CN115645366A

CN115645366A - Oral solution of ammonia bromine terluo and preparation process thereof

Info

Publication number: CN115645366A
Application number: CN202211431132.0A
Authority: CN
Inventors: 孙逸威; 邓艾平; 王谦
Original assignee: Shandong Jikun Biopharmaceutical Co ltd
Current assignee: Shandong Jikun Biopharmaceutical Co ltd
Priority date: 2022-11-15
Filing date: 2022-11-15
Publication date: 2023-01-31

Abstract

The invention discloses an oral solution composition of ambroxol and a preparation process thereof. The composition comprises: the invention takes solution sorbitol or maltitol as a sweetening agent, shortens the dissolving time in the feeding process, further shortens the production time limit, reduces the exposure time of liquid medicine, effectively controls the risk of microbial contamination, reduces the use of preservatives and reduces the risk of organ injury of children; and sorbitol or maltitol is used as a sweetener, so that the use of the sweeteners such as sucrose, glucose and the like is reduced, and the occurrence probability of children dental caries is reduced. The product uses the pH regulator to regulate the pH, and the antioxidant is added, so that the problem of product instability is effectively solved, the use of the stabilizer propylene glycol is reduced, the medication possibility is provided for patients allergic to propylene glycol, and the clinical audience population is increased.

Description

Oral solution of ambroxol and preparation process thereof

Technical Field

The invention belongs to the field of pharmaceutical preparations, and particularly relates to an oral solution of ambroxol and a preparation process thereof.

Background

Expectoration is a common symptom of respiratory diseases, and the increase of sputum can stimulate respiratory mucosa to cause cough. When bronchioles are blocked, not only asthma but also secondary infection can be caused, further damaging the respiratory tract and exacerbating cough, expectoration and asthma. Severe patients can suppress death by breathing or asphyxia. Excessive secretion of mucus can cause mucus cilia clearance dysfunction and local defense function damage, so that infection is difficult to control and airway obstruction is aggravated, disease progress and subjective feeling of a patient are directly influenced, and whether the sticky sputum is expectorated from the airway or not is one of important factors influencing curative effect and prognosis of the patient. Therefore, the application of expectorant to promote the discharge of the endocrine in the airway as soon as possible is an important auxiliary measure for treating airway inflammation.

The ambroxol oral solution is a compound preparation consisting of ambroxol hydrochloride and clenbuterol hydrochloride. The ambroxol hydrochloride is a mucolytic agent, reduces mucus gland secretion, reduces sputum viscosity, promotes secretion of lung surfactant, increases bronchial ciliary movement, and makes sputum easy to expectorate. Clenbuterol hydrochloride is a selective beta receptor agonist and has the effects of relaxing bronchial smooth muscle, enhancing ciliary movement, dissolving mucus and promoting sputum excretion.

The prior art patent CN114601793A provides an oral solution of ambroxol, propylene glycol and a preservative are added in a prescription, the propylene glycol increases the allergy probability of allergic people, and the number of audiences is reduced; the product audience crowd is mostly children, the children are in the key period of growth and development, the excessive use of the preservative can influence the growth of the children, so that the product does not contain the preservative, and the medicine for increasing the number of the allergic reaction audience crowd is to be developed.

Disclosure of Invention

The invention provides an oral solution of ambroxol hydrochloride, which comprises two active ingredients of ambroxol hydrochloride and clenbuterol hydrochloride and a pharmaceutically acceptable auxiliary material carrier.

Wherein, the pharmaceutically acceptable auxiliary material carriers comprise cosolvent, thickening agent, sweetening agent, flavoring agent, pH regulator, antioxidant, solvent and the like.

Optionally, the oral solution comprises the following components: calculated by 100ml, contains 0.1-0.6g of ambroxol hydrochloride, 0.08-0.15mg of clenbuterol hydrochloride, 9-12g of cosolvent, 0.3-0.4g of thickening agent, 30-40g of sweetening agent, 0.11-0.20g of antioxidant, 0.3-0.5g of flavoring agent, 1-10mg of pH regulator and 55-70g of solvent.

Preferably, the following components are contained: based on 100ml, the compound preparation contains 0.15g of ambroxol hydrochloride, 0.1mg of clenbuterol hydrochloride, 10g of cosolvent, 0.35g of thickening agent, 30g of sweetening agent, 0.15g of antioxidant, 0.4g of flavoring agent, 5mg of pH regulator and 68g of solvent.

Wherein the sweetener is a solution type sweetener, preferably one of maltitol solution or sorbitol solution or a composition thereof.

Preferably, the co-solvent is glycerol.

Preferably, the antioxidant is one or a combination of sodium metabisulfite and ascorbic acid.

Optionally, the thickener is cellulose, collagen, polysaccharide, preferably one or a combination of hydroxyethylcellulose and hypromellose.

Optionally, the pH regulator is one or a combination of citric acid, malic acid or hydrochloric acid.

The invention also provides a preparation process of the ammonia bromine Terro oral solution, which comprises the following steps: uniformly mixing purified water, a thickening agent, a cosolvent, a sweetening agent and an antioxidant in a formula, and stirring for dissolving; adding active ingredients of ambroxol hydrochloride and clenbuterol hydrochloride, stirring for dissolving, and mixing uniformly; adding correctant, stirring, mixing, adjusting pH to 3.0-4.0 with pH regulator, and adding purified water.

The invention has the following beneficial effects:

the invention takes the solution sorbitol or maltitol as the sweetening agent, shortens the dissolving time in the feeding process, further shortens the production time limit, reduces the exposure time of the liquid medicine, effectively controls the microbial contamination risk, reduces the use of the preservative, and reduces the organ injury risk of children; and sorbitol or maltitol is used as a sweetener, so that the use of the sweeteners such as sucrose, glucose and the like is reduced, and the occurrence probability of children dental caries is reduced. The product is adjusted to 3.0-4.0 by using the pH regulator, and the antioxidant is added, so that the problem of product instability is effectively solved, the use of the stabilizer propylene glycol is reduced, the medication possibility is provided for patients allergic to propylene glycol, and the clinical audience population is increased.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention clearer and more complete, the technical solutions in the embodiments of the present invention will be described below, and the following embodiments are only used to illustrate the technical solutions of the present invention, but not to limit the technical solutions obviously, and the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

Uniformly mixing purified water, a thickening agent, a cosolvent, a sweetening agent and an antioxidant, and stirring for dissolving; adding active ingredients of ambroxol hydrochloride and clenbuterol hydrochloride, stirring for dissolving, and mixing uniformly; adding a flavoring agent, uniformly stirring, adjusting the pH by using a pH regulator, and adding the balance of purified water to a fixed volume of 100mL to obtain the oral liquid of ambroxol.

Comparative example 1

68g of purified water, 0.35g of thickening agent, 10g of cosolvent, 30g of sweetener and 0.15g of antioxidant are uniformly mixed and stirred to be dissolved; adding 0.15g of ambroxol hydrochloride and 0.1mg of clenbuterol hydrochloride as active ingredients, stirring for dissolving, and mixing uniformly; adding 0.4g of flavoring agent, stirring and mixing uniformly, adjusting the pH value by using citric acid as a pH adjusting agent, and adding 100mL of the rest purified water to obtain the oral liquid of the ambroxol.

Wherein the compositions of formulas 4-6 are shown in the following table:

comparative example 2

68g of purified water, 0.35g of thickening agent, 10g of cosolvent, 30g of sweetener and 0.15g of antioxidant are uniformly mixed and stirred to be dissolved; adding 0.15g of ambroxol hydrochloride and 0.1mg of clenbuterol hydrochloride as active ingredients, stirring for dissolving, and mixing uniformly; adding 0.4g of flavoring agent, stirring and mixing uniformly, adjusting the pH value by using a pH regulator citric acid, and adding 100mL of the rest purified water to obtain the oral liquid of the ambroxol.

Wherein, the compositions and the processes of the prescriptions 7 to 11 are shown in the following table:

Claims

1. an oral ambroxol solution is characterized by comprising two active ingredients of ambroxol hydrochloride and clenbuterol hydrochloride and a pharmaceutically acceptable auxiliary material carrier.

2. The oral solution of amoeboro according to claim 1, wherein the pharmaceutically acceptable vehicle of excipients comprises a cosolvent, a thickener, a sweetener, a flavoring agent, a pH modifier, an antioxidant, and a solvent.

3. Oral solution of ambroxol according to claim 2, characterized by comprising the following components: calculated by 100mL, the ambroxol hydrochloride-containing aqueous solution contains 0.1-0.6g of ambroxol hydrochloride, 0.08-0.15mg of clenbuterol hydrochloride, 9-12g of cosolvent, 0.3-0.4g of thickening agent, 30-40g of sweetening agent, 0.11-0.20g of antioxidant, 0.3-0.5g of flavoring agent, 1-10mg of pH regulator and 55-70g of solvent.

4. Oral solution of amoeboro according to claim 3, characterized by comprising the following components: calculated by 100ml, the ambroxol hydrochloride oral liquid comprises 0.15g of ambroxol hydrochloride, 0.1mg of clenbuterol hydrochloride, 10g of cosolvent, 0.35g of thickening agent, 30g of sweetening agent, 0.15g of antioxidant, 0.4g of flavoring agent, 5mg of pH regulator and 68g of solvent.

5. Oral solution of ambroxol according to claim 2, characterized in that said sweetener is a solution sweetener.

6. Oral solution of amoeboro according to claim 5, characterized in that the sweetener is one or both of a maltitol solution or a sorbitol solution.

7. The oral solution of amortisone as claimed in claim 2, wherein the thickener is one or two of hydroxyethylcellulose and hypromellose, the cosolvent is glycerol, the antioxidant is one or two of sodium metabisulfite and ascorbic acid, the pH regulator is one or more of citric acid, malic acid and hydrochloric acid, and the correctant is essence.

8. Process for the preparation of an oral solution of ambroxol according to any one of claims 1 to 7, characterized in that it comprises the following steps:

(1) Uniformly mixing purified water, a thickening agent, a cosolvent, a sweetening agent and an antioxidant in the formula, and stirring for dissolving;

(2) Adding the active ingredients of ambroxol hydrochloride and clenbuterol hydrochloride into the mixture obtained in the step (1), stirring and dissolving, and mixing uniformly;

(3) Adding correctant, stirring, regulating pH with pH regulator, and adding purified water.

9. The process of claim 8, wherein the pH adjusting agent is one of citric acid and malic acid.

10. The process according to claim 8, wherein the pH is adjusted to 3.0-4.0.