The Future Cough Remedy

The future cough remedy

Acebrophylline is an airway mucoregulator and anti-inflammatory agent.  The molecule contains Ambroxol, which facilitates various steps in the biosynthesis of pulmonary surfactant, theophylline-7 acetic acid whose carrier function raises blood levels of Ambroxol, thus rapidly and intensely stimulating surfactant production. 

Acebrophylline: Mechanism of action

Solid-state chemistry of Ambroxol theophylline-7-acetate Anastasia Foppoli 1 , Lucia Zema 1 , et.all Abstract: Ambroxol theophylline-7-acetate (ACE) is the salt obtained by reaction of equimolar amounts of ambroxol (AMB), a drug showing mucolytic and expectorant properties, and theophylline-7-acetic acid (TAA), a xanthine derivative with specific bronchodilator activity. ACE is used for the treatment of bronchial and pulmonary diseases (bronchitis, asthma, emphysema, chronic obstructive disease). Recrystallization experiments of ACE resulted in the isolation of two polymorphs (monotropically related) and four solvated forms. X-ray diffractometry, DSC, TGA, and HSM techniques were used to investigate the forms that are obtained by thermal desolvation of the solvates. The phase diagram of the TAA-AMB binary system was constructed by performing thermal analyses on mixtures of TAA-AMB and of each component plus the interaction compound (TAA-ACE and ACE-AMB). The SchroederVan Laar equation proved to be a very useful tool for checking the consistency between the experimental data and the theoretical model related to the general system, showing complete miscibility in the liquid phase and complete immiscibility in the solid phase. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1139-1146, 2007

AUC… 792 ng/ml Cmax of 125ng/ml Tmax was - 4.0 (- 22.9 ~ 14.9). This satisfies the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines.

Clinical Trials on Acebrophylline

J Int Med Res. 1996 May-Jun;24(3):302-10.

Effects of a short course of treatment with Acebrophylline on the mucus rheological characteristics and respiratory function parameters in patients suffering from chronic obstructive pulmonary disease. Agliati G. Vaprio d'Adda Hospital, Medical Department, Milan, Italy.

Method: A total of 30 patients (27 males and 3 females) with a mean age of 62.6 +/- 3.9 years, suffering from chronic obstructive pulmonary disease were recruited into this open study to evaluate the clinical efficacy and the safety of a short course of treatment with 100 mg Acebrophylline, twice daily for 14 days. To assess the effectiveness of the drug, symptoms and signs, such as cough intensity and frequency, auscultatory pattern, dyspnoea, cyanosis, difficulty of expectoration, sputum quantity, appearance and density, were evaluated at baseline and after 1, 3, 5, 7, 10 and 14 days of therapy. In addition the rheological properties of the bronchial mucus (viscosity and spinnability) were measured and respiratory function tests were performed before and after treatment.

Result: There was a progressive improvement of all evaluated symptoms and signs, resulting in improvement of the auscultatory pattern, as well as dyspnoea. This was accompanied by improvement or normalization of the respiratory function indices, which showed statistically significant differences (P < 0.01) between the baseline and the endpoint values, apart from total lung capacity. Blood-gas analysis demonstrated a significant increase of PaO2 and a significant decrease of PaCO2 values at the end of the treatment period (both P < 0.01).

Conclusion: In general, acebrophylline was well tolerated. No clinically relevant or significant changes in any of the routine laboratory parameters were found on comparing the values obtained before and after treatment. Only three patients complained of epigastric pain, but this was not so severe or longlasting as to require the discontinuation of the treatment.

Clin Ther. 1985;7(6):733-6.

Therapeutic activity of ambroxol theophyllinacetate in chronic obstructive pulmonary diseases. Primbs K.

Method: In an open study, 50 patients suffering from chronic obstructive pulmonary disease in an acute infectious phase were treated with ambroxol theophyllinacetate. The drug was given orally in a dosage of 100 mg BID for ten days. Result: Viscosimetric data showed a significant decrease of viscosity of the mucus, leading to easier expectoration and reduction in the severity and frequency of cough. Conclusion: These improvements had positive effects on respiratory function and on the condition of the patients.

Arzneimittelforschung. 1988 Jun;38(6):828-30. Modification of mucociliary clearance by a combination of theophylline with ambroxol and of ambroxol in monotherapy Dorow P, Weiss T. Abteilung für Kardiologie und Pneumologie, Freien Universität Berlin.

Influence on Mucociliary Clearance by a TheophyllineAmbroxol Combination and by Ambroxol in Monotherapy. Method: In a controlled randomised double-blind study the influence of theophylline + ambroxol (TA) and ambroxol (A) on lung function and mucociliary clearance was investigated. 19 patients with chronic obstructive lung disease were treated after a 5-day wash-out period for 5 days with TA (700 mg theophylline, 60 mg ambroxol/d) or A (60 mg ambroxol/d), respectively. Measurements were done on the 5th and 10th day.

Result Under the treatment with TA a marked improvement of lung function was observed.

Conclusion: The mucociliary clearance improved under treatment with TA and A, with TA being significantly better compared with treatment group A.

A Review of Acebrophylline …an airway mucoregulator and anti-inflammatory agent. Monaldi archives for chest disease 2007, vol. 67, no2, pp. 106-115 [10 page(s) (article)]

Pozzi E. Acebrophylline is an airway mucus regulator with anti-inflammatory action. The drug's approach involves several points of attack in obstructive airway disease. The molecule contains Ambroxol, which facilitates various steps in the biosynthesis of pulmonary surfactant, theophylline-7 acetic acid whose carrier function raises blood levels of Ambroxol, thus rapidly and intensely stimulating surfactant production. The resulting reduction in the viscosity and adhesivity of the mucus greatly improves ciliary clearance. By deviating phosphatidylcholine towards surfactant synthesis, making it no longer available for the synthesis of inflammatory mediators such as the leukotrienes, Acebrophylline also exerts an inflammatory effect. This is confirmed in vivo by the reduction in a specific bronchial hyper-responsiveness in patients with stable bronchial asthma. On a clinical level, Acebrophylline is therapeutically effective in patients with acute or chronic bronchitis, chronic obstructive or asthma-like bronchitis and recurrence of chronic bronchitis; it reduces the frequency of episodes of bronchial obstruction and reduces the need for beta2-agonists, and improves indexes of ventilatory function.

It is estimated that the Asthma and COPD market in INDIA is around 370-380 Crs growing at around 510%. In this market the share of Ambroxol is around 8-10%. This becomes a lucrative market to launch Acebrophylline.

Brand: SURFOLASE Switzerland.

Company

Indication: Expectorant. Bronchodilatator and mucolytic agent. Presentation: 50 - 100 mg capsules, 25 - 100 mg sachets, 120 200 ml syrup Brand: BUROPHIL Country Korea Indication: Expectorant. Bronchodilatator and mucolytic agent. Presentation: 50 - 100 mg capsules, 25 - 100 mg sachets, 120 200 ml syrup

In India approved by DCGI Product : Acebrophylline capsules 100mg Indication: For the treatment of adult patients with chronic obstructive pulmonary disease and bronchial asthma Approved on 29.05.08

Proposed Formulation in Syrup Form: Syrup Each 5ml of syrup would contain Acebrophylline 50mg. Guaiphenesin 250mg. Menthol 0.5mg

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