Preservative-free composition for topical use including hyaluronic acid

Abstract

The present invention relates to a sterile and/or decontaminated composition for topical use, including hyaluronic acid at a concentration of greater than or equal to 0.1 wt % relative to the total weight of the composition, at least one skin wound healing agent, optionally at least one plant extract, and at least one solvent. The invention also relates to a unit including such a composition, to a method for preparing such a composition, and to the uses thereof.

Claims

1. A preservatives free composition, said composition is decontaminated and/or sterile, for topical use, wherein said composition comprises: a combination of low molecular weight hyaluronic acid, having a molecular weight below 800 kDa, and high molecular weight hyaluronic acid having a molecular weight equal to or higher than 800 kDa, at a concentration greater than or equal to 0.1% by weight in relation to the total weight of the composition, wherein said high molecular weight hyaluronic acid has a molecular weight greater than the molecular weight of said low molecular weight hyaluronic acid, and the weight ratio of said high molecular weight hyaluronic acid to said low molecular weight hyaluronic acid ranges from 0.2 to 2, at least one skin cicatrization agent, and at least one solvent.

2. The composition of claim 1, wherein high molecular weight hyaluronic acid has a molecular weight of 800 to 1200 kDa and wherein low molecular weight hyaluronic acid has a molecular weight of 10 to 600 kDa.

3. The composition of claim 1 wherein said skin cicatrization agent is selected from the group consisting of allantoin, vitamin A and sucralfate.

4. A method for cleaning the palpebral edge in a patient in need thereof comprising applying the composition of claim 1 on the eyelid.

5. A method for preventing and/or treating eye dryness in a patient in need thereof comprising applying the composition of claim 1 on the eyelid.

Description

EXAMPLES

Example 1

(1) A composition 1 and a composition 2 including 200 mg of hyaluronic acid of about 800 kDa and about 500 kDa, respectively, in 100 ml of water undergo the heat treatments described in Table 1.

(2) The hyaluronic acids used for these compositions can be for example provided by FIDIA Farmaceutici S.p.A. with the product references HYALOFTIL, HA 1,000,000 Da or HA 500,000 Da, or HTL Biotechnology, manufactured according to the desired molecular weight.

(3) TABLE-US-00001 TABLE 1 Sample Treatment Molecular weight (Da) Composition 1 None 871,400 Composition 1 75 C., 15 min 844,900 Composition 1 75 C., 19 min 856,800 Composition 1 80 C., 10 min 851,200 Composition 2 None 565,000 Composition 2 75 C., 15 min 553,000 Composition 2 80 C., 10 min 574,000

(4) It emerges from these tests that the molecular weight of the hyaluronic acid present in these compositions is decreased by less than 20%.

Example 2

(5) Three compositions were prepared: composition A containing a 0.2% concentration of hyaluronic acid of 2 different molecular weights, one between 700 and 750 kDa, the other between 750 and 800 kDa, in a 1:1 proportion in 100 ml of water, composition B containing a 0.5% concentration of hyaluronic acid of molecular weight between 700 and 750 kDa in 100 ml of water, and composition C containing a 0.5% concentration of hyaluronic acid of another molecular weight from 750 to 800 kDa in 100 ml of water.

(6) The 3 compositions underwent 3 different temperature treatments: a treatment at 70 C. for 1 hour followed by cooling once per day for 3 days, a treatment at 100 C. for 1 hour followed by cooling, and a treatment at 121 C. for 20 minutes followed by cooling.

(7) TABLE-US-00002 TABLE 2 Sample Treatment Molecular weight (Da) Composition A None 758,000 Composition A 70 C., 1 h, 3x/24 h 741,000 Composition A 100 C., 1 h, 1x 615,000 Composition A 121 C., 20 min, 1x 204,000 Composition B None 731,000 Composition B 70 C., 1 h, 3x/24 h 696,000 Composition B 100 C., 1 h, 1x 398,000 Composition B 121 C., 20 min, 1x 291,000 Composition C None 750,000 Composition C 70 C., 1 h, 3x/24 h 761,000 Composition C 100 C., 1 h, 1x 692,000 Composition C 121 C., 20 min, 1x 400,000

(8) The treatments at 100 C. for 1 hour and 121 C. for 20 minutes lead to significant degradation of the molecular weight of the hyaluronic acid, whereas the treatment at 70 C. for 1 hour followed by cooling to room temperature carried out 3 times at 24-hour intervals did not lead to significant modification of the molecular weight of the hyaluronic acid. Furthermore, in all the samples having undergone heat treatment, the level of microbiological cleanliness was evaluated to be in conformity (<1 CFU/g) and moreover sterile in the context of the European Pharmacopoeia.