Composition for use in the prevention and/or treatment of epistaxis

Abstract

A synergistic composition of naturally occurring active ingredients is described, which has proved particularly effective in the treatment and/or prevention of epistaxis, particularly in acute or chronic episodes of infectious and inflammatory epistaxis. The composition includes the synergistic combination of hyaluronic acid or a salt thereof, silver, vitamin B5 or pro-vitamin B5, and optionally vitamin E or an ester thereof.

Claims

1. A method of treating epistaxis in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of a composition comprising hyaluronic acid or a salt thereof, silver, vitamin B5 or pro-vitamin B5, and vitamin E or an ester thereof, wherein treating epistaxis includes hemostasis.

2. The method according to claim 1, wherein the silver is in the form of colloidal silver, silver proteinate, elementary silver, micronized silver, silver salts, or silver complexed with other ingredients.

3. The method according to claim 1, wherein the composition is a pharmaceutical dosage form for topical application.

4. The method according to claim 3, wherein the pharmaceutical dosage form comprises from 0.05 to 5,500 mg of hyaluronic acid or a salt thereof, from 0.0001 to 6,000 mg of silver, including one of ionic or salified or complexed silver, from 0.1 to 7,000 mg of vitamin B5 or pro-vitamin B5, and optionally from 0.01 to 10,000 mg of vitamin E or an ester thereof.

5. The method according to claim 3, wherein the pharmaceutical dosage form comprises from 0.01 to 50 wt % of hyaluronic acid or a salt thereof, from 0.0001 to 20 wt % of silver including one of ionic or salified or complexed silver, from 0.1 to 50 wt % of vitamin B5 or pro-vitamin B5, and optionally from 0.01% to 50 wt % of vitamin E or an ester thereof.

6. The method according to claim 3, wherein the pharmaceutical dosage form for topical application is selected from the group consisting of nasal drops, nasal cream, nasal ointment, nasal spray, nasal gel, and nasal gauze.

7. The method according to claim 1, wherein the epistaxis is infectious or inflammatory in nature.

8. The method according to claim 1, wherein the composition is administered topically.

Description

EXAMPLES

(1) TABLE-US-00001 EXAMPLE 1 Active Amount based on the total ingredient weight of the composition Hyaluronic acid  0.15% Silver 0.005% Dexpanthenol    1% Vitamin E    2% Pharmaceutical form: nasal drops

(2) TABLE-US-00002 EXAMPLE 2 Active Amount based on the total ingredient weight of the composition Hyaluronic acid   0.2% Silver 0.0006% Dexpanthenol    5% Vitamin E    2% Pharmaceutical form: nasal cream

(3) TABLE-US-00003 EXAMPLE 3 Active Amount based on the total ingredient weight of the composition Hyaluronic acid 0.2% Silver 1.5% Dexpanthenol 2.5% Vitamin E 1.5% Pharmaceutical form: nasal spray

(4) TABLE-US-00004 EXAMPLE 4 Active Amount based on the total ingredient weight of the composition Hyaluronic acid 0.3% Silver   2% Dexpanthenol   5% Vitamin E 2.5% Pharmaceutical form: nasal gel

(5) TABLE-US-00005 EXAMPLE 5 Active Amount based on the total ingredient weight of the composition Hyaluronic acid 0.5% Silver   2% Dexpanthenol   5% Vitamin E   2% Pharmaceutical form: nasal gauze
Efficacy Testing

(6) The efficacy of the composition object of the present invention has been assessed according to experimental protocols known to those skilled in the art. In particular, in vitro and/or in vivo assays known in the scientific literature can be used for assessing the different actions of the composition according to the present invention.

(7) In vitro assays, such as, for example, the measurement of the TEWL (Trans-Epidermal Water Loss), are suitable to demonstrate the moisturizing effect of the composition according to the present invention. TEWL is an indicator of the efficiency of the skin barrier function and its measurement provides an indication of the resistance offered by the stratum corneum to the passage of water from the inside to the outside, and vice versa.

(8) In vitro assays, such as, for example, the DPPH test, the radical scavenging activity on nitric oxide or on the peroxy-nitrile radical, the TEAC (total radical-trapping antioxidant parameter), FRAP (ferric reducing-antioxidant power), HORAC (hydroxyl radical averting capacity), ORAC (oxygen radical absorbance capacity) tests, and the like, are suitable to demonstrate the antioxidant efficacy of the composition according to the present invention.

(9) In vitro assays, such as, for example, broth dilution (the sensitivity of the microorganism is estimated based on whether it grows or not in a culture medium at different concentrations of the sample) and agar diffusion (where a standardized concentration of the sample is applied in a broth culture of bacteria and the diffusivity of the sample within the medium is calculated), are suitable to demonstrate the antibacterial efficacy of the composition according to the present invention.

(10) In vitro assays which assess the ability to inhibit the release of inflammatory cytokines such as IL-1, IL-6 and TNF-α and to inhibit the expression of enzymes such as COX-2 and IL-1β-induced metalloprotease-13 in primary human cell cultures (e.g. macrophages, chondrocytes, and fibroblasts), are suitable to demonstrate the anti-inflammatory efficacy of the composition according to the present invention.

(11) According to an in vivo model, the composition is tested for its haemostatic effect on different types of animals. The animals are sedated by administering appropriate agents (such as, for example, ketamine, lidocaine) by injection. Then, the wounds are reproduced on the front, right and left sides of the nasal septum by applying a light pressure with surgical forceps, thus causing bleeding. The wounds are then treated on one side with the individual components of the composition or with a combination thereof (the object of the present invention), and on the other side of the nasal septum with saline until bleeding stops. The estimated parameter will therefore be the duration of the bleeding, which is significantly shorter in the case of treatment with the composition object of the present invention, compared to the application of the individual components and to saline.