KR20090047676A - Method for stabilizing vitamin c using chitosan derivative - Google Patents

Abstract

The present invention provides a composition comprising a) vitamin C or a derivative thereof; And b) a chitosan derivative substituted with a hydrocarbon group of C6 to C20, wherein the vitamin C or a derivative thereof forms an electrostatic bond with the chitosan derivative; And it provides a method for producing the composite.

Description

Method for stabilizing vitamin C using chitosan derivatives {Method for stabilizing vitamin C using chitosan derivative}

The present invention provides a composition comprising a) vitamin C or a derivative thereof; And b) a chitosan derivative substituted with a hydrocarbon group of C6 to C20, wherein the vitamin C or a derivative thereof is formed by electrostatic bonding with the chitosan derivative; And it relates to a method for producing the composite.

Vitamin C is involved in the collagen synthesis process and promotes collagen synthesis, improving skin wrinkles, and can also act as a sunscreen. Vitamin C also acts as a powerful biological antioxidant in skin, blood and other tissues. In addition, vitamin C has a variety of physiological activities, such as involved in the metabolic process of folate metabolism and amino acids in vivo, or increase the body's resistance to infectious diseases. While vitamin C biosynthesizes vitamin C from glucose (glucose) in most animals, humans continue to use vitamin C by food and other methods because they do not biosynthesize due to lack of glucose (glucose) to vitamin C conversion enzymes. Must be supplied. Therefore, a proper daily recommended amount of vitamin C should be taken, and a substance such as vitamin C-containing cosmetics as a transdermal absorbent should be used for skin protection.

However, vitamin C is very unstable in heat, light, oxygen, etc., and is easily exposed to the air or oxidized in an aqueous solution, resulting in lowered titer, discoloration, and deodorization, which greatly affects stability. In particular, vitamin C is poorly dispersed in organic solvents commonly used in external preparations such as cosmetic compositions, for example, glycerin, propylene glycol, various fats, and the like. For this reason, there are restrictions on the use of vitamin C or its derivatives in industries such as medicine, food and cosmetics.

The present inventors have found that when a chitosan derivative substituted with a hydrocarbon group is combined with vitamin C or a derivative thereof to form a complex, it is possible to solve the dispersibility and safety problems of pure vitamin C or a derivative thereof. Based on this, the present invention seeks to improve the dispersibility and safety of vitamin C.

The present invention provides a composition comprising a) vitamin C or a derivative thereof; And b) a chitosan derivative substituted with a hydrocarbon group of C6 to C20, wherein the vitamin C or a derivative thereof forms an electrostatic bond with the chitosan derivative; And it provides a method for producing the composite.

The present invention also provides an antioxidant composition comprising the complex.

Hereinafter, the present invention will be described in detail.

The complex according to the present invention is characterized in that the vitamin C or a derivative thereof having a negative charge and a chitosan derivative substituted with a hydrocarbon group of C6 to C20 are formed by electrostatic bonding with each other.

Chitosan is N-deacetylated chitin, a component of lower animal exoskeleton, such as the shells of shellfish, insects and fungi, and 2-amino-2-deoxy-D-glucose (2-amino-2-deoxy -D-glucose) is a polysaccharide combined with β-1,4. Chitosan has been listed as a natural food additive since the mid-1990s in Korea, and has been widely used in the medical and chemical industries due to the hydroxyl and amino groups of chitosan. Has been applied in. When the chitosan is used together with vitamin C, it exhibits the synergistic effect of vitamin C, and has the property of increasing the efficacy and stability of vitamin C. However, the above-described pure chitosan-vitamin C complex has a problem that it does not disperse well in hydrophobic environments such as oil.

The present invention recognizes that the above-mentioned dispersibility problem in hydrophobic environment is related to the hydrophilicity of vitamin C or chitosan C, and uses a chitosan derivative having increased hydrophobicity (for example, a chitosan derivative including a hydrocarbon group of C6 to C20). By doing so, it is possible to fundamentally solve the problem of dispersion in a hydrophobic environment of vitamin C.

In addition, the complex of the chitosan derivative-vitamin C of the present invention has the advantage that the oxidation, dissolution, etc. of vitamin C by the chitosan derivative is prevented, thereby improving the safety of vitamin C.

The chitosan derivatives according to the present invention include a substituted hydrocarbon group, thereby increasing hydrophobicity compared to pure chitosan, thereby allowing the vitamin C or derivatives thereof to be stably dispersed even in a hydrophobic environment. In particular, the substituted hydrocarbon group of the chitosan derivative is preferably oriented out of the complex according to the present invention. Since the hydrocarbon group of C6 to C20 is a hydrophobic group, when the hydrocarbon group is oriented outside of the composite, dispersibility in a hydrophobic environment can be further improved.

The complex according to the present invention is formed by binding a chitosan derivative substituted with a hydrocarbon group to the endiol structure of the vitamin oxidized by water and oxygen, thereby preventing oxidation and dissolution of vitamin C by the combined chitosan derivative. The hydrophobic hydrocarbon group of the chitosan derivative prevents contact between the vitamin C and water, thereby improving the stability of the vitamin C (see Experimental Example 3).

The chitosan derivative of the present invention may be dissolved in a solvent to carry a positive charge, and is not particularly limited as long as it is substituted with a hydrocarbon group of C6 to C20, and may be represented by the following [Formula 1]. Non-limiting examples thereof include octanoyl chitosan, palmitoyl chitosan and the like.

 (R1 is C6-C20 alkyl, alkenyl group, n is 20-40)

The derivative of vitamin C of the present invention can be used without limitation as long as it can dissolve in a solvent and carry a negative charge.

Vitamin C is also called ascorbic acid. The chemical formula is a white crystalline solid with an endodiol structure in which two hydroxyl groups are attached to a single double bond of C ₆ H ₈ O ₆ .

The derivative of vitamin C is sodium ascorbylphosphate (SAP), magnesium ascorbylphosphate (MAP), calcium ascorbylphosphate (Calsium ascorbylphosphate), ascorbic acid polypeptide (Ascorbic acid polypeptide) Ethyl ascorbyl ether, Ascorbyl dipalmitate, Ascorbyl palmitate, Ascorbyl stearate, Ascorbyl glucoside And ascorbyl ethyl silanol pectinate (Ascorbyl ethylsilanol pectinate) can be used one or more selected from the group consisting of. However, it is not limited thereto.

Composite according to the present invention comprises the steps of: a) preparing a chitosan derivative by reacting a chitosan oligomer and a halide hydrocarbon compound; b) titrating the chitosan derivative to pH 6-7; And c) mixing the resultant product of b) with vitamin C or a derivative thereof.

The chitosan derivative may be prepared by reacting a chitosan oligomer with a halide hydrocarbon compound. Preferably, the chitosan oligomer having a molecular weight of 3000 to 7000 and a halide-based hydrocarbon compound containing 6 to 20 carbon atoms of hydrophobic aliphatic group may be reacted to prepare. The chitosan oligomer may be prepared by nitrous acid decomposition and methanol precipitation. The halide hydrocarbon compound containing 6 to 20 carbon atoms is acylated with the amine group of the chitosan and the hydrogen of the hydroxyl group, and the chitosan derivative according to the present invention is substituted with the hydroxyl group of the chitosan. Can be prepared. The reaction scheme is as follows.

Octanoyl chloride, palmitoyl chloride, etc. may be used as the halide hydrocarbon compound.

The chitosan derivatives prepared by performing the above reaction have a cation by a conventional method, and vitamin C or a derivative thereof is also dissolved in a solvent to give an anionic charge. Preferably, the chitosan derivative can be titrated to pH 6-7 to exhibit a cationic charge, and the vitamin C or derivatives of vitamin C are dissolved in polar solvents other than water such as ethanol and methanol, and vitamin C or derivatives thereof. Can have an anionic charge. In the case of dissolving vitamin C or a derivative thereof in ethanol, it is possible to dissolve in ethanol at a concentration of 40 to 70% to make 0.5 to 3% by weight of vitamin C. The chitosan derivative is also dissolved in an organic solvent and then mixed with dissolved vitamin C or a derivative thereof to prepare a complex. Preferably, the chitosan derivative may be used by dissolving in a nonpolar solvent such as methylene chloride, chloroform and the like.

In addition, the present invention provides an composition for antioxidant, comprising the complex.

In the antioxidant composition comprising the complex according to the present invention, the complex according to the present invention may be contained as an active ingredient in an amount of 0.01 to 20.0% by weight of the total composition.

The composition may be used as a cosmetic, food composition, pharmaceutical composition and the like. Since the cosmetic composition including the complex of the present invention contains vitamin C or a derivative thereof as an active ingredient, the cosmetic of the present invention can be used for various purposes known in the art for vitamin C or a derivative thereof. Therefore, the cosmetic of the present invention may be represented as a cosmetic for wrinkle improvement, a cosmetic for whitening, a cosmetic for preventing skin aging, and a cosmetic for protecting against ultraviolet rays. Ingredients included in the compositions and cosmetics of the present invention include, in addition to the complex according to the present invention as an active ingredient, those components conventionally used in the composition, for example, such as antioxidants, stabilizers, solubilizers, vitamins, pigments and perfumes. Phosphorus adjuvants, and carriers. Antioxidants that may be included may be used to further enhance the stabilizing effect of vitamin C or derivatives thereof. Tyrosine, tryptophan, alpha lipoic acid, vitamin E and its derivatives, vitamin A and its derivatives, sodium sulfite, sodum disulfite and the like can be used. However, when an antioxidant is included in excess, it may block the interaction of vitamin C or its derivatives with chitosan derivatives, and thus may have a problem that destroys the stability or does not show any further stability increase effect. Thus, the antioxidant may be contained in an amount of 10% by weight or less, preferably in an amount of 5% by weight or less based on the total weight of the composition.

Antioxidant compositions comprising the complex of the present invention can be prepared in any formulation commonly prepared in the art, for example, to be formulated with cleansing oil, powder foundation, emulsion foundation, wax foundation, spray, and the like. It may be, but is not limited thereto. More specifically, the cosmetic composition comprising the complex of the present invention is prepared in the formulation of cleansing oil, softening lotion, nourishing lotion, massage cream, nourishing cream, pack, gel, essence, lipstick, makeup base, foundation, lotion or spray Can be. When the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components. Can be. When the formulation of the present invention is a spray, lactose, talc, silica, aluminum hydroxide, or calcium silicate may be used as the carrier component, and additionally, a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether may be used. It may include. When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsion may be used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol Fatty acid esters of 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan may be used. When the formulation of the present invention is a suspension, a liquid diluent such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, and microcrystals are used as carrier components. Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

Cosmetics comprising a complex according to the present invention contains a chitosan derivative that effectively stabilizes vitamin C or derivatives thereof against the external environment, and vitamin C or derivatives thereof, so that the physiological activity of vitamin C, that is, a whitening effect (eg, tyrosinase activity) Inhibition), anti-wrinkle effect and antioxidant effect (eg free radical scavenging ability) can be effectively delivered to the skin.

The present invention can improve the safety of vitamin C by fundamentally solving the problem of dispersibility of vitamin C in a hydrophobic environment by using a chitosan derivative having increased hydrophobicity, and preventing oxidation, dissolution of vitamin C, and the like. Therefore, it is possible to increase the applicability of vitamin C in various industries.

Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples. However, the following examples are illustrative of the present invention, and the contents of the present invention are not limited by the examples.

 [ Example  One]

Example  1-1  : Synthesis of Chitosan Derivatives Palmitoyl  Chitosan synthesis

1.5 g of chitosan oligomer (Mw 4445.9) was put in a reactor, and about 20 ml of methanesulfonic acid (MeSO 3 H, sigma) was added until the chitosan oligomer was completely dissolved. When the chitosan oligomer was completely dissolved, palmitoyl chloride (Sigma) was added to 5.11 ml of 2 times the molar ratio of glucosamine, a monomer of chitosan, and stirred at room temperature for 12 hours. The ice was added and the reaction stopped. Initially, the reaction was dialyzed for one day, changing the deionized water about 5 times at 1 hour intervals. After that, the water was changed every two to four hours. After dialysis, the pH was adjusted to 7.4 with saturated sodium bicarbonate. Salt was removed by filtration with deionized water. Soxhlet extraction with methanol for 8 hours. What was left in the filter without dissolving in methanol was Soxhlet extracted with chloroform for 4 hours. The chloroform solution was evaporated solvent and the remaining material was vacuum dried to prepare palmitoyl chitosan.

Example  1-2: Palmitoyl  Chitosan and Vitamin C Complex Preparation

Vitamin C (Na-ascrobic acid, Sigma-Aldrich) was dissolved in 1% by weight of ethanol at 68% concentration to prepare a first solution. Palmitoyl chitosan synthesized in Example 1-1 was dissolved in methylene chloride at 1% by weight to prepare a second solution. 0.5 ml of the second solution was added dropwise while stirring 0.3 ml of the first solution to prepare a third solution. 0.4 ml of pure ethanol was added to the third solution to form particles, thereby preparing a vitamin C complex with palmitoyl chitosan.

[ Experimental Example  One]

The vitamin C / palmitoyl chitosan electrostatic complex prepared in Example 1 was analyzed and photographed by an electron microscope (SEM, S-3500N, HITACHI Co., Japan).

It could be seen that a sphere having a micron size or less was formed (FIG. 1A), and after 30 minutes of preparation, the sphere was aggregated in an aqueous solution (FIG. 1B). The spherical body is produced by the electrostatic attraction of the anionic charge of vitamin C and the cation charge of palmitoyl chitosan. The aggregation of the complex of FIG. Able to know. Thus, it can be seen that the hydrophobic hydrocarbon group of the chitosan derivative is oriented outside the complex, so that the complex containing vitamin C according to the present invention can be well dispersed in the oil phase. In addition, since the hydrophobic hydrocarbon group of the chitosan derivative plays a role of blocking the vitamin C from the external environment, it can be seen that the vitamin C according to the present invention can be prevented from being dissolved and oxidized in a hydrophilic environment such as water.

[ Experimental Example  2]

The UV spectrometer (OPTIZEN 2120UV) was used to compare the properties of pure vitamin C and vitamin C in the complex according to the present invention.

The vitamin C / palmitoyl chitosan electrostatic complex prepared in Example 1 and pure vitamin C were passed through an ultraviolet spectrometer, and the graphs were compared. The OD of vitamin C in the complex is lowered but the slope is similar to that of pure vitamin C.

That is, even if vitamin C or derivatives thereof form a complex with chitosan derivatives, it can be seen that the intrinsic properties of vitamin C or derivatives thereof do not change (see FIG. 2).

[ Experimental Example  3] Palmitoyl  Evaluation of Temperature Stability of Chitosan / Vitamin C Complex

The third solution of Example 1, a solution of vitamin C (Na-ascrobic acid) dissolved in water at 1% by weight (Comparative Example 1), except that chitosan was used instead of palmitoyl chitosan in Example 1-2. A solution containing the chitosan / vitamin C complex prepared by the method (Comparative Example 2) was prepared and placed at a temperature of 25 ° C., 37 ° C., and 47 ° C. for 1 hour (25 ° C. at room temperature, 37 ° C. and 47 ° C.). Carried out in a water bath). After leaving the solution for 1 hour, the third solution of Example 1 and the solution of Comparative Example 2 were centrifuged to settle the particles, leaving the particles but leaving the solution. 0.8 ml of methylene chloride and water were added to the remaining particles purified from the third solution of Example 1 and the purified particles of Comparative Example 2 to completely dissolve the particles. Since only the water layer was extracted to measure the stability (reactivity to water) at 280nm of the ultraviolet spectrometer (OPTIZEN 2120UV). Comparative Example 1 also measured the stability at 280 nm of the ultraviolet spectrometer.

As shown in Figure 3, the vitamin C of Comparative Example 1 and Comparative Example 2 has a sharp decrease in stability as the temperature increases, it can be seen that the vitamin C of Example 1 that forms the electrostatic complex is not. It can be seen that the vitamin C in which the complex of Example 1 was formed was inferior in solubility about 4 times as compared with that of Comparative Example 1 and Comparative Example 2 at a temperature of 47 ° C (see FIG. 3).

As described above, it can be seen that the vitamin C complex formed by the present invention is superior in stability to vitamin C not forming a complex.

In addition, it can be seen that the complex according to the present invention containing a chitosan derivative having a substituted hydrocarbon group is superior in stability to that of the complex containing pure chitosan.

Figure 1a is a photograph showing the electrostatic complex of the synthesized palmitoyl chitosan and vitamin C, a photograph immediately after the formation of the complex.

Figure 1b is a photograph showing the aggregation of the complex of palmitoyl chitosan and vitamin C, a photograph 30 minutes after the formation of the complex.

Figure 2 shows a graph measuring the properties of the complex and vitamin C prepared in Example 2 by ultraviolet spectroscopy (dotted line: complex prepared in Example 2, solid line: vitamin C).

Figure 3 shows a graph comparing the stability of the composite prepared in Example 3 and Comparative Example 1, Comparative Example 2 (VC / PC: composite prepared in Example 3, solution: Comparative Example 1, VC / chitosan: Comparative Example 2).

Claims (11)

a) vitamin C or derivatives thereof; And b) a chitosan derivative substituted with a hydrocarbon group of C6 to C20, wherein the vitamin C or a derivative thereof forms an electrostatic bond with the chitosan derivative. The complex according to claim 1, wherein the C6 to C20 hydrocarbon group of the chitosan derivative is oriented outside the complex. The method of claim 1, wherein the chitosan derivative is octanoyl chitosan Or palmitoyl chitosan. The method of claim 1, wherein the derivative of vitamin C is sodium ascorbylphosphate (SAP), magnesium ascorbyl phosphate (MAP), calcium ascorbylphosphate (Calsium ascorbylphosphate), ascorbic acid polypeptide (Ascorbic acid polypeptide, ethyl ascorbyl ether, ascorbyl dipalmitate, ascorbyl palmitate, ascorbylstearate, ascorbylstearate, ascorbyl glucoside ) And ascorbylethylsilanolpectinate (Ascorbylethylsilanolpectinate). Antioxidant composition comprising a complex of any one of claims 1 to 4. The method of claim 5, wherein the complex is 0.01 Antioxidant composition, characterized in that it comprises from 20.0% by weight. 6. The composition of claim 5, further comprising an antioxidant in an amount of up to 10% by weight based on the total weight of the composition. 8. The composition of claim 7, wherein the antioxidant is at least one selected from the group consisting of tyrosine, tryptophan, alpha lipoic acid, vitamin A and derivatives thereof, sodium sulfite and sodium disulfite. The composition of claim 5, wherein the composition is a cosmetic. 10. The method of claim 9, wherein the cosmetic is selected from the group consisting of cleansing oil, softening longevity, nourishing longevity, massage cream, nutrition cream, pack, gel, essence, lipstick, makeup base, foundation, lotion and spray Composition. a) reacting the chitosan oligomer with a halide hydrocarbon compound to prepare a chitosan derivative; b) titrating the product of a) to pH 6-7; And c) mixing the resultant of b) with vitamin C or derivatives thereof; Method for producing a complex of any one of claims 1 to 4, characterized in that consisting of.

Images