JP2016222694A - Production method of nano liposome for cosmetics in which oleanolic acid is collected - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide production methods of nano liposome for cosmetics in which oleanolic acid is collected as an active ingredient having excellent wrinkle improving effect.SOLUTION: The invention provides a production method of nano liposome for cosmetics in which oleanolic acid is collected, comprising the steps of: homogeneously mixing one or more polyol components selected from the group consisting of propylene glycol, glycerin, and these mixtures, an oil soluble component that is C10-40 fatty alcohol, and a phospholipid component that is lecithin, and obtaining a mixture; adding oleanolic acid into the mixture; cooling it, adding ethanol, and then homogeneously mixing; and adding a surfactant and water into the mixed solution and then homogeneously mixing it.SELECTED DRAWING: None

Description

  The present invention relates to a method for producing nanoliposomes for cosmetics in which oleanolic acid is collected as an active ingredient for improving wrinkles.

  The skin is the primary protective film of the human body, protecting various organs in the body from changes in temperature and humidity, ultraviolet rays, pollutants, and other external environmental stimuli, and also important for maintaining homeostasis such as body temperature regulation. Has a role to play. However, excessive physical and chemical stimuli, stress, and nutritional deficiencies received from the outside reduce the normal function of the skin and promote skin aging phenomena such as loss of elasticity, keratinization, and generation of wrinkles. In order to prevent such a phenomenon and maintain a healthier and more elastic skin, most of the cosmetics used in the past have various problems such as weak efficacy and inducing side effects on the skin. (Korean Patent Publication 10-2010-0064451).

  While research on raw materials having anti-aging effects on skin without inducing skin side effects, oleanolic acid is applied to skin cosmetic compositions to exhibit excellent anti-aging effects on skin. discovered. Oleanolic acid, a type of hydroxypentacyclic terpene, is an active ingredient in many natural plants such as Eriobotrya japonica (loquata), Perilla frutescens, Staphyleohalocarpa, and is also found in fruits such as apples or pears. In addition, it has pharmacological effects such as anti-inflammatory, anti-cancer, anti-allergy, anti-depressive, antibacterial and anti-fungal. Especially, it has anti-inflammatory and stimulating effects related to the physiological activity of the skin. Have. It is an enzyme that promotes the synthesis of procollagen, which is important for the production of collagen as an anti-aging function, promotes the synthesis of ceramide and filler green, which are important for the prevention of aging, and destroys macromolecular proteins such as collagen produced. It is characterized by having a double anti-aging system that inhibits the activity of MMP-1 to promote collagen production and prevent collagen destruction. In this way, oleanolic acid, which has an excellent effect on improving skin wrinkles, has been used as a wrinkle-improving raw material in various emulsified cosmetic dosage forms, but it is not only slightly soluble in water but also cosmetics. Even if it is applied to the above, there is a limit to including a certain content or more due to problems of stability and instability. In particular, due to such poorly soluble properties, it has been impossible to directly use oleanolic acid as a wrinkle-improving raw material in solubilizing agents such as skin lotions.

  Recently, by using nanotechnology of skin lipid-like composition, oleanolic acid components are encapsulated in nanoemulsions with a size of 100-150 nm, and then secondary encapsulated with a polymer emulsifier using natural polysaccharide inulin. The situation where oleanolic acid can be used regardless of the cosmetic dosage form has been developed to improve stability, but in emulsified products, when oleanolic acid thus encapsulated is put into the dosage form, In order to prevent capsule breakage due to the process, there is annoyance that it must be introduced at a temperature of 50 ° C. or lower and a low homomixing speed, and in particular, in the solubilizer form, stability and titer instability still exist. It is the actual situation. It is not only more expensive than simply using oleanolic acid, but also the product feel by using additional ingredients in addition to oleanolic acid for oleanolic acid encapsulation. Can have a negative effect.

  In addition, at the time when the market for organic agricultural certified cosmetics has grown globally, oleanolic acid was only recognized as a naturally-occurring wrinkle functional ingredient. When oleanolic acid is encapsulated using technology, many ingredients that cannot be used in organic agricultural certified cosmetics are contained, and therefore cannot be used as raw materials for organic agricultural certified cosmetics.

  In order to solve the above-mentioned problems of the prior art, the present invention is to stabilize oleanolic acid excellent in wrinkle improvement effect into nanoliposomes alone without encapsulating using other additional raw materials. It aims at providing the manufacturing method which makes it collect.

  In order to achieve the above object, the present invention provides a method for producing nanoliposomes for cosmetics in which oleanolic acid is collected.

  The cosmetic composition containing the nanoliposome obtained by the production method of the present invention is obtained by collecting oleanolic acid effective in improving skin wrinkle in the nanoliposome and stabilizing it in the dosage form. Increases the rate of percutaneous absorption, promotes the synthesis of collagen, provides an excellent wrinkle-improving effect, and does not require additional raw materials to stabilize oleanolic acid. Can be reduced. In addition, it is possible to provide a refreshing and moist feeling after absorption, thereby satisfying the consumer demand for organic agricultural wrinkle functional cosmetics that are increasing worldwide.

  The present invention provides nanoliposomes containing oleanolic acid as an active ingredient, and a cosmetic composition comprising the nanoliposomes can be formulated in a solubilized form. The oleanolic acid is collected in the nanoliposomes, and stabilized by the nanoliposomes can increase the stability and solubility of the oleanolic acid within the solubilized dosage form, increasing the transdermal absorption rate. be able to.

  The oleanolic acid used in the present invention is uniquely recognized as a naturally occurring wrinkle functional ingredient, and in the present invention, 0.0001 to 5.0% by weight based on the total weight of the composition, Preferably it is contained in an amount of 0.0005 to 1.0% by weight. If the concentration is less than 0.0001% by weight, a clear effect cannot be expected. If the concentration exceeds 5.0% by weight, not only a clear increase in the effect due to an increase in the content does not appear, but also the dosage form is stable. This is because it has a bad effect every time.

  The nanoliposome obtained by the production method of the present invention has a liposome form, means a liposome having an average particle diameter of 10 to 500 nm, and the size of the nanoliposome formed by the present invention is preferably 50 to 300 nm. This is because, when the average particle diameter of the nanoliposome exceeds 300 nm, among the technical effects to be achieved by the present invention, improvement of skin penetration and improvement of dosage form stability are very weak.

  The nanoliposomes formed for the stabilization of oleanolic acid in the present invention are produced by a mixture comprising a polyol, an oily component, a surfactant, a phospholipid, and water. In addition, nanoliposomes that collect oleanolic acid contained in solubilized cosmetic compositions are formed spontaneously when producing solubilized cosmetic compositions simply without high-pressure emulsification or a separate manufacturing process. It is characterized by being.

  The polyol used in the solubilized cosmetic composition containing nanoliposomes obtained by the production method of the present invention is not particularly limited, and is preferably propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, methylpropane. One or more selected from the group consisting of diol, isopropylene glycol, pentylene glycol, erythritol, xylitol, sorbitol, and mixtures thereof. The polyol is used in an amount of 5 to 50% by weight, preferably 15 to 30% by weight, based on the total weight of the solubilized cosmetic composition containing nanoliposomes.

As the oil component used in the solubilized cosmetic composition containing nanoliposomes obtained by the production method of the present invention, various oils known in the art can be used, preferably hexadecane and paraffin oil. Hydrocarbon oils, ester synthetic oils, silicone oils such as dimethicone and cyclomethicone, sunflower oil, corn oil, soybean oil, avocado oil, sesame oil, and animal and vegetable oils such as fishing oil, ethoxylation alkyl ether-based oil, propoxylated alkyl ether-based oil, sphingolipids such as phytosphingosine (phytosphingosine), sphingosine and sphinganine, cerebroside, cholesterol, sitosterol cholesteryl sulfate, sitosterol sulfate, C _10-40 fat Alcohol, and mixtures thereof. The usage-amount is 0.01 to 10.0 weight% with respect to the total weight of the solubilized cosmetic composition containing a nanoliposome, Preferably it is 1.0 to 5.0 weight%.

  As the surfactant used in the solubilized cosmetic composition containing nanoliposomes obtained by the production method of the present invention, any surfactant known in the art may be used. For example, as the surfactant in the present invention, an anionic surfactant, a cationic surfactant, an amphoteric surfactant, and a nonionic surfactant can be used, and preferably an anionic surfactant And nonionic surfactants can be used. Specific examples of the anionic surfactant include alkyl acyl glutamate, alkyl phosphate, alkyl lactic acid, dialkyl phosphate and trialkyl phosphate. Specific examples of nonionic surfactants include polysorbates, alkoxylated alkyl ethers, alkoxylated alkyl esters, alkyl polyglycosides, polyglyceryl esters, and sugar esters. The amount of the surfactant used is 0.001 to 5.0% by weight, preferably 0.1 to 1.0% by weight, based on the total weight of the solubilized cosmetic composition containing nanoliposomes. .

  In the nanoliposomes formed in the present invention, an amphipathic lipid is used as the phospholipid, and a natural phospholipid (eg, egg yolk lecithin or soybean lecithin, sphingomyelin) and a synthetic phospholipid (eg, dipalmitoyl phosphatidylcholine or hydrogenated lecithin) ), Preferably lecithin. In particular, naturally derived unsaturated lecithin or saturated lecithin extracted with soybean or egg yolk is preferable. Usually naturally derived lecithin has a phosphatidylcholine content of 23-95% and a phosphatidylethanolamine content of 20% or less. In the production of the solubilized cosmetic composition containing the nanoliposome of the present invention, the amount of phospholipid used is 0.01 to 5.0% by weight with respect to the total weight of the solubilized cosmetic composition, preferably 0.5 to 2.0% by weight.

  The water used in the solubilized cosmetic composition containing nanoliposomes obtained by the production method of the present invention is generally deionized distilled water, and the amount of water used is the total amount of the solubilized cosmetic composition. It is 25.0-90.0 weight% with respect to a weight.

  The solubilized cosmetic composition containing the nanoliposome obtained by the production method of the present invention is used as an anti-aging composition which provides a particularly excellent wrinkle-improving effect by containing oleanolic acid.

  In addition, the composition containing the nanoliposome obtained by the production method of the present invention is not particularly limited in its dosage form, but considering the transparent or suspension appearance and the advantages in use, Basic cosmetics such as nourishing lotions, sprays, mists or gels; hair cosmetic compositions such as hair tonics, hair essences or hair treatments; other pharmaceuticals and quasi-drugs It can be used as a skin wrinkle-improving agent that is safe and effective without side effects even when applied to human skin.

  The composition containing nanoliposomes obtained by the production method of the present invention comprises a fatty substance, an organic solvent, a solubilizer, a thickener and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizing agent, and a foaming agent. , Fragrances, surfactants, water, ionic or non-ionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic Adjuncts commonly used in the cosmetics or dermatological field such as active or lipophilic active agents, lipid vesicles, or any other ingredient normally used in cosmetics. These adjuvants are introduced in amounts commonly used in the cosmetics or dermatological fields.

  Hereinafter, the present invention will be described more specifically through examples and test examples. However, the following examples, experimental examples, and preparation examples are provided for illustrative purposes only to assist in understanding the present invention, and it is clear that the scope and scope of the present invention is not limited thereto. To do.

[Reference Example 1] Preparation of oleanolic acid-stabilized skin lotion stabilized with nanoliposomes Solubilized makeup for improving wrinkles of Examples 1 to 3 and Comparative Examples 1 to 4 according to the composition described in Table 1 below Water was produced (unit: wt%).
Examples 1 to 3 are solubilized lotions that form the nanoliposomes according to the present invention and that contain the nanoliposomes. Comparative Examples 1 and 2 are generally acceptable different from Examples 1 to 3. A solubilizer is used, and Comparative Example 3 contains oleanolic acid in an encapsulated oleanolic acid nano-based form. In Comparative Example 4, oleanolic acid was dissolved in a mixture of ethanol and propylene glycol 4: 1.

The manufacturing method is as follows.
1) Components 1 to 3 and polyol components 4 to 5 were added at a time, heated and dissolved at 80 ° C., and then components 6 to 9 were added and mixed uniformly.
2) After the mixture of 1) was cooled at 65 ° C., ethanol (component 10) was added and mixed well.
3) The water phase components of components 11 to 14 were uniformly mixed in advance, then heated at 65 ° C., and then uniformly mixed with the mixture of 2).
4) The above 3) was cooled and stored at room temperature.

  On the other hand, in the case of Comparative Example 3, after step 3), encapsulated oleanolic acid nanobase (component 15) is charged.

[Test Example 1] Composition Stability Evaluation Solubilized makeup produced in Examples 1 to 3 and Comparative Examples 1 to 4 in order to examine the stability of the solubilized cosmetic composition for improving wrinkles due to changes over time. The water was stored for 1 month in a thermostat bath at room temperature, 45 ° C. and a thermostat bath circulated from −10 ° C. to 45 ° C. at intervals of 12 hours, and the change in appearance was observed.

  If the result in the said Table 2 is seen, Examples 1-3 which collected oleanolic acid in the nano liposome may be stabilized in the long term rather than Comparative Examples 1-2 which used another general solubilizer. I understand. In addition, comparing Example 2 with Comparative Examples 1-2, the amount of surfactant used in Example 2 in which oleanolic acid was collected and stabilized in nanoliposomes was compared with 1- It can be seen that it is much less than the amount of surfactant used in 2. This indicates that when nanoliposomes are formed to collect oleanolic acid, the amount of surfactant that must be used in the dosage form can be significantly reduced, and the skin when using large amounts of surfactant. Risk of irritation can also be avoided.

[Test Example 2] Comparison of feeling of use between a composition in which nanoliposomes are formed to stabilize oleanolic acid and a composition using encapsulated oleanolic acid In order to evaluate, a sensory test was carried out on the solubilized cosmetic composition for improving wrinkles produced in Example 2 and Comparative Example 3. For 20 women aged 25 to 35 years old, each wrinkle-improving solubilized cosmetic composition was applied to the back of the hand by a general usage method, and the satisfaction with the feeling of use was evaluated. . The sensory evaluation is a total of four items: stickiness, absorption, moisturizing, and nutrition. Very good (10 points), excellent (7.5 points), normal (5 points), and bad for each item. Based on the criteria of (2.5 points) and very bad (0 points), this value was averaged and shown in Table 3 below.

  When comparing Example 2 where nanoliposomes were formed in a dosage form to stabilize oleanolic acid and Comparative Example 3 using encapsulated oleanolic acid, the same amount of oleanolic acid was used. However, Comparative Example 3 using encapsulated oleanolic acid uses about 2.4% or more more of the stabilizing material than Example 2 to produce encapsulated oleanolic acid nanobases. When it was found that it had an unfavorable effect on the feeling and the feeling of use was compared, the feeling of use of the dosage form in which nanoliposomes were formed in the dosage form to stabilize oleanolic acid as shown in Table 3 was far You can see that it is good.

[Test Example 3] Measurement of collagen biosynthesis promoting effect The collagen biosynthesis promoting effect of Example 2 was measured in comparison with tocopherol and EGCG which are known to promote collagen biosynthesis. First, human fibroblasts (PromoCell, Germany) were seeded in 24 wells at a rate of 10 ⁵ per well and cultured until they grew to about 90%. This was cultured in serum-free DMEM medium for 24 hours, then treated with Example ⁴ tocopherol and EGCG dissolved in serum-free medium at 10 ^-4 molar concentrations, respectively, and in a CO ₂ incubator for 24 hours. Cultured. These upper layer solutions were taken, and the presence or absence of increase or decrease of procollagen was observed using a procollagen type (I) ELISA (ELISA) kit (procollagen type (I)). The results are shown in Table 4 below. Here, the synthetic ability is compared with the untreated group as 100.

  As can be seen from Table 4 above, the composition of Example 2 promotes collagen biosynthesis, which is far superior to tocopherol and EGCG, which are known to promote collagen biosynthesis. You can see that

[Test Example 4] Measurement of skin absorption The skin absorption was measured using a Franz permeation cell for guinea pig skin. Immediately before the test, the skin of the abdomen of the guinea pig was collected and cut in an area of 1 cm ² square, and then placed in a transmission cell having a transmission mirror diameter of 0.9 cm and fixed with a clamp. One side of the skin (donor container) was formed with nanoliposomes and samples of Comparative Example 4 in which oleanolic acid was dissolved in ethanol and propylene glycol (4: 1) to stabilize oleanolic acid. The sample of Example 2 was applied in an amount of 0.2 g each, and the other surface (receptor container) was brought into contact with a solvent in which purified water and ethanol were mixed at a weight ratio of 4: 1. The temperature during the test was maintained at 32 ° C., which is the actual skin temperature. After the start of the test, a part of the solvent was collected at regular time intervals, and then the amount of oleanolic acid absorbed into the skin was measured using HPLC, and the amount of skin absorbed per application concentration over time (μg / cm ² / weight%). The results are shown in Table 5 below.

<HPLC analysis conditions>
-Column: Waters Novapak C18 (3.9 mm x 250 mm, 4 um)
-Solvent flow rate: 1 ml / min -Detection UV: 210 nm
Sample measurement concentration: 10 to 100 ug / mL
-Sample injection volume: 20 uL
-Eluent: MeOH / 0.1% H ₃ PO ₄ = 82/18

  From the results of Table 5, it can be seen that the transdermal absorption amount of Example 2 in which oleanolic acid is stabilized by the formation of nanoliposomes is far superior.

Claims (6)

1) Uniformly comprising at least one polyol component selected from the group consisting of propylene glycol, glycerin and mixtures thereof, an oil-soluble component which is C _10-40 fatty alcohol, and a phospholipid component which is lecithin Mixing to obtain a mixture;
2) adding oleanolic acid to the mixture of step 1);
3) cooling the mixture of step 2), adding ethanol and then mixing uniformly;
4) A method for producing nanoliposomes for cosmetics in which oleanolic acid is collected, which comprises the step of adding a surfactant and water to the mixed solution of step 3) and then uniformly mixing them.   The method according to claim 1, wherein the lecithin is hydrogenated lecithin.   The production method according to claim 1 or 2, wherein the lecithin content is 0.05 to 1.0% by weight based on the total weight of the composition.   The said nanoliposome has an average particle diameter of 50-300 nm, The manufacturing method in any one of Claims 1-3 characterized by the above-mentioned.   The manufacturing method according to any one of claims 1 to 4, wherein the use ratio of the lecithin to the oleanolic acid is 1: 4 based on weight.   The said cosmetics are cosmetics which have a solubilizer form, The manufacturing method in any one of Claims 1-5 characterized by the above-mentioned.