ELECTROSPUN FIBERS CONTAINING NANODISPERSIONS AND THEIR USE FOR THE TREATMENT OF WOUNDS

Abstract

The present invention relates to compositions based on nanodispersions which are preferably further processed to electrospun fibers comprising such nanodispersions. The nanodispersions may optionally contain birch bark extract. The electrospun fibers can be used in particular for the treatment of wounds. For this purpose the compositions containing electrospun fibers are preferably applied as such or in a spray or a foam.

Claims

1. A composition containing a Nanodispersion which is stabilized with at least one phospholipid.

2. The composition according to claim 1, wherein characterized in that the nanodispersion further contains a birch bark extract.

3. The composition according to claim 1, wherein the nanodispersion is contained within an electrospun fiber integrated with a pharmaceutically acceptably polymer carrier.

4. The composition according claim 1, wherein the phospholipid is selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatic acid and phosphatidylserine or combinations thereof.

5. The composition according to claim 1, wherein the Nanodispersion is prepared by high shear or ultrasonic emulsification, or high pressure homogenization or microfluidization.

6. The composition according to claim 1, wherein at least 95% of the particles of the Nanodispersion have a particle size below 1 μm.

7. The composition according to claim 2, wherein the birch bark extract in the Nanodispersion comprises the following components calculated in percentage by weight: betulin 74-85 wt. %, lupeol 1.0-4.0 wt. %, betulinic acid 3.0-5.0 wt. %, erythrodiol 0.3-2.8 wt. % and other components, in particular derived from the birch bark like oleanolic acid, betulinic acid, methyl ester of betulinic acid 2-13 wt. %, whereby all components add up to 100 wt %.

8. The composition according to claim 1, wherein the nanodispersion contains 0.1 to less than 5.0% by weight of birch bark extract.

9. The composition according to claim 1, wherein the nanodispersion is prepared by mixing the phospholipid as emulsifying agent and water optionally with the birch bark extract with a pharmaceutically acceptable oil, and second to perform a high shear or ultrasonic emulsification or a high pressure homogenization of the mixture in order to obtain a nanodispersion whereby at least 95% of the particle droplets have a diameter of less than 1 μm.

10. The composition according to claim 1, wherein it is contained within an electrospun fiber integrated with a pharmaceutically acceptably polymer carrier.

11. The composition according to claim 10 wherein the polymer is selected from the group comprising polyvinyl alcohol, poly(glycolide), polylactide-polyglycolide-copolymer, polyurethane, polyvinyl alcohol/cellulose acetate, silk fibroin, silk/chitosan, gelatin, collagen/chitosan.

12. The composition containing an electrospun fiber according to claim 10, wherein the electrospun nanofiber contains 1.0-60 wt. % of the nanodispersion calculated on the basis of the total weight of the electrospun nanofiber.

13. The process for making a nanodispersion contained within an electrospun fiber whereby said process comprises: a) preparing a nanodisperson of a phospholipid, an oil and water, optionally the birch bark extract, and b) blending the nanodispersions obtained in step a) with a PVA polymer solution and c) electrospin the mixture to form a fleece.

14. The composition according to claim 1 for the use in the treatment of wounds.

15. The composition according to claim 1 in the form of a spray or a foam for the use in the treatment of wounds.

Description

EXAMPLES

[0046] In the following examples, different nanodispersions having variable amounts of birch bark extract were used. The nanodispersions were mixed with a PVA solution and the mixture was electrospun. The different mixtures of Examples 1-4 are shown below.

TABLE-US-00001 Example 1 Example 2 Nanodispersion Phospholipon 90 H 2.5% Phospholipon 90 H 2.5% sunflower oil 1.0% sunflower oil 1.0% birch bark extract 0.5% Water 96.5% Water 96.0% PVA Solution PVA 10% PVA 10% Water 90% Water 90% Electrospun mixture Nanodispersion 40% Nanodispersion 40% PVA Solution 60% PVA Solution 60% Example 3 Example 4 Nanodispersion Phospholipon 90 H 8.0% Phospholipon 90 H 8.0% sunflower oil 10.0% sunflower oil 10.0% birch bark extract 5.0% Water 82.0% Water 77.0% PVA Solution PVA 10% PVA 10% Water 90% Water 90% Electrospun mixture Nanodispersion 30% Nanodispersion 30% PVA Solution 70% PVA Solution 70%

[0047] The properties of the mat obtained with the mixture of Example 1 are shown in Table 1:

TABLE-US-00002 Sample type Content Emulsion composition (wt %) 2.5% Phospholipon 90 H:1% sunflower oil:0.5% birch bark extract and 96% water Pre-emulsion droplet size 3360/0.89 (nm)/polydispersity index Nanodispersions droplet size 399.91/0.52  (nm)/polydispersity index 10% PVA/nanodispersions 60%/40% blend proportion (wt %) 10% PVA/nanodispersions 306-420 (60%/40%) fleece fiber diameter range (nm) 10% PVA fleece porosity 87.34 with nanodispersions (%) Pure 10% PVA fleece fiber 482-863 diameter range (nm) 10% PVA fleece porosity 80.40 without nanodispersions (%) Applied voltage (kV): 15

[0048] An electron microscope picture of a 10% PVA nanofiber containing phospholipid birch bark extract nanodispersions (60%/40%) is shown in FIG. 1.

Example 5

[0049] In order to show the superior activity of the embodiments of the present invention a porcine ex vivo wound healing assay has been performed. Briefly, pig ears obtained from a slaughter house (for human consumption) were directly delivered after slaughtering to the laboratory, cleaned and disinfected. Thereafter, 6 mm punch biopsies were taken from the plicae of the ears and fat and subcutis were removed. Consequently, wounds were generated by the removal of the epidermis and upper dermis in a central area of 7.1 mm.sup.2. Then, the so formed ex-vivo wound healing model was placed dermis-down on gauze in culture dishes and incubated air-liquid interface with Dulbecco's modified Eagle's medium supplemented with hydrocortisone, 2% fetal calf serum, penicillin and streptomycin. 4 cm.sup.2 of the electrospun mat/5 μl of the oleogel were immediately applied after wounding and the models incubated for 48 h at 37° C. and 5% CO.sub.2. Further steps involved shock freezing, cryostat sections of the central parts of the wound healing models were identified using a ruler in the microscope and by checking the total length of the wound during evaluation were stained with hematoxylin and eosin. Wound healing process (reepithelialization) was assessed by measuring the distance between the wound margin and the tip of the regenerated epidermis with a microscope.

[0050] In the Example as control the wound has not been treated at all. As comparison with the prior art an oleogel was used. A slight improvement could be observed. Furthermore, a polyvinyl alcohol mat without birch bark extract (PVA mat) was used. It can be seen that the healing properties are better than in the control and even better than with oleogel.

[0051] When the polyvinyl alcohol mat contained birch bark extract, a significant improvement in the healing activity could be observed. This can be seen with 5% birch bark extract (TE) and more effectively with 0.5% birch bark extract (TE).

Example 6

[0052] a) In further experiments (results not shown in FIG. 2) the preparations according to Example 5 are compared with preparations being essentially free of birch bark extract. Surprisingly, the results achieved with preparations without birch bark extract are comparable to those with birch bark extract.

[0053] b) In additional experiments (results not shown in FIG. 2) the preparations containing electrospun fibers according to Examples 1-4 are converted into foam preparations which are used as described in Example 5. Again, the results achieved with foam preparations without birch bark extract are comparable to those foam preparations with birch bark extract.