, which is ventilatingd the lung and resolving phlegm relieving sore-throat,；It is aided with orange peel tincture, ammonium chloride, Integrated TCM, enhancing is treated Effect.Children's clinical application nearly 30 years, be OTC Class A kind, and safety and validity have obtained clinical approval already.

There was only syrup currently with the dosage form that child cough prescription lists, patent application document CN101574425A, CN105497221A also discloses granule and preparation method thereof.However, granule disclosed in the syrup and document of listing is deposited In following defect:

1, contain preservative sodium benzoate in the syrup listed, there is reported literature sodium benzoate to influence the absorption of drug, Some adverse reactions can be brought, such as vomiting, hyperglycemia, hypokalemia, convulsions and moral damage, or even have a few peoples to benzene first Sour sodium allergy, there are also health agencies to find that children's hyperactive may be deepened or be induced to this preservative；

2, listing syrup is large dosage packaging, repeatedly uncaps and causes the secondary pollution of syrup；

3, it listing granule disclosed in syrup and document and adds carbohydrate, syrup sugar content is excessively high, and dry is sweet, Granula adds the food additives such as sucrose, dextrin, and causing children to take in sugar excess, indigestion etc. influences children growth hair It educates；

4, syrup and granule are oral, and dosage is larger, need the first pass effect by liver, into the circulatory system Effect and patient part work slower, limit the medication of patient to a certain extent.

Sucking preparation is that drug dispersion nebulizes by propellant, compressed air or special device, and it is molten to form medicine air Glue makes drug directly reach site of action.The inhalant dosage form listed at present has dry powder sucking, aerosol and inhalation solution.Dry powder Sucking needs the device by Special complex, and complicated structure results in the raising of device production cost, is unfavorable for universal trouble Person affects effective control of disease to the compliance of suction apparatus, frequency of use and dry powder Transfer Technology.Aerosol needs Pressure vessel and valve system, higher cost need cooling and filling mechanical equipment, and preparation manipulation is cumbersome, aerosol It with certain internal pressure, heat or easily explodes after being impacted, while borrowing the pressure of the vapour pressure of propellant and working, it can be because The leakage of propellant and fail.

And aerosol inhalation solution preparation can directly act on patient part as respiratory tract or pulmonary administration preparation, it can The administration concentration of respiratory tract or lung is improved, it is rapid-action, and said preparation avoids the first pass effect of liver, reduces the administration of drug Dosage improves drug bioavailability, and reduces drug in the distribution of its hetero-organization, reduces side effect, has inhalation thorn Swash small, easy to use, good patient compliance, toxic side effect it is small, be suitable for long-term treatment the advantages that, the World Health Organization it has been recommended that It is the preferred therapy of the respiratory diseases such as asthma, eliminating the phlegm, tracheitis, bronchitis, pneumonia, chronic obstructive pulmonary disease.Neulized inhalation at present The product listed with pharmaceutical solutions is relatively fewer, predominantly imported product.Clinically with injection application Neulized inhalation the case where It is more, but there is no the application method of specification in specification, there is security risk in use.

Sucking with child cough solution eliminating the phlegm, in terms of, it is contemplated that will have good curative effect.It does not deposit in the prior art In sucking child cough solution special preparation, it will have good market prospects.

Summary of the invention

The technical problem to be solved by the present invention is to provide one kind safely, effectively, the sucking of good quality child cough solution Preparation；The present invention also provides the preparation methods of said preparation.

An object of the present invention is to provide that a kind of bioavilability is high, directly acts on lesions position, is rapid-action, more pacifying Complete effective sucking child cough pharmaceutical solutions, are achieved through the following technical solutions:

A kind of sucking child cough pharmaceutical solutions, the pharmaceutical solutions include:

(1) effective liquorice, campanulaceae effective component, orange peel tincture, ammonium chloride；

(2) isotonic agent and solvent；

Wherein, sucking is obtained with the effective liquorice in child cough pharmaceutical solutions by liquid extract of liquorice ultrafiltration；It is described Campanulaceae effective component is obtained by Platycodon glaucus fluidextract ultrafiltration.

Of the present invention suck uses child cough pharmaceutical solutions, uses liquid extract of liquorice in every liter of pharmaceutical solutions 37.5-187.5ml, Platycodon glaucus fluidextract 7.5-37.5ml, orange peel tincture 5-25ml, ammonium chloride 2.5-12.5g.

Further, as a preferred embodiment, the dosage of the liquid extract of liquorice is 62-182ml, campanulaceae stream Medicinal extract dosage is 12.5-36ml, orange peel tincture dosage is 8.5-24ml, and ammonium chloride dosage is 4-12g；Preferably, the Radix Glycyrrhizae stream The dosage of medicinal extract is 94.5-175ml, Platycodon glaucus fluidextract dosage is 23.5-34.5ml, orange peel tincture dosage is 16.5-22.5ml, chlorine Change ammonium dosage is 8-11g；It is furthermore preferred that the dosage of the liquid extract of liquorice is 145-165ml, Platycodon glaucus fluidextract dosage is 28- 32ml, orange peel tincture dosage are 18.5-21.5ml, and ammonium chloride dosage is 9.5-10.5g.

Further, in sucking child cough pharmaceutical solutions of the present invention, the solvent is purified water, injection Water or sterile water for injection.

Further, in sucking child cough pharmaceutical solutions of the present invention, the isotonic agent refers to inorganic salts Isotonic agent or carbohydrate isotonic agent, preferably inorganic salts isotonic agent.The inorganic salts isotonic agent is sodium chloride, magnesium chloride, chlorine Change one of calcium or a variety of, preferably sodium chloride；The carbohydrate isotonic agent be one of glucose, fructose, mannitol or It is a variety of, preferably glucose.

Further, in sucking child cough pharmaceutical solutions of the present invention, inorganic salts are contained in each preparation unit The amount of class isotonic agent is 0.15%-0.7%, preferably 0.2%-0.5%, more preferable 0.35%-0.5%.Children are used in the sucking The amount of the isotonic agent containing carbohydrate is 1%-10%, preferably 2%-8%, more preferable 2%- in each preparation unit of cough-relieving pharmaceutical solutions 6.5%.

It further, also include cosolvent in sucking child cough pharmaceutical solutions of the present invention.The cosolvent choosing From one of ethyl alcohol, propylene glycol, glycerol, polyethylene glycol, Emulsifier EL-60, poloxamer, sapn or polysorbate or It is a variety of, preferably polysorbate or ethyl alcohol；More preferable polyoxyethylene sorbitan monoleate.

Further, the dosage of the cosolvent in the formulation is 0.005-0.02%, preferably 0.01-0.02%.By Poor in effective component of chinese medicine dissolubility, the present invention is selected by type to cosolvent and dosage, can effectively eliminate small Muddiness or opalescence in youngster's cough-relieving pharmaceutical solutions, keep medical fluid clear and bright, the dissolubility of the effective elements of the medicine in a solvent in raising.

Further, the sucking of the present invention preferred 3.0-7.5 of pH value of child cough pharmaceutical solutions, more preferably For 4-6, most preferably 5-6.The preferably common inorganic acid of pH adjusting agent or inorganic base；The pH adjusting agent be selected from hydrochloric acid, phosphoric acid, Citric acid, glacial acetic acid, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate or phosphorus One of sour hydrogen dipotassium is a variety of, preferably hydrochloric acid and sodium hydroxide.

In the present invention, gained aerosol inhalation solution preparation is made to inhale with ultrasonic atomizer or air compression type atomizer Enter child cough solution and respiratory system is directly sucked in atomised form, directly acts on respiratory tract lesions position, it is rapid-action, it reduces The toxic side effect of drug, it is safer and more effective.

The second object of the present invention is to provide a kind of preparation method of sucking child cough solution, the method packet It includes:

(1) raw material liquid extract of liquorice, Platycodon glaucus fluidextract, orange peel tincture, ammonium chloride are weighed according to prescription ratio；

(2) extracting liquorice liquid extract adds 1-4 times of water, is stood more than for 24 hours after stirring evenly, and filtration, ultrafiltration obtains effective liquorice；

(3) Platycodon glaucus fluidextract is taken, adds 1-4 times of water, is stood after stirring evenly more than for 24 hours, is filtered, ultrafiltration obtains campanulaceae effective component；

(4) effective liquorice and campanulaceae effective component are mixed, is stood after stirring evenly more than for 24 hours, filtered, add 0.1- 0.5% active carbon boils 10-60min, filters after letting cool, and ammonium chloride, orange peel tincture, cosolvent is added, filtration, ultrafiltration after stirring evenly, Adjust pH value 3.0-7.5, add isotonic agent, dissolve, filtration, encapsulating to get.

Further, as a preferred embodiment, in the step (2), add 2-3 times of water every time, stand every time 48h or more.

Further, as a preferred embodiment, in the step (3), add 2-3 times of water every time, stand every time 48h or more.

Further, as a preferred embodiment, in the step (4), 48h or more is stood every time, adds 0.1- 0.5% active carbon boils 10-30min, adjusts the preferred 4-6 of pH value, most preferably 5-6.

Further, as a preferred embodiment, the orange peel tincture can be charged first in the step (4) After being completely dissolved in aqueous solution containing cosolvent, then mixed again with other ingredients.

Sucking child cough pharmaceutical solutions of the present invention have the effect of eliminating the phlegm, antibechic, can be used for eliminating the phlegm, cough-relieving Deng.Therefore, the third object of the present invention is to provide a kind of sucking child cough pharmaceutical solutions and treats respiratory tract disease in preparation Effect in the drug of disease, the respiratory disease includes but is not limited to abundant expectoration, cough and asthma etc..

Compared with prior art, the present invention has the following technical effect that

1, sucking child cough pharmaceutical solutions provided by the invention, quickly form aerosol by atomizer, formation Aerosol can directly snap action at sufferer, and the drug for acting on affected part can quickly be absorbed action, local lesion Drug concentration is high, reduces drug in the distribution of other histoorgans, rapid-action；

2, sucking child cough pharmaceutical solutions provided by the invention, are free of preservative, can be free of carbohydrate or contents of saccharide It significantly reduces, more former dosage form is compared, had no toxic side effect；First pass effect stomach function regulating intestinal degradation is avoided simultaneously, and improves lesion portion Position drug concentration, reduces dosage, reduces distribution of the drug in its hetero-organization, reduces drug side-effect, children are using more Add safety；

3, pharmaceutical solutions prepared by the present invention compensate for the blank on domestic market, and solution prepared by the present invention Preparation is to aim at Neulized inhalation to be designed with patient, is matched with atomizer, use process is convenient.

Specific embodiment

The dosage of substance used in substance used in the production process and preparation of following pharmaceutical preparation embodiment or preparation is not limited to Character express, all formulation methods containing pharmaceutical composition provided by the invention, all belongs to the scope of protection of the present invention.