WO2007091801A1

WO2007091801A1 - A sheet device comprising bio-cellulose for alleviating skin damage and relieving skin problem

Info

Publication number: WO2007091801A1
Application number: PCT/KR2007/000544
Authority: WO
Inventors: Won Kook Moon; Dong Woo Kim; In Koo Hwang
Original assignee: Natural F & P Corp.
Priority date: 2006-02-07
Filing date: 2007-02-01
Publication date: 2007-08-16
Also published as: TW200803924A

Abstract

The present invention relates to a sheet device comprising bio-cellulose for alleviating skin damage and relieving skin problem. Specifically, when used to treat skin damage due to a wound and a burn, a sheet device according to the present invention may effectively absorb the exudates, contains various water retention agents as well as a wound-treating agent and easily adheres to skin without using other material, thus being usefully usable as a sheet device that may effectively alleviate skin damage while relieving skin problem without skin irritation.

Description

A SHEET DEVICE COMPRISING BIO-CELLULOSE FOR ALLEVIATING SKIN DAMAGE AND RELIEVING SKIN

PROBLEM

Technical Field

[1] The present invention relates to a natural sheet device comprising bio-cellulose for alleviating skin damage and relieving skin problem. Specifically, when applied to a wound or a burn in the form of a sheet, a patch or a mask pack, a sheet device herein, which comprises microbial cellulose and optionally further comprises pure or mixed active drug, may effectively absorb the exudates, thus being useful as a sheet device that may effectively alleviate skin damage such as a wound and a burn, etc. and relieve skin problem without skin irritation.

Background Art

[2] For skin care or helping treatment or alleviation of skin damages, the use of a sheet device such as a sheet, a patch and a mask pack has been on the increase instead of cream and lotion. Various sheets, patches and mask packs for skin care is commercially available, and a sheet device useful in delivering skin care activator such as vitamin activator, treatment activator and moisture supplier is also known and used in medical treatment for the transdermal delivery of medicines.

[3] However, these sheets have drawbacks in physical shape of goods and in uncom- fortableness for users. For example, a cosmetic mask pack is prepared by infiltrating face lotion in non-woven fabric, which contains plant cellulose as a main ingredient, or by coating collagen on non-woven fabric. However, the non-woven fabric has a drawback of low water retentive property. Further, some sheet devices easily become damp and sticky because they do not form solid gel structure, thus being difficult to handle and apply to the skin. Other patches also show too strong adhesion during the attachment or detachment, thus giving tight and uncomfortable feeling, and do not make active drug effectively released and penetrated. Moreover, some sheet devices can not be conformed to the curvature of skin due to the dry and non-flexible property.

[4] For the effective treatment of wounds, it is necessary to remove impurities, remains and necrotic tissue without damaging healthy cells. Further, dry wounds should be supplied with certain amount of moisture although too much moisture may soften skin around the wounds. A general treatment of a wound or a burn has been to clean wounds about twice a day using a soft soap, to apply an ointment to the wound or the burn and then to cover the wound or the burn with gauze. However, when exudate is leaked from the wound or the burn, it usually flows out of the gauze due to the low water absorptive property of the gauze. Use of multi-layers of gauze for overcoming the aforementioned problems causes elevation of the temperature in the wound or the burn, thus promoting inflammation. Further, the continuous use of gauze, which is made of synthetic resins, may irritate the skin. Owing to the limited usage of gauze, there is a need to develop a substitute for gauze using natural material.

[5] Microbial cellulose is a polymer produced through cultivating strains in various bacteria, particularly Acetobacter genus, and obtained in the form of semi-transparent pellicle existing in culture medium under the stationary cultivation [GB patent No. 2131701]. Although it is linked by β-1,4 glucosidic bonds like cellulose, microbial cellulose has significant industrial utility in that the fiber width is about 0.04-0. lμm, i.e. about 150 times smaller than that of cellulose (20-50μm) and that it has three- dimensional network structure.

[6] Therefore, the inventors have exerted extensive efforts to find natural material that

(i) may create humid atmosphere and decrease the dead space in the wounds (Wound Hydration), (ii) may protect the wounds from exterior pollution source and bacteria, and may create and maintain the optimum humid atmosphere for assisting natural recovery, (iii) may manage excess exudates (Exudate Management), and (iv) is safe and non-noxious. As a result, the present inventors perceived that a microbial cellulose gel plate has very similar properties to pulp, while being superior in water-absorptive and water-retentive property owing to the three-dimensional network structure, which is denser than that of pulp. Therefore, the present invention has been completed based on the findings that bio-cellulose may be prepared by post-treating microbial cellulose produced through cultivating strains in Acetobacter genus, while maintaining the original gel phase, followed by compression and removal of moisture, and that thus prepared bio-cellulose may maintain the characteristic three-dimensional network structure and contain a wound-treating agent and various water retention agents, thus being useful as a material for manufacturing a sheet or patch for effectively alleviating skin damage or a mask pack for relieving skin problem. Disclosure of Invention Technical Problem

[7] The present invention aims to provide a sheet device useful in alleviating skin damage due to a burn and a wound and relieving skin problem without irritation. Technical Solution

[8] To serve the aforementioned purpose, the present invention provides a sheet device comprising bio-cellulose.

[9] A sheet device herein may be prepared into a sheet, a patch for treating or alleviating skin damage due to a burn and a mask pack for relieving skin problem. [10] Bio-cellulose herein may comprise microbial cellulose, an active drug and moisture.

Specifically, bio-cellulose herein may comprise 1-50 wt% of microbial cellulose, 1-10 wt% of an active drug and 40-98 wt% of moisture, preferably 3-10 wt% of microbial cellulose, 1-5 wt% of an active drug and 70-96 wt% of moisture.

[11] An active drug herein may be selected among sulfonamide acetate, sulfamylon, silver sulfadiazine, silvadene, Vaseline and a mixture thereof.

[12] Besides bio-cellulose, an active drug and moisture, a sheet device herein may further comprise a water-retention agent in the amount of 15.0-20.0 wt% relative to the total weight of the sheet device. A water-retention agent herein may be selected among glycerin, propylene glycol, butylene glycol, polyethylene glycol, sorbitol, maltitol, polyhydric alcohol, hyaluronic acid, amino acid, natto gum and sodium lactate. Further, a sheet device may also comprise a growth factor (e.g. TGF-,TGF-, TNF-, PDGF, bFGF, GM-CSF, IL-I, IL-6, IL-8 and fibronectin) to promote the treatment of a wound by accelerating the proliferation and movement of keratinocyte and fibroblast. A combinational secretion of various factors stimulates dermal fibroblast and promotes the generation of collagen, thus creating an atmosphere where the re-epitheliatization of wounds may happen from periwound skin and skin appendages.

[13] To inactivate residual metal ions, a sheet device herein may comprise a sequestering agent (or a chelating agent) such as EDTA (ethylenediamine tetraacetic acid), citric acid and NTA (nitrilotriacetic acid) in the amount of 0.01-0.5 wt% relative to the weight of total weight of the sheet device. A sheet device herein may further comprise an antioxidant such as WHITE TEA, tocopherol, gallic acids, BHT and BHA in the amount of 0.5-1.0 wt% to inhibit the oxidation; a soothing agent such as DPG (dipotassium glycyrrhizate) in the amount of 0.01-0.5 wt%; a solubilizing agent such as POE hydrogenated castor oil and POE oleyl alcohol ether in the amount of 0.01-0.1 wt%; and a saponifying agent such as triethanolamine in the amount of 0.01-0.2wt%. The aforementioned ingredients may be incorporated into the sheet device in combination with deionized water, and the amounts above are relative to the total weight of the sheet device. Advantageous Effects

[14] A sheet device comprising bio-cellulose herein has a very dense structure and shows superiority in skin adhesion and water retention. When applied to the damaged skin of men or animals, a sheet device herein has been ascertained as effective in rapidly alleviating skin damage, and also as effective in safely relieving skin problem without irritation. Thus, a skin device herein may be useful for the purpose of alleviating skin damage and relieving skin problem.

Brief Description of the Drawings [15] Figure 1 is a photograph, which compares change of the skin condition after applying bio-cellulose sheet of the present invention {series (b)} with that after applying commercially available gauze {series (a)} to a burn-induced hairless mouse.

[16] Figure 2 is a SEM photograph, which compares between cellulose of the present invention {photograph (a)} and plant cellulose {photograph (b)}. Best Mode for Carrying Out the Invention

[17] Bio-cellulose of the present invention may be prepared by adding fructose and moisture in a microbial cellulose as described below.

[18] Specifically, a process for preparing bio-cellulose from a microbial cellulose comprises the steps of:

[19] (a) preparing microbial cellulose in a semi-transparent gel phase by (i) inoculating microbial cellulose producing strain, preferably Acetobacter genus, to microbial cellulose producing culture medium, preferably fruit juice containing acetic acid and sugar; (ii) incubating the strain in a shaking or air lift type incubator, thus providing the dispersion of particle-shaped or pellet-shaped microbial cellulose; and (iii) inoculating the culture to microbial cellulose producing medium using the culture per se as a starter and performing stationary cultivation;

[20] (b) preparing a wet sheet with the thickness of about 0.2-1 mm, preferably 0.,4-0.8 mm and the moisture of 40-90%, preferably 50-80% by (i) immersing the semi- transparent microbial cellulose in water, and washing and heating the microbial cellulose to remove media ingredients and fungus bodies inside, thus providing impurity-free gel-phased microbial cellulose; and (ii) compressing the gel-phased microbial cellulose in an air or oil compressor using sponge or filter cloth;

[21] (c) preparing bio-cellulose wet sheet, which is restored into the thickness of 0.5-10 mm, preferably 1-8 mm, by immersing the wet sheet in the pre-manufactured 10-80% solution of active drug such as sulfonamide acetate, sulfamylon, silver sulfadiazine, silvadene or Vaseline for 0.1-10 day, preferably 1-3 days, to allow the wet sheet to contain the active drug in the concentration of 1-10 wt%, preferably 1-5 wt%.

[22] The present invention provides a thus prepared sheet device comprising bio- cellulose as an active ingredient, which is useful in alleviating skin damage due to a wound and a burn and relieving skin problem. The followings have been ascertained with regard to the sheet device: (i) it has a very dense structure by SEM analysis, (ii) it shows superiority in skin adhesion and water retention, (iii) when applied to the damaged skin of human or animal, it is effective in rapidly alleviating skin damage and safely relieving skin problem without irritation. The present invention has been completed based on the aforementioned advantages of a sheet device herein. Mode for the Invention [23] The present invention is described more specifically by the following Examples and

Experimental Examples. Examples and Experimental Examples herein are meant only to illustrate the present invention, but in no way to limit the scope of the claimed invention.

[24] Example 1: Preparation of bio-cellulose sheet

[25] 1-1. Preparation of microbial cellulose

[26] Bio-cellulose of the present invention may be prepared by adding fructose and moisture in microbial cellulose. For the manufacture of microbial cellulose, 400 mL of culture medium (pH 3-4), which was prepared by diluting apple juice with water to 35% (v/v) and adding acetic acid 1% (v/v), was placed in a 1 L Erlenmeyer flask, and inoculated with Acetobacter xylinum, followed by incubation with shaking at 30°C and 150 rpm for 1-3 days. Then, the prepared culture as a starter was inoculated to a 1 L beaker containing 400 mL of apple juice diluted solution (pH 3-4) with the concentration of 5% (v/v), followed by stationary culture at 30°C for 5-8 days. The apple juice diluted solution was prepared by diluting apple juice to 35% (v/v) with water and adding with acetic acid 1% (v/v) and sugar 10% (v/v).

[27] 1-2. Preparation of wet sheet

[28] Thus prepared microbial cellulose with thickness of 5-8 mm in a semi-transparent phase contains media ingredients and fungus bodies. To remove the impurities, the microbial cellulose was immersed in water for 1-2 days, washed with pure water once or twice and heated at 100°C for 20-60 minutes. The impurity-free microbial cellulose in a gel phase was compressed in an air compressor into a thickness of 0.4-0.8mm using sponge, thus providing a wet sheet of microbial cellulose with a moisture content of 50-80%.

[29] 1-3. Preparation of wet sheet comprising active drug

[30] Thus prepared wet sheet was immersed in 200 mL of a treating agent for a burn,

Vaseline 50% (w/v), for 1-2 days, which was prepared in advance. The wet sheet was allowed to absorb the treating agent for a burn again and restored into the thickness of 2-6 mm with moisture 40-60%, thus providing a sheet for treating a burn.

[31] Referential Example 1: Structure Evaluation cellulose sheet

[32] After dried sufficiently, a cellulose sheet was coated with metal according to a sputter coating procedure [Bell PB Jr, Lindroth M, Fredriksson BA, J. Electron Microsc Tech., Nov:7 (3). ppl49-159, 1987]. SEM photograph was taken by using a scan electron microscope (Hitachi S-2350, Japan). As shown in Figure 2, the prepared sheet was observed to have fine-shaped fibers even when enlarged 20,000 times, thus ascertaining fine fibrous structure and superior skin adhesion of the cellulose sheet along with superior water-retentive effect.

[33] Experimental Example 1: Evaluation of efficacy of bio-cellulose sheet in al- leviating skin damage

[34] The efficacy of bio-cellulose sheet in alleviating skin damage was evaluated as described below.

[35] Twenty hairless BALB/c mice (Samtako, Inc., Korea) were marked in the back to make 2 cm x 2 cm square. Third-degree burns were induced by applying 100 mM lactate ringer solution to the marked skin. After 30 minutes, ten mice were applied with bio-cellulose sheets prepared in Example 1, while the other ten mice were applied with commercially available gauzes. Bio-cellulose sheets and gauzes were replaced with new ones every day , and the change of skin condition was observed.

[36] As shown in Figure 1, the group applied with bio-cellulose sheets herein {series

(b)} were more rapid in skin damage relief than the group applied with gauzes {series (a)}. Crusts were formed after 3 days and 1 day in the gauze-applied group and the bio- cellulose sheet-applied group, respectively. Thus, it was ascertained that bio-cellulose sheet has an efficacy of alleviating skin damage.

[37] Experimental Example 2: Evaluation of efficacy of bio-cellulose sheet in relieving skin problem

[38] To evaluate the efficacy of bio-cellulose sheet herein in relieving skin problem, skin patch test was performed as described in a publication (Notice issued by Korea Food & Drug Administration No. 1999-61; Preclinical safety evaluation of biotechnology- derived pharmaceuticals Article 9; Local irritation test).

[39] Following inducing burns on New Zealand white rabbits (Korean Laboratory

Animal Center, Korea), the change of skin condition was evaluated at the predetermined interval after the application, and scored based on the evaluation standards presented in Table 1 (Draize et al., J. Pharmacol. Exp. Then, 82_» pp377-390, 1944). As shown in Table 2, bio-cellulose sheet according to the present invention showed no skin reddishness such as erythema, thus being superior in relieving skin problems without skin irritation.

[40] Table 1

[41] Table 2

Industrial Applicability

[42] A sheet device comprising bio-cellulose herein has a very dense structure and shows superiority in skin adhesion and water retention. When applied to the damaged skin of human or animal, a sheet device herein has been ascertained as effective in rapidly alleviating skin damage, and also as effective in safely relieving skin problem without irritation. Thus, a skin device herein may be usefully used for the purpose of alleviating skin damage and relieving skin problem.

[43]

Claims

[1] A sheet device for alleviating skin damage and relieving skin problem, comprising bio-cellulose.

[2] The sheet device of claim 1, wherein the sheet device is in the form selected from the group consisting of a sheet, a patch and a mask pack.

[3] The sheet device of claim 1, further comprising an active drug and moisture.

[4] The sheet device of claim 3, wherein the active drug is at least one selected from the group consisting of sulfonamide acetate, sulfamylon, silver sulfadiazine, silvadene and Vaseline. [5] The sheet device of claim 1, wherein the bio-cellulose comprises 1-50 wt% of a microbial cellulose, 1-10 wt% of a active drug and 40-98 wt% of moisture.