COMPOSITION FOR THE PREVENTION AND/OR TREATMENT OF RESPIRATORY TRACT DISORDERS

Abstract

The present invention relates to a composition comprising or, alternatively, consisting of an effective amount of a mixture which comprises at least, or consists of: a) an extract of Pelargonium sidoides; b) an extract of Adhatoda vasica; and c) N-acetyl cysteine for use in a method for the preventive or therapeutic treatment of at least one respiratory tract disorder in a subject, wherein said treatment method comprises the administration of said composition to the subject.

Claims

1. A composition comprising an effective amount of a mixture which comprises or, alternatively, consists of: a) an extract of Pelargonium sidoides; b) an extract of Adhatoda vasica; and c) N-acetyl cysteine for use in a method for the preventive or therapeutic treatment of at least one respiratory tract disorder in a subject, wherein said treatment method comprises the administration of said composition to the subject.

2. The composition for use according to the claim 1, wherein said composition is administered to said subject via the oral, nasal or inhalation route.

3. The composition for use according to the claim 1, wherein the composition is in the form of a liquid composition for oral use or a powder that is soluble or dispersible in a liquid.

4. The composition for use according to claim 1, wherein said mixture comprises an amount of extract of Pelargonium sidoides a) ranging from 1 mg to 100 mg, more preferably 10 mg to 60 mg; an amount of extract of Adhatoda vasica b) ranging from 50 mg to 1000 mg, preferably 100 mg to 500 mg; and/or an amount of N-acetyl cysteine ranging from 50 mg to 2000 mg, preferably 200 mg to 1200 mg, each amount independent of the other.

5. The composition for use according to claim 1, wherein said mixture comprises an extract of Pelargonium sidoides a) and an extract of Adhatoda vasica b) in a weight ratio of 1:2 to 1:50, preferably 1:5 to 1:30 or 1:9 to 1:20.

6. The composition for use according to claim 1, wherein said mixture comprises an amount of N-acetyl cysteine in a weight ratio with the total weight of the extract of Pelargonium sidoides a) and extract of Adhatoda vasica b) ranging from 50:1 to 1:10, preferably 30:1 to 1:3 or 10:1 to 6:1.

7. The composition for use according to claim 1, wherein said at least one respiratory tract disorder is at least one among rhinitis, sinusitis, pharyngitis, epiglottitis, laryngitis, bronchitis, bronchiolitis, cystic fibrosis, chronic obstructive pulmonary disease and bronchiectasis.

8. A pharmaceutical composition, dietary supplement or composition for a medical device comprising an effective amount of a mixture which comprises or, alternatively, consists of: a) an extract of Pelargonium sidoides; b) an extract of Adhatoda vasica; and c) N-acetyl cysteine and at least one inert ingredient or excipient adapted for pharmaceutical, dietary or nutraceutical use.

Description

EXAMPLE 1

[0116]

TABLE-US-00001 Active ingredient Daily dose N-Acetylcysteine 600 mg Adhatoda vasica, d.e. 300 mg Pelargonium sidoides 30 mg d.e.: dry extract Pharmaceutical form: Sachets.

EXAMPLE 2

[0117]

TABLE-US-00002 Active ingredient Daily dose N-Acetylcysteine 1,200 mg Adhatoda vasica, d.e. 600 mg Pelargonium sidoides 60 mg Pharmaceutical form: Sachets.

EXAMPLE 3

[0118]

TABLE-US-00003 Active ingredient Daily dose N-Acetylcysteine 600 mg Adhatoda vasica, d.e. 300 mg Pelargonium sidoides 30 mg Pharmaceutical form: Bottle of oral liquid.

EXAMPLE 4

[0119]

TABLE-US-00004 Active ingredient Daily dose N-Acetylcysteine 200 mg Adhatoda vasica, d.e. 100 mg Pelargonium sidoides 20 mg Pharmaceutical form: Bottle of oral liquid.

EXAMPLE 5

[0120]

TABLE-US-00005 Active ingredient Daily dose N-Acetylcysteine 600 mg Adhatoda vasica, d.e. 100 mg Pelargonium sidoides 20 mg Pharmaceutical form: Sachets.

EXAMPLE 6

[0121]

TABLE-US-00006 Active ingredient Daily dose Adhatoda vasica, d.e. 300 mg N-Acetylcysteine 100 mg Pelargonium sidoides 10 mg Pharmaceutical form: Bottle of oral liquid.

[0122] The following experimental part provides examples of practical embodiments of the invention, without limiting the scope thereof.

EXPERIMENTAL PART

1) Material

[0123] The pharmaceutical forms illustrated below are prepared according to standard techniques known to the person skilled in the art for the preparation of solid and liquid compositions for pharmaceutical, nutraceutical and/or dietary use in humans.

EXAMPLE 1

[0124]

TABLE-US-00007 Active ingredient Daily dose N-Acetylcysteine 600 mg Adhatoda vasica, d.e. 300 mg Pelargonium sidoides 30 mg Pharmaceutical form: Sachets.

EXAMPLE 2

[0125]

TABLE-US-00008 Active ingredient Daily dose N-Acetylcysteine 1,200 mg Adhatoda vasica, d.e. 600 mg Pelargonium sidoides 60 mg Pharmaceutical form: Sachets.

EXAMPLE 3

[0126]

TABLE-US-00009 Active ingredient Daily dose N-Acetylcysteine 600 mg Adhatoda vasica, d.e. 300 mg Pelargonium sidoides 30 mg Pharmaceutical form: Bottle of oral liquid.

EXAMPLE 4

[0127]

TABLE-US-00010 Active ingredient Daily dose N-Acetylcysteine 200 mg Adhatoda vasica, d.e. 100 mg Pelargonium sidoides 20 mg Pharmaceutical form: Bottle of oral liquid.

EXAMPLE 5

[0128]

TABLE-US-00011 Active ingredient Daily dose N-Acetylcysteine 600 mg Adhatoda vasica, d.e. 100 mg Pelargonium sidoides 20 mg Pharmaceutical form: Sachets.

EXAMPLE 6

[0129]

TABLE-US-00012 Active ingredient Daily dose Adhatoda vasica, d.e. 300 mg N-Acetylcysteine 100 mg Pelargonium sidoides 10 mg Pharmaceutical form: Bottle of oral liquid.

2) Methods

[0130] The effectiveness of the composition of the present invention in a method for the treatment of at least one respiratory tract disorder and/or the synergistic action of components a), b) and c) of the composition itself was assessed using in vitro and in vivo methods known to the person skilled in the art, as described below.

[0131] The anti-inflammatory activity of the individual components compared to the combination thereof (composition of the present invention) and compared to the control was assessed in vitro. Specifically, mouse monocyte/macrophage J774 cell lines were selected and grown in DMEM (Dulbecco's Modification of Eagle Medium) with the addition of glutamine, Hepes, penicillin, foetal bovine serum and sodium pyruvate. The cells were plated and kept in an incubator at a controlled temperature and atmosphere. Cell viability was assessed by means of the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and the growth thereof was subsequently stimulated. At this point, specific methods were used to measure the concentration of nitrites, levels of TNF- and IL-1 as parameters for assessing anti-inflammatory activity.

[0132] The antimicrobial activity of the composition of the present invention was assessed in vitro. Suitable assays include broth dilution (with the calculation of the MIC, or minimum inhibitory concentration, and MBC, or minimum bactericidal concentration) and diffusion in agar (where a standardised concentration of the sample is applied in a broth culture of bacteria and the diffusion of the sample within the medium is calculated). The antimicrobial activity was assessed in the main bacterial strains belonging to the Gram-positive and/or Gram-negative categories and/or other microbial species.

[0133] The antioxidant activity of the composition of the present invention, of particular interest for alleviating respiratory tract disorders, was assessed in vitro. Suitable in vitro assays include, for example: DPPH assay (nitrogen radical 2,2-diphenyl-1-picrylhydrazyl), radical scavenging activity on nitric oxide or on the peroxynitrile radical, TEAC assay (total radical-trapping antioxidant parameter), FRAP (ferric reducing-antioxidant power), HORAC (hydroxyl radical averting capacity), ORAC (oxygen radical absorbance capacity) and the like.

[0134] The expectorant activity of the composition of the present invention was assessed in vivo in CD1 mice. Specifically, the animals were treated with different formulations (e.g. individual active components, active components in association, vehicle, control) administered orally. Several minutes after treatment, the animals received an intraperitoneal injection of phenol red; the mice were subsequently anaesthetised, the upper front part of the neck was shaved and the trachea was exposed. The mice then underwent a tracheobronchial lavage with saline solution and the lavage fluid was subsequently recovered and centrifuged. As a parameter for evaluating the expectorant activity, the post-lavage concentration of red phenol was measured by spectrophotometry.

[0135] The anti-tussive effect of the composition of the present invention was tested in an in vivo model of guinea pigs with coughing provoked by inhalation of capsaicin. The anaesthetised animals were exposed to a nebulised aqueous solution of capsaicin and during exposure they were observed constantly in order to assess the number of coughing episodes. The majority of coughing episodes occurred within 10 minutes, which was the time then established as the duration of exposure. This model proposes pre-treating the guinea pigs with the active components of the present invention (a), b) and c)) orally administered, individually or in a mixture (composition according to the invention), 30 minutes before inhalation with capsaicin, to demonstrate how the number of coughing episodes is considerably reduced by the synergistic action of the components compared to the same ones tested individually.