Composition comprising physically crosslinked high molecular hyaluronic acid or a salt thereof

Abstract

The present invention relates to a composition comprising a physically crosslinked high-molecular hyaluronic acid or a salt thereof. The present invention also relates to a crosslinking agent composition for physically crosslinking a high-molecular hyaluronic acid or a salt thereof. The composition of the present invention can be provided not only as a dosage form in a thick or gelled form, but also exhibits strong spinnability, thereby providing specificity in terms of appearance and use feeling. Furthermore, due to the properties of the dosage form, excellent moisturizing power can be provided.

Description

Technical Field

[0001] This invention relates to a composition comprising physically cross-linked polymeric hyaluronic acid or a salt thereof. Background Technology

[0002] In existing emulsion-based cosmetic formulations, carbomer, natural or synthetic polymers are often used to adjust viscosity. However, using linear polymers alone presents limitations, particularly in achieving the desired user experience. To overcome these limitations, gelled water-soluble polymers can be used to prepare high-viscosity compositions, especially hyaluronic acid.

[0003] There are various mechanisms for preparing gelled hyaluronic acid. For example, as a chemical crosslinking method for hyaluronic acid, it can be modified and crosslinked using a bridge agent (e.g., HA-NH2), or the hyaluronic acid can be directly reacted with a crosslinking agent to achieve crosslinking (e.g., HA-BDDE-HA (BDDE: ether)). In the case of chemically crosslinked hyaluronic acid, the use of chemicals or buffer solutions to create a chemical reaction environment often requires specific pH or temperature conditions due to toxicity or chemical reaction considerations. Therefore, a neutralization process is required after synthesis, making the process very complex and potentially reducing productivity. Therefore, there is a need to develop a composition that contains hyaluronic acid that is physically crosslinked through pH, ​​temperature, light, ionic strength, etc., while also possessing high viscosity.

[0004] [Existing Technical Documents]

[0005] [Patent Documents]

[0006] Patent document 1: Japanese Patent Publication No. JP4460617B2 (February 19, 2010). Summary of the Invention

[0007] Technical issues

[0008] In one aspect, the present invention aims to provide a composition having a differentiated appearance and dosage form by physically crosslinking hyaluronic acid.

[0009] Technical solution

[0010] To address the aforementioned problems, one embodiment of the present invention provides a composition comprising physically cross-linked polymeric hyaluronic acid or its salt, wherein the polymeric hyaluronic acid or its salt is obtained by physical cross-linking with a cross-linking agent, wherein the cross-linking agent is terephthaloyl dicamphorsulfonic acid.

[0011] Furthermore, in one embodiment of the present invention, a crosslinking agent composition of polymeric hyaluronic acid or its salt is provided, the composition comprising terephthaloyl dicamphorsulfonic acid as an active ingredient.

[0012] Beneficial effects

[0013] This specification discloses a composition comprising physically crosslinked polymeric hyaluronic acid or a salt thereof, and a crosslinking agent composition for physically crosslinking said polymeric hyaluronic acid or a salt thereof. The compositions of the present invention not only provide dosage forms in a thick or gel-like form, but also exhibit strong spinnability, thereby providing specificity in appearance and feel. Furthermore, due to the properties of said dosage form, excellent moisturizing power is provided. Attached Figure Description

[0014] Figure 1 The results of tensile length measurement, which is used as an indicator of spinnability evaluation, are shown in one embodiment of the present invention.

[0015] Figure 2 The results of the tensile length measurement for the comparative example are shown.

[0016] Figure 3 The results of viscoelasticity measurement according to an embodiment of the present invention are shown.

[0017] Figure 4 The results show a comparison of skin moisture content used to evaluate the moisturizing power of one embodiment and a comparative example of the present invention.

[0018] Figure 5 The results of the transdermal water loss (TEWL) used to evaluate the moisturizing power of one embodiment and a comparative example of the present invention are shown. Detailed Implementation

[0019] The embodiments of this application will now be described in more detail with reference to the accompanying drawings. However, the technology disclosed in this application is not limited to the embodiments described herein and can be implemented in other forms. It should be understood that the purpose of providing embodiments in this specification is to make the disclosure more thorough and complete, and to fully convey the concept of this application to those skilled in the art. Furthermore, those skilled in the art can implement the concept of this application in various other forms without departing from the technical concept of this application.

[0020] In this specification, singular expressions include plural forms unless the context clearly indicates otherwise. In this application, terms such as “comprising,” “including,” or “having” are intended to indicate the presence of features, numbers, steps, operations, components, or combinations thereof described in the specification, but do not preclude the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, or combinations thereof.

[0021] In one embodiment, the present invention provides a composition comprising physically cross-linked polymeric hyaluronic acid or a salt thereof, wherein the polymeric hyaluronic acid or salt thereof is obtained by physical cross-linking with a cross-linking agent, wherein the cross-linking agent is terephthalic acid dicamphor sulfonic acid. In another embodiment, the present invention provides a composition comprising polymeric hyaluronic acid or a salt thereof physically cross-linked with terephthalic acid dicamphor sulfonic acid.

[0022] In this invention, the hyaluronic acid is a linear anionic natural polysaccharide composed of alternating bonds of β-DN-acetylglucosamine and β-D-glucuronic acid, existing in the form of a salt. The molecular structure of hyaluronic acid can be represented by the following chemical formula 1.

[0023]

Chemical Formula 1

[0024]

[0025] Wherein, x is between 200 and 25,000, and the unit of x is mol.

[0026] In one embodiment of the present invention, the salt may be an acid addition salt, a base addition salt, or an amino acid salt, but is not particularly limited thereto. For example, the salt may include: inorganic acid salts, such as hydrochloride, hydrobromide, sulfate, hydroiodide, nitrate, phosphate, etc.; organic acid salts, such as citrate, oxalate, acetate, formate, propionate, benzoate, trifluoroacetate, maleate, tartrate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, etc.; inorganic base salts, such as sodium salt, potassium salt, calcium salt, magnesium salt, copper salt, zinc salt, aluminum salt, ammonium salt, etc.; organic base salts, such as triethylammonium salt, triethanolamine salt, pyridine salt, diisopropylammonium salt, etc.; and amino acid salts, such as lysine salt, arginine salt, histidine salt, aspartate salt, glutamate salt. In one embodiment, the salt may be sodium hyaluronate, potassium hyaluronate, hyaluronate acetate, hyaluronate ammonium, or C12-13 alkyl glycerol hydrolyzed hyaluronate. In this invention, the weight-average molecular weight of the polymeric hyaluronate or its salt varies depending on the length of the sugar chain; as an example, the weight-average molecular weight of the polymeric hyaluronate or its salt may be 10 to 5,000 kDa. Specifically, the weight-average molecular weight of the high molecular weight hyaluronic acid or its salt may be 10 kDa or above, 100 kDa or above, 300 kDa or above, 500 kDa or above, 700 kDa or above, 900 kDa or above, 1,100 kDa or above, 1,300 kDa or above, 1,400 kDa or above, 1,500 kDa or above, or 1,600 kDa or above, and 5,000 kDa or below, 4,000 kDa or below, 3,000 kDa or below, 2,700 kDa or below, 2,400 kDa or below, 2,100 kDa or below, 1,800 kDa or below, 1,700 kDa or below, 1,600 kDa or below, 1,500 kDa or below, or 1,400 kDa or below. More specifically, the weight-average molecular weight of the polymeric hyaluronic acid or its salt can be from 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, a cross-linking reaction may not occur, while when the weight-average molecular weight of the polymeric hyaluronic acid is greater than 5,000 kDa, the viscosity may be difficult to control before cross-linking due to its excessively high viscosity.

[0027] Natural hyaluronic acid has poor structural stability and is easily decomposed and removed in the body. Therefore, existing technologies use cross-linking agents to chemically form covalent bonds, thus achieving cross-linking. However, chemical cross-linking has drawbacks: the process for removing the cross-linking agent after the reaction is complex and it is less safe for the skin. In this invention, the hyaluronic acid or its salt does not form additional covalent bonds, but rather comprises hyaluronic acid cross-links that are physically interconnected through gelation. Therefore, while being non-irritating and stable, it maximizes the skin-beneficial effects of hyaluronic acid.

[0028] In one embodiment of the invention, terephthalic acid may be included as a crosslinking agent for physically crosslinking the polymeric hyaluronic acid or its salts. In this regard, one embodiment of the invention provides a crosslinking agent composition for polymeric hyaluronic acid or its salts, the composition comprising terephthalic acid as an active ingredient. In another embodiment, the use of terephthalic acid as an active ingredient in the preparation of a crosslinking agent for physically crosslinking polymeric hyaluronic acid or its salts may be provided. In yet another embodiment, a method for crosslinking polymeric hyaluronic acid or its salts may be provided, the method comprising the step of physically crosslinking polymeric hyaluronic acid or its salts by adding an effective dose of terephthalic acid. As an example, when the crosslinking agent described above is used to crosslink polymeric hyaluronic acid or its salts, the physical stability of natural hyaluronic acid is improved, while also providing a spinnable appearance and a dosage form with a unique user experience.

[0029] As an example, the crosslinking agent may be terephthalic dicamphor sulfonic acid (TDSA). In this invention, the terephthalic dicamphor sulfonic acid is an organic compound with CAS number 92761-26-7 and having the following structure. The terephthalic dicamphor sulfonic acid exhibits strong hydrogen ion dissociation in aqueous solution, thus displaying a low pH value of 0.5 to 2. Although the terephthalic dicamphor sulfonic acid is known to be used as a sunscreen agent, hyaluronic acid as a crosslinking agent as described in this invention has not been disclosed.

[0030] [Chemical Formula 2]

[0031]

[0032] In one embodiment, the content of the polymeric hyaluronic acid or its salt, based on the total weight of the composition, may be from 0.1 to 3% by weight. Specifically, based on the total weight of the composition, the content of the polymeric hyaluronic acid or its salt 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, 0.9% by weight or more, 1.1% by weight or more, 1.3% by weight or more, 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, and 3% by weight or less, 2.5% by weight or less, 2% by weight or less, 1.7% by weight or less, 1.5% by weight or less, 1.3% by weight or less, 1.1% by weight or less, 1% by weight or less, 0.9% by weight or less, or 0.8% by weight or less. When the content is less than 0.1% by weight, the skin-beneficial effects are minimal and it may be difficult to form a gel, while when it exceeds 3% by weight, it is difficult to mix with other substances due to excessive viscosity, and the dosage form desired by the present invention may not be achieved.

[0033] In one embodiment, the content of the crosslinking agent may be from 0.1 to 2% by weight, based on the total weight of the composition. Specifically, based on the total weight of the composition, the content of the crosslinking agent may be 0.1% or more by weight, 0.3% or more by weight, 0.5% or more by weight, 0.7% or more by weight, or 0.9% or more by weight, and less than 2% by weight, less than 1% by weight, less than 0.9% by weight, less than 0.8% by weight, less than 0.7% by weight, less than 0.6% by weight, or less than 0.5% by weight. When the content of the crosslinking agent is less than 0.1% by weight, the polymeric hyaluronic acid or its salts cannot be effectively crosslinked, and therefore the dosage form desired by the present invention may not be achieved. When the content of the crosslinking agent exceeds 2% by weight, it may cause skin irritation and may lead to a reverse crosslinking reaction, which in turn reduces spinnability.

[0034] In one embodiment, the weight ratio of the polymeric hyaluronic acid or its salt to the crosslinking agent is not particularly limited, as long as it enables physical crosslinking of the polymeric hyaluronic acid or its salt. However, considering the provision of a spinnable composition, the weight ratio may be from 0.1 to 10:1. Specifically, the weight ratio of the polymeric hyaluronic acid or its salt to the crosslinking agent may be from 0.5 to 7:1, and more specifically, the weight ratio may be from 1 to 5:1.

[0035] In one embodiment, the composition may further comprise one or more selected from polyols, nonionic surfactants, and n-valent alcohols.

[0036] In one embodiment of the invention, when polyols and / or n-valent alcohols are also included, skin irritation can be prevented by setting the isoelectric point, which reduces the solubility of hyaluronic acid, to pH 3 or higher. Specifically, the polyol may include at least one selected from glycerol, propylene glycol, butylene glycol, glycerol, erythritol, xylitol, maltitol glycerol, sorbitol, polyglycerol, polyethylene glycol, pentylene glycol, and isopentylene glycol, but is not limited thereto. Specifically, n in the n-valent alcohol may be 1 to 10. That is, it may be a monovalent to decavalent alcohol. More specifically, the n-valent alcohol may include at least one selected from methanol, ethanol, propanol, and butanol. In one embodiment, the content of the polyol may be 0.01 to 20% by weight based on the total weight of the composition, but is not limited thereto. More specifically, based on the total weight of the composition, the content of the polyol may be 0.01% by weight or more, 0.1% by weight or more, 0.5% by weight or more, 1% by weight or more, 2% by weight or more, 4% by weight or more, 6% by weight or more, 8% by weight 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. In one embodiment, based on the total weight of the composition, the content of the n-valent alcohol may be from 0.01% to 10% by weight, but is not limited thereto. More specifically, based on the total weight of the composition, the content of the n-valent alcohol may be 0.01% by weight or more, 0.1% by weight or more, 0.5% by weight or more, 1% by weight or more, 2% by weight or more, 4% by weight or more, 6% by weight or more, or 8% by weight or more, and 10% by weight or less, 9% by weight or less, or 8% by weight or less.

[0037] In one embodiment of the invention, the nonionic surfactant is a surfactant used to solubilize substances insoluble in water, and may comprise nonionic surfactants such as poly(oxyethylene)alkyl ethers, poly(oxyethylene)alkylphenyl ethers, etc. More specifically, the nonionic surfactant may comprise one or more selected from PPG-13-decyltetradecetyl alcohol polyether-24, polyglycerol-6 caprylate, polyglycerol-4 caprate, polyglycerol-5 trioleate, polyglycerol-10 laurate, and PEG-60 hydrogenated castor oil. In one embodiment, the content of the nonionic surfactant may be from 0.01 to 10% by weight, based on the total weight of the composition. More specifically, based on the total weight of the composition, the content of the nonionic surfactant may be 0.01% by weight or more, 0.05% by weight or more, 0.1% by weight or more, 0.15% by weight or more, 0.2% by weight or more, 0.25% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 1% by weight or more, 2% by weight or more, 3% by weight or more, or 0.4% by weight or more, and 10% by weight or less, 7% by weight or less, 5% by weight or less, 4% by weight or less, 3.5% by weight or less, 3% by weight or less, 2.5% by weight or less, 2% by weight or less, 1.5% by weight or less, 1% by weight or less, 0.5% by weight or less, 0.1% by weight or less, or 0.05% by weight or less.

[0038] In one embodiment of the invention, the composition may be in the form of a gel. In another embodiment of the invention, the composition exhibits spinnability. In this invention, spinnability refers to the property of a highly viscous liquid composition to be stretched like a viscous liquid to form a continuous filament. Spinnability is a specific physical property distinct from the viscosity or elasticity of a composition, and may be influenced by the combination of the composition's surface tension, viscoelasticity, adhesiveness, etc., but is not a characteristic expressed solely by their magnitude. For example, a gel formulation may not exhibit spinnability when the surface tension or viscoelasticity is high. Spinnability can be visually confirmed by attaching the tip of a rod to the surface of the composition and pulling it up at a certain speed, and the criterion for judging spinnability can be the length or time at which the liquid column breaks. For example, when measured using a Kinexus from Marlvern, spinnability can be defined as the stretch length (mm). Specifically, the tackiness mode of the aforementioned equipment can be set to a gap size of 1.0 mm to 180 mm, a gap speed of 1 mm / s, a unit type of PU20, and a temperature of 25°C. Then, while stretching the composition, the moment when the resistance experienced by the unit disappears is observed is used to determine the spinnability. In this case, when the composition according to an embodiment of the present invention is measured using a Marlvern Kinexus, the stretch length of the composition can be 100 to 180 mm.

[0039] In one embodiment, when the composition is measured using a Brookfield viscometer, the viscosity of the composition can be from 300 to 10,000 cps. Specifically, a Brookfield LV viscometer or a Brookfield RV viscometer can be used to measure the viscosity, wherein the spindle shaft rotation speed and measurement time are 12 rpm and 2 min, and a No. 62 spindle shaft is used for the measurement. Specifically, the viscosity of the composition can 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, and 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, spinnability may not occur when the viscosity of the composition exceeds the above range.

[0040] In one embodiment, the tackiness of the composition can be measured from 0.060 to 0.200 N using a rheometer from Maven Corporation (USA). Specifically, the tackiness can be measured using a rheometer (Maven Corporation, USA). The conditions can be set as follows: a pullaway test is performed at 25°C using a plate type with 20 mm parallel units, with a gap speed of 1 mm / s, a gap size of 1 mm, and a maximum gap of 180 mm. In this invention, the normal force value at the peak value is measured, and the specifications of the G' and G” test samples are standardized to a disc form with a diameter of 20 mm and a thickness of 1 mm.

[0041] In one embodiment, the composition may be a composition for skin moisturizing. One embodiment of the invention has spinnability, thus allowing it to spread thinly and over a long distance when applied to the skin to form a moisturizing film. Therefore, excellent skin moisturizing power is provided.

[0042] In one embodiment, the composition may be a cosmetic composition.

[0043] In one aspect, the cosmetic composition comprises a cosmetically or dermatologically acceptable medium or matrix. It can be any dosage form suitable for topical application, for example, it can be prepared as a solution, gel, an anhydrous paste, emulsion, suspension, microemulsion, microcapsule, microsphere, or ionic (liposome) and nonionic vesicle dispersion obtained by dispersing an oil phase in an aqueous phase, or in the form of cream, toner, lotion, ointment, etc. These compositions can be prepared according to conventional methods in the art. According to one embodiment of the cosmetic composition, the dosage form is not particularly limited; for example, it can be prepared as ampoules, creams, softening lotions, astringent lotions, nourishing lotions, nourishing creams, massage creams, serums, eye creams, eye serums, cleansing creams, cleansing foams, cleansing waters, cleansing wipes containing the cosmetic composition, masks, body lotions, body creams, body oils, and body serums, etc.

[0044] When the dosage form according to one embodiment of the present invention is a paste, cream, or gel, animal fibers, plant fibers, waxes, paraffin wax, starch, tragacanth gum, cellulose derivatives, polyethylene glycol, silicon, bentonite, silica, talc, or zinc oxide can be used as the carrier component. When the dosage form according to one embodiment of the present invention is a solution or emulsion, solvents, solvators, or emulsifiers are used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol oil, glycerol fatty acid esters, polyethylene glycol, or fatty acid esters of dehydrated sorbitol. When the dosage form according to one embodiment of the present invention is a suspension, liquid diluents such as water, ethanol, or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters, and polyoxyethylene dehydrated sorbitol esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar, or tragacanth gum can be used as the carrier component. When the dosage form according to one embodiment of the present invention is a facial cleanser containing a surfactant, the carrier component may include fatty alcohol sulfate, fatty alcohol ether sulfate, sulfosuccinate monoester, hydroxyethyl sulfonate, imidazoline derivative, methyl taurine, sarcosinate, fatty acid amide ether sulfate, alkylamide betaine, fatty alcohol, fatty acid glycerides, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester, etc.

[0045] A cosmetic composition according to an embodiment of the present invention may further comprise functional additives and ingredients typically found in cosmetic compositions. The functional additives may comprise ingredients selected from water-soluble vitamins, oil-soluble vitamins, high-molecular-weight peptides, high-molecular-weight polysaccharides, sphingolipids, and seaweed extracts. Other included formulation ingredients may be oil components, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation promoters, coolants, antiperspirants, purified water, etc.

[0046] In one embodiment, the composition may be a pharmaceutical composition.

[0047] When the composition according to an embodiment of the present invention is applied to a pharmaceutical product, it can be prepared into a semi-solid or liquid parenteral dosage form by adding a commonly used inorganic or organic carrier to the active ingredient used in one embodiment of the present invention. The composition according to an embodiment of the present invention can be readily dosage-formulated according to conventional methods known in the art, where surfactants, excipients, colorants, fragrances, preservatives, stabilizers, buffers, suspending agents, and other commonly used adjuvants may be appropriately used. The dosage of the active ingredient in the pharmaceutical composition according to an embodiment of the present invention will vary depending on the age, sex, weight, pathological condition and its severity, route of administration, or the prescriber's judgment of the subject receiving the medication. Determining an appropriate dosage based on these factors is within the skill of a person skilled in the art, and the daily dosage may, for example, be from 0.1 mg / kg / day to 100 mg / kg / day, more specifically from 5 mg / kg / day to 50 mg / kg / day, but is not limited thereto.

[0048] The present invention will now be described in more detail through the following embodiments. However, these embodiments are provided only to aid in understanding the present invention, and the scope and range of the present invention are not limited thereto.

[0049]

Preparation Examples

[0050] The examples and comparative examples were prepared according to the compositions shown in Table 1 below. Specifically, all components except dimethyl camphor sulfonic acid (TDSA) were added to purified water and mixed at 25°C for 1 hour using an AGI mixer. After confirming that all components were dissolved, TDSA was added and mixed. The hyaluronic acid used in the following examples and comparative examples was sodium hyaluronate from Modern Bioland Corporation.

[0051] Table 1

[0052]

[0053] (weight%)

[0054]

Experimental Example 1

[0055] The viscosity, tackiness, and spinnability (stretch length) of the above-prepared examples and comparative examples were measured as follows.

[0056] Viscosity was measured using a Brookfield RV viscometer. The spindle shaft rotation speed and measurement time were 12 rpm and 2 min, respectively, and a No. 62 spindle shaft was used.

[0057] Adhesion was determined using a rheometer (Maven, USA). The conditions were set as follows: a tensile test was conducted using plates with 20mm parallel elements, with a gap speed of 1mm / s, a gap size of 1mm, and a maximum gap of 180mm. The normal force value at the peak was measured. The G' and G” test samples were standardized to a disc shape with a diameter of 20mm and a thickness of 1mm.

[0058] The elongation length was measured using a Malvern Kinexus. Specifically, the viscous mode was set to a gap size of 1.0 mm to 180 mm, a gap speed of 1 mm / s, a cell type of PU20, and a temperature of 25°C. The composition was then stretched while using a method such as... Figure 1 and Figure 2 The moment when the resistance experienced by the ruler's visually measured unit disappears.

[0059] Table 2

[0060] Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Viscosity (cps) 2369 2010 1862 2032 1720 3050 Adhesion (N) 0.089 0.077 0.052 0.032 0.029 0.055 Length of extension (mm) 133 131 81 5 6 10

[0061] As a result, Examples 1 and 2, as well as Comparative Examples 1 to 3, exhibited similar viscosities. However, Comparative Example 4, obtained by dissolving a chemically crosslinked sodium hyaluronate crosslinked polymer of hyaluronic acid in water and then adding terephthalimide dicamphor sulfonic acid, exhibited a relatively higher viscosity. Examples 1 and 2 showed higher values ​​in terms of tackiness, and also exhibited higher stretch lengths and spinnability. Conversely, although lactic acid was used as a crosslinking agent in Comparative Example 1, the crosslinking reaction was carried out, but it exhibited high elasticity, low tackiness and stretch length, and did not show spinnability. Figure 1 (Example 1) and Figure 2 In Comparative Example 1, the aforementioned characteristics can be clearly compared. In Comparative Example 1, the gel exhibits a short and thick stretch length due to its high elasticity, while in Example 1, a long and thin spinnable structure is evident. In Comparative Example 2, which uses phenylbenzimidazole sulfonic acid at pH 6-7 as a crosslinking agent, and Comparative Example 3, which does not contain a crosslinking agent, low adhesion and stretch length are observed due to the absence of a crosslinking reaction, resulting in no spinnability. In Comparative Example 4, terephthalic acid was not used as a crosslinking agent; instead, chemical crosslinking was performed before the addition of terephthalic acid. It is confirmed that Comparative Example 4 also does not exhibit spinnability.

[0062] This means that when terephthalic acid dicamphor sulfonic acid is used as a crosslinking agent for hyaluronic acid or its salts according to this invention, the composition is spinnable, thereby providing a differentiated appearance and the resulting special feel.

[0063]

Experimental Example 2

[0064] The viscoelasticity of Example 1 according to an embodiment of the present invention was measured as follows.

[0065] Specifically, a rheometer (Maven, USA) was used to determine the elastic modulus (G'; Elastic modulus) and viscous modulus (G”; Viscos modulus). The settings included "oscillation," "frequency scan," "shear stress," and "adhesion." A 20mm parallel-unit plate was used at 25°C, and measurements were performed at an oscillation stress of 1 Pa, a frequency range of 0.1 to 10 Hz, a shear stress of 1 Pa, and a gap of 1 mm. The G' and G” values ​​were measured at 1 Hz. The G' and G” samples were standardized to a disc shape with a diameter of 20 mm and a thickness of 1 mm.

[0066] The measurement results are as follows Figure 3 As shown, it can be confirmed that Example 1 has a G' value of 6.9 Pa and a G” value of 5.8 Pa at a frequency of 1 Hz, forming a gel with low viscoelasticity and high viscosity.

[0067]

Experimental Example 3

[0068] The moisturizing power of the above-prepared examples and comparative examples was evaluated as follows.

[0069] Specifically, skin moisture content and transepidermal water loss (TEWL) were measured. A corneometer (product name: GP SKIN BARRIER, manufacturer: G-Power) was used to measure skin moisture content and transepidermal water loss.

[0070] The comparison results of moisture content are shown in Table 3 and Figure 4 As shown in Table 4, the comparison results of transepidermal water loss are presented in Table 4 and 5. Figure 5 As shown.

[0071] Table 3

[0072] Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Apply immediately (30 minutes later) 65 62 47 45 44 1 hour after coating 51 52 47 44 44 2 hours after coating 51 49 47 41 42 6 hours after coating 50 49 45 36 35

[0073] Table 4

[0074] Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Moments before coating 5.6 5.6 6.2 5.6 5.7 Apply immediately (30 minutes later) 1.2 1.6 1.8 2.6 2.3 1 hour after coating 1.2 1.8 2.3 2.7 2.7 2 hours after coating 1.6 1.8 2.9 3.3 3.5 6 hours after coating 4 4.2 5.8 5.3 5.2

[0075] The results are shown in Tables 3 and 4. Figure 4 and Figure 5 As shown, Examples 1 and 2 of the present invention are superior to Comparative Examples 1 to 3 in terms of moisture content and transepidermal water loss. This means that the embodiments of the present invention provide excellent moisturizing and transepidermal water loss prevention effects by forming a water film on the skin through spinnability.

[0076] The present invention can provide the following implementation as an example.

[0077] The first embodiment provides a composition comprising physically cross-linked polymeric hyaluronic acid or its salt, wherein the polymeric hyaluronic acid or its salt is physically cross-linked by a cross-linking agent, wherein the cross-linking agent is terephthalic dicamphor sulfonic acid.

[0078] The second embodiment provides a composition according to the first embodiment, wherein the weight ratio of the polymeric hyaluronic acid or its salt to the crosslinking agent is 0.1 to 10:1.

[0079] The third embodiment may provide a composition according to the first or second embodiment, wherein the composition further comprises one or more selected from polyols, nonionic surfactants and n-valent alcohols, wherein n is 1 to 10.

[0080] The fourth embodiment provides a composition according to any one of the first to third embodiments, wherein the tensile length of the composition, as measured by a Kinexus instrument from Malvern Corporation, is 100 to 180 mm.

[0081] The fifth embodiment provides a composition according to any one of the first to fourth embodiments, wherein the viscosity of the composition, as measured by a Brookfield viscometer, is 300 to 10,000 cps.

[0082] The sixth embodiment provides a composition according to any one of the first to fifth embodiments, wherein the adhesiveness of the composition, as measured by a Maven rheometer, is 0.060 to 0.200 N.

[0083] The seventh embodiment provides a composition according to any one of the first to sixth embodiments, wherein the composition is a gel formulation.

[0084] The eighth embodiment may provide a composition according to any one of the first to seventh embodiments, wherein the composition is a cosmetic composition.

[0085] The ninth embodiment may provide a composition according to any one of the first to eighth embodiments, wherein the composition is a pharmaceutical composition.

[0086] The 10th embodiment provides the use of physically cross-linked polymeric hyaluronic acid or its salt in the preparation of a composition for skin moisturizing, wherein the polymeric hyaluronic acid or its salt is obtained by physical cross-linking via a cross-linking agent, wherein the cross-linking agent is terephthaloyl dicamphorsulfonic acid.

[0087] The 11th embodiment provides the use according to the 10th embodiment, wherein the weight ratio of the polymeric hyaluronic acid or its salt to terephthalic acid dicamphor sulfonic acid is 0.1 to 10:1.

[0088] The 12th embodiment can provide the use described in the 10th or 11th embodiment, wherein the composition further comprises one or more selected from polyols, nonionic surfactants and n-valent alcohols, wherein n is 1 to 10.

[0089] The 13th embodiment can provide the use according to any one of the 10th to 12th embodiments, wherein the tensile length of the composition, as measured by a Kinexus of Malvern Corporation, is 100 to 180 mm.

[0090] The 14th embodiment can provide the use according to any one of the 10th to 13th embodiments, wherein the viscosity of the composition, as measured by a Brookfield viscometer, is 300 to 10,000 cps.

[0091] The 15th embodiment can provide the use according to any one of the 10th to 14th embodiments, wherein the adhesiveness of the composition, as measured by a Maven rheometer, is 0.060 to 0.200 N.

[0092] The 16th embodiment can provide the use according to any one of the 10th to 15th embodiments, wherein the composition is a gel formulation.

[0093] The 17th embodiment can provide the use according to any one of the 10th to 16th embodiments, wherein the composition is a cosmetic composition.

[0094] The 18th embodiment can provide the use according to any one of the 10th to 17th embodiments, wherein the composition is a pharmaceutical composition.

[0095] Embodiment 19 provides the use of terephthalimide dicamphorsulfonic acid as an active ingredient in the preparation of crosslinking agents for physically crosslinking polymeric hyaluronic acid or its salts.

[0096] The 20th embodiment provides the use according to the 19th embodiment, wherein the weight ratio of the polymeric hyaluronic acid or a salt thereof to terephthalic acid dicamphor sulfonic acid is 0.1 to 10:1.

Claims

1. A composition comprising physically cross-linked polymeric hyaluronic acid or a salt thereof, wherein, The high molecular weight hyaluronic acid or its salt is obtained by physical cross-linking with a cross-linking agent. The crosslinking agent is terephthaloyl dicamphorsulfonic acid. The weight ratio of the polymeric hyaluronic acid or its salt to the crosslinking agent is 0.1 to 10:

1. The weight-average molecular weight of the hyaluronic acid or its salt is 10 to 5,000 kDa. Based on the total weight of the composition, the content of the polymeric hyaluronic acid or its salt is 0.1 to 3% by weight, and the content of the crosslinking agent is 0.1 to 2% by weight.

2. The composition according to claim 1, characterized in that, The composition further comprises one or more substances selected from polyols, nonionic surfactants and n-valent alcohols, wherein n is 1 to 10.

3. The composition according to claim 1, characterized in that, The tensile length of the composition, measured by Malvern's Kinexus, is 100 to 180 mm.

4. The composition according to claim 1, characterized in that, The viscosity of the composition, as measured by a Brinell viscometer, is 300 to 10,000 cps.

5. The composition according to claim 1, characterized in that, The adhesiveness of the composition, as measured by a Maven rheometer, ranges from 0.060 to 0.200 N.

6. The composition according to claim 1, characterized in that, The composition is a gel formulation.

7. Use of physically cross-linked polymeric hyaluronic acid or its salts in the preparation of compositions for skin moisturizing, wherein, The high molecular weight hyaluronic acid or its salt is obtained by physical cross-linking with a cross-linking agent. The crosslinking agent is terephthaloyl dicamphorsulfonic acid. The weight ratio of the polymeric hyaluronic acid or its salt to terephthalic acid dicamphor sulfonic acid is 0.1 to 10:

1. The weight-average molecular weight of the hyaluronic acid or its salt is 10 to 5,000 kDa. Based on the total weight of the composition, the content of the polymeric hyaluronic acid or its salt is 0.1 to 3% by weight, and the content of the crosslinking agent is 0.1 to 2% by weight.

8. The use according to claim 7, characterized in that, The composition is a cosmetic composition or a pharmaceutical composition.

9. The use according to claim 7, characterized in that, The composition further comprises one or more substances selected from polyols, nonionic surfactants and n-valent alcohols, wherein n is 1 to 10.

10. The use of terephthaloyl dicamphorsulfonic acid as an active ingredient in the preparation of crosslinking agents for physically crosslinking polymeric hyaluronic acid or its salts, wherein, The weight ratio of the polymeric hyaluronic acid or its salt to terephthalic acid dicamphor sulfonic acid is 0.1 to 10:

1. The weight-average molecular weight of the hyaluronic acid or its salt is 10 to 5,000 kDa. Based on the total weight of the composition comprising physically cross-linked polymeric hyaluronic acid or its salt, the content of said polymeric hyaluronic acid or its salt is 0.1 to 3% by weight, and the content of said cross-linking agent is 0.1 to 2% by weight.

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