KR20230041421A - Composition comprising physically crosslinked high-molecular hyaluronic acid or salt thereof - Google Patents

Abstract

The present disclosure describes a composition including a physically cross-linked polymeric hyaluronic acid or salt thereof. In addition, the present disclosure describes a crosslinker composition for use in physically cross-linking polymeric hyaluronic acid or salt thereof. The composition of the present disclosure can not only provide a thick or gelled formulation, but also provide specificity in terms of an appearance and feeling of use by exhibiting strong stringiness. In addition, due to the characteristics of the formulation, excellent moisturizing power can be provided.

Description

Composition comprising physically cross-linked polymeric hyaluronic acid or a salt thereof

The present specification describes a composition comprising a physically cross-linked polymeric hyaluronic acid or a salt thereof.

In order to control the viscosity in conventional emulsion-type cosmetic formulations, application of carbomer, natural or synthetic polymers, etc. has been considered, but there is a limit in terms of implementing a specific feeling of use when simply applying linear polymers. In order to overcome these limitations, a high-viscosity composition may be prepared using a gelled water-soluble polymer, and in particular, a high-viscosity composition may be prepared using hyaluronic acid.

There are various mechanisms for producing gelled hyaluronic acid. For example, as a chemical cross-linking method of hyaluronic acid, hyaluronic acid can be modified and cross-linked using a bridge agent (ex: HA-NH ₂ ), or cross-linked by reacting a cross-linker directly with hyaluronic acid (ex: HA-NH 2 ). -BDDE-HA (BDDE: Ether)). When hyaluronic acid is chemically crosslinked, when using a chemical product or a buffer to form a chemical reaction environment, toxicity concerns or specific pH conditions or temperature conditions for chemical reactions are often required, so a neutralization process after synthesis is required. Therefore, the process is very complicated and mass productivity may be poor. Therefore, it is required to develop a composition having high viscosity while containing hyaluronic acid physically crosslinked by pH, temperature, light, ionic strength conditions, and the like.

JP 4460617 B2 (2010.2.19)

In one aspect, the problem to be solved by the present disclosure is to provide a composition having a differentiated appearance and formulation by physically crosslinking hyaluronic acid.

In order to solve the above problems, one embodiment of the present disclosure is a composition comprising a physically crosslinked polymeric hyaluronic acid or a salt thereof, wherein the polymeric hyaluronic acid or a salt thereof is physically crosslinked by a crosslinking agent, and the crosslinking agent Provided is a composition that is terephthalylidene dicamphor sulfonic acid (Terephthalylidene Dicamphor Sulfonic Acid, TDSA).

In addition, one embodiment of the present disclosure provides a crosslinker composition of polymeric hyaluronic acid or a salt thereof, wherein the composition includes terephthalylidene dicamphorsulfonic acid as an active ingredient.

The present specification describes a composition comprising a physically crosslinked polymeric hyaluronic acid or a salt thereof and a crosslinker composition for use in physically crosslinking the polymeric hyaluronic acid or a salt thereof. The composition of the present disclosure may not only provide a thick or gelled formulation, but also exhibit strong stringiness to provide specificity in terms of appearance and feeling of use. In addition, due to the characteristics of the formulation, it can provide excellent moisturizing power.

1 is a diagram showing the results of measuring the tensile length with the stringiness evaluation index of one embodiment of the present disclosure.
2 is a diagram showing the tensile length measurement results of Comparative Example.
3 is a diagram showing viscoelasticity measurement results of an embodiment of the present disclosure.
Figure 4 is a diagram showing the results of comparison of skin moisture content in order to evaluate the moisturizing power of one embodiment of the present disclosure and a comparative example.
5 is a diagram showing a comparison result of transepidermal water loss (TEWL) in order to evaluate the moisturizing power of one embodiment of the present disclosure and a comparative example.

Hereinafter, embodiments of the present application will be described in detail with reference to the accompanying drawings. However, the technology disclosed in this application is not limited to the embodiments described herein and may be embodied in other forms. However, the embodiments introduced herein are provided so that the disclosed content can be thorough and complete and the spirit of the present application can be sufficiently conveyed to those skilled in the art. In addition, those skilled in the art may implement the spirit of the present application in various other forms without departing from the technical spirit of the present application.

In this specification, singular expressions include plural expressions unless the context clearly dictates otherwise. In this application, terms such as "comprise", "include" or "have" are intended to designate that there is a feature, number, step, operation, component, or combination thereof described in the specification, and one or the The possibility of the presence or addition of other features or numbers, steps, operations, components or combinations thereof is not excluded.

One embodiment of the present disclosure is a composition comprising a physically crosslinked polymeric hyaluronic acid or a salt thereof, wherein the polymeric hyaluronic acid or a salt thereof is physically crosslinked by a crosslinking agent, and the crosslinking agent is terephthalylidene dicamphorsulfonic acid. , to provide a composition. One embodiment of the present disclosure provides a composition comprising a polymeric hyaluronic acid or a salt thereof physically crosslinked by terephthalylidene dicamphorsulfonic acid.

In the present disclosure, hyaluronic acid is a linear anionic natural polysaccharide in which β-D-N-acetylglucosamine and β-D-glucuronic acid are alternately bonded, and is present in the form of a salt. The molecular structure of may be represented by Formula 1 below.

[Formula 1]

Here, the x is 200 - 25,000, and the unit of the x is mol.

In one embodiment of the present disclosure, the salt is not particularly limited, but may be an acid addition salt, a base addition salt, or an amino acid salt. For example, "the salt is an inorganic acid salt such as hydrochloride, hydrobromide, sulfate, hydroiodide, nitrate, phosphate"; organic acid salts such as citrate, oxalate, acetate, formate, propionate, benzoate, trifluoroacetate, maleate, tartrate, methanesulfonate, benzenesulfonate and p-toluenesulfonate; Inorganic base salts, such as sodium salt, potassium salt, calcium salt, magnesium salt, copper salt, zinc salt, aluminum salt, and ammonium salt; organic base salts such as triethylammonium salt, triethanolammonium salt, pyridinium salt, and diisopropylammonium salt; It may be an amino acid salt such as a lysine salt, an arginine salt, a histidine salt, aspartate, or glutamate. In one embodiment, the salt is hyaluronic acid sodium salt, hyaluronic acid potassium salt, hyaluronic acid acetate, hyaluronic acid ammonium salt or C12-13 alkyl glyceryl hydrolyzed hyaluronate (C12-13 Alkyl Glyceryl Hydrolyzed Hyaluronate). can In the present disclosure, the weight average molecular weight of the polymeric hyaluronic acid or its salt varies depending on the length of the sugar chain. As an example, the weight average molecular weight of the polymeric hyaluronic acid or its salt may be 10 to 5,000 kDa. Specifically, the weight average molecular weight of the polymeric hyaluronic acid or its salt is 10 kDa or more, 100 kDa or more, 300 kDa or more, 500 kDa or more, 700 kDa or more, 900 kDa or more, 1,100 kDa or more, 1,300 kDa or more, 1,400 kDa or more, 1,500 kDa or more, or 1,600 kDa or more, 5,000 kDa or less, 4,000 kDa or less, 3,000 kDa or less, 2,700 kDa or less, 2,400 kDa or less, 2,100 kDa or less, 1,800 kDa or less, 1,700 kDa or less, 1,600 kDa or less, 1,50 kDa or less , or less than 1,400 kDa. More specifically, the weight average molecular weight of the polymeric hyaluronic acid or its salt may be 1,300 to 1,800 kDa. When the weight average molecular weight of the polymeric hyaluronic acid or its salt is less than 10 kDa, the crosslinking reaction may not occur, and if the weight average molecular weight of the polymeric hyaluronic acid exceeds 5000 kDa, the viscosity is excessively high before crosslinking, making it difficult to control.

Natural hyaluronic acid has poor structural stability and is easily decomposed and removed from the body. Conventionally, it has been provided in a crosslinked form by forming a covalent bond through a chemical crosslinking agent, but in the case of chemical crosslinking, the process for removing the crosslinking agent after the reaction is complicated and has a disadvantage in terms of skin safety. The present disclosure includes a cross-linked hyaluronic acid in which the hyaluronic acid or a salt thereof is physically linked to each other through gelation without forming an additional covalent bond, so that it is stable without irritation to the skin and maximizes the useful effect of hyaluronic acid on the skin. can be provided.

One embodiment of the present disclosure may include terephthalylidene dicamphorsulfonic acid as a crosslinking agent for physically crosslinking the polymeric hyaluronic acid or its salt. In view of the above, one embodiment of the present disclosure may provide a cross-linking agent composition of polymeric hyaluronic acid or a salt thereof, and the composition may include terephthalylidene dicamphorsulfonic acid as an active ingredient. Another embodiment may provide the use of terephthalylidene dicamphorsulfonic acid as an active ingredient for preparing a crosslinking agent for physically crosslinking high molecular weight hyaluronic acid or a salt thereof. Another embodiment may provide a crosslinking method for polymeric hyaluronic acid or a salt thereof, which includes physically crosslinking the polymeric hyaluronic acid or a salt thereof by adding an effective amount of terephthalylidene dicamphorsulfonic acid. As an example, when polymeric hyaluronic acid or a salt thereof is crosslinked using the above crosslinking agent, it is possible to improve the physical stability of natural hyaluronic acid while providing a formulation having a similar appearance and a specific feeling of use.

As an example, the crosslinking agent may be terephthalylidene dicamphor sulfonic acid (TDSA). In the present disclosure, the terephthalylidene dicamphorsulfonic acid is an organic compound having the following structure of CAS No.92761-26-7. The terephthalylidene dicamphorsulfonic acid has a strong degree of dissociation of hydrogen ions in an aqueous solution, and thus exhibits a low pH value of pH 0.5 to 2. The terephthalylidene dicamphorsulfonic acid is known as a sunscreen, but has never been used as a cross-linking agent for hyaluronic acid as in the present disclosure.

[Formula 2]

As an example, the polymeric hyaluronic acid or a salt thereof may be included in an amount of 0.1 to 3% by weight based on the total weight of the composition. Specifically, the content of the polymeric hyaluronic acid or its salt is 0.1% by weight or more, 0.3% by weight or more, 0.5% by weight or more, 0.7% by weight or more, 0.9% by weight or more, 1.1% by weight or more, 1.3% by weight or more, based on the total weight of the composition. 1.5% by weight or more, 1.7% by weight or more, 2% by weight or more, 2.2% by weight or more, 2.4% by weight or more, 2.6% by weight or more or 2.8% by weight or more, 3% by weight or less, 2.5% by weight or less, 2 1.7 wt% or less, 1.5 wt% or less, 1.3 wt% or less, 1.1 wt% or less, 1 wt% or less, 0.9 wt% or less, or 0.8 wt% or less. If the content is less than 0.1% by weight, the useful effect on the skin is insignificant and gel formation may be difficult, and if the content is more than 3% by weight, the viscosity is too high, making it difficult to mix with other substances and the desired formulation in the present disclosure may not appear. can

As an example, the crosslinking agent may be included in an amount of 0.1 to 2% by weight based on the total weight of the composition. Specifically, the content of the crosslinking agent may be 0.1% by weight or more, 0.3% by weight or more, 0.5% by weight or more, 0.7% by weight or more, or 0.9% by weight or more, based on the total weight of the composition, 2% by weight or less, 1% by weight or less, 0.9 wt% or less, 0.8 wt% or less, 0.7 wt% or less, 0.6 wt% or less, or 0.5 wt% or less. When the crosslinking agent is included in an amount of less than 0.1% by weight, the polymeric hyaluronic acid or a salt thereof may not be effectively crosslinked, and thus, a formulation desired in the present disclosure may not be obtained. If the amount of the crosslinking agent exceeds 2% by weight, skin irritation may occur, and an additional reverse crosslinking reaction may occur, resulting in a decrease in stringiness.

As an example, the weight ratio of the polymeric hyaluronic acid or its salt and the crosslinking agent is not limited as long as it can physically crosslink the polymeric hyaluronic acid or its salt, but is 0.1 from the viewpoint of providing a composition having a typical dosage form. to 10:1. Specifically, the weight ratio of the polymeric hyaluronic acid or salt thereof and the crosslinking agent may be 0.5 to 7:1, more specifically 1 to 5:1.

As an example, the composition may further include at least one of a polyol, a nonionic surfactant, and an n-hydric alcohol.

If the present disclosure further includes polyol and/or n-valent alcohol as an example, it is possible to prevent irritation to the skin by applying an isoelectric point that can reduce the solubility of hyaluronic acid to a pH of 3 or higher. Specifically, the polyol may include at least one selected from the group consisting of glycerin, propylene glycol, butylene glycol, glycerol, erythritol, xylitol, maltitol glycerin, sorbitol, polyglycerin, polyethylene glycol, pentanediol, and isoprene glycol. However, it is not limited thereto. Specifically, n of the n-hydric alcohol may be 1 to 10. That is, it may be monohydric to decahydric alcohol. More specifically, the n-hydric alcohol may include one or more selected from the group consisting of methanol, ethanol, propanol, and butanol. As an example, the polyol may be included in an amount of 0.01 to 20% by weight based on the total weight of the composition, but is not limited thereto. More specifically, the polyol is present in an amount of 0.01 wt% or more, 0.1 wt% or more, 0.5 wt% or more, 1 wt% or more, 2 wt% or more, 4 wt% or more, 6 wt% or more, or 8 wt% based on the total weight of the composition. or more, 10% by weight or more, 12% by weight or more, 15% by weight or more, or 18% by weight or more, and 20% by weight or less, 17% by weight or less, 15% by weight or less, or 10% by weight or less. As an example, the n-hydric alcohol may be included in an amount of 0.01 to 10% by weight based on the total weight of the composition, but is not limited thereto. More specifically, the n-hydric alcohol is present in an amount of 0.01 wt% or more, 0.1 wt% or more, 0.5 wt% or more, 1 wt% or more, 2 wt% or more, 4 wt% or more, 6 wt% or more, or 8 wt% or more, based on the total weight of the composition. It may be included in weight % or more, and may be included in 10 weight % or less, 9 weight % or less, or 8 weight % or less.

As an embodiment of the present disclosure, the nonionic surfactant is a surfactant used to solubilize a material insoluble in water, for example, poly(oxyethylene)alkylether, poly(oxyethylene)alkylphenylether, etc. Non-ionic surfactants may be included. More specifically, the nonionic surfactant is PPG-13-DECYLTETRADECETH-24, POLYGLYCERYL-6 CAPRYLATE, polyglyceryl- 4 caprate (POLYGLYCERYL-4 CAPRATE), POLYGLYCERYL-5 TRIOLEATE (POLYGLYCERYL-5 TRIOLEATE), POLYGLYCERYL-10 LAURATE (POLYGLYCERYL-10 LAURATE) and PEG-60 Hydrogenated Castor Oil (PEG -60 HYDROGENATED CASTOR OIL). As an example, the nonionic surfactant may be included in an amount of 0.01 to 10% by weight based on the total weight of the composition. More specifically, the nonionic surfactant is present in an amount of 0.01 wt% or more, 0.05 wt% or more, 0.1 wt% or more, 0.15 wt% or more, 0.2 wt% or more, 0.25 wt% or more, 0.3 wt% or more, based on the total weight of the composition. 0.4 wt% or more, 0.5 wt% or more, 1 wt% or more, 2 wt% or more, 3 wt% or more, or 4 wt% or more, 10 wt% or less, 7 wt% or less, 5 wt% or less, 4 less than 3.5%, less than 3%, less than 2.5%, less than 2%, less than 1.5%, less than 1%, less than 0.5%, less than 0.1% or less than 0.05% by weight. can

As an embodiment of the present disclosure, the composition may have a gel formulation. As an embodiment of the present disclosure, the composition may exhibit spinnability. In the present disclosure, the stringy property means that a liquid composition having high viscosity stretches like mucus to form a long continuous filament. Stringiness is a specific physical property that is distinguished from the viscosity or elasticity of the composition, and the surface tension, viscoelasticity, adhesiveness, etc. of the composition may have a complex effect, but it is not a property that appears only in their size. For example, if the surface tension or viscoelasticity is high, stringiness may not appear in a jelly-like formulation. Stringiness can be confirmed with the naked eye, and the length or time when the liquid column is cut by attaching the tip of the rod to the surface of the composition and pulling it up at a constant speed can be used as the standard for stringiness. For example, the stringiness can be defined as tensile length (mm) when measured through Marlvern's Kinexus. Specifically, the device's tackiness mode is set to a gap size of 1.0 mm to 180 mm, the gapping speed is 1 mm / s, the unit type is set to PU20, the temperature is set to 25 ° C, and the composition It is possible to measure the similarity by checking the moment when the resistance force received by the unit is cut off while increasing . At this time, the tensile length of the composition according to an embodiment of the present disclosure may be 100 to 180 mm when measured through Marlvern's Kinexus.

As an example, the viscosity of the composition may be 300 to 10,000 cps when measured using a Brookfield Viscometer. Specifically, the viscosity may be measured using a Brookfield LV Viscometer or a Brookfield RV Viscometer, wherein the spindle rotation rpm and measurement time are 12 rpm and 2 min, and No. It can be measured using 62 spindles. Specifically, the viscosity of the composition may be 300 cps or more, 500 cps or more, 700 cps or more, 1,000 cps or more, 1,200 cps or more, 1,500 cps or more, or 2,000 cps or more, 10,000 cps or less, 8,000 cps or less, 6,000 cps or less, 4,000 cps or less, 3,500 cps or less, 3,000 cps or less, or 2,500 cps or less. As an example, if the viscosity of the composition is out of the above range, stringiness may not appear.

As an example, the adhesiveness of the composition may be 0.060 to 0.200 N when measured using a Maven Rheometer. Specifically, the tackiness can be measured using a rheometer (Maven, USA). At this time, the setting conditions were carried out as a pullaway test using a plate type: 20 mm parallel unit at 25 ° C., a gapping speed of 1 mm / s, and a gap size ( Measurement can be performed under the conditions of gap size 1mm and maximum gap 180mm. In the present disclosure, the normal force value at the peak was measured, and the G' and G" measurement samples were standardized in the form of a disk with a diameter of 20 mm and a thickness of 1 mm.

As an example, the composition may be used for moisturizing the skin. Since one embodiment of the present disclosure has stringiness, when applied to the skin, it can be spread thinly and long to form a moisture retention film. This can provide excellent skin moisturizing power.

In one embodiment, the composition may be a cosmetic composition.

In one aspect, the appearance of the cosmetic composition contains a cosmetically or dermatologically acceptable medium or base. These are all formulations suitable for topical application, e.g. solutions, gels, pasty anhydrous products, emulsions obtained by dispersing an oily phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or, ionic (liposomes) and nonionic It may be provided in the form of a vesicular dispersion of the type, or in the form of a cream, toner, lotion, ointment, and the like. These compositions can be prepared according to conventional methods in the art. The cosmetic composition according to one embodiment of the present disclosure is not particularly limited in its dosage form, and for example, ampoule, cream, softening lotion, astringent lotion, nutrient lotion, nutrient cream, massage cream, essence, eye cream, eye It can be formulated into cosmetics such as essence, cleansing cream, cleansing foam, cleansing water, cleansing tissue containing the cosmetic composition, pack, body lotion, body cream, body oil and body essence.

When the formulation according to an embodiment of the present disclosure is a paste, cream, or gel, animal fibers, vegetable fibers, wax, paraffin, starch, tracanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, or oxide as a carrier component Zinc and the like may be used. When the formulation according to one embodiment of the present disclosure is a solution or emulsion, a solvent, solvating agent, or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, or benzyl benzoate. , propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan. When the formulation according to an embodiment of the present disclosure is a suspension, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspension such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester as a carrier component agent, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracanth, and the like may be used. When the formulation according to one embodiment of the present disclosure is surfactant-containing cleansing, as carrier components, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarco Cinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

The cosmetic composition according to an embodiment of the present disclosure may further include functional additives and components included in general cosmetic compositions. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high-molecular peptides, high-molecular polysaccharides, sphingolipids, and seaweed extracts. Ingredients other than those included include fats and oils, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation accelerators, cooling agents, antiperspirants, purified water and the like.

In one embodiment, the composition may be a pharmaceutical composition.

When the composition according to one embodiment of the present disclosure is applied to pharmaceuticals, an inorganic or organic carrier commonly used in the active ingredient used in one embodiment of the present disclosure is added to formulate a parenteral administration in a semi-solid or liquid form. can The composition according to one embodiment of the present disclosure can be easily formulated with active ingredients by carrying out a conventional method widely known in the art, wherein surfactants, excipients, coloring agents, spices, preservatives, stabilizers, buffers, suspensions agent, and other commonly used adjuvants can be appropriately used. The dosage of the active ingredient of the pharmaceutical composition according to one embodiment of the present disclosure will vary depending on the age, sex, weight, pathological condition and severity of the subject to be administered, the route of administration, or the judgment of the prescriber. Determination of an appropriate dose based on these factors is within the level of those skilled in the art, and its daily administration dose is, for example, 0.1 mg/kg/day to 100 mg/kg/day, more specifically 5 mg/kg/day to 50 mg/kg. / can be, but is not limited to.

Hereinafter, the present disclosure will be described in more detail through the following examples. However, the following examples are provided only for illustrative purposes to aid understanding of the present disclosure, and the scope and scope of the present disclosure are not limited thereto.

[Production Example]

Examples and comparative examples were prepared with the same composition as in Table 1 below. Specifically, all components except terephthalylidene dicamphorsulfonic acid (TDSA) were added to purified water and mixed using an azimixer at 25 ° C. for 1 hour, and after confirming that all components were dissolved, TDSA was added and mixed. Hyaluronic acid used in the following Examples and Comparative Examples was applied as a raw material of sodium hyaluronic acid from Hyundai Bioland.

Raw material Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Purified water (WATER) To 100 To 100 To 100 To 100 To 100 To 100 GLYCERINE 10 10 10 10 10 10 SODIUM HYALURONATE 0.72 0.72 0.72 0.72 0.72 - Sodium Hyaluronate Crosspolymer (SODIUM HYALURONATE CROSSPOLYMER) - - - - - 0.72 HYDROLYZED HYALURONIC ACID 0.1 0.1 0.1 0.1 0.1 0.1 BETAINE One One One One One One PPG-13-decyltetradeceth-24 (PPG-13-DECYLTETRADECETH-24) 0.1 0.1 0.1 0.1 0.1 0.1 Butylene Glycol (BUTYLENE GLYCOL) 8 8 8 8 8 8 Propanediol 6 6 6 6 6 6 Denatured alcohol (ALCOHOL DENAT.) 8.2 8.2 8.2 8.2 8.2 8.2 TEREPHTHALYLIDENE DICAMPHOR SULFONIC ACID (TDSA) 0.2 0.5 - - - 0.2 LACTIC ACID - - 0.5 - - - Phenylbenzimidazole sulfonic acid (PHENYLBENZIMIDAZOLE SULFONIC ACID) - - - 0.5 - - 1,2-hexanediol (1,2-HEXANEDIOL) 1.5 1.5 1.5 1.5 1.5 1.5

(weight%)

[Test Example 1]

Viscosity, adhesiveness and stringiness (tensile length) of the prepared examples and comparative examples were measured as follows.

Viscosity was measured using a Brookfield RV Viscometer. At this time, the spindle rotation rpm and measurement time were 12 rpm and 2 min, and No. Measured using 62 spindles.

Tackiness was measured using a rheometer (Maven, USA). At this time, the setting conditions were carried out as a pullaway test using a plate type: 20 mm parallel unit, a gapping speed of 1 mm / s, and a gap size It was measured under conditions of 1 mm and maximum gap of 180 mm. At this time, the normal force value at the peak was measured, and the G' and G" measurement samples were unified in the form of a disk with a diameter of 20 mm and a thickness of 1 mm.

Tensile length was measured using Marlvern's Kinexus. Specifically, a gap size of 1.0 mm to 180 mm in Tackiness Mode, a gapping speed of 1 mm/s, a unit type of PU20, and a temperature of 25° C. The moment when the resistance received by the unit was cut off was visually measured using a ruler as shown in FIGS. 1 and 2.

Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Viscosity (cps) 2369 2010 1862 2032 1720 3050 Tackiness (N) 0.089 0.077 0.052 0.032 0.029 0.055 Tensile length (mm) 133 131 81 5 6 10

As a result, the viscosity was similar in Examples 1 and 2 and Comparative Examples 1-3, but after dissolving sodium hyaluronate crosspolymer in which hyaluronic acid is chemically crosslinked in water, terephthalylidene dicamphorsulfonic acid was added. The prepared Comparative Example 4 showed a relatively high viscosity. In the case of adhesiveness, it was found to have stringiness with high values in Examples 1 and 2 and a high tensile length. On the other hand, in Comparative Example 1, the crosslinking reaction proceeded using lactic acid as a crosslinking agent, but the elasticity was high and the adhesiveness and tensile length were low, so stringiness was not observed. This can be clearly compared in its aspect in Figure 1 (Example 1) and Figure 2 (Comparative Example 1). Comparative Example 1 shows a thick and short tensile length due to the high elasticity of the gel, and Example 1 shows a thin It can be seen that the long stringiness stands out. Comparative Example 2 using phenylbenzimidazole sulfonic acid having a pH of 6-7 as a crosslinking agent and Comparative Example 3 not including a crosslinking agent showed low tackiness and tensile length without stringency due to no crosslinking reaction. In Comparative Example 4, that is, when hyaluronic acid was chemically crosslinked before adding terephthalylidene dicamphorsulfonic acid without using terephthalylidene dicamphorsulfonic acid as a crosslinking agent, it was confirmed that stringiness was not observed.

This means that when terephthalylidene dicamphorsulfonic acid is used as a crosslinking agent for hyaluronic acid or a salt thereof according to the present disclosure, the composition has a stringy property and thus has a differentiated appearance to provide a specific feeling of use.

[Test Example 2]

The viscoelasticity of Example 1 according to an example of the present disclosure was measured as follows.

Specifically, a rheometer (Maven, USA) was used for the elastic modulus (G') and the viscous modulus (GViscos modulus). The setting conditions are the same as 'Oscillation', 'frequency sweep', 'shear stress', 'tackiness', Plate type at 25 ℃: oscillation stress adjusted to 1 Pa using a 20 mm plate corn, frequency of 0.1 ~ 10 Hz range, 1 Pa shear stress, measurement is performed at 1 mm gap. Among them, the G' and G" values at 1Hz were measured. The G' and G" measurement samples were standardized in the form of a disk with a diameter of 20mm and a thickness of 1mm.

As a result of the measurement, as shown in FIG. 3, Example 1 showed a G' value of 6.9Pa and a G" value of 5.8Pa at a frequency of 1Hz, and it was confirmed that a sticky gel with low viscoelasticity was made.

[Test Example 3]

Moisturizing power of the prepared Examples and Comparative Examples was evaluated as follows.

Specifically, skin moisture content and transepidermal water loss (TEWL) were measured. Skin moisture content and transepidermal water loss were measured using a corneometer (product name: GP SKIN BARRIER, manufacturer: G-Power).

The moisture content comparison results are shown in Table 3 and FIG. 4, and the transepidermal water loss comparison results are shown in Table 4 and FIG. 5.

Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Immediately after application (30 minutes) 65 62 47 45 44 1 hour after application 51 52 47 44 44 2 hours after application 51 49 47 41 42 6 hours after application 50 49 45 36 35

Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 just before application 5.6 5.6 6.2 5.6 5.7 Immediately after application (30 minutes) 1.2 1.6 1.8 2.6 2.3 1 hour after application 1.2 1.8 2.3 2.7 2.7 2 hours after application 1.6 1.8 2.9 3.3 3.5 6 hours after application 4 4.2 5.8 5.3 5.2

As a result, as shown in Tables 3 and 4 and FIGS. 4 and 5, Examples 1 and 2 of the present disclosure were superior to Comparative Examples 1 to 3 in terms of moisture content and transepidermal water loss. This means that the embodiments of the present disclosure provide excellent efficacy in moisturizing and preventing transepidermal water loss by forming a water film on the skin through stringiness.

The present disclosure may provide the following embodiments as an example.

A first embodiment is a composition comprising a physically crosslinked polymeric hyaluronic acid or a salt thereof, wherein the polymeric hyaluronic acid or a salt thereof is physically crosslinked by a crosslinking agent, and the crosslinking agent is terephthalylidene dicamphorsulfonic acid (TEREPHTHALYLIDENE DICAMPHOR SULFONIC ACID), it is possible to provide a composition.

In the second embodiment, in the first embodiment, the weight ratio of the polymeric hyaluronic acid or its salt and the crosslinking agent is 0.1 to 10:1, it is possible to provide a composition.

A third embodiment provides the composition according to the first or second embodiment, wherein the composition further includes at least one of a polyol, a nonionic surfactant, and an n-valent alcohol, wherein n is 1 to 10. can do.

A fourth embodiment may provide a composition according to any one of the first to third embodiments, wherein the composition has a tensile length of 100 to 180 mm as measured by Marlvern's Kinexus.

A fifth embodiment may provide a composition according to any one of the first to fourth embodiments, wherein the viscosity of the composition is 300 to 10,000 cps when measured using a Brookfield Viscometer.

The sixth embodiment may provide a composition according to any one of the first to fifth embodiments, wherein the composition has an adhesiveness of 0.060 to 0.200N when measured using a Maven Rheometer.

A seventh embodiment can provide a composition according to any one of the first to sixth embodiments, wherein the composition is a gel formulation.

An eighth embodiment can provide a composition according to any one of the first to seventh embodiments, wherein the composition is for skin moisturizing.

A ninth embodiment can provide a composition according to any one of the first to eighth embodiments, wherein the composition is a cosmetic composition.

A tenth embodiment can provide a composition according to any one of the first to ninth embodiments, wherein the composition is a pharmaceutical composition.

An eleventh embodiment is a crosslinking agent composition of polymeric hyaluronic acid or a salt thereof, wherein the composition includes terephthalylidene dicamphorsulfonic acid as an active ingredient. It can provide a crosslinking agent composition.

A twelfth embodiment may provide a composition according to the eleventh embodiment, wherein the weight ratio of terephthalylidene dicamphorsulfonic acid to the polymeric hyaluronic acid or salt thereof is 1:0.1 to 10.

Claims (12)

A composition comprising a physically cross-linked polymeric hyaluronic acid or a salt thereof,
The polymeric hyaluronic acid or its salt is physically crosslinked by a crosslinking agent,
The crosslinking agent is terephthalylidene dicamphorsulfonic acid (TEREPHTHALYLIDENE DICAMPHOR SULFONIC ACID), the composition. The composition according to claim 1, wherein the weight ratio of the polymeric hyaluronic acid or salt thereof and the crosslinking agent is 0.1 to 10:1. The composition of claim 1 , wherein the composition further comprises at least one of a polyol, a nonionic surfactant, and an n-valent alcohol, wherein n is 1 to 10. The composition according to claim 1, wherein the tensile length of the composition is 100 to 180 mm as measured by Marlvern's Kinexus. The composition of claim 1, wherein the composition has a viscosity of 300 to 10,000 cps as measured using a Brookfield Viscometer. The composition according to claim 1, wherein the composition has an adhesiveness of 0.060 to 0.200N when measured using Maven's Rheometer. The composition of claim 1 , wherein the composition is a gel formulation. According to claim 1, wherein the composition is for skin moisturizing, the composition. The composition according to claim 1, wherein the composition is a cosmetic composition. The composition according to claim 1, wherein the composition is a pharmaceutical composition. As a cross-linking agent composition of high-molecular weight hyaluronic acid or a salt thereof,
The composition comprises terephthalylidene dicamphor sulfonic acid (TEREPHTHALYLIDENE DICAMPHOR SULFONIC ACID) as an active ingredient, a crosslinking agent composition. The composition according to claim 11, wherein the weight ratio of terephthalylidene dicamphorsulfonic acid to the polymeric hyaluronic acid or its salt is 1:0.1 to 10.

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