KR20110013563A - Preparation method of particles composed of chitosan and fatty acid for stabilization of vitamin c derivatives - Google Patents

Abstract

PURPOSE: A particle composition comprising hydrophilic chitosan chain and lipophilic fatty acid chain for stabilizing vitamin C derivative is provided to be used as a carrier of physiologically active material. CONSTITUTION: A chitosan-fatty acid solution composition contains chitosan-fatty acid complex, water, and vitamin C derivative. A method for preparing the chitosan-fatty acid solution composition comprises: a step of mixing chitosan solution and fatty acid; a step of raising temperature to dissolving the fatty acid and form a complex of chitosan amino acid group and fatty acid carbonyl group; a step of removing solvent and raising by 150-180°C to form an amide group; a step of washing and decompression-distilling and freeze-drying to obtain a chitosan-fatty acid amphiphilic complex powder; and a step of dissolving in a solvent and mixing with vitamin C derivative.

Description

Preparation method of particles composed of chitosan and fatty acid for stabilization of vitamin C derivatives}

The present invention relates to a particle composition composed of a hydrophilic chitosan chain and a lipophilic fatty acid chain for stabilizing a vitamin C derivative, and forms an ion complex between a chitosan amine group and a fatty acid chain, and induces an amide reaction between two chains at a high temperature. A technique for forming a composition is disclosed.

Vitamin C stimulates connective tissue on the skin, enhances skin tissue defenses from environmental factors such as ultraviolet light and pollution, removes skin pigments, and has anti-free radical function. In particular, due to its superiority such as skin whitening effect of promoting collagen synthesis in skin dermal layer which is a useful biological effect and removing harmful oxygen generated from ultraviolet rays, etc. This has been presented.

   Despite the physiological and chemical benefits of vitamin C, vitamin C, which is generally used in cosmetics or medicines, has the disadvantage of being very weak and easily degraded by light or heat. Therefore, when formulated in cosmetics, there are many problems in stability such as discoloration and odor change, but the industry concentrates on the stabilization technology of vitamin C, but does not achieve great research results. Therefore, it does not use pure vitamin C, but has a limit of usability by using a vitamin C derivative or by dispersing pure vitamin C in oils or dissolving it in a polyol.

     As a preparation for stabilizing vitamin C, Korean Patent Publication No. 92-10272 used a multiphase emulsified emulsion cosmetic, and Korean Patent Application No. 98-53973 used a water-in-oil type using 2-hydroxypropyl cyclodextrin. It was.

U.S. Patent No. 6,10267 discloses a water-soluble polymer and L-ascorbic acid particles by cooling a mixture of an aqueous solution in which a water-soluble polymer is dissolved with L-ascorbic acid and an aqueous solution mixed with a surfactant, followed by emulsification and cooling. A method of solidifying in form to disperse in oil is proposed.

An object of the present invention is to provide a method of binding by heating and decompression after the formation of a complex of two compositions through the control of ionic groups in the synthesis of an amphiphilic polymer composed of chitosan and fatty acids, rather than using a conventional solvent binding method. .

In another aspect, the present invention is to provide a self-particle-forming complex that can capture the vitamin C derivatives stably without significant damage to the antioxidant capacity of the vitamin C derivatives and can function sufficiently for a long time without degradation in vivo.

In another aspect, the present invention is to provide a method for providing a vitamin C derivative-containing magnetic particle-forming complex is not significantly impaired antioxidant capacity.

The present invention relates to a composition composed of a hydrophilic chitosan chain and a lipophilic fatty acid chain, and forms a complex of fatty acid chains in a chitosan amine group without using a conventional synthetic method. A method of forming particles.

In another aspect, the present invention is to provide a complex that can fully exhibit the antioxidant capacity by incorporating vitamin C in the self-assembly particles.

As a result of many studies to solve the above problems, the present inventors

(a) mixing a fatty acid into the chitosan solution;

(b) raising the temperature of the mixture to dissolve the fatty acid and to form a complex of the chitosan amino acid group and the carbonyl group of the fatty acid;

(c) raising the complex to 150-180 ° C. under reduced pressure to form an amide group;

(d) preparing the powder by lyophilization through a washing process;

By developing a material characterized in that the production, including that they have the amphipathy to capture vitamin C to form a complex to complete the present invention.

 The vitamin C derivative (ethyl ascorbyl ether) used in the present invention is not limited as long as it is a conventional vitamin C derivative. More preferably, in the present invention, a compound in which a 3-position hydroxyl group of vitamin C is substituted with an Ethoxy group, and a vitamin C derivative In the case of the stability of the improved compared to the pure vitamin C itself, but there is room for improvement by a new stabilization method and in the present invention to prepare the particles using the natural polysaccharides chitosan and fatty acids to improve the stability.

  Chitosan, which is used to improve the stability of vitamin C derivatives, is the deacetylated form of chitin, which is rich after cellulose in nature, and D-glucosamine obtained by deacetylating chitin obtained from shellfish such as crabs, shrimp, and crayfish. Is a polysaccharide-based biopolymer in which a monosaccharide or a disaccharide is polymerized with a monomer and has a basic unit of β- (1,4) -2-amino-2-deoxy-D-glucopyranose.

 Fatty acid, which is a hydrophobic part in the present invention, occupies 90% or more of fats and oils, and has a structure in which a carboxyl group is bonded to a carbon chain. The name is determined by the number of carbons and double bonds forming the skeleton.

12 carbon atoms: lauric acid

16 carbon atoms: palmitic acid

-18 carbon atoms: stearic acid

-18 carbon atoms, 1 double bond: oleic acid

 -18 carbon atoms, 2 double bonds: linoleic acid

 -18 carbon atoms, 3 double bonds: linolenic acid

 20 carbon atoms, 4 double bonds: arachidonic acid

Therefore, the amphiphilic polymer having both hydrophilicity and hydrophobicity forms a self-assembly through interaction between hydrophobic blocks to stabilize interfacial energy in an aqueous solution. The polymer particles formed by the amphiphilic polymer are known to exhibit different sizes, distributions, rheological properties, and thermodynamic stability depending on the degree of hydrophilicity and hydrophobicity.

Looking at patents related to self-assembly of polysaccharide amphiphilic polymers, Korean Patent Application No. 10-2001-0049772 prepared a complex composed of an anticancer agent and a hydrophilic chitosan to form a self-assembly, and 10-2003-0048240 and 10-2006-0003468 Also prepared a complex that forms a self-assembly consisting of hydrophobic bile acids and hydrophilic chitosan, through which the self-assembly can effectively encapsulate various hydrophobic drugs and therapeutic proteins, including anticancer drugs, and thus can be useful as medical drug carriers. Can be.

Korean Patent Application No. 10-2005-0102307 shows a method of stabilizing an active material using a hydrogel self-assembly including a hydrophilic natural polysaccharide polymer and a hydrophobic compound as a nanocarrier. In Korean Patent Application No. 10-2003-0005472, a polysaccharide copolymer having temperature sensitivity was prepared by graft copolymerization of PNIPAAm on radicalized chitosan using ammonium nitrate as a redox initiator. Temperature-sensitive polymers such as PNIPAAm change the lower critical temperature according to the abundance ratio of hydrophilic or hydrophobic moieties bound to the polymer backbone. The applicability to the medical temperature sensitive polymer was confirmed.

Looking at the amphiphilic polymer for drug delivery forming the self-assembly in the above patents, it can be seen that it is composed of chitosan, a natural polysaccharide having excellent biocompatibility, considering that the drug is transported in the human body.

The present inventors, while studying a method of grafting hydrophobic fatty acid to the hydrophilic chitosan backbone with excellent antioxidant properties to stabilize the vitamin C derivatives, instead of the conventional synthetic method using a solvent, an ionic complex between chitosan and hydrophobic fatty acid After formation, the amide bond was formed at 150-180 ° C., and the substance obtained by the above method was confirmed the stability of the vitamin C derivative against external stimulation and completed the present invention.

As described above, the present invention has an effect of providing a method of improving stability by incorporating a vitamin C derivative having a disadvantage of being very weak and easily decomposed by light or heat into particles using a chitosan-fatty acid complex. The chitosan-fatty acid complex according to the present invention can be usefully used as a cosmetic raw material to stabilize the bioactive substance. In addition, it can be seen that the effect is maintained even when the self-aggregating complex such as radical activity of vitamin C is not greatly reduced.

Simple modifications and variations of the present invention can be readily used by those skilled in the art, and all such variations or modifications can be considered to be included within the scope of the present invention.

Figure 1 shows a molecular diagram for the formation of chitosan monomer-fatty acid complex according to the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, and the scope of the present invention should not be construed as being limited by these examples.

Example  1 to 5:

Dissolve 0.6 g of chitosan (Mw = 300,000) in a solution consisting of 14.7 ml of distilled water and 0.3 ml of hydrochloric acid, and add fatty acids (lauric acid) in the amounts shown in Table 1 in various weight fractions from 0.6 to 3 g. After raising to ℃ ℃ to dissolve fatty acids for 30 minutes. After distilled water was removed by stirring the mixed chitosan and fatty acid solution at 60 ° C. under reduced pressure for 1 hour, the chitosan and the dissolved fatty acid were raised to 170 ° C. and stirred for 10 minutes under reduced pressure, and then cooled at room temperature. The prepared complex is washed in turn with excess acetic acid and distilled water, and then lyophilized to obtain a powder form. Formation of the obtained powdery amide group was confirmed using IR and H1-NMR.

In order to confirm the particle formation and size of the nano-magnetic assembly formed by the polymer prepared in the present invention, the polymer was dispersed in an aqueous solution and then observed to form particles.

Example  6 to 10:

In order to check the vitamin C derivatives and the capturing and releasing ability, 1 g of the chitosan-fatty acid polymer prepared in Examples 1 to 5 was added to 1 ml of ethanol in a solution containing 1 g of vitamin C derivatives, stirred, and then put into distilled water to form particles. . In order to determine the collection rate, uncaptured vitamin C derivatives were separated using a centrifugal filter, and the amount of vitamin C derivatives was measured using high performance liquid chromatography (HPLC).

The capture efficiency of the vitamin C derivatives determined through this is shown in [Table 2].

Example  11 to 15:

 In order to test the thermal stability of the composite prepared in the present invention, the solution prepared in Examples 1 to 5 was stored in an opaque glass container in a constant temperature bath at 25 ℃, 45 ℃ stored for 2 weeks, the vitamin C derivative remaining after storage The amount of was measured using high performance liquid chromatography (HPLC). Each residual rate was determined by the following formula.

Example  16, Comparative example  1 to 2:

 The free radical scavenging ability of the composite prepared in the present invention was measured as follows. Specifically, it measured using the method of 1, 1- diphenyl- 2-picryl- hydrazine (DPPH). DPPH is a relatively stable radical, exhibiting maximum absorption at 517 nm and losing absorbance upon radical disappearance.

The solution of Example 3 was placed in 100 μl of each well of a 96 well plate. 10 μl of DPPH solution was added thereto, followed by standing at room temperature for 30 minutes, and then the absorbance at 517 nm was measured using a microplate reader. In this case, 100 μl of a solution of each of chitosan and vitamin C derivatives having the same concentration as in Example 3 was used.

Claims (2)

A chitosan-fatty acid complex-containing chitosan-fatty acid complex containing water, and a vitamin C derivative containing chitosan-fatty acid complex solution composition.
Vitamin C derivative-containing chitosan-fatty acid complex solution composition, characterized in that prepared in the following steps.
(a) mixing a fatty acid into the chitosan solution;
(b) raising the temperature of the mixture to dissolve the fatty acid and to form a complex of the chitosan amino acid group and the carbonyl group of the fatty acid;
(c) removing the solvent under reduced pressure and raising the complex to 150 to 180 ° C to form an amide group;
(d) preparing a chitosan-fatty acid amphiphilic composite powder by additional processes such as vacuum distillation and lyophilization or spray drying after washing; And
(e) dissolving the chitosan-fatty acid amphiphilic complex in a solvent to dissolve the vitamin C derivatives and dispersing it in water to form particles

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