KR20160102722A - Agent for inhibiting decomposition of hyaluronic acid comprising sodium 2-mercaptoethane sulfonate, and the composition comprising the same - Google Patents

Abstract

The present invention relates to a composition for inhibiting decomposition of hyaluronic acid or a derivative thereof. More specifically, the present invention relates to a composition for inhibiting decomposition of hyaluronic acid or a derivative thereof, containing sodium 2-mercaptoethane sulfonate and thus exhibiting increased resistance to activity of hyaluronidase. The present invention further relates to a composition for bioinjection or cosmetic surgery, containing the composition for inhibiting decomposition and hyaluronic acid or the derivative thereof, particularly a composition for biotissue restoration.

Description

Disclosed is a composition for inhibiting the decomposition of hyaluronic acid containing sodium 2-mercaptoethanesulfonate and a composition containing the same.

The present invention relates to a composition for inhibiting the degradation of hyaluronic acid or a derivative thereof, and more particularly, to a composition for inhibiting the degradation of hyaluronic acid or a derivative thereof. More particularly, the present invention relates to a composition containing hyaluronic acid or a derivative thereof A decomposition inhibitor, and a composition for biomedical or cosmetic molding, particularly a composition for protecting a living tissue, containing the decomposition inhibitor and hyaluronic acid or a derivative thereof.

Hyaluronic acid is a complex polysaccharide composed of amino acid and uronic acid, and is a macromolecular compound having a molecular weight of 200,000 to 400,000 in which N-acetylglucosamine and glucuronic acid are alternately linked in a chain. It is involved in cell division, differentiation and migration, as well as being involved in storage and diffusion of water retention, intercellular space maintenance, cell growth factors and nutrients as main constituents of extracellular matrix. Hyaluronic acid is a component that exists in many vitamins (琉璃 體), joint fluid, cartilage, and skin of animal. It is combined with a large amount of water to become a gel state, and is involved in lubrication of joints and flexibility of skin. It also plays an important role in preventing penetration and penetration of toxins into the skin.

It has been reported that hyaluronic acid is a component existing naturally in all living organisms. It has been reported that more than 50% of hyaluronic acid present in the mammalian body is distributed in the intercellular spaces of the skin, especially the intercellular spaces of the epidermis and the connective tissues of the dermis. Are mainly synthesized by keratinocytes and fibroblasts. Hyaluronic acid makes skin elastic and reduces damage to the lower part of the skin when it is damaged. And important collagen smoothes the movement between cells, and acts as lubricant to smooth movements of bones and joints. Hyaluronic acid also prevents penetration of foreign substances such as bacteria and prevents skin diseases such as infection.

As the age increases, the amount of hyaluronic acid in the skin decreases and the production capacity decreases. Usually, it is the highest at about 18 years old, and it is said to be beautiful and volumey, and to decrease after that. As such, the amount of hyaluronic acid in human skin decreases with aging, which is one of the direct causes of reduced skin elasticity and moisture content due to aging.

On the other hand, sodium 2-mercaptoethanesulfonate is an organic sulfur compound used as an adjuvant in the chemotherapy regimen involving cyclophosphamide and ifosfamide, and is useful for the treatment of hemorrhagic cystitis due to the use of cyclophosphamide and ifosfamide, And has been mainly used as a drug to lower the incidence of hematuria. In addition, U.S. Patent Publication No. 2014-142063 discloses that a thiol additive such as sodium 2-mercaptoethanesulfonate promotes the hydrogel formation process and accelerates the hydrogel decomposition formed, but sodium 2-mercaptoethanesulfonate How the sulfonate works in the skin or skin tissue is not specifically disclosed.

In order to prevent the degradation of hyaluronic acid, there has been a method of delaying the degradation of hyaluronic acid by adjusting the ratio of the gel and the sol constituting the hyaluronic acid filler. However, this method has a limitation in effectively preventing the degradation of hyaluronic acid.

In addition, it is mentioned that style age filler developed by Vivacy of France can slow down the decomposition of hyaluronic acid by adding mannitol, which is an antioxidant, by suppressing active oxygen, but the specific mechanism of action thereof is not known, It is not a method that can directly inhibit the degradation of hyaluronic acid.

Korean Patent Publication No. 10-2011-0057895 (published on June 1, 2011) U.S. Patent Publication No. 2014-142063 (published on May 22, 2014) Korean Patent Laid-Open No. 10-2013-0132503 (published Dec. 14, 2013) Korean Patent Laid-Open No. 10-2004-0020789 (published on March 30, 2004)

Kim, Mi Sook et al., Biomaterials Application of Hyaluronic Acid Derivatives, Biomaterials Research (2008) 12 (3): 83-95

The present inventors have sought to find a substance capable of preventing the degradation of hyaluronic acid or its derivative by hyaluronidase as an approach capable of increasing the amount and / or lifetime of hyaluronic acid or a derivative thereof. Surprisingly, The inventors of the present invention have found that the caffeoethanesulfonate can impart resistance to hyaluronidase, thus completing the present invention.

Accordingly, it is an object of the present invention to provide a composition having resistance to hyaluronidase by using sodium 2-mercaptoethanesulfonate.

In order to accomplish the above object, the present invention provides an agent for inhibiting the decomposition of hyaluronic acid or a derivative thereof containing sodium 2-mercaptoethane sulfonate as an active ingredient.

The present invention also provides a composition for inhibiting the decomposition of hyaluronic acid or a derivative thereof containing sodium 2-mercaptoethane sulfonate as an active ingredient.

The present invention also provides a composition for biomedical administration or cosmetic molding containing the decomposition inhibitor and hyaluronic acid or a derivative thereof.

The inhibitor of decomposition of hyaluronic acid or its derivative of the present invention has increased resistance to degradation of hyaluronic acid by hyaluronidase by containing sodium 2-mercaptoethanesulfonate, and thus, hyaluronic acid or hyaluronic acid in skin or skin tissue It is possible to prevent the reduction of the derivatives thereof and to effectively suppress skin elasticity and moisture content reduction due to aging. In addition, the composition of the present invention contains sodium 2-mercaptoethanesulfonate and hyaluronic acid, thereby effectively increasing the skin volume and maintaining it for a long period of time, thereby providing excellent biocompatibility.

Figure 1 shows the result of measuring the resistance to degradation of hyaluronic acid by hyaluronidase.
FIG. 2 shows the results of measurement of cytotoxicity by MESNA concentration.

The present invention relates to a composition capable of inhibiting the degradation of hyaluronic acid by hyaluronidase, specifically a composition comprising hyaluronic acid containing sodium 2-mercaptoethane sulfonate as an active ingredient or And a decomposition inhibitor of the derivative thereof.

The present invention also provides a composition for inhibiting the decomposition of hyaluronic acid or a derivative thereof containing sodium 2-mercaptoethane sulfonate as an active ingredient.

The present invention also relates to a composition containing the decomposition inhibitor or decomposition inhibiting composition and a biodegradable polymer, preferably hyaluronic acid or a derivative thereof, particularly a composition for biomedical or cosmetic molding, will be.

As used herein, the term " biodegradable polymer " refers to a substance capable of degradation in the body when it is inserted into a living body. Examples of the biodegradable polymer include natural polymers such as hyaluronic acid, collagen, albumin, and chitosan, polyglycolide, polylactide, And synthetic polymers such as polyvinyl alcohol and polyvinyl alcohol.

As the derivatives of hyaluronic acid, there are no particular limitations on the kind of hyaluronic acid. Examples of hyaluronic acid derivatives include hyaluronic acid-collagen complex, hyaluronic acid-polycarboxylic acid-containing natural polymer complex, hyaluronic acid-chitosan complex, hyaluronic acid-based blend (For example, a blend of polyvinyl alcohol or polyacrylic acid and hyaluronic acid), graft hyaluronic acid copolymer (refer to Biomaterials Research (2008) 12 (3): 83-95, application of biomaterials of hyaluronic acid derivatives, .

The composition of the present invention includes 2-mercaptoethanesulfonate and a salt thereof, preferably a metal salt of 2-mercaptoethanesulfonate may be used. The type of the metal ion forming the metal salt is not particularly limited, but includes sodium, potassium, lithium, calcium, magnesium and the like, and sodium cation is particularly preferably used.

The sodium 2-mercaptoethanesulfonate used in the present invention is a compound represented by the following formula (1) and is referred to as 2-mercaptoethane sulfonate Na or briefly MESNA (hereinafter referred to as "MESNA" Quot;).

[Chemical Formula 1]

The composition of the present invention contains 0.0001 to 20% by weight, preferably 0.0005 to 15% by weight, more preferably 0.001 to 10% by weight, of 2-mercaptoethanesulfonate and salts thereof, preferably MESNA, By weight, even more preferably 0.005 to 2% by weight and even more preferably 0.01 to 1.5% by weight. If it is less than 0.0001% by weight, the desired effect can not be obtained, and it is inappropriate to exceed 20% by weight in consideration of irritation to the skin and blending with other ingredients.

When the composition for vital administration of the present invention is formulated into a liquid parenteral preparation such as an injection or filler, the osmotic pressure of the final product is in the range of the osmotic pressure suitable for biological administration, that is, 250-350 mOsm Mercaptoethanesulfonate and salts thereof, preferably MESNA, so as to be in the range of from 300 to 350 mOsm. Considering such an osmotic pressure range, in a liquid parenteral dosage form, 2-mercaptoethanesulfonate and its salt, preferably MESNA, is used in an amount of 0.0001 to 100 mg, preferably 0.001 to 20 mg, May be included in an amount of 0.001 to 15 mg per 1 ml of the composition volume.

According to the present invention, 2-mercaptoethanesulfonate and salts thereof, preferably MESNA, inhibit the decomposition of hyaluronic acid or derivatives thereof due to the activity of enzymes, particularly hyaluronidase, so that the moisturizing power, skin elasticity and volume It is possible to effectively prevent the deterioration of the skin, and further, the effect of preventing skin aging is exhibited.

In addition, according to the present invention, a composition comprising 2-mercaptoethanesulfonate and a salt thereof, preferably MESNA as an active ingredient, may exhibit a skin whitening effect in addition to the above effect.

The composition for biomedical administration of the present invention may contain 0.001 to 90% by weight, preferably 0.005 to 70% by weight, more preferably 0.01 to 50% by weight, of biodegradable polymer, preferably hyaluronic acid or a derivative thereof, By weight.

As described above, when hyaluronic acid and MESNA are used together, the degradation of hyaluronic acid is suppressed, and the time for retaining hyaluronic acid in the cells is remarkably increased, thereby improving the moisturizing power and elasticity of the skin, And it is also effective to improve the aging of the skin.

In addition, a composition according to the present invention, particularly preferably a composition containing MESNA, more preferably a composition containing both hyaluronic acid and MESNA is used as a parenteral administration agent in a liquid form such as an injection or filler, When applied to a region where the volume of the skin tissue is desired to be increased, such as forehead, nose, etc., not only excellent skin restoration effect can be obtained, but the effect can be maintained for a longer period of time.

The present invention also provides a method for inhibiting degradation of hyaluronic acid by using 2-mercaptoethanesulfonate and a salt thereof, preferably MESNA.

The composition of the present invention may also be formulated as an external preparation for skin, in particular as a cosmetic composition, and may be formulated containing a cosmetically or dermatologically acceptable medium or base. These are all formulations suitable for topical application, for example as a solution, a gel, a solid, a paste anhydrous product, an emulsion obtained by dispersing an oil phase in water, a suspension, a microemulsion, a microcapsule, a microgranule or an ionic form (liposome) In the form of ionic fibrin dispersions, or in the form of creams, skins, lotions, powders, ointments, sprays or conical sticks. It can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

The composition of the present invention can be used on the face, especially around the eyes, around the mouth, on the cheeks, or on the forehead, neck, hands, feet, but is not limited thereto. Specifically, the composition may include softening longevity (skin lotion and milk lotion) A body lotion, a body cream, a body oil, and a body essence, selected from the group consisting of body lotion, essence, nutritional cream, massage cream, pack, gel, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, May be prepared in one or more formulations, but is not limited thereto. These compositions may be prepared according to conventional methods in the art.

In addition, the composition according to the present invention may further comprise at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickening agents, gelling agents, softening agents, antioxidants, suspending agents, stabilizing agents, Such as fillers, emulsifiers, emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blockers, moisturizers, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or any other ingredient commonly used in cosmetics May contain adjuvants commonly used in the field of cosmetics or dermatology. Such adjuvants are introduced in amounts commonly used in the cosmetics or dermatological fields.

In addition, the cosmetic composition of the present invention may contain a skin absorption promoting substance to increase the effect.

In addition, the composition of the present invention can be formulated as a pharmaceutical composition. When the composition according to the present invention is applied to medicines, it may be formulated into a parenteral administration form in the form of a semi-solid or a liquid by adding an inorganic or organic carrier compatible with the active ingredient used in the present invention. The pharmaceutical composition may be administered parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, and the like.

Examples of the formulations for parenteral administration include injections, fillers, drops, ointments, lotions, sprays, suspensions, emulsions and suppositories. The composition according to the present invention can be easily formulated into an active ingredient by carrying out a conventional method well known in the art, wherein the surfactant, excipient, coloring agent, spice, preservative, stabilizer, buffer, Commercially available adjuvants can be used appropriately.

In particular, when the composition of the present invention is formulated in the form of injections, fillers, etc., it can be formulated into prefilled syringes, vials and the like.

The dosage of the active ingredient of the pharmaceutical composition of the present invention will vary depending on the age, sex, body weight, pathological condition and severity of the subject to be treated, route of administration, or judgment of the prescriber. Determination of the appropriate dose based on these factors is well within the level of ordinary skill in the art and its daily dose is, for example, from 0.1 mg / kg / day to 100 mg / kg / day, more specifically from 5 mg / kg / day to 50 mg / / Day, but is not limited thereto.

Hereinafter, the constitution and effects of the present invention will be described in more detail with reference to test examples and formulation examples. However, these test examples and formulation examples are provided for illustrative purposes only for the sake of understanding of the present invention, and the scope and scope of the present invention are not limited by the following examples.

[Test Example 1] Evaluation of resistance to degradation of hyaluronic acid

1. Sample

Test samples of Example 1 and Comparative Examples 1 and 2 were prepared for the enzymatic degradation resistance test. At this time, Example 1 and Comparative Examples 1 and 2 used one of MESNA, NaCl and mannitol as candidate substances for degradation-resistant substance of hyaluronidase, respectively, and a sol-state The gel consisted of a liquid containing gel and hyaluronic acid (HA), and sol and gel were mixed in a volume ratio of 6: 4. The specific composition is shown in Table 1 below, and the hyaluronic acid material used as Gel is specifically described below.

(When the total volume is 3 mL) division ingredient Example 1 Comparative Example 1 Comparative Example 2 Sol
(1.8 mL) ¹⁾ Phosphate buffer 10 mM 1.8 mL 1.8 mL 1.8 mL ²⁾ Lidocaine 9 mg 9 mg 9 mg ³⁾ MESNA 45 mg - - ³⁾ NaCl - 23.7 mg - ³⁾ Mannitol - - 144 mg HA gel ⁴⁾ Hyaluronic acid 1.2 mL 1.2 mL 1.2 mL

1) Phosphate buffer 10 mM

= Sodium phosphate monobasic dehydrate 0.49 g

+ Sodium phosphate dibasic dehydrate (2.45 g)

+ Distilled water 1L

2) Lidocaine: added to a concentration of 0.3%

3) Since the osmotic pressure inside the human body is 250 ~ 350mOsm, use MESNA, NaCl and mannitol so that the final osmotic pressure is 300mOsm.

- MESNA: Jiangsu Hengrui Medicin.Co., Batch number 642130904

- NaCl: Samchun chemical, lot 080207

- Mannitol: Sigma, lot 31K0003

4) Hyaluronic acid:

1 g of sodium hyaluronate fiber (NaHA, Mw = 0.5 to 3 MDa) was mixed with 10 g of 1% sodium hydroxide solution and the mixture was allowed to hydrate for 5 hours. 150 mg of 1,4-butanediol diglycidyl ether was added to the NaHA gel to homogeneously mix the mixture, and the resulting crosslinked hydrogel was neutralized with an equimolar amount of hydrochloric acid (HCl) and washed with PBS (pH about 7). The hydrogel thus obtained was mechanically homogenized and used in the preparation of the examples and comparative examples.

2. Test protocol

1) Pretreatment

The samples of Example 1 and Comparative Examples 1 and 2 were precisely weighed in 0.1 ml each into 15 ml tubes. Hyaluronidase was dissolved in phosphate buffer (pH 7.0, 10 mM PBS, NaCl 0.8%, hereinafter referred to as 'PBS') to make 100 IU / ml (1500 IU / 15 ml) and 100 IU / ml hyaluronan The solution was administered to each sample as shown in Table 3 below, and PBS was added to give a total volume of 1 ml.

Target sample Sample content (ml) The amount of enzyme required (IU, 50 IU / HA mg) Amount of enzyme solution (ml) Example 1 HA gel + MESNA / PB buffer (HA 13.2 mg / mL) 0.1 26.4 IU 264 [mu] L,
PBS 636L Comparative Example 1 HA gel + NaCl / PB buffer (HA 13.2 mg / mL) 0.1 26.4 IU 264 [mu] L,
PBS 636L Comparative Example 2 HA gel + mannitol / PB buffer (HA13.2 mg / mL) 0.1 26.4 IU 264 [mu] L,
PBS 636L

2) Processing

The enzyme solution was added to each of the samples of Example 1 and Comparative Examples 1 and 2, and the mixture was reacted at 37 DEG C and 80 rpm for 30 minutes. One milliliter of 0.1N HCl solution was added to each sample, and the reaction was stopped by vigorous stirring for 10 seconds. After completion of the stirring, 1 ml of 0.1 N NaOH and PBS were added to all the samples to neutralize the total to 4 ml. The solution made up to 4 ml was filtered with a membrane having a pore diameter of 0.2 탆 and then stored in a refrigerator.

3. Quantitative-Carbazole analysis

Carbazole and reacted with carbazole to measure the content of glucuronic acid. Specifically, 0.170 g of each of Example 1, Comparative Example 1 or Comparative Example 2 was precisely measured and dissolved in water to make 100 g of an aqueous solution. 10 g of the aqueous solution was precisely measured, , And then used as a sample solution to prepare three kinds of sample solutions each containing Example 1 and Comparative Examples 1 and 2. About 0.1 g of D-glucuronic acid dried at constant pressure under reduced pressure was accurately weighed and water was added thereto to prepare an aqueous solution of 100 g accurately. Water was added to a predetermined amount of the above aqueous solution to obtain 6.5 g of glucuronic acid and 16.3 g , 32.5 占 퐂, 48.8 占 퐂 and 65 占 퐂 were prepared as standard solutions. 25 test tubes were prepared and labeled 1 to 25 and placed in ice water. Take 1.0 mL of each of the above 5 standard solutions three times for each concentration and put them in a test tube to make a standard solution test tube (1 to 15). Then, 3 kinds of test solutions are taken 3 times each in 1.0 mL each, put in 9 test tubes, 24). The last test tube was filled with water and used as a test tube (25). Each tube was filled with 5 mL of freshly prepared 0.95 w / v% borax sulfuric acid solution, sealed with a plastic stopper, shaken, allowed to stand in a water bath for 15 minutes, and then cooled in ice water. Each tube was filled with 0.2 mL of 0.125 w / v% carbazole ethanol solution, the cap was closed tightly and shaken, allowed to stand in a water bath for 15 minutes, and then cooled to room temperature. These solutions were used to measure the absorbance at a wavelength of 530 nm in accordance with the method of measuring external absorbance by a blank test solution. The average concentration of D-glucuronic acid in the sample solution was determined using a calibration curve (corresponding to Equation 1 below) prepared from the average absorbance of the standard solution.

Cg: Average concentration of D-glucuronic acid in the test solutions (mg / g)

Cs: The average concentration (mg / g) of the test solutions of Example 1, Comparative Example 1 or Comparative Example 2,

Z: Content of D-glucuronic acid (%)

h: Loss on drying (%)

401.3: relative molecular weight of the disaccharide

194.1: Relative molecular weight of glucuronic acid

The percentage of hyaluronic acid degraded on the basis of the amount of sodium hyaluronate determined according to Equation (1) above was calculated. The results are shown in FIG.

As shown in FIG. 1, in the case of the samples of Example 1 and Comparative Examples 1 and 2 containing the test substances, that is, MESNA, NaCl or mannitol as a result of enzyme treatment for 30 minutes, Although showing resistance, the degradation rate of hyaluronic acid was 88% in Comparative Example 1 and 92% in Comparative Example 2, indicating that the degree of resistance to degradation of hyaluronic acid by hyaluronidase was weak , Whereas in the case of Example 1, the degradation rate of hyaluronic acid was about 79%, which means that the degradation of hyaluronic acid was considerably inhibited.

This suggests that MESNA shows high resistance to the degradative activity of hyaluronidase, and that when mixed with MESNA, hyaluronic acid can be effectively inhibited from being degraded by hyaluronidase.

[Test Example 2] Evaluation of safety for MESNA - Evaluation of cytotoxicity in Melan a cells

In order to verify the safety of MESNA, the cytotoxicity of Melan a cells according to the dose of the test substance was evaluated.

MESNA was diluted in cell culture medium (RPMI media (Gibco), 10% fetal bovine serum (Gibco), 1% penicillin streptomycin (Gibco)) as shown in Table 4 below, Respectively. Cytotoxicity testing was carried out using Cell Counting Kit-8 (CCK8 kit; Dojindo). The specific evaluation method is as follows.

CCK8 reagent and cell culture medium were mixed at a volume ratio of 1:10, and 500 μl of the cells were added to 48 wells in which cells were growing. The cells were incubated in a 37 ° C 5% CO ₂ incubator for 1 hour and a half. OD values (synergy2, Biotek Instruments, Inc.) were measured at 450 nm after incubation.

The O.D value of the group 1 that did not process anything was taken as 100%, and the O.D value of the remaining group was converted and calculated. When the contrast value was more than 80%, it was judged that there was no toxicity. The results are shown in Table 5 and Fig.

number Test group Group 1 badge Group 2 MESNA 30 μM + medium Group 3 MESNA 100 μM + medium Group 4 MESNA 300 μM + medium Group 5 MESNA 900 μM + medium

MESNA  density Cytotoxicity (%) 0 μM 100 30 μM 97.58 100 μM 96.34 300 μM 99.65 900 μM 97.55

As shown in Table 5 and Fig. 2, no cytotoxicity was observed in all of the evaluated groups. Therefore, it can be confirmed that MESNA is a safe substance without side effects.

[Referential Example 1] Preparation of Formulation Example 1 and Comparative Formulation Examples 1 and 2

Formulation Example 1 and Comparative Formulation Examples 1 and 2 were prepared according to the composition shown in Table 6 below (unit: wt%).

Raw material name Formulation Example 1 Comparative Formulation Example 1 Comparative Formulation Example 2 Awards
ingredient One MESNA 1.5 - - Mannitol - 1.5 - NaCl - - 1.5 2 Purified water To 100 To 100 To 100 3 Disodium iodide 0.02 0.02 0.02 4 glycerin 5.0 5.0 5.0 5 Xanthan gum 0.15 0.15 0.15 6 Methylglucose-20 2.0 2.0 2.0 7 Hyaluronic acid 2.0 2.0 2.0 8 Ammonium acryloyldimethyltaurate / Vpicopolymer 0.3 0.3 0.3 Ethanol phase component 9 ethanol 3.0 3.0 3.0 10 Hydrogenated castor oil 0.3 0.3 0.3 11 incense 0.1 0.1 0.1 12 antiseptic 0.3 0.3 0.3

<Manufacturing Method>

(1) The aqueous phase components (1 to 8) are uniformly mixed at room temperature.

(2) Ethanol phase components (9-12) are heated to 50-55 ° C to dissolve and mix uniformly.

(3) The above-mentioned (1) is added to the above-mentioned (2) under agitation so as to be solubilized uniformly.

[Test Example 3] Evaluation of improving skin elasticity

In order to confirm the effect of improving the skin elasticity of the composition according to the present invention, the following test was conducted using Formulation Example 1 and Comparative Formulation Examples 1 and 2 as follows.

35 women in their 30s and 40s were divided into 7 groups each consisting of 5 individuals. Each of the groups was coated with Formulation 1, Comparative Formulation Example 1 or Comparative Formulation Example 2 for 2 weeks (morning and evening) for 4 weeks. The skin elasticity was measured by using a skin elasticity tester (Cutometer SEM 575, C + K Electronic Co., Germany) before the start of application and at 4 weeks after application, and the skin elasticity improvement effect was calculated. Table 7 shows the results. The results in Table 7 indicate the degree of improvement in viscoelasticity properties.

Test substance Skin elasticity improvement effect Formulation Example 1 0.76 + - 0.10 Comparative Formulation Example 1 0.50 0.09 Comparative Formulation Example 2 0.45 0.10

From the results shown in Table 7, it can be confirmed that Formulation Example 1 including MESNA exhibits remarkably excellent skin elasticity improvement effect of about 152% to 168% as compared to Comparative Formulation Examples 1 and 2 which do not contain MESNA .

[Test Example 4] Sensory evaluation of lifting effect

In order to confirm the lifting effect of the composition according to the present invention, the following test was conducted using Formulation Example 1 and Comparative Formulation Examples 1 and 2 as follows.

35 women aged 25 to 35 years who are suffering from skin sagging were divided into seven groups of five each, and each of the above-mentioned Formulation 1, Comparative Formulation 1 and Comparative Formulation Example 2 was administered twice daily (morning and evening) After using the same method as usual lotion, users' skin lifting efficacy level was evaluated by questionnaire according to the following evaluation criteria. The results are shown in Table 8 below.

<Evaluation Criteria>

+++: Very good improvement

++: Significant improvement

+: Has some improvement

±: No improvement, but no deterioration

-: No improvement, but rather worse

Test substance term 1 week 2 weeks 3 weeks 4 weeks Formulation Example 1 ++ ++ +++ +++ Comparative Formulation Example 1 + + ++ ++ Comparative Formulation Example 2 + + + ++

From the results shown in Table 8 above, it can be confirmed that Formulation Example 1 including MESNA exhibits faster and more excellent lifting efficacy than Comparative Formulations 1 and 2 which do not contain MESNA.

[Test Example 5] Measurement of skin barrier function recovery effect

In order to confirm the effect of the composition according to the present invention on the recovery of damaged skin barrier function due to skin damage, the following test was conducted using Formulation Example 1 and Comparative Formulation Examples 1 and 2 as follows.

Ten adult males and females were injured on the skin barrier using a tape stripping method and applied with the three compositions of Formulation 1, Comparative Formulation Example 1 and Comparative Formulation Example 2 daily for 7 days The recovery of TWEL was measured and compared with a Vapometer (Delfin, Finland). The experimental results are shown in Table 9 below. Table 9 compares the pre-treatment differences before barrier damage and after barrier damage on the basis of 100%.

Test group TWEL Change (%) Before processing 1 day 2 days 3 days 4 days 5 days 6 days Formulation Example 1 100 79.9 60.1 31.1 26.4 18.8 15.9 Comparative Formulation Example 1 100 97.7 87.3 71.6 65.4 51.7 46.6 Comparative Formulation Example 2 100 96.4 90.5 79.7 70.3 62.4 57.7

From the results shown in the above Table 9, it can be confirmed that Formulation Example 1 including MESNA returns to the normal state of the transdermal water loss at a rapid rate and restores the barrier damage as compared with Comparative Formulations 1 and 2 which do not contain MESNA .

[Test Example 6] Measurement of skin moisturizing effect

In order to confirm the skin moisturizing effect of the composition according to the present invention, the following test was carried out using Formulation Example 1 and Comparative Formulation Examples 1 and 2 as follows.

The dry skin was divided into three groups each consisting of 20 men and 40 women in the 40s and 50s. Each of the menstrual cycles was divided into two groups: Formulation 1, Comparative Formulation 1 and Comparative Formulation 2 for 2 weeks (morning and evening) And applied to the face. (24 ° C, relative humidity 40%) after 1 week, 2 weeks, and 4 weeks after application, and after 2 weeks (total 6 weeks) (Corneometer CM825, C + K Electronic Co., Germany). The results are shown in Table 10 below. The results in Table 10 are the percentages of the increase in the measured value after treatment for a certain period based on the skin moisture meter measured immediately before the start of the test.

Test substance Moisture growth rate (%) 1 week Two weeks 4 weeks 6 weeks Formulation Example 1 42 41 43 34 Comparative Formulation Example 1 31 30 32 16 Comparative Formulation Example 2 30 32 30 15

The results of Table 10 show that when Comparative Formulation Examples 1 and 2 were applied, the moisture increase rate was about 30% until 4 weeks of application, but after the application was stopped, the amount of skin moisture decreased, whereas MESNA It can be confirmed that the skin moisture increase rate is 30% or more even after stopping the application. Thus, it can be seen that the composition containing MESNA has excellent skin moisturizing effect.

Claims (17)

An agent for inhibiting the decomposition of hyaluronic acid or a derivative thereof, which contains sodium 2-mercaptoethane sulfonate as an active ingredient. A composition for inhibiting the decomposition of hyaluronic acid or a derivative thereof, which contains sodium 2-mercaptoethane sulfonate as an active ingredient. The composition of claim 2, wherein the sodium 2-mercaptoethanesulfonate is present in an amount of 0.0001 to 20% by weight based on the total weight of the composition. A decomposition inhibitor according to claim 1 or a composition for decomposition inhibition according to claim 2; And a hyaluronic acid or a derivative thereof. 5. The composition according to claim 4, wherein the composition is for biopsy. 5. The composition of claim 4, wherein the composition is for skin moisturization. 5. The composition of claim 4, wherein the composition is for enhancing skin elasticity. 5. The composition of claim 4, wherein the composition is for improving skin wrinkles. 5. The composition of claim 4, wherein the composition is for increasing skin volume. 5. The composition of claim 4, wherein the composition is for skin aging. 5. The composition of claim 4, wherein the composition is for skin whitening. 5. The composition according to claim 4, wherein the composition is formulated in the form of an external preparation for skin. A decomposition inhibitor according to claim 1 or a composition for decomposition inhibition according to claim 2; And a prefilled syringe for biopsy containing biodegradable polymer as an active ingredient. 14. The pre-field syringe as claimed in claim 13, wherein the biodegradable polymer is hyaluronic acid or a derivative thereof. A decomposition inhibitor according to claim 1 or a composition for decomposition inhibition according to claim 2; And a biodegradable polymer as an active ingredient. 16. The injection according to claim 15, wherein the biodegradable polymer is hyaluronic acid or a derivative thereof. The injection according to claim 16, wherein the injection is formulated in the form of a vial.

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