KR20220094959A - Cosmetic composition containing active materials of Pinus Densiflora Leaf - Google Patents

Abstract

The present invention relates to particles in which a pine needle extract is encapsulated in a derivative in which a carboxyl group of poly-gamma-glutamic acid is bound to an amine group of a phenylalanine derivative and a cosmetic composition comprising the same. The particles encapsulated with a pine needle extract can improve water dispersibility, stability, and delivery efficiency and are used for in cosmetics or medicine to achieve efficient application.

Description

Cosmetic composition containing active materials of Pinus Densiflora Leaf}

The present invention relates to the development of pine needle extract encapsulated particles capable of increasing water dispersibility, stability and delivery efficiency by encapsulating the pine needle extract, and a cosmetic composition containing the same.

Among the raw materials of cosmetics or pharmaceuticals, poor solubility and low stability are problematic.

There are many substances. Among the active ingredients widely used as cosmetic raw materials, fat-soluble ingredients often have problems with poor solubility and low stability. Pine trees are widely distributed across diverse ecological ranges, from the cold northern alpine regions to the warm coastal waters of Jeju Island. It contains vitamin C and vitamin A as main ingredients. In addition, it contains a substance called carotene, which is converted into vitamin A in the human body, and is known to contain iron and has been used for medicinal purposes. In recent studies, it is known that pine needle extract-derived ingredients have anti-inflammatory and antibacterial effects. (J.Choi et al, J Soc. The Plant Resorueces Korea, (2019), 119-119). Among pine needle extracts, trans-Communic acid is a poorly soluble substance and is known to be effective in anticancer, anti-inflammatory, antibacterial, and hair loss prevention. (Barrero, Et al, J Soc. Molecules, (2012),17(2),1448- 67.)

Poorly soluble substances contain a hydrophobic portion in the structure of the compound, so they are not easily soluble in water.

It means a drug that is not soluble, and its practicality is often limited due to poor solubility. Of the drugs developed as new drugs, more than 41% of them are being discontinued due to poor solubility, and more than one-third of drugs listed in the US Pharmacopeia are classified as poorly soluble drugs (Korea Disclosure). Patent No. 2010-0096038). In order to improve the solubility of poorly soluble drugs, salt formation and solubilization using a surfactant are also used, but this method has a problem in that side effects occur due to the toxicity of the solubilizing solvent. In the case of cremophore, a solubilizing agent used due to the poor solubility of the anticancer drug taxol, side effects such as severe anaphylactic reaction, hyperlipidemia, aggregation of red blood cells and peripheral neuropathy due to the toxicity of cremaphore has been reported (H. Gelderblom et al., European Journal of Cancer, (2001), 37,1590-1598). On the other hand, various methods for maximizing the delivery efficiency of active ingredients have been studied, and the active substance delivery system (DDS) technology in medicine has been applied and tried in cosmetics. uses a lecithin emulsifier and a nano-liposome preparation through a high-temperature and high-pressure emulsification method is common, but this method reduces the active ingredient activity under high-temperature conditions for inducing nozzle pressure during the manufacturing process, and the instability of nano-liposomes and the capture of active substances in the liposome It is not widely used due to problems such as limited and low economic feasibility.

Synthetic polymer as a method of enhancing the solubility of poorly soluble substances in aqueous solution

The particles of the material are being studied. However, in the case of synthetic polymer material particles, due to the toxicity problem of decomposition products during decomposition, there are practically no polymer material particles applied to clinical practice except for poly-lactide-glycolide material. .

On the other hand, polygamma-glutamic acid is a polymer in which D.L-glutamic acid is combined with gamma-glutamyl, and is a viscous substance. Produced from a strain, this polygamma-glutamic acid is an edible, water-soluble and biodegradable high molecular material, and is already widely used as a raw material for cosmetics as a humectant and humectant (Aditya R Bhat et al., AMB).

express, 2013, (1), 36; Joerg M. Buescher et al., Critical Reviews in

Biotechnology, 2007, 27, 1-19).

An object of the present invention is to develop pine needle extract encapsulated particles capable of increasing water dispersibility, stability and delivery efficiency by encapsulating the pine needle extract and a cosmetic composition containing the same.

It was possible to achieve the above object through the specific aspects of the present invention as follows:

(1) a polygammaglutamic acid derivative having both a hydrophilic group and a lipophilic group, wherein the carboxy group of polygammaglutamic acid is bonded to the amine group of a phenylalanine derivative;

(2) The particles according to (1), in which the pine needle extract or a derivative thereof is encapsulated;

(3) the particle according to (2), wherein the particle size is 20 to 900 nm;

(4) Cosmetic composition comprising the particles of (4) above

The particles encapsulating the pine needle extract in the polygamma-glutamic acid derivative of the present invention enable efficient delivery that can increase water dispersibility, stability and delivery efficiency in cosmetics or pharmaceuticals.

The particles prepared with the polygamma-glutamic acid derivative of the present invention are

Because the inside is hydrophobic and the outside is hydrophilic, the active material of pine needle extract is stably enclosed inside, and the enclosed active material of pine needle extract is easily and stably dispersed in water in the form of particles. and furthermore provides application as an efficient delivery agent.

In addition, the particles encapsulating the pine needle extract in the derivative prepared from polygamma glutamic acid of the present invention block the exposure of the pine needle active material from the external environment, thereby increasing the physicochemical stability and enhancing the delivery effect, resulting in the delivery of the active material It increases the functional efficiency as a formulation and makes it possible to apply it to cosmetics or medicines.

1 is a particle size test result of Example (2)-1 particles in which the pine needle extract is encapsulated in a polygamma-glutamic acid derivative;
Figure 2 is a pine needle extract HPLC analysis test results when the pine needle extract is encapsulated in the polygamma-glutamic acid derivative Example (2)-3 proper encapsulation efficiency is investigated;
3 is a yield test result when the pine needle extract is encapsulated in the polygamma-glutamic acid derivative in Example (2)-3 and the proper encapsulation efficiency is investigated;
4 is a test result of the encapsulation rate when the pine needle extract is encapsulated in the polygamma-glutamic acid derivative Example (2)-3 and the proper encapsulation efficiency is investigated;
5 is a stability test result of particles encapsulated in a polygamma-glutamic acid derivative with a pine needle extract;
6 is a skin absorption test result of particles encapsulated in a polygamma-glutamic acid derivative with a pine needle extract;
7 is a pH stability test result under harsh conditions of Example (4) of a cosmetic composition containing particles containing a pine needle extract encapsulated in a polygamma-glutamic acid derivative;
8 is a specific gravity stability test result under severe conditions of Example (4) of a cosmetic composition containing particles containing a pine needle extract encapsulated in a polygamma-glutamic acid derivative;
9 is a skin irritation clinical test test result of Example (5) of a cosmetic composition containing pine needle extract in a polygamma-glutamic acid derivative.

The present invention relates to the development of pine needle encapsulated particles capable of increasing water dispersibility, stability and delivery efficiency by encapsulating a pine needle extract, and a cosmetic composition containing the same.

The present inventors have succeeded in manufacturing self-assembling pine needle encapsulated particles capable of increasing dispersibility, stability and delivery efficiency by encapsulating the pine needle extract in a derivative prepared from polygamma-glutamic acid, a natural material polymer with strong hydrophilicity. These particles can be used by adding them to various cosmetic formulations.

In order to selectively bind the amine group (-NH2) of phenylalanine to the carboxyl group (-COOH) of polygammaglutamic acid, it is preferable to use a phenylalanine derivative in which the carboxyl group of phenylalanine is shielded.

The polygamma-glutamic acid derivative of the present invention is preferably a polygamma-glutamic acid derivative.

10 to 60% of the carboxyl groups are bonded to the amine group of the phenylalanine derivative.

The molecular weight of gamma glutamic acid in the polygammaglutamic acid derivative of the present invention is 3K

to 450K is preferred.

The polygamma-glutamic acid derivative of the present invention prepared in this way has a central axis (backbone).

The glutamic acids forming the hydrophilic part constitute the hydrophilic part, and the substituted phenylalanine part constitutes the hydrophobic part. That is, the polygamma-glutamic acid derivative of the present invention has amphiphilic properties. Therefore, when the polygamma-glutamic acid derivative of the present invention is dispersed in water, the hydrophilic part faces outward and the hydrophobic part gathers toward the center of the sphere to easily form micelles. The active material can be easily encapsulated in the particles. If the pine needle extract comes into contact with water while not encapsulated in the particle, it will precipitate immediately, or if it is oil, it will float on the surface of the water and immediately separate the layer. Since the hydrophilic portion is occupied, it may be stably dispersed. In addition, the pine needle active material encapsulated in the particles is not exposed to the external environment of the particles and is protected by the particle components, so its stability can be guaranteed even when exposed to various environments such as cosmetics. It is possible to increase the delivery efficiency of the active material.

There is no particular limitation on the size of the pine needle extract encapsulated particles of the present invention within the nanoscale as long as the particles are stably formed. However, it is particularly preferable that the particle size is 20 to 900 nm.

The polygamma-glutamic acid derivative of the present invention is described through the following examples, etc.

Although specific examples are described with respect to the preparation of the pine needle extract encapsulated particles in half, the content of the present invention is not limited thereto.

Example (1). Preparation of polygamma-glutamic acid derivatives

In a 250 ml round flask, 1 g of polygamma-glutamic acid having a molecular weight of 50K is dissolved in a solution of 40 ml of 0.3M sodium bicarbonate concentration. For coupling with phenylalanine, 1.5 g of ethyl (dimethylaminopropyl) carbodiimide: EDC] was added to polygammaglutamic acid with a molecular weight of 50K in an equivalent ratio of 1:387, and sodium hydrogen carbonate 0.3M concentration 5ml was dissolved in a 250ml round flask and reacted for 30 minutes at 0 ℃ environment. After that, 1.8 g of phenylalanine ethyl ester in a 1:387 equivalent ratio was placed in a 15 ml conical tube, and then added as a powder while gradually dissolving in a 250 ml round flask. After washing with the solution, it is added to a 250 ml round flask and reacted for 12 hours.

After that, using a MWCO (molcular weight cut off) 3,500 filtration membrane, unreacted phenylalanine, ethyl (dimethylaminopropyl) carbodiimide (EDC) and carbonic acid in tertiary distilled water for one day and methanol (MeOH) for the next two days Sodium hydrogen is filtered off. The polygamma-glutamic acid to which phenylalanine is bound is transferred from the filtration membrane to a 250 ml round flask again, and methanol (MeOH), a result of solvent exchange due to the filtration membrane, is removed using a pressure reducing device, and the polygammaglutamic acid derivative of the present invention (polygammaglutamic acid molecular weight 50K) and phenylalanine conjugation ratio of 30%) was obtained.

Example (2) Preparation of particles containing pine needle extract

The polygamma-glutamic acid derivative prepared in Example (1) was dissolved in methanol (MeOH) at a concentration of 10 mg/ml. The pine needle extract was dissolved in methanol at a concentration of 5 mg/ml. Then, after mixing the two solutions in a mass ratio of 1:1, the solvent was removed using a rotary pressure reducer, dispersed in 1 ml of tertiary distilled water, and stirred to obtain a nanoparticle suspension. Thereafter, the particles were stored in powder form by freeze-drying.

Experimental Example 1. Measurement of the size of nanoparticles

Each of the nanoparticles of Example (2) was dispersed in tertiary distilled water, and

For the formed nanoparticle suspension, the particle size was measured by requesting the Korea Research Institute of Chemical Convergence. It was confirmed that the nanoparticles encapsulated in the pine needle extract had a uniform size, and showed an average particle size of 537.2 nm (FIG. 1).

Experimental Example 2. Experiment to confirm improvement of water dispersibility by encapsulation in particles

An experiment was conducted to confirm whether the water dispersability of the pine needle extract is improved after encapsulation in the particles of the present invention. The water dispersibility of the pine needle extract not encapsulated in the particles and the pine needle extract encapsulated in the particles of the present invention (Example (2)) was compared. First, in the case of the pine needle extract not encapsulated in the particles, 1 mg of the pine needle extract was weighed and added to 1 ml of tertiary distilled water, and then ultrasound was used for dispersion. The powdery particles encapsulated in the pine needle extract were dispersed in tertiary distilled water at a concentration of 1 mg/ml. The difference in water dispersibility was compared by taking pictures of each dispersed in tertiary distilled water. As a result, in the case of the pine needle extract itself that was not encapsulated in the particles, the pine needle extract was not dispersed or dissolved in water and a clear layer separation occurred. However, when the pine needle extract is encapsulated in the particles of the present invention, it can be confirmed that the particles in which the pine needle extract is encapsulated are dispersed in a stable state in the tertiary distilled water.

Experimental Example 3. Investigation of proper encapsulation efficiency of pine needle extract in particles

To investigate the proper encapsulation efficiency, 0.1 g, 0.2 g, 0.3 g, 0.4 g, and 0.5 g of the pine needle extract were added to 1 g of the polygamma-glutamic acid derivative of Example (1), respectively, and then freeze-dried after encapsulation to obtain a powder form. 10 mg of powder was dissolved in 10 ml of methanol (MeOH) solution to prepare a test solution. In addition, trans-Communic acid (trans-Communic acid) standard, an indicator material of the pine needle extract, was dissolved in methanol (MeOH) to prepare 1, 10, and 100 ug/ml. The prepared sample solution and standard solution were analyzed through HPLC chromatography. Analysis conditions were measured at 232.7 nm wavelength at a flow rate of 1 ml/min by mixing acetonitrile with distilled water with 0.1% trifluoro acetic acid added to a VDSpher 100 C18-E 150*4.6mm 5um column and measuring the main peak of the standard solution. Calculate the content of trans-Communic acid, an index component of pine needle extract, by obtaining a standard test curve (linearity r2 = 0.999997) from the area value between delayed meals and substituting the area value of the sample solution peak at the same location as between delayed meals of the main peak of the standard solution did The amount of trans-Communic acid in the encapsulated pine needle extract was divided by the amount of trans-Communic acid in the pine needle extract added at the time of encapsulation, and the percentage was used as the yield. The weight of the self-assembled particles containing Jeju pine needle extract obtained after encapsulation was divided by the sum of the weight of Jeju pine needle extract and self-assembled particles, and the percentage was calculated as the encapsulation rate. As a result, in 0.5 g, it was confirmed that the yield was about 68% and the encapsulation rate was about 3.5% ( FIGS. 2, 3 and 4 ).

Experimental Example 4. Investigation of Stability of Encapsulated Pine Leaf Extract Particles

The particles of Example (2) were dispersed at a concentration of 0.1% in purified water at room temperature, and the degree of dispersion in vitro was analyzed through light scattering. It was confirmed that the scattering value at 12-hour intervals for 8 days was maintained without a change in the scattering pattern within 50%. In addition, it was confirmed that the constant dispersion of the particles was maintained as the light scattering was kept constant at the top and bottom of the test tube. That is, it can be seen that the stability is maintained in the observation for 8 days at room temperature, which has the sensitivity of the equipment up to 200 times, so it was confirmed that the stability will be maintained until after 160 days (FIG. 5).

Experimental Example 5. Pine leaf extract derivative encapsulated particle skin absorption test

According to the Korean Food and Drug Administration (KFDA) in vitro skin absorption test guideline, the skin absorption of the particles of Example (2) was analyzed using a skin penetrating device. In the donor compartment of the skin penetrating device, 5 mg/cm2 of the particles containing the pine needle extract of Example (2) was evenly applied on artificial skin (Membrane Strat-M, manufactured by Merck MIllipore), and the sample was collected after 24 hours at 32 ℃ temperature condition. The amount of trans-Communic acid, an indicator component absorbed and permeated into the skin, was analyzed through HPLC. As a result, it was confirmed that about 49.01% of the particles were absorbed into the skin with 0.74% for skin and 48.27% for receptor (FIG. 6).

Example (3) Preparation of a cosmetic composition containing pine needle extract encapsulated particles

The particle containing the pine needle extract of Example (2) was 100 ppm, and the Bulgaris leaf extract 63.3557%, glycerin 6.2%, butylene glycol 5.2%, purified water 3.85%, ethylhexyl palmitate 3.5%, ethoxydie Glycol 3%, Glycereth-26 3%, Tranexamic Acid 3%, White Rice Flower Extract 2%, Reed Root Extract 1.5%, Cetylethyl Hexanoate 1.4%, Hydrogenated Lecithin 0.28%, Polyglutamic Acid 0.0001%, sodium hyaluronate 0.02%, dipotassium glycyrrhizate 0.05%, ethylphenylalanamidopolygamma glutamic acid 0.05%, pine leaf extract 0.05%, phenylalanine 0.0001%, hydrolyzed collagen 0.0001 %, star anise extract 0.15%, hydroxycinnamic acid 0.005%, octyldodeses-16 0.5%, hydroxyethyl cellulose 0.15%, polyglyceryl-10 oleate 0.7%, carbomer 0.6%, arginine 0.6% , betaine salicylate 0.1%, caprylyl glycol 0.25%, 1,2-hexanediol 0.47%, rosemary leaf oil 0.019% to prepare a cosmetic composition in an appropriate amount.

Example (4) Stability investigation of pine needle extract-encapsulated particles in a cosmetic composition

Severe condition stability test was performed on the cosmetic composition containing the pine needle extract-encapsulated particles of the invention prepared in Example (3). The test method was stored repeatedly at 50℃ -> room temperature -> -20℃ according to the guidelines, and the results of pH, specific gravity and change over time were investigated for 2 weeks as follows. As can be seen, it was confirmed that stable results were exhibited without significant changes in pH, specific gravity, and changes with time ( FIGS. 7 and 8 ).

Example (5) Skin irritation test of cosmetic composition containing pine needle extract derivative encapsulated particles

The cosmetic composition containing the pine needle extract encapsulated particles of the invention prepared in Example (3) was requested for a skin irritation clinical test to the Clinical Support Center for Oriental Medicine Bio Industry at Semyung University. It was conducted for 30 women in their 20s and 50s, and the skin type and condition of the subjects were confirmed to be safe as non-irritating, with no irritation at all (FIG. 9).

Claims (3)

Particles characterized in that the pine needle extract is encapsulated in the derivative in which the carboxy group of polygamma-glutamic acid is bound to the amine group of the phenylalanine derivative. The particle according to claim 1, wherein the particle size is from 20 to 900 nm. A cosmetic composition comprising the particles of claim 1

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