KR20040100070A - Nano sphere comprising egf, hardy-orange extracts and tocopherol and an oral hygiene composition containing the nano sphere - Google Patents

Abstract

PURPOSE: Provided are a nano sphere comprising EGF, hardy-orange extracts and tocopherol which are stabilized in their structure and have increased bioavailability and a tooth paste composition containing the same as an active ingredient. The tooth paste has excellent tooth decay preventing effect, anti-oxidation effect and wound healing effect. CONSTITUTION: The nano sphere composition having a particular size of 200-300nm is characterized by containing 1-5 wt.% of unsaturated lecithin, 1-20.0 wt.% of ethanol, 1-5.0 wt.% of oleic acid, 1-20.0 wt.% of hardy-orange extract, 1-20.0 wt.% of tocopherol, 0.000001-0.01 wt.% of EGF, 0.01-1.00 wt.% of DEA-cetyl phosphate, 0.1-0.5 wt.% of BHT and purified water based on 100 wt.% of the total composition.

Description

NANO SPHERE COMPRISING EGF, HARDY-ORANGE EXTRACTS AND TOCOPHEROL AND AN ORAL HYGIENE COMPOSITION CONTAINING THE NANO SPHERE}

The present invention relates to a nanosphere containing epidermal growth factor, tanza extract and tocopherol and a toothpaste composition containing the same, and more particularly, to the epidermal growth factor, tanza extract and tocopherol having low bioavailability due to the characteristics of the molecule The present invention relates to a toothpaste composition, which is prepared in the form of a stable nanosphere and further contains the nanosphere as an active ingredient.

Nano spheres consist of two types: liposomes and nanoemulsions. Molecular groups in equilibrium with water are formed by forming a double-layered closed membrane composed of phospholipids such as phosphatidylcholine (PC). Liposomes are water-soluble components that form bilayers rather than spherical when dispersed in water. The nanoemulsion captures oil soluble components that are soluble in oil.

Nanospheres with these structures contain poorly soluble bioactive substances or materials with low bioavailability to enhance their bioavailability, allowing them to be rapidly absorbed into the skin, mucous membranes and gums of the mouth, thereby enhancing their effectiveness. It can act to make.

Epidermal Growth Factor (EGF) is a protein that functions to heal skin wounds and is a biologic that is used to treat foot ulcers in diabetics.

EGF similar to that derived from human body from microorganisms was isolated and purified using genetic engineering technology and protein separation and purification technology. In other words, recombinant human EGF is produced by a technology that inserts the same protein as the human EGF into the microorganism by genetic engineering method to allow the microorganism to produce EGF and then isolate and purify it.

EGF is known to have a skin regeneration effect that naturally heals wounds without scars. Therefore, EGF can be used for the treatment of diabetic foot ulcers, burns, wounds, etc., corneal ulcers, corneal damage caused by contact lenses, corneal injury after chemical damage, and early healing and scar minimization after major surgery (such as caesarean section). It is used as a cosmetic for improving wrinkles and improving skin function, and for skin rejuvenation and skin ulcer treatment after skin peeling for cosmetic purposes. In addition, the oral action effects of EGF are known to regulate tooth growth, growth of periodontal tissue, periodontal ligament cells and enamel matrix, increase of fibroblasts adhered to tooth cementum adhesion protein.

Tocopherol is also called vitamin E, and the substance on which vitamin E functions is tocol, ie chromane based on only 2-methyl-2- [trimethyl-tridecyl] -6-hydroxychrome Derivatives. The side chain of the tocol is derived from phytol, and the trienol having a double bond at the 3,7,11 positions of the side chain has a structure similar to the tocol. Tocols and trienols are various isomers due to the position and number of methyl groups in the chroman ring. Tocopherols include alpha, beta, gamma, and delta-tocopherol.

Tocopherol has antioxidant activity and prevents the oxidation of vitamin A in vivo. In addition, it is also known to have a periodontal prevention effect, the antioxidant activity is alpha: beta: gamma: delta = 1: 1.3: 1.8: 2.7 at room temperature, delta tocopherol is relatively excellent. Tocopherol itself is unstable, and derivatives thereof are mainly used. In particular, various types of derivatives such as tocopheryl acetate and tocopheryl palmitate exist. Vitamin E is effective against severe periodontal disease. If the teeth have silver plating, the antioxidant effect of tocopherol is essential. Mercury depletes the antioxidant enzymes SOD, glutathione peroxidase, and catalase in silver tissues. Animal experiments have shown that tocopherol reduces the toxicity of silver.

It is an object of the present invention to structurally repair skin cell regeneration, in particular, tooth mucous membranes and gum wounds caused by brushing, and effective tannin extracts that are effective against EGF and gums, tocopherol acetate with low absorption in the body and cavities that strengthen gums. It is prepared and provided in the form of a stable nano sphere.

It is also an object of the present invention to provide a toothpaste composition having excellent skin cell regeneration ability, antioxidant activity and antimicrobial activity, containing nanospheres consisting of EGF, tocopherol and tanza extract.

1 is a graph showing the particle distribution of the nanospheres prepared according to the present invention,

Figure 2 is a frozen electron micrograph of the nanosphere particles prepared according to the present invention,

3 and 4 are the results of the caries bacterium inhibitory effect experiment of the tanza glycoprotein extract extracted by the method of the present invention, Figure 3 is a control and Figure 4 is a photo showing the results of the tanza glycoprotein extract.

Hereinafter, the present invention will be described in detail.

The present invention is 1 to 5% by weight of unsaturated lecithin, 1 to 20.0% by weight of ethanol, 1 to 5.0% by weight of oleic acid, 1 to 20.0% by weight of tanza extract, 1 to 20.0% by weight of tocopheryl acetate, 0.000001 to 0.01% by weight of EGF It is a nano sphere composition characterized in that the particle distribution is prepared by adjusting the weight of the total composition to 100% by weight of 0.01 to 1.00% by weight of dieceyl phosphate, 0.1 to 0.5% and BHT and purified water. .

Hereinafter, the present invention will be described in more detail.

EGF, tanza extract, and tocopherol contained in the nanosphere composition of the present invention are components having disadvantages of low bioavailability due to their low solubility in water due to their molecular properties despite the effective efficacy of each component. In the present invention, in order to improve the bioavailability of these components by the production of nanospheres are stabilized in the nanosphere structure to increase its own stability as well as to increase the penetration into the living body such as skin and gums.

Tenza is a deciduous deciduous arborescent tree, native to China, and grows in the south of Gyeonggi Province in our country. In general, the fruit peel of the plant of the genus Tangerine or Citrus contains both essential oils and flavonoid glycosides. The skin of the young fruit contains an essential oil called neohesperidin, which gradually disappears as the fruit ripens. The fruit of young fruit contains 0.2-0.4% of essential oil, and the ripe fruit contains 0.5% of essential oil. As the fruit ripens, the content of essential oil increases.

Looking at the main ingredients in tanza, essential oils include D-limonene, which is good for blood pressure strengthening, linalool, which has excellent antioxidant effects, linali acetate, which has a mutagenic effect, and anti-allergy. It has excellent action, such as tepineol, carotenoids that are vitamin A precursors, hesperidin, flavonoids, hesperidin, naringin, and rutin, and alkaloids such as synephin and pectin. have.

These tanzas have been using the fruit and the crust, which are fruits for a long time, as a herb, and when they have a wall, they have a feeling of fullness, stuffiness, and coughing. It is known that it is good to use when. In addition, when the skin is itchy or paralyzed by the wind, intestinal bleeding, hemorrhoids, etc., it is effective. In addition, it promotes gastrointestinal activity, helps the gas and stool in the intestine to go out, and cures the outbreak, treats when the chest and abdomen is full, and the species, gastric and sewage, uterine sewage, food, etc., and helps other activities. It is a fragrance-flavored medicinal placebo, and it is also used for gastric swelling, gastrointestinal dyspepsia, allergic constitution, gastric gas removal, uterine sewage, visceral relaxation, and asthenia. Constipation, ripening, thoracic swelling only, food, stomach, sewage, uterine sewage, edema, prolapse, hemorrhoids, intestinal bleeding, dry stomach, digestion, expectoration, upset pain, bowel movement, bowel stomach, gusts, five intestines, joints It is known to have an effect on the back.

Flavonoid compounds contained in tanza are components having important activities for periodontal disease. Flavonoids reduce inflammation and contribute to stabilizing collagen structure. In other words, by reducing the membrane permeability, it reduces the inflammatory mediators and bacterial products, inhibits free radical damage, and affects the collagen structure that inhibits the breakdown of collagen.

In the present invention, the molecular and biological glycoproteins and flavonoids isolated and purified from the tanza known to be effective as described above sterilize caries and effectively remove free radicals involved in aging and necrosis of cells caused by ultraviolet rays and bacteria. Experimentally proved.

According to the present invention, the glycoprotein is extracted from the tanza and used. In extracting the tanza glycoprotein, the tanza is sufficiently immersed in 100% ethanol and the soaked tanza is first filtered using filter paper, then placed in a condenser and concentrated until ethanol is completely evaporated. The concentrated tanza extract is dissolved in water, centrifuged, and the supernatant is taken to saturate the protein in 80% ammonium sulfate. To precipitate the protein, this solution is centrifuged at 4 ° C, the supernatant is discarded, only the pellet is taken, dissolved in water and passed through the dialysis membrane. The protein obtained through the dialysis membrane is lyophilized, and the lyophilized protein is passed through a Sephadex G150 column to collect the desired fractions to obtain a tanza glycoprotein extract.

The tanza extract obtained as described above is prepared in nanospheres with EGF and tocopherol.

Nanospheres according to the present invention is 1 to 5% by weight of unsaturated lecithin, 1 to 20.0% by weight of ethanol, 1 to 5.0% by weight of oleic acid, 1 to 20.0% by weight of tanza extract, 1 to 20% by weight of tocopherol acetate, 0.000001 to EGF Purified water is added to 0.01% by weight, 0.01% to 1.00% of diecetyl phosphate, and 0.1% to 0.5% by weight of butylate hydroxytoluene (BHT) to make the total composition 100% by weight, and then the solution is mixed well. It is prepared by stirring by passing through a high pressure fine homogenizer, cooling, and defoaming.

2 is a graph showing the particle distribution of the nanospheres prepared according to the present invention by Malvern Zetasizer 1000HS. As shown in FIG. 1, nanospheres having a diameter of 200 to 300 nm may be obtained. Figure 2 is a particle picture of the nanospheres prepared according to the present invention measured using a Freeze Fracture Scanning Electron Microscopy. The nanospheres are so tiny that they cannot be measured with a conventional optical microscope. The rounded part of the frozen electron micrograph shows the monolayer part, which indicates that the nanosphere was produced.

Since the nanospheres have a particle size of 200 to 300 nm in diameter, the nanospheres can easily penetrate into tissue cells because they easily penetrate into the skin and gums having an intercellular lipid between 200 and 300 nm.

Hereinafter, the present invention will be described in more detail with reference to Examples.

Example 1 Extraction of Tangza Glycoprotein

5 kg of tanza were immersed in 25% of 100% ethanol for about 3 weeks. The ethanol solution in which the tank was immersed was filtered using a filter paper, and then placed in a condenser and concentrated until ethanol was completely evaporated. The obtained tanza concentrate was dissolved in water and centrifuged at 15,000 rpm for 30 minutes to obtain the supernatant and saturated in 80% ammonium sulfate solution at 4 ° C. overnight. The solution was centrifuged at 15,000 rpm for 30 minutes at 4 ° C to discard the supernatant and collect only protein pellets. The collected pellets were again dissolved in water, passed through the dialysis membrane, and the dialyzed protein was lyophilized. Lyophilized protein was passed through a Sephadex G150 column to extract Tanga glycoproteins.

Example 2 Preparation of Nanospheres Using EGF, Tanza Extract and Tocopheryl Acetate

Each of the components described below was quantified in the following amounts, and the weight of the total composition was adjusted to 100% by weight with purified water, followed by well mixing and passing through a high pressure fine homogenizer. The solution passed through the homogenizer was cooled and degassed to prepare a nanosphere containing tanza extract, tocopherol acetate, and EGF.

Unsaturated lecithin 1 to 5%

Ethanol 1 to 20.00%

Oleic Acid 1 to 5.00%

Tanza extract 1-2%

Tocopheryl acetate 1 to 20.00%

EGF 0.000001-0.01%

Diecetyl phosphate 0.01 to 1.00%

BHT 0.1-0.5%

Purified water (to make 100% by weight in total)

Example 3 Preparation of Paste Type Toothpaste Composition

The components of group a) consisting of a moisturizer, a sweetener and nanospheres prepared in Example 2 were measured and dissolved by stirring and mixing at 25 to 35 ° C. for 15 minutes as described below, and of group b) consisting of powder and a viscous agent. The components were prepared with silica by mixing carboxy ethylcellulose with calcium carbonate in powder at 25-35 ° C.

Each component of group c) was added at 70 to 75 ° C., stirred for 20 minutes, and then the prepared components a) and b) were added to dissolve completely and cooled to room temperature.

Separately, the foaming agent of group d) was mixed and primary defoaming was completed within 40 minutes at 25 to 35 ° C. to mix the fragrance of group e) and secondary defoaming at 25 to 35 ° C. to prepare a dentifrice composition.

a) 30.00 wt% sorbitol

Glycerin 1.00 wt%

Sodium saccharin 0.50% by weight

Nano spheres 1.00 to 5.00 wt%

b) 30.00% by weight of calcium carbonate

Silica 26.00 wt%

2.00% by weight of carboxy ethyl cellulose

c) 100.0% by weight of purified water

Sodium Phosphate 0.80 wt%

0.25 wt% sodium benzoate

Polysorbitan 20 0.30% by weight

d) 2.00% by weight sodium laurylsulfite

e) fragrance

Example 4 Liquid Type Toothpaste Composition

A liquid type toothpaste composition was prepared in the same manner as in Example 3, except that the following ingredients were used.

Glycerin 5.00 wt%

Sorbitol 20.00 wt%

0.10% by weight of methyl paraben

Nano spheres 1.00 to 5.00 wt%

Sodium saccharin 0.25% by weight

Dicalcium phosphate dihydrate 48.00 wt%

1.50% by weight of sodium lauryl sulfate

1.00% by weight of carboxyl methylcellulose

Incense

Purified water (100% by weight in total)

Example 5 Clear Gel Type Toothpaste Composition

A transparent gel type toothpaste composition was prepared in the same manner as in Example 3, except that the following ingredients were used.

Sorbitol (70% solution) 50.81% by weight

33.00 wt% silica

Propylene glycol 10.00 wt%

Fiji-400 3.00 wt%

Sodium Lauryl Sulfate 1.20 wt%

Incense

0.50% by weight sodium benzoate

Sodium Floride 0.24 wt%

Sodium Saccharin 0.20% by weight

Nano spheres 1.00 to 5.00 wt%

Purified water (100% by weight in total)

Example 6 Caries Inhibition Test of Tangerine Extract

After spreading the causative bacteria Streptococcus Mutans strain evenly to the medium, ethanol and tanza extract (0.1, 1.0, 5, 10, 20 μl) was dropped on a circular paper disk and dried on a sterile bench. After the disk was dried, the disk was placed on a medium to which the strain was applied. The medium was stored in an incubator at 37 ° C. for one day and then analyzed and the results are shown in FIGS. 3 and 4.

The larger the size of the circle shown in the accompanying drawings, the higher the antimicrobial effect can confirm the antimicrobial effect of the tanza extract.

According to the present invention, the low solubility in water may stabilize EGF, tanza extract, and tocopherol, which have low bioavailability, to increase penetration into skin tissue.

Therefore, the toothpaste composition containing the nanosphere composition according to the present invention is effective in the oral hygiene and periodontal disease because the effective effect of the active ingredients are fully expressed, it is excellent in inhibiting caries bacteria, excellent antioxidant and wound healing effect.

Claims (3)

Unsaturated lecithin 1 to 5%, ethanol 1 to 20.0%, oleic acid 1 to 5.0%, tanza extract 1 to 20.0%, tocopherol acetate 1 to 20.0%, EGF 0.000001 to 0.01%, diecetyl Nanosphere composition, characterized in that the particle distribution is prepared by adjusting the weight of the total composition to 100% by weight of 0.01 to 1.00% by weight of phosphate, 0.1 to 0.5% of BHT and purified water. A toothpaste composition comprising the nanospheres composition according to claim 1. The dentifrice composition according to claim 2, wherein the dentifrice composition is a liquid, paste or transparent gel type formulation.