Ternary composition for stabilizing urea

Abstract

The invention discloses a ternary composition for stabilizing urea. The ternary composition comprises the following components in percentage by weight: 0.1-20% of urea; the sodium hyaluronate is selected from sodium hyaluronate, hydrolyzed sodium hyaluronate or a combination of the sodium hyaluronate and the hydrolyzed sodium hyaluronate; 0.01 to 3% by weight of triethyl citrate and water; wherein the weight ratio of the sodium hyaluronate to the triethyl citrate is (0.4-2.5): 1. The invention also relates to a preparation method of the ternary composition for stabilizing urea, and application of a combination containing sodium hyaluronate and triethyl citrate in stabilizing urea.

Description

Technical Field

[0001] The present invention relates to the fields of fine chemistry and cosmetics, and particularly relates to a preparation method and application of a ternary composition for stabilizing urea, and the use of a combination containing sodium hyaluronate and triethyl citrate in stabilizing urea. Background Art

[0002] Urea is a low molecular weight organic molecule composed of a carbonyl group linked to two amine residues. It is mainly produced after the digestion of proteins in the liver. Urea is a hygroscopic molecule (able to absorb moisture) and exists as a component of the natural moisturizing factor (NMF) in the epidermis, which is crucial for the adequate hydration and integrity of the stratum corneum. A decrease in the skin's moisture absorption capacity increases transepidermal water loss (TEWL), leads to uncontrolled epidermal proliferation and inhibits skin desquamation, inducing hyperkeratosis and itching.

[0003] Urea is a topical emollient, humectant, keratolytic, and antipruritic agent, and it plays a key role in the gene regulation of keratinocytes. In Asia, Africa, and Europe, the therapeutic use of urine (urine therapy) has a history of hundreds of years. One of the first uses of urea in modern medicine was for the topical treatment of wounds due to its proteolytic and antibacterial properties. Currently, urea is widely used in dermatology. It is used to treat various skin diseases characterized by scaly and dry skin, such as atopic dermatitis, ichthyosis, seborrheic dermatitis, and psoriasis, etc. In addition, urea can increase skin penetration and optimize the action of topical drugs. There are various formulations and concentrations of urea-containing formulations available for selection.

[0004] Urea can be easily incorporated into dermatological preparations because of its high water solubility. There are various carriers and formulations (creams, lotions, emulsions, ointments, gels, shampoos, and nail polishes, etc.) and urea concentrations in over-the-counter and prescription drugs, which makes its prescription highly versatile. Before selecting the most suitable product, multiple factors must be considered: the disease to be treated, its severity, the body area involved (and its extent), and cosmetic acceptability. Generally, compounds with low concentrations of urea (2% - 10%) are used for moisturizing and optimizing the skin's barrier function, compounds with medium concentrations (10% - 30%) are used as humectants and keratolytics, and compounds with high concentrations (≥30%) are used as keratolytics and for debriding necrotic tissues.

[0005] Although the application of urea in cosmetics brings many benefits, such as moisturizing and cutin conditioning, it also faces some technical barriers. Urea is a relatively stable compound, but under certain special conditions, such as high temperature, high humidity or acid-base environment, it may decompose to produce ammonia gas, thus generating a pungent smell. This requires that cosmetic formulators must strictly control the stability and safety of urea during the production process to avoid its decomposition and the resulting bad smell and impact on the product's user experience.

[0006] The concentration control of urea in cosmetics is also a technical difficulty. On the one hand, urea has the functions of moisturizing and cutin conditioning. On the other hand, if the concentration is too high, it may cause irritation and discomfort to the skin. Therefore, in the cosmetic formula, it is necessary to accurately control the content of urea to ensure that it can play its role without causing negative impacts on the skin. This requires formulators to have precise measurement and proportioning techniques and strictly conduct quality control.

[0007] In summary, the technical barriers in the application of urea in cosmetics mainly include aspects such as the stability of urea, concentration ratio and control. To overcome these technical barriers, cosmetic enterprises need to strengthen research and development and innovation, improve product quality and safety to meet the needs and expectations of consumers.

[0008] Chinese Patent Application CN113150187A discloses a complex of ultra-low molecular weight calcium hyaluronate and urea. The molecular weight of the complex is 9063626. Using high molecular weight sodium hyaluronate, urea and calcium nitrate tetrahydrate as raw materials and formic acid as an acidifying agent, through acid hydrolysis and hyaluronidase hydrolysis, the high molecular weight sodium hyaluronate is turned into ultra-low molecular weight sodium hyaluronate, and then reacts with calcium nitrate tetrahydrate and urea to generate a complex of ultra-low molecular weight calcium hyaluronate and urea. The complex of ultra-low molecular weight calcium hyaluronate and urea has excellent water solubility, with a water solubility of up to 30%, which is convenient for human absorption, excellent penetration and moisturizing ability, soft tissue repair ability, and calcium supplementation ability. It has obvious curative effects on arthritis and rheumatoid arthritis, penetrates into the subcutaneous dermis layer, has an obvious anti-wrinkle beauty effect, and has the ability to promote tissue injury and wound healing after surgery. It can be widely used in the fields of pharmaceutical products, health products, etc.

[0009] Chinese Patent Application CN105451786A discloses the use of a cross-linked biopolymer based on hyaluronic acid cross-linked with urea, which is compatible with the tissues of the human organism, as a dermal filler. The biopolymer of hyaluronic acid and urea can be applied or injected into the soft tissues of the human body for tissue enhancement.

[0010] Chinese Patent Application CN113648232B provides a stable composition carrying urea or its derivatives, which composition comprises: (a) an oil; (b) a cationic emulsifier which is distearyldimethylammonium chloride; (c) a long-chain fatty alcohol with a carbon chain length of 16-22; (d) an aqueous phase; wherein, the urea derivative is a hydroxyalkylate of urea with 16 carbon atoms, and wherein, the weight ratio of the cationic emulsifier to the long-chain fatty alcohol is from 10:1 to 1:4, and the weight ratio of the cationic emulsifier to the carried urea or its derivative is from 1:10 to 50:1.

[0011] The above Chinese patent applications all improve the stability of urea by the formulation carrier or conduct chemical reactions on urea using sodium hyaluronate and its homologues to synthesize new substance components. There is no research on the application stability and concentration control of urea as a component in skin care products. This application not only screens out a ternary composition that can stabilize urea, especially the unexpected discovery of the stabilization of the pH value of urea in aqueous solution by sodium hyaluronate, which further promotes the wide application of urea in multi-form skin care products. Summary of the Invention

[0012] The object of the present invention is to provide a ternary composition for stabilizing urea. By preparing a ternary composition containing urea according to the provided components and precise ratios, it can be applied to various skin care product dosage forms. Its ternary composition can stabilize the state of urea in skin care products, improve the stability of the preparation itself, stabilize the system pH, and reduce the odor caused by urea hydrolysis.

[0013] On the one hand, the present invention provides a ternary composition for stabilizing urea, which comprises:

[0014] 0.1-20% by weight of urea;

[0015] 0.001-5% by weight of sodium hyaluronate, wherein the sodium hyaluronate is selected from: sodium hyaluronate, hydrolyzed sodium hyaluronate, or a combination thereof;

[0016] 0.01-3% by weight of triethyl citrate and water; wherein the weight ratio of the sodium hyaluronate to the triethyl citrate is 0.4-2.5:1.

[0017] In a preferred embodiment, the pH of the composition is 4.0-8.0,

[0018] In a more preferred embodiment, the pH of the composition is 4.0-6.0.

[0019] In a preferred embodiment, the composition contains 0.1-10% by weight of urea,

[0020] In a further preferred embodiment, the composition preferably contains 0.1 - 5% by weight of urea.

[0021] In a preferred embodiment, the composition contains 0.001 - 3% by weight of sodium hyaluronate.

[0022] In a further preferred embodiment, the sodium hyaluronate is sodium hyaluronate at 0.2 - 0.5% by weight or hydrolyzed sodium hyaluronate at 0.2 - 0.5% by weight.

[0023] In a preferred embodiment, the composition contains 0.01 - 2% by weight of triethyl citrate. In a further preferred embodiment, the composition contains 0.2 - 0.5% by weight of triethyl citrate.

[0024] In a preferred embodiment, the composition further includes 0.1 - 2.3% by weight of a thickening agent selected from polyacrylic acid - 30 polymer, cetearyl alcohol, xanthan gum, or a combination thereof, wherein the thickening agent combination is a polyacrylic acid - 30 polymer, cetearyl alcohol, and xanthan gum in a weight ratio of 2:20:1.

[0025] In a preferred embodiment, the composition further includes 0.5 - 2% by weight of an emulsifier selected from PEG - 20 methyl glucoside sesquistearate, cetyl / stearyl glucoside, or a combination thereof, wherein the emulsifier combination is PEG - 20 methyl glucoside sesquistearate and cetyl / stearyl glucoside in a weight ratio of 1:3.

[0026] In a preferred embodiment, the composition further includes 2 - 6% by weight of an oil selected from petrolatum, dicaprylyl carbonate, or a combination thereof, wherein the oil is a combination of petrolatum and dicaprylyl carbonate in a weight ratio of 1:2.

[0027] In a preferred embodiment, the composition further includes 0.1% by weight of triethanolamine.

[0028] In another aspect, the present invention provides the use of a combination of sodium hyaluronate and triethyl citrate in stabilizing urea, wherein the weight ratio of sodium hyaluronate to triethyl citrate is 0.4 - 2.5:1.

[0029] In another aspect, the present invention provides a method for preparing the above - mentioned composition, comprising the following steps:

[0030] a) Weigh the thickening agent, sodium hyaluronate, and deionized water, heat them to 80 - 85°C and mix, and mix and stir at a rotation speed of 100 rpm until completely dissolved to obtain an aqueous phase;

[0031] b) Weigh the emulsifier, add it to the oil, and place it in an 85°C water bath to completely melt it to obtain the oil phase.

[0032] c) Slowly add the oil phase from step b) to the aqueous phase from step a) at 80 - 85°C and homogenize at a rotation speed of 2500 - 3000 rpm for 10 - 15 minutes until it is uniform and free of particles. Wait until the temperature drops to 55 - 60°C, add triethanolamine, and carry out a neutralization stirring reaction to obtain the material.

[0033] d) Add urea to deionized water, stir to dissolve it, then add it to the material from step c) and stir evenly. Finally, add triethyl citrate, and add deionized water to make up to 100. Continue to mix and stir at a rotation speed of 100 rpm for 10 - 20 minutes. Then let it stand at room temperature for 12 hours to obtain the composition. Detailed implementation mode

[0034] The purpose of the present invention is to provide a ternary composition for stabilizing urea. By preparing a ternary composition containing urea according to the provided ingredients and precise ratios, it can be applied to various skin care product dosage forms. Its ternary composition can stabilize the state of urea in skin care products, improve the stability of the preparation itself, stabilize the system pH, and reduce the odor caused by urea hydrolysis.

[0035] This application specifically studies the application stability and concentration control of urea in skin care products. This application not only screens out a ternary composition that can stabilize urea, especially the unexpected discovery of the stability of sodium hyaluronate on the pH value of urea in aqueous solution, which further promotes the wide application of urea in multi-dosage form skin care products.

[0036] For the purpose of providing a more concise description, some quantitative expressions given herein are not modified by the term "about". It should be understood that whether or not the term "about" is explicitly used, each quantity given herein is intended to refer to the actual given value, and also intended to refer to the approximate value of these given values reasonably inferred by those of ordinary skill in the art, including the approximate values caused by experimental and / or measurement conditions of these given values.

[0037] Embodiment

[0038] Hereinafter, the technical solutions of the present invention will be described in detail through preferred implementation modes. However, the scope of the present invention is not limited to these implementation modes. It is intended to illustrate the technical solutions of the present invention rather than limit the scope of the present invention. The test methods without specific conditions noted in the following examples are usually carried out under conventional conditions or according to the conditions recommended by the manufacturer. Unless otherwise specified, all percentages and parts are by weight.

[0039] The experimental materials used in the examples of the present invention are as follows:

[0040] Urea, trade name Urea, purchased from Sinopharm Chemical Reagent Co., Ltd.

[0041] Hydrolyzed sodium hyaluronate, trade name Nano Enzymatically digested oligomeric sodium hyaluronate, purchased from Bloomage Biotechnology Corporation Limited

[0042] Sodium hyaluronate, trade name Hybloom TM Sodium hyaluronate (HA-TG), purchased from Bloomage Biotechnology Corporation Limited

[0043] Hyaluronic acid, trade name Hybloom TM Oligomeric hyaluronic acid (HA-Oligo), sample provided by Bloomage Biotechnology Corporation Limited

[0044] Triethyl citrate, trade name Triethyl citrate, purchased from Shanghai Guanying Biotechnology Development Co., Ltd.

[0045] Cetearyl glucoside, trade name Montanov 68MB, purchased from SEPPIC S.A.

[0046] Polyacrylic acid-30 polymer, trade name STABYLEN 30, purchased from 3V SIGMA S.p.A.

[0047] Triethanolamine, trade name Triethanolamine 99%, purchased from Dow Chemical (Shanghai) Co., Ltd.

[0048] PEG-20 methyl glucoside sesquistearate, trade name Glucamate TM SSE-20 emulsifier, purchased from Lubrizol Advanced Materials, Inc.

[0049] Xanthan gum, trade name Xanthan Gum FN-PC, purchased from Jungbunzlauer International AG.

[0050] Dioctyl carbonate, trade name CC, purchased from BASF (China) Co., Ltd.

[0051] Cetearyl alcohol, trade name C16-18 30:70 MY, purchased from Edenor Oleochemicals (M) Sdn. Bhd.

[0052] Vaseline, trade name White Vaseline, purchased from Hebei Lanlian Feitian Petrochemical Co., Ltd.

[0053] Example 1: Preparation of an aqueous solution containing a urea composition

[0054] Weigh 5 parts by mass of urea and 90 parts by mass of deionized water, mix and dissolve them, and mix and stir at a rotation speed of 100 rpm at room temperature until completely dissolved or uniformly mixed; add deionized water to make up to 100, and continue to mix and stir at a rotation speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for standby.

[0055] Example 2: Preparation of an aqueous solution containing a urea composition

[0056] Weigh 1 part by mass of sodium hyaluronate and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or uniformly mixed; wait until it cools to 40 - 50 °C, add 5 parts by mass of urea, stir at a rotation speed of 100 rpm until completely dissolved and uniform, add deionized water to make up to 100, and continue to mix and stir at a rotation speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for standby.

[0057] Example 3: Preparation of an aqueous solution containing a urea composition

[0058] Weigh 1 part by mass of hyaluronic acid and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or uniformly mixed; wait until it cools to 40 - 50 °C, add 5 parts by mass of urea, stir at a rotation speed of 100 rpm until completely dissolved and uniform, add deionized water to make up to 100, and continue to mix and stir at a rotation speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for standby.

[0059] Example 4: Preparation of an aqueous solution containing a urea composition

[0060] Weigh 1 part by mass of hydrolyzed sodium hyaluronate and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or uniformly mixed; wait until it cools to 40 - 50 °C, add 5 parts by mass of urea, stir at a rotation speed of 100 rpm until completely dissolved and uniform, add deionized water to make up to 100, and continue to mix and stir at a rotation speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for standby.

[0061] Example 5: Preparation of an aqueous solution containing a urea composition

[0062] Weigh 0.01 parts by mass of hyaluronic acid and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools down to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, make up to 100 with deionized water, and continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0063] Example 6: Preparation of an aqueous solution containing a urea composition

[0064] Weigh 0.05 parts by mass of hyaluronic acid and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools down to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, make up to 100 with deionized water, and continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0065] Example 7: Preparation of an aqueous solution containing a urea composition

[0066] Weigh 5 parts by mass of urea and 90 parts by mass of deionized water, mix and dissolve them, and mix and stir at a speed of 100 rpm at room temperature until completely dissolved or evenly mixed; add 0.2 parts by mass of triethyl citrate, make up to 100 with deionized water, and continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0067] Example 8: Preparation of an aqueous solution containing a urea composition

[0068] Weigh 5 parts by mass of urea and 90 parts by mass of deionized water, mix and dissolve them, and mix and stir at a speed of 100 rpm at room temperature until completely dissolved or evenly mixed; add 0.5 parts by mass of triethyl citrate, make up to 100 with deionized water, and continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0069] Example 9: Preparation of an aqueous solution containing a urea composition

[0070] Weigh 0.5 parts by mass of sodium hyaluronate and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools down to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.2 parts by mass of triethyl citrate, make up to 100 with deionized water, and continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0071] Example 10: Preparation of an aqueous solution containing a urea composition

[0072] Weigh 0.5 parts by mass of sodium hyaluronate and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools down to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.5 parts by mass of triethyl citrate, and make up to 100 with deionized water. Continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0073] Example 11: Preparation of an aqueous solution containing a urea composition

[0074] Weigh 0.5 parts by mass of hydrolyzed sodium hyaluronate and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools down to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.2 parts by mass of triethyl citrate, and make up to 100 with deionized water. Continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0075] Example 12: Preparation of an aqueous solution containing a urea composition

[0076] Weigh 0.5 parts by mass of hydrolyzed sodium hyaluronate and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools down to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.5 parts by mass of triethyl citrate, and make up to 100 with deionized water. Continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0077] Example 13: Preparation of an aqueous solution containing a urea composition

[0078] Weigh 0.01 parts by mass of hyaluronic acid and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools down to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.2 parts by mass of triethyl citrate, and make up to 100 with deionized water. Continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0079] Example 14: Preparation of an aqueous solution containing a urea composition

[0080] Weigh 0.01 part by mass of hyaluronic acid and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools back to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.5 part by mass of triethyl citrate, and make up to 100 with deionized water. Continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0081] Example 15: Preparation of an aqueous solution containing a urea composition

[0082] Weigh 0.2 part by mass of sodium hyaluronate and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools back to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.2 part by mass of triethyl citrate, and make up to 100 with deionized water. Continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0083] Example 16: Preparation of an aqueous solution containing a urea composition

[0084] Weigh 0.2 part by mass of sodium hyaluronate and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools back to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.5 part by mass of triethyl citrate, and make up to 100 with deionized water. Continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0085] Example 17: Preparation of an aqueous solution containing a urea composition

[0086] Weigh 0.2 part by mass of hydrolyzed sodium hyaluronate and 90 parts by mass of deionized water, heat to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools back to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.2 part by mass of triethyl citrate, and make up to 100 with deionized water. Continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0087] Example 18: Preparation of an aqueous solution containing a urea composition

[0088] Weigh 0.2 parts by mass of hydrolyzed sodium hyaluronate and 90 parts by mass of deionized water, heat them to 80 °C, and homogenize and stir at a speed of 3000 rpm until completely dissolved or evenly mixed; wait until it cools down to 40 - 50 °C, add 5 parts by mass of urea, stir at a speed of 100 rpm until completely dissolved and homogeneous, add 0.5 parts by mass of triethyl citrate, and make up to 100 with deionized water, continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for later use.

[0089] Test Example 1: High and low temperature stability pH test of the product

[0090] After measuring the initial pH of the systems in Examples 1 - 18, conduct high and low temperature stability investigation on them. After the stability investigation is completed, perform a rewarming treatment on the test samples and then conduct pH tests. The pH test method is as follows:

[0091] Use a pH meter (S400 - K and Mettler) with an accuracy of at least 0.02 (including a temperature compensation system), sample test temperature: 25 °C, keep it at a constant temperature for 4 h. After instrument calibration, rinse the electrode with deionized water and then dry it with filter paper. Carefully insert the electrode into the sample so that the electrode is immersed. Wait until the pH meter reading is stable and record the reading. After reading, thoroughly clean the electrode for later use. The test results of the pH value are expressed as the average of two measurements, accurate to 0.1, and the parallel test error should be ≤0.1.

[0092] The results are shown in the following table.

[0093] Table 1: Initial pH and stability pH results of different examples

[0094]

[0095]

[0096] Conclusion: Since urea is extremely easy to hydrolyze in aqueous solution, and the hydrolysis will cause the pH of the system to be extremely high, even exceeding the regulatory requirements range for cosmetics (pH 4.0 - 8.5), so for this series of examples, the pH investigation of stability is focused on.

[0097] Table 1 shows the stability performance of aqueous agent examples of different urea compositions, and examines the stability of different urea composition components in the aqueous agent system. From the above experimental results, it can be obtained that: for the aqueous agent containing only urea in Example 1, the stability pH at 48°C exceeds 8 and cannot meet the stability requirements. The pH values of the urea ternary compositions in Examples 9-12 and Examples 15-18 are all between 4.0 and 8.0, maintaining a relatively stable state and meeting the regulatory requirements. That is, the urea ternary composition with good stability performance is: 0.2-0.5 parts by mass of sodium hyaluronate or hydrolyzed sodium hyaluronate, 0.2-0.5 parts by mass of triethyl citrate, and 5 parts by mass of urea. The aqueous agent of the composition containing hyaluronic acid cannot meet the stability requirements because the initial pH is too low and the pH exceeds 8 after urea hydrolysis. Similarly, according to the results in the above table, the binary compositions of urea (urea combined with sodium hyaluronate / hydrolyzed sodium hyaluronate or urea combined with triethyl citrate) also do not meet the requirements of pH being 4-8 at each temperature in the stability test.

[0098] Test Example 2: Appearance and odor test of the product

[0099] Test samples: Aqueous agent compositions containing urea prepared in Examples 1-18 (at 48°C for 30 days at high temperature)

[0100] The age of the fragrance evaluation personnel should be between 18 and 45 years old. The evaluation personnel should be in good health, without chronic rhinitis, allergic constitution or other diseases that may affect the sense of smell. They should not participate in the evaluation when having a cold or being unwell.

[0101] A 5-person evaluation group observes and tries the product, then scores and takes the average value of the 5-person evaluation group. Evaluate the appearance and odor test of the product.

[0102] Among them, for the appearance of the material body, on a scale of 0-10: 0-3 points indicate a turbid material body with abnormal color, 4-6 points indicate a semi-transparent material body with normal color, 7-10 points indicate a transparent material body with normal color, and the larger the score, the more stable the appearance of the material body;

[0103] For the odor score during use (ammonia smell from urea decomposition), on a scale of 0-10: 0-3 points indicate that the smell of the material body is pungent and unacceptable, 4-6 points generally indicate that the smell of the material body is abnormally acceptable, 7-10 points indicate that the smell of the material body is normal and pleasant, and the larger the score, the better the smell performance of the material body, thus proving that the material body is more stable.

[0104] Table 2 Stability data of appearance and odor of different urea compositions

[0105]

[0106] Conclusion: Prepare aqueous solutions containing different urea compositions, and investigate the stability of the appearance and odor of different urea composition aqueous agents at high temperatures. Considering test deviations and addition losses, a test score of 7-10 is generally considered the qualified range for the appearance and odor of the product. A score below 7 is considered a poor scoring experience. After high temperature treatment of different urea composition aqueous agents, the test scores of Examples 9-12 & Examples 15-18 are all within the range of 7-10, indicating that the stability test of the appearance and odor at high temperature is qualified and the consumer experience is good.

[0107] Example 19: Preparation of an emulsion containing a ternary urea composition

[0108] Aqueous phase: Weigh 0.2 parts by mass of polyacrylic acid-30 polymer, 0.5 parts by mass of PEG-20 methylglucose sesquistearate, 0.1 parts by mass of xanthan gum, 0.2 parts by mass of sodium hyaluronate and 70 parts by mass of deionized water, heat to 80-85 °C and mix, and mix and stir at a speed of 100 rpm until completely dissolved;

[0109] Oil phase: Add 2 parts by mass of cetearyl alcohol and 1.5 parts by mass of cetearyl glucoside to 2 parts by mass of petrolatum and 4 parts by mass of dicaprylyl carbonate, and place in an 85 °C water bath to completely melt it.

[0110] At 80-85 °C, slowly add the oil phase to the aqueous phase and homogenize at 2500-3000 revolutions per minute. After homogenizing for 10-15 minutes, it should be uniform and without particles; when the temperature drops to 55-60 °C, add 0.1 parts by mass of triethanolamine (10% aqueous solution) and carry out a neutralization stirring reaction.

[0111] Add 5 parts by mass of urea to 10 parts by mass of deionized water, stir to dissolve and then add it to the material and stir evenly. Finally, add 0.2 parts by mass of triethyl citrate, and add deionized water to make up to 100, and continue to mix and stir at a speed of 100 rpm for 10-20 min; then let it stand at room temperature for 12 hours for later use.

[0112] Example 20: Preparation of an emulsion containing a ternary urea composition

[0113] Aqueous phase: Weigh 0.2 parts by mass of polyacrylic acid-30 polymer, 0.5 parts by mass of PEG-20 methylglucose sesquistearate, 0.1 parts by mass of xanthan gum, 0.2 parts by mass of sodium hyaluronate and 70 parts by mass of deionized water, heat to 80-85 °C and mix, and mix and stir at a speed of 100 rpm until completely dissolved;

[0114] Oil phase: Add 2 parts by mass of cetearyl alcohol and 1.5 parts by mass of cetearyl glucoside to 2 parts by mass of petrolatum and 4 parts by mass of dicaprylyl carbonate, and place in an 85 °C water bath to completely melt it.

[0115] Slowly add the oil phase to the water phase at 80 - 85°C and homogenize at 2500 - 3000 rpm. After homogenizing for 10 - 15 minutes, it should be uniform without particles. After the temperature drops to 55 - 60°C, add 0.1 part by mass of triethanolamine (10% aqueous solution) and carry out a neutralization stirring reaction.

[0116] Add 5 parts by mass of urea to 10 parts by mass of deionized water. After stirring and dissolving, add it to the material and stir evenly. Finally, add 0.5 part by mass of triethyl citrate, and add deionized water to make up to 100. Continue to mix and stir at a rotation speed of 100 rpm for 10 - 20 minutes. Then let it stand at room temperature for 12 hours for standby.

[0117] Example 21: Preparation of an emulsion containing a ternary composition of urea

[0118] Water phase: Weigh 0.2 part by mass of polyacrylic acid - 30 polymer, 0.5 part by mass of PEG - 20 methyl glucoside sesquistearate, 0.1 part by mass of xanthan gum, 0.5 part by mass of sodium hyaluronate and 70 parts by mass of deionized water. Heat to 80 - 85°C and mix, and mix and stir at a rotation speed of 100 rpm until completely dissolved.

[0119] Oil phase: Add 2 parts by mass of cetearyl alcohol and 1.5 parts by mass of cetearyl glucoside to 2 parts by mass of petrolatum and 4 parts by mass of dicaprylyl carbonate, and place it in an 85°C water bath to completely melt it.

[0120] Slowly add the oil phase to the water phase at 80 - 85°C and homogenize at 2500 - 3000 rpm. After homogenizing for 10 - 15 minutes, it should be uniform without particles. After the temperature drops to 55 - 60°C, add 0.1 part by mass of triethanolamine (10% aqueous solution) and carry out a neutralization stirring reaction.

[0121] Add 5 parts by mass of urea to 10 parts by mass of deionized water. After stirring and dissolving, add it to the material and stir evenly. Finally, add 0.2 part by mass of triethyl citrate, and add deionized water to make up to 100. Continue to mix and stir at a rotation speed of 100 rpm for 10 - 20 minutes. Then let it stand at room temperature for 12 hours for standby.

[0122] Example 22: Preparation of an emulsion containing a ternary composition of urea

[0123] Water phase: Weigh 0.2 part by mass of polyacrylic acid - 30 polymer, 0.5 part by mass of PEG - 20 methyl glucoside sesquistearate, 0.1 part by mass of xanthan gum, 0.5 part by mass of sodium hyaluronate and 70 parts by mass of deionized water. Heat to 80 - 85°C and mix, and mix and stir at a rotation speed of 100 rpm until completely dissolved.

[0124] Oil phase: Add 2 parts by mass of cetearyl alcohol and 1.5 parts by mass of cetearyl glucoside to 2 parts by mass of petrolatum and 4 parts by mass of dicaprylyl carbonate, and place it in an 85°C water bath to completely melt it.

[0125] Slowly add the oil phase to the water phase at 80 - 85°C and homogenize at 2500 - 3000 revolutions per minute. After homogenizing for 10 - 15 minutes, it should be uniform and without particles; when the temperature drops to 55 - 60°C, add 0.1 part by mass of triethanolamine (10% aqueous solution) and carry out a neutralization stirring reaction.

[0126] Add 5 parts by mass of urea to 10 parts by mass of deionized water, stir to dissolve and then add it to the material and stir evenly. Finally, add 0.5 part by mass of triethyl citrate, and add deionized water to make up to 100, and continue to mix and stir at a speed of 100 rpm for 10 - 20 minutes; then let it stand at room temperature for 12 hours for standby.

[0127] Example 23: Preparation of an emulsion containing a ternary composition of urea

[0128] Water phase: Weigh 0.2 part by mass of polyacrylic acid - 30 polymer, 0.5 part by mass of PEG - 20 methyl glucoside sesquistearate, 0.1 part by mass of xanthan gum, 0.2 part by mass of hydrolyzed sodium hyaluronate and 70 parts by mass of deionized water, heat to 80 - 85°C and mix, and mix and stir at a speed of 100 rpm until completely dissolved;

[0129] Oil phase: Add 2 parts by mass of cetearyl alcohol and 1.5 parts by mass of cetearyl glucoside to 2 parts by mass of petrolatum and 4 parts by mass of dicaprylyl carbonate, and place it in an 85°C water bath to completely melt it.

[0130] Slowly add the oil phase to the water phase at 80 - 85°C and homogenize at 2500 - 3000 revolutions per minute. After homogenizing for 10 - 15 minutes, it should be uniform and without particles; when the temperature drops to 55 - 60°C, add 0.1 part by mass of triethanolamine (10% aqueous solution) and carry out a neutralization stirring reaction.

[0131] Add 5 parts by mass of urea to 10 parts by mass of deionized water, stir to dissolve and then add it to the material and stir evenly. Finally, add 0.2 part by mass of triethyl citrate, and add deionized water to make up to 100, and continue to mix and stir at a speed of 100 rpm for 10 - 20 minutes; then let it stand at room temperature for 12 hours for standby.

[0132] Example 24: Preparation of an emulsion containing a ternary composition of urea

[0133] Aqueous phase: Weigh 0.2 parts by mass of polyacrylic acid-30 polymer, 0.5 parts by mass of PEG-20 methyl glucoside sesquistearate, 0.1 parts by mass of xanthan gum, 0.2 parts by mass of hydrolyzed sodium hyaluronate and 70 parts by mass of deionized water, heat to 80 - 85 °C and mix, and mix and stir at a speed of 100 rpm until completely dissolved;

[0134] Oil phase: Add 2 parts by mass of cetearyl alcohol and 1.5 parts by mass of cetearyl glucoside to 2 parts by mass of petrolatum and 4 parts by mass of dicaprylyl carbonate, place in an 85 °C water bath to completely melt it.

[0135] At 80 - 85 °C, slowly add the oil phase to the aqueous phase and homogenize at 2500 - 3000 rpm. After homogenizing for 10 - 15 minutes, it should be uniform and without particles; when the temperature drops to 55 - 60 °C, add 0.1 parts by mass of triethanolamine (10% aqueous solution) and carry out a neutralization stirring reaction.

[0136] Add 5 parts by mass of urea to 10 parts by mass of deionized water, stir to dissolve and then add it to the material and stir evenly. Finally, add 0.5 parts by mass of triethyl citrate, and add deionized water to make up to 100, and continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 hours for standby.

[0137] Example 25: Preparation of an emulsion containing a ternary composition of urea

[0138] Aqueous phase: Weigh 0.2 parts by mass of polyacrylic acid-30 polymer, 0.5 parts by mass of PEG-20 methyl glucoside sesquistearate, 0.1 parts by mass of xanthan gum, 0.5 parts by mass of hydrolyzed sodium hyaluronate and 70 parts by mass of deionized water, heat to 80 - 85 °C and mix, and mix and stir at a speed of 100 rpm until completely dissolved;

[0139] Oil phase: Add 2 parts by mass of cetearyl alcohol and 1.5 parts by mass of cetearyl glucoside to 2 parts by mass of petrolatum and 4 parts by mass of dicaprylyl carbonate, place in an 85 °C water bath to completely melt it.

[0140] At 80 - 85 °C, slowly add the oil phase to the aqueous phase and homogenize at 2500 - 3000 rpm. After homogenizing for 10 - 15 minutes, it should be uniform and without particles; when the temperature drops to 55 - 60 °C, add 0.1 parts by mass of triethanolamine (10% aqueous solution) and carry out a neutralization stirring reaction.

[0141] Add 5 parts by mass of urea to 10 parts by mass of deionized water, stir to dissolve, then add to the material and stir evenly. Finally, add 0.2 parts by mass of triethyl citrate, and add deionized water to make up to 100, continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for use.

[0142] Example 26: Preparation of an emulsion containing a ternary composition of urea

[0143] Aqueous phase: weigh 0.2 parts by mass of polyacrylic acid-30 polymer, 0.5 parts by mass of PEG-20 methyl glucose sesquistearate, 0.1 parts by mass of xanthan gum, 0.5 parts by mass of hydrolyzed sodium hyaluronate and 70 parts by mass of deionized water, heat to 80-85°C, mix, and stir at a speed of 100 rpm until all dissolved;

[0144] Oil phase: Add 2 parts by mass of cetostearyl alcohol and 1.5 parts by mass of cetostearyl glucoside to 2 parts by mass of vaseline and 4 parts by mass of dioctyl carbonate, and place in a 85°C water bath to completely melt. Slowly add the oil phase to the water phase at 80-85°C and homogenize at 2500-3000 rpm. Homogenize for 10-15 minutes until the mixture is uniform and free of particles. When the temperature drops to 55-60°C, add 0.1 parts by mass of triethanolamine (10% aqueous solution) to neutralize and stir the reaction.

[0145] Add 5 parts by mass of urea to 10 parts by mass of deionized water, stir to dissolve, then add to the material and stir evenly. Finally, add 0.5 parts by mass of triethyl citrate, and add deionized water to make up to 100, continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for use.

[0146] Test Example 3: pH test of high and low temperature stability of products

[0147] After measuring the initial pH of the systems of Examples 19-26, the high and low temperature stability was investigated. After the stability investigation was completed, the test samples were subjected to a temperature recovery treatment and then a pH test was performed. The pH test method is as follows:

[0148] Use a pH meter (S400-K and Mettler) with an accuracy of at least 0.02 (including temperature compensation system), sample test temperature: 25°C, constant temperature for 4 hours. After instrument calibration, rinse the electrode with deionized water and then dry it with filter paper. Carefully insert the electrode into the sample so that the electrode is immersed. When the pH meter reading is stable, record the reading. After reading, the electrode needs to be thoroughly cleaned and set aside. The test result of pH value is expressed as the average of two measurements, accurate to 0.1, and the error of parallel tests should be ≤0.1.

[0149] The results are shown in the following table.

[0150] Table 3: Initial pH and stability pH results of different embodiments

[0151]

[0152] Conclusion: Since urea is extremely prone to hydrolysis at high temperatures, and the hydrolysis will cause the pH of the system to be extremely high, even exceeding the regulatory requirements for cosmetics (pH 4.0 - 8.5), the pH stability of this series of embodiments was therefore investigated in detail.

[0153] Table 3 shows the stability performance of emulsion embodiments of different urea ternary compositions, and the stability of different urea ternary components in the emulsion system was investigated. From the above experimental results, it can be obtained that the pH values of the urea ternary compositions in Examples 19 - 26 are all between 4.0 and 8.0, maintaining a relatively stable state and meeting regulatory requirements. This further indicates that the ternary stable composition of this urea can be stably applied in the emulsion dosage form.

[0154] Test Example 4: Product viscosity test and high and low temperature stability test

[0155] After measuring the system viscosities of Examples 19 - 26, their high and low temperature stabilities were investigated.

[0156] Use a BROOKFIELD RVDVC digital display viscometer (equipped with RV and T type rotors). Sample test temperature: 25°C, constant temperature for 1 h. Sample test container: Try to use the same specification beaker (180 - milliliter bottle) for different batches of the same sample during testing; Reading recording time: 60 s for LV / RV type rotors; 90 s for T type rotors; Before measuring the sample, it should be confirmed that there is no bubble interference. Select the corresponding rotor and rotation speed according to the standard regulations. After taking the sample to be measured out of the constant temperature bath, immediately measure its viscosity with a rotational viscometer. When selecting LV and RV rotors, insert the rotor obliquely into the sample so that the liquid level is just located in the depression of the rotor, and keep no bubbles around the rotor wall; When selecting the T type rotor, make the rotor just close to the liquid level, and select a certain up and down moving distance so that the rotor has enough up and down lifting space without touching the bottom of the beaker and causing damage. Record the viscosity result after the reading is stable (or after the standard - specified time).

[0157] The results are shown in the following table.

[0158] Table 4: Initial viscosity and stability viscosity results of different embodiments

[0159]

[0160] Conclusion: Since urea is extremely prone to hydrolysis at high temperatures, the hydrolysis will cause the pH of the system to be extremely high, which will in turn destroy the emulsion system, resulting in a decrease in viscosity or demulsification, etc.

[0161] Table 4 shows the stability performance of emulsion examples of different urea ternary compositions, and examines the viscosity stability of different urea ternary composition components in the emulsion system. From the above experimental results, it can be obtained that the viscosities of the urea ternary compositions in Examples 19-26 are all between 3000 and 11000 m.pas, maintaining a relatively stable state and having a moderate viscosity for use. Furthermore, it shows that the ternary stable composition of this urea can be stably applied in the emulsion dosage form.

[0162] Test Example 5: Test on the appearance and odor of the product during use

[0163] Test samples: The urea ternary compositions prepared in Examples 19-26 (at 48°C high temperature for 30 days).

[0164] The age of the fragrance evaluation personnel should be between 18 and 45 years old. The evaluation personnel should be in good health, without chronic rhinitis, allergic constitution or other diseases that may affect the sense of smell. They should not participate in the evaluation when having a cold or being unwell.

[0165] A 5-person evaluation group observes and tries the product, then scores and takes the average value of the 5-person evaluation group. Evaluate the appearance and odor of the product during use. Among the 0-10 points for the appearance of the material: 0-3 points indicate a turbid material with abnormal color, 4-6 points indicate a semi-transparent material with normal color, 7-10 points indicate a transparent material with normal color, and the higher the score, the more stable the appearance of the material; for the odor score during use (ammonia smell from urea decomposition) of 0-10 points: 0-3 points indicate that the odor of the material is pungent and unacceptable, 4-6 points generally indicate that the odor of the material is abnormally acceptable, 7-10 points indicate that the odor of the material is normal and pleasant, and the higher the score, the better the odor performance of the material, thus proving that the material is more stable;

[0166] Table 5 Stability data of the appearance and odor of different urea compositions

[0167]

[0168] Conclusion: Emulsions containing different urea ternary compositions are prepared, and the stability of the appearance and odor of different urea composition aqueous agents at high temperature is investigated. Considering the test deviation and addition loss, it is generally considered that the test score of 7-10 is the qualified range for the appearance and odor of the product, and a score lower than 7 is considered to have a poor scoring experience. After the high temperature of different urea ternary composition emulsions, the test scores of Examples 19-26 are all within 7-10 points, so it is considered that the stability test of the appearance and odor at high temperature is qualified and the consumer experience is good.

Claims

1. A ternary composition for stabilizing urea, comprising: 0.1 - 20% by weight of urea; 0.001 - 5% by weight of sodium hyaluronate, wherein the sodium hyaluronate is selected from: sodium hyaluronate, hydrolyzed sodium hyaluronate, or a combination thereof; 0.01 - 3% by weight of triethyl citrate and water; wherein the weight ratio of sodium hyaluronate to triethyl citrate is 0.4 - 2.5:

1.

2. The composition according to claim 1, wherein The pH of the composition is 4.0 - 8.0, preferably the pH is 4.0 - 6.

0.

3. The composition according to claim 1, wherein The composition contains 0.1 - 10% by weight of urea, preferably contains 0.1 - 5% by weight of urea.

4. The composition according to claim 1, wherein The composition contains 0.001 - 3% by weight of sodium hyaluronate.

5. The composition according to claim 4, wherein The sodium hyaluronate is 0.2 - 0.5% by weight of sodium hyaluronate or 0.2 - 0.5% by weight of hydrolyzed sodium hyaluronate.

6. The composition according to claim 1, wherein The composition contains 0.01 - 2% by weight of triethyl citrate, preferably 0.2 - 0.5% by weight of triethyl citrate.

7. The composition according to claim 1, wherein The composition further includes 0.1 - 2.3% by weight of a thickener, wherein the thickener is selected from: polyacrylic acid - 30 polymer, cetearyl alcohol, xanthan gum, or a combination thereof, and the thickener combination is a polyacrylic acid - 30 polymer, cetearyl alcohol and xanthan gum with a weight ratio of 2:20:

1.

8. The composition according to claim 1, wherein The composition further includes 0.5 - 2% by weight of an emulsifier, wherein the emulsifier is selected from: PEG - 20 methyl glucoside sesquistearate, cetearyl glucoside, or a combination thereof, and the emulsifier combination is PEG - 20 methyl glucoside sesquistearate and cetearyl glucoside with a weight ratio of 1:

3.

9. The composition according to claim 1, characterized in that, The composition further includes 2 - 6% by weight of an oil, wherein the oil is selected from: petrolatum, dicaprylyl carbonate, or a combination thereof, and the oil is a combination of petrolatum and dicaprylyl carbonate with a weight ratio of 1:

2.

10. The composition according to claim 1, characterized in that, The composition further includes 0.1% by weight of triethanolamine.

11. Use of a combination of sodium hyaluronate and triethyl citrate in stabilizing urea, wherein the weight ratio of sodium hyaluronate to triethyl citrate is 0.4 - 2.5:

1.

12. A method for preparing the composition according to any one of claims 1 - 10, comprising the following steps: a) Weigh the thickener, sodium hyaluronate and deionized water, heat to 80 - 85°C and mix, and mix and stir at a speed of 100 rpm until completely dissolved to obtain an aqueous phase; b) Weigh the emulsifier, add it to the oil, place it in an 85°C water bath to completely melt it to obtain an oil phase; c) Slowly add the oil phase in step b) to the aqueous phase in step a) at 80 - 85°C and homogenize at a speed of 2500 - 3000 rpm for 10 - 15 min until it is uniform and free of particles; wait until the temperature drops to 55 - 60°C, add triethanolamine, and carry out a neutralization stirring reaction to obtain a mass; d) Add urea to deionized water, stir and dissolve it, then add it to the mass in step c) and stir evenly; finally, add triethyl citrate, add deionized water to make up to 100, continue to mix and stir at a speed of 100 rpm for 10 - 20 min; then let it stand at room temperature for 12 h to obtain the composition.

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