CN112823776A

CN112823776A - Composition containing urea

Info

Publication number: CN112823776A
Application number: CN201911148883.XA
Authority: CN
Inventors: 王峥; 黄诚赟; 郭奕光
Original assignee: Shanghai Jahwa United Co Ltd
Current assignee: Shanghai Jahwa United Co Ltd
Priority date: 2019-11-21
Filing date: 2019-11-21
Publication date: 2021-05-21
Anticipated expiration: 2039-11-21
Also published as: CN112823776B

Abstract

The present invention provides an aqueous composition comprising urea as an effective ingredient having moisturizing effect, the composition further comprising betaine, the weight ratio of urea to betaine being 1:99 to 85: 15. The invention also discloses application of the aqueous composition as an efficacy additive with a moisturizing effect in a skin external preparation and the skin external preparation containing the aqueous composition.

Description

Composition containing urea

Technical Field

The invention relates to the field of cosmetics, in particular to an aqueous composition containing urea as an effective component with moisturizing effect and application of the aqueous composition in cosmetics.

Background

Urea is a well-used moisturizing ingredient, is present in the stratum corneum of the skin and belongs to a main ingredient of the natural moisturizing factor NMF of the skin. For skin, urea has the effects of moisturizing and softening cutin. Urea is one of natural moisturizing factors in skin, and the effects of moisturizing, softening skin, promoting percutaneous penetration and the like are widely reported in documents.

The literature "instruments and dermatologists evaluate the effect of glycerol and urea on the dry skin of atopic dermatitis patients" ("skin research and technology", Lod é M., et al.) reports that the mean value of the skin capacitance of 35 subjects increased from 35A.U. to 42A.U. (the higher the moisture content of the skin surface, the higher the capacitance), and the mean value of the epidermal water loss of about 11 g/(m) after 30 days of use of a moisturizer containing 4% urea²H) down to about 8,5g/, (m²H), the average value of the total dryness fraction is reduced from 3.2 to 0.8, the experimental results are obviously superior to those of a control group without urea, and the statistical difference proves that the urea has the effects of moisturizing, softening and strengthening the skin barrier.

The literature "effect of urea on human epidermis, skin" (Hellgren et al) reports that by immersing the dried epidermis in a 10% urea solution, the water absorption of the epidermis after 90 hours has reached substantially equilibrium is close to 300% of the initial mass, which is approximately 3 times that of the sample immersed in distilled water. The increase of water absorption of dry skin comes from the fact that the urea aqueous solution increases the permeability of the epidermis.

The effect of urea on conjugated zinc linoleate and zinc betaine was studied in the literature "New Effect of transdermal penetration enhancer on two zinc salts" (Science Technology and Engineering, 2016; 16:1671-²Rises to 388.04 mu g/cm²The cumulative osmotic quantity of the zinc betaine per unit time is 682.26 mu g/cm²Rises to 1020.49 mu g/cm²And the permeation rate is still further improved with the increase of the urea content.

Recent researches show that urea can also achieve the effects of improving skin barrier and resisting bacteria by regulating gene expression. For example, the literature, "urea uptake enhances human barrier function and antibacterial defense by regulating epidermal gene expression" (Susanne G. -B., (2012)132, 1561-. According to the results of the study, the authors believe that not just the body metabolites, but rather, as a small molecule regulator, have the effect of modifying the expression of skin barrier-related genes. Further, urea and skin: a famous molecular revisit discloses that urea can be used as a medicine for treating skin diseases such as psoriasis, allergic dermatitis, eczema, seborrheic dermatitis and the like.

However, the applicant has found that when the urea aqueous solution is simply applied to the skin surface, the precipitation and crystallization phenomenon is severe. The precipitated urea solid cannot penetrate through the stratum corneum and is absorbed and utilized by the skin, and finally, the bioavailability of the urea solid is reduced.

To solve the problem of low bioavailability, EP1214931 ("anhydrous skin care formulation containing micro-urea and process for its manufacture)" and CN101511329A ("anhydrous urea-containing dermatological or cosmetic formulation") disclose that dissolving urea with an anhydrous formulation can solve the problem of urea precipitation stability. However, with this formulation the urea dissolution is limited and there are severe limitations in its use in cosmetic formulations.

Other documents disclose the use of urea derivatives. For example, CN1778287A used hydroxyalkyl urea to improve moisturizing efficacy. As another example, CA2209432 ("moisturizing effect of amino alcohol derivatives containing urea function in cosmetic or dermatological ingredients") discloses that amino alcohol substances may alleviate the problem of crystallization on the basis of partial retention of urea function. However, urea derivatives are more expensive than urea and may lose some of the specific biological properties of urea.

Other documents disclose formulating urea with other materials to form compositions. For example, carnitine as disclosed in DE102012214034 (cosmetic or dermatological preparations in the form of an oil-water emulsion using active ingredients containing urea, carnitine and/or acylcarnitines, in order to tighten and strengthen the skin, treat and/or prevent cellulite); sulfamic acid disclosed in CA2280985 (urea-containing ingredients and their use in cosmetics and dermatology); the formulation techniques of polyurethanes disclosed in EP1797868 (cosmetic compositions containing a (thio) urethane/(thio) urea copolymer capable of forming at least 3 hydrogen bonds, and cosmetic treatment methods) are reported in patents. However, carnitine is expensive, and the possible irritation and strong ionic property of sulfamic acid are not favorable for the stability of the formula, the sticky film-forming feeling of polyurethane and other factors, so that the application of the technologies in cosmetics is limited.

The invention has the unexpected discovery that the combination of urea, betaine and water can reduce urea crystallization and improve skin availability. Therefore, the invention combines urea and betaine for the first time, provides a novel synergistic composition with better moisturizing effect, and can be added into a skin external preparation to achieve the moisturizing effect.

Disclosure of Invention

In one aspect, the present invention provides an aqueous composition comprising urea as an effective ingredient having moisturizing effect, wherein the composition further comprises betaine, and the weight ratio of the urea to the betaine is 1:99 to 85: 15.

In a preferred embodiment, the weight ratio of urea to betaine in the aqueous composition of the invention is from 3:7 to 1: 1.

In a more preferred embodiment, the weight ratio of urea to betaine in the aqueous composition of the invention is 4: 6.

In a preferred embodiment, the aqueous composition of the invention has a water content of more than 10% by weight.

In another aspect, the present invention provides the use of an aqueous composition comprising urea and betaine for skin moisturization.

In still another aspect, the present invention provides the use of an aqueous composition comprising urea and betaine in a skin external preparation having a skin moisturizing effect.

In a preferred embodiment, the external preparation for skin is selected from: face cleaning lotion, cosmetic water, lotion, cream and facial mask.

In still another aspect, the present invention also provides an external preparation for skin comprising the aqueous composition of the present invention. In a preferred embodiment, the external preparation for skin comprises 0.001 to 20% by weight of the aqueous composition of the present invention.

Detailed Description

The invention discovers for the first time that the combined use of urea and betaine has the synergistic moisturizing effect, and the aqueous composition of the urea and the betaine is suitable to be used as an efficacy additive to be added into a skin external preparation to achieve the moisturizing effect. The composition disclosed by the invention can better keep the skin moisture and is beneficial to the moisturizing effect of the skin. Meanwhile, the composition can also be used as an effect additive to be added into cosmetics for skin care and improvement of skin moisturizing effect.

To provide a more concise description, some of the quantitative representations presented herein are not modified by the term "about". It is understood that each quantity given herein is intended to refer to the actual given value, regardless of whether the term "about" is explicitly used, and also to refer to the approximation to such given value that would reasonably be inferred by one of ordinary skill in the art, including approximations due to experimental and/or measurement conditions for such given value.

To provide a more concise description, some quantitative expressions are recited herein as a range from about an X amount to about a Y amount. It should be understood that when a range is recited, the range is not limited to the upper and lower limits recited, but includes the entire range from about the X amount to about the Y amount or any amount therebetween.

Urea

Urea is a well-used moisturizing ingredient, is present in the stratum corneum of the skin and belongs to a main ingredient of the natural moisturizing factor NMF of the skin. Urea has the effects of moisturizing and softening cutin for the skin, so that it can prevent the cutin layer from blocking the pores, thereby improving the problem of acne. Urea is commonly used as a moisturizing component in products such as facial masks, skin lotions, creams, hand creams and the like.

However, when the urea aqueous solution is simply applied to the skin surface, the phenomenon of serious precipitation and crystallization occurs. The precipitated urea solid cannot penetrate through the stratum corneum and is absorbed and utilized by the skin, and finally, the bioavailability of the urea solid is reduced.

The moisture retention performance examination of the invention further proves that the urea aqueous solution alone cannot show positive moisture retention efficacy. After the urea aqueous solution was applied to the skin surface, it was observed that urea crystals precipitated and adhered to the skin surface. The test for the moisture content of the top layer of the skin showed no improvement in the moisture content of the urea solution alone compared to the background value at all test points (e.g., time points of 15min, 30min and 60 min). In combination with this experimental phenomenon, it is considered that urea that is not absorbed does not exhibit the moisturizing effect it should have because of precipitation of crystals on the skin surface.

The invention combines urea and betaine for the first time, can reduce the absorption of urea crystals and improve the bioavailability of urea. Compared with a pure urea aqueous solution, the compound composition has excellent moisturizing effect. Moreover, the aqueous composition containing urea and betaine has obvious improvement in high-temperature water retention, low-temperature stability and freeze-thaw stability.

In some embodiments of the invention, the composition comprises 5 to 50 wt.% urea. In some embodiments of the invention, the composition comprises 10 to 50 wt.% urea. In some embodiments of the invention, the composition comprises 10 to 40 wt.% urea. In some embodiments of the invention, the composition comprises 10 to 30 wt.% urea. In some embodiments of the invention, the composition comprises 15 to 30 wt.% urea. In some embodiments of the invention, the composition comprises 20 to 30 wt.% urea.

Betaine

Betaine, also known as trimethylglycine, is naturally derived, non-irritating and allergenic, and can be used in medical, cosmetic, food, juice industries, and the like. In the cosmetic industry, betaine can be used for moisturizing, solubilizing and reducing stimulation, and has wide application prospect.

However, no moisturizing properties were found when the aqueous betaine solution alone was applied to the skin surface. It follows that the bioavailability of aqueous betaine solutions is a considerable problem. The moisturizing performance study of the present invention further demonstrated that betaine aqueous solution alone did not exhibit positive moisturizing efficacy (see the experimental results of example 9 of the present invention).

The present invention has surprisingly found that the combination of betaine and urea results in a synergistic effect of the two, and that the combination of the two results in an improved skin moisturising effect compared to a pure aqueous urea solution or a pure aqueous betaine solution.

In addition, the betaine has low cost, good safety, weak ionicity and small influence on the stability of the formula, so that the betaine is more favorable for application in cosmetics. Therefore, the invention provides an innovative additive combination with better effect for skin care products and skin pharmaceuticals.

Any of a variety of suitable betaines may be used in the compositions of the present invention. For example, in one particular embodiment, betaine, available from Kosher trade (Shanghai) Inc., is used in the compositions of the present invention.

In some embodiments of the invention, the compositions of the invention comprise from 5 to 70% by weight betaine. In some embodiments of the invention, the composition comprises 10-70% by weight betaine. In some embodiments of the invention, the composition comprises 15-70% by weight betaine. In some embodiments of the invention, the composition comprises 20-70% by weight betaine. In some embodiments of the invention, the compositions of the invention comprise from 5 to 60% by weight betaine. In some embodiments of the invention, the composition comprises 10-60% by weight betaine. In some embodiments of the invention, the composition comprises 15-60% by weight betaine. In some embodiments of the invention, the composition comprises 20-60% by weight betaine. In some embodiments of the invention, the compositions of the invention comprise from 5 to 50% by weight betaine. In some embodiments of the invention, the composition comprises 10-50% by weight betaine. In some embodiments of the invention, the composition comprises 15-50% by weight betaine. In some embodiments of the invention, the composition comprises 20-50% by weight betaine. In some embodiments of the invention, the composition comprises 25-50% by weight betaine. In some embodiments of the invention, the composition comprises 30-50% by weight betaine. In some embodiments of the invention, the composition comprises 40-50% by weight betaine. In some embodiments of the invention, the composition comprises 20-40% by weight betaine. In some embodiments of the invention, the composition comprises 20-30% by weight betaine. In some embodiments of the invention, the composition comprises 30-40% by weight betaine.

In some embodiments of the invention, the weight ratio of urea to betaine in the compositions of the invention is from 1:99 to 85: 15. In some embodiments of the invention, the weight ratio of urea to betaine in the compositions of the invention is from 1:99 to 8: 2. In some embodiments of the invention, the weight ratio of urea to betaine in the compositions of the invention is from 2:8 to 8: 2. In some embodiments of the invention, the weight ratio of urea to betaine in the compositions of the invention is from 2:8 to 1: 1. In some embodiments of the invention, the weight ratio of urea to betaine in the compositions of the invention is from 2:8 to 4: 6. In some embodiments of the invention, the weight ratio of urea to betaine in the compositions of the invention is from 3:7 to 4: 6. In a particular embodiment of the invention, the weight ratio of urea to betaine in the composition of the invention is 4: 6.

Water content

The compositions of the present invention may also comprise water or other aqueous carriers. In a preferred embodiment, the weight proportion of water in the composition of the invention is greater than 10%. In some embodiments of the invention, the composition has a water content of 11 to 80% by weight. In some embodiments of the invention, the composition has a water content of 11 to 70% by weight. In some embodiments of the invention, the composition has a water content of 11 to 60% by weight. In some embodiments of the invention, the composition has a water content of 11 to 50% by weight. In some embodiments of the invention, the composition has a water content of 11 to 40% by weight. In other preferred embodiments, the weight ratio of water in the composition of the invention is at least 15%. In some embodiments of the invention, the composition has a water content of 15 to 80% by weight. In some embodiments of the invention, the composition has a water content of 15 to 70% by weight. In some embodiments of the invention, the composition has a water content of 15 to 60% by weight. In some embodiments of the invention, the composition has a water content of 15 to 50% by weight. In some embodiments of the invention, the composition has a water content of 15 to 40% by weight. In other preferred embodiments, the weight ratio of water in the composition of the invention is at least 20%. In some embodiments of the invention, the composition has a water content of 20 to 80% by weight. In some embodiments of the invention, the composition has a water content of 20 to 70% by weight. In some embodiments of the invention, the composition has a water content of 20 to 60% by weight. In some embodiments of the invention, the composition has a water content of 20 to 50% by weight. In some embodiments of the invention, the composition has a water content of 20 to 40% by weight. In some embodiments of the invention, the composition has a water content of 30 to 50% by weight.

The inventors have surprisingly found that urea, betaine and water in the composition of the invention are capable of forming a low melting point co-solution, thereby achieving excellent moisturizing effect.

External preparation for skin

The composition of the present invention can be applied to a skin external preparation as an additive having a moisturizing effect. In a particular embodiment, the composition of the present invention may be applied to cosmetics as an additive having moisturizing effect. In a particular embodiment, the cosmetic is selected from: face cleaning lotion, cosmetic water, lotion, cream, jelly and facial mask. Different amounts are added according to different types of preparations.

In another aspect of the present invention, there is provided a skin external preparation having moisturizing effect, comprising the composition of the present invention prepared according to the method of the present invention and a cosmetically acceptable vehicle.

The external preparation for skin is a general concept of all ingredients generally used for the external part of skin, and may be, for example, a cosmetic composition. The cosmetic composition can be basic cosmetics, face makeup cosmetics, body makeup cosmetics, hair care cosmetics and the like, and the dosage form of the cosmetic composition is not particularly limited and can be reasonably selected according to different purposes.

The cosmetic composition also contains different cosmetically acceptable media or matrix excipients according to different dosage forms and purposes.

In some preferred embodiments, the composition of the present invention may be used in an amount of 0.001 to 20% by weight in the external preparation for skin. The preferred weight percentage is 0.01-20 wt%. More preferably 0.01 to 10 wt%. More preferably 0.1 to 5% by weight. In some preferred embodiments of the present invention, the composition of the present invention may be used in the external preparation for skin in an amount of 0.001 to 10% by weight, 0.002 to 10% by weight, 0.003 to 10% by weight, 0.01 to 10% by weight, 0.02 to 10% by weight, 0.03 to 10% by weight, 0.1 to 10% by weight, 0.2 to 10% by weight, 0.3 to 10% by weight. In some preferred embodiments of the present invention, the composition of the present invention may be used in the external preparation for skin in an amount of 0.001 to 1% by weight, for example, 0.002 to 1% by weight, 0.003 to 1% by weight, 0.01 to 1% by weight, 0.02 to 1% by weight, 0.03 to 1% by weight, 0.1 to 1% by weight, 0.2 to 1% by weight, 0.3 to 1% by weight.

Application method

The product may be applied to the skin of the user in any desired manner. In some aspects, the product may be applied directly by hand, or the product may be applied using a device such as a cosmetic cotton swab or other implement. The composition is advantageously applied to the skin in order to facilitate sample absorption. The composition may be left on the area to be applied for a desired level of time, such as from about 5 seconds to about 5 minutes. Alternatively, the composition may be left on the area of application and continued to be applied until absorption.

Detailed Description

The invention will be further illustrated by the following specific examples. It should be noted that the examples are given solely for the purpose of illustration and are not to be construed as limitations on the scope of the invention, as many insubstantial modifications and variations of the invention may be made by those skilled in the art in light of the above teachings. Test methods in which specific conditions are not specified in the following examples are generally carried out under conventional conditions or under conditions recommended by the manufacturer. All percentages and parts are by weight unless otherwise indicated.

Experimental materials:

urea, available from national pharmaceutical group chemical reagents Ltd

Betaine (anhydrous betaine) available from Konik Europe trade (Shanghai) Co., Ltd

An experimental instrument:

constant temperature shaking machine:

THZ-D

weighing a balance: METTLER TOLEDO PB4002-N

48 ℃ oven: MMM group MMM707

4 ℃ refrigerator: MMM group FRIOCELL 70790570

-18 ℃ refrigerator: haier DW-40L

Moisture content tester: cornemeter CM825

Examples 1 to 9: preparation of urea-containing compositions

Weighing appropriate amount of urea and betaine according to the weight shown in Table 1, adding into a sealed PET bottle with the specification of 200ml, weighing appropriate amount of deionized water, adding into the sealed PET bottle, sealing the sealed PET bottle, placing in a constant temperature shaking machine, and shaking at 38 deg.C for 60min at the frequency of 200 times/min. Cooling to room temperature for later use.

Table 1 shows compositions comprising urea and betaine in different weight percentages and their properties for immediate performance.

TABLE 1

The saturated solubility of urea at room temperature was 105g/100g water and the saturated solubility of betaine was 160g/100g water. In this series of experiments, the water content of the composition was set to 38%, slightly less than the water content of the saturated betaine solution at room temperature (38.5%).

As shown in table 1, the composition of example 1 containing only urea completely dissolved the solids at 38 ℃, and the amount of precipitated solids increased significantly upon cooling to room temperature. Example 9 compositions containing only betaine were completely soluble after shaking at 38 ℃, but a small amount of solid precipitated after a period of time after cooling to room temperature and standing.

Examples 2-8 prepared compositions comprising urea and betaine, the solubility of the samples changed significantly upon addition of the same weight ratio of deionized water. As shown in Table 1, in examples 2 to 8 (urea-betaine weight ratio from 85:15 to 1:99), no solid precipitated after shaking at 38 ℃ or after cooling to room temperature again and standing, and the solution appeared to be a clear and clear solution.

The experiment results show that the compound of urea and betaine can improve the solubility of the composition.

Test example 1: investigation of high temperature stability

10g of the compositions of examples 1 to 9 were weighed and added to a petri dish. The petri dish was placed in an oven at 48 ℃ for 168 hours (h), the petri dish was removed from the oven and cooled to room temperature for observation of the material properties.

Table 2 shows the behavior of various weight ratios of urea and betaine compositions after drying at 48 ℃ for 168 hours.

TABLE 2

When dried at 48 ℃, the liquid mixture placed in an open container loses water and a solid is crystallized. As shown in table 2, after drying in an oven at 48 ℃, in examples 1 and 9, a large amount of crystals precipitated within 24 hours due to water loss, and the presence of a liquid could not be observed.

After the urea-betaine is compounded, the high-temperature anti-crystallization property of the urea-betaine can be obviously improved. The three samples of examples 4-7 (urea-betaine weight ratio from 50:50 to 20:80) had longer crystallization time and still had flowable liquid after being placed in an open oven at 48 ℃ for 168 hours. It is particularly worth mentioning that example 5 (urea-betaine weight ratio 40:60) does not have any crystal precipitation under the same conditions of drying and still shows a clear and clear liquid.

The above results show that the high-temperature crystallization resistance of the aqueous solution of urea-betaine can be obviously improved after the urea-betaine is compounded, the crystallization resistance is directly influenced by the weight ratio of urea to betaine, and example 5 with the weight ratio of urea to betaine of 40:60 has the optimal high-temperature crystallization resistance.

Test example 2: investigation of Low temperature stability

90g of the compositions of examples 1 to 9 were weighed, put into a PET sealed plastic bottle, and cooled in a refrigerator at 4 ℃ for 24 hours. And taking the PET sealed plastic bottle out of the refrigerator, and immediately observing the material body properties.

Table 3 shows the behavior of urea-betaine compositions at different weight ratios cooled at 4 ℃ for 24 h.

TABLE 3

Examples	Standing in a refrigerator at 4 deg.C for 24h
		1	A large amount of solid is separated out
2	A large amount of solid is separated out
		3	Clear and clear liquid
4	Clear and clear liquid
		5	Clear and clear liquid
6	Clear and clear liquid
		7	Clear and clear liquid
8	A large amount of solid is separated out
		9	A large amount of solid is separated out

The solubility of urea and betaine decreases with decreasing temperature. As shown in Table 3, in both examples 1 and 9, a large amount of crystals precipitated after cooling in a refrigerator at 4 ℃ for 24 hours. For the urea-betaine compound composition, only the example 2 (the weight ratio of urea to betaine is 85:15) and the example 8 (the weight ratio of urea to betaine is 1:99) have a large amount of crystal precipitation after cooling at 4 ℃. For examples 3-8 (urea-betaine weight ratio from 80:20 to 20:80), a clear solution was obtained after cooling in a refrigerator at 4 ℃ for 24 h. The results show that the urea-betaine after compounding has the low-temperature crystallization resistance superior to that of a single substance solution.

Test example 3: investigation of Freeze thaw stability

Weighing 90g of the composition of examples 1-9, adding the composition into a PET sealed plastic bottle, placing the PET sealed plastic bottle into a refrigerator at the temperature of-18 ℃ for cooling for 24h, taking the PET sealed plastic bottle out of the refrigerator, and immediately observing the material body properties.

Table 4 shows the properties of urea-betaine compositions at different weight ratios after freezing at-18 ℃ for 24h and thawing at room temperature for 24 h.

TABLE 4

As shown in Table 4, example 1 was completely transformed into a solid state after being frozen in a refrigerator at-18 ℃ for 24 hours, and a large amount of needle-like solids remained after thawing, with almost no mixture of flowable liquids. Example 9 after freezing at-18 ℃, the upper layer was a clear solution, a large amount of crystals precipitated from the lower layer, and a small amount of crystals remained undissolved in the thawed clear solution. Example 2 (urea-betaine weight ratio 85:15) exhibited similar freeze-thaw properties as example 1. However, in examples 3 to 8 (urea-betaine weight ratio from 80:20 to 1:99) after freezing at-18 ℃ for 24 hours, no freezing of the liquid and precipitation of the solid were observed. The experimental results show that the urea-betaine compound has freezing resistance superior to that of a single substance solution.

Test example 4: examination of moisture retention

(1) Volunteer selection: 15 healthy 18-60 years old adults with no obvious scars, no obvious dry desquamation and no pigmentation on the forearm parts of hands are selected as subjects.

(2) Selecting a test object: 83.9g of deionized water was weighed, 16.1g of the example composition was added to make the combined weight ratio of urea to betaine 10% of the total weight, the solution was uniformly dispersed by shaking, and clear water was used as a control.

(3) Dotting and grouping: the forearm sites were spotted and grouped, each volunteer had a spot area of 2X 4cm2, and the experiment was divided into 5 groups: blank, example 1, example 3, example 5, example 9.

(4) Measuring basic values of skin physiological parameters: the forearm of the subject was cleaned with clean water, allowed to sit in a constant temperature and humidity chamber (21. + -. 1 ℃ C., 50% + -5% humidity) for 30 minutes, and then tested on the forearm of the subject using a Cornemeter CM825 moisture content tester to measure the basal value of the medial aspect of the forearm of the subject, including the parameter index of skin moisture. Smearing the sample with the dosage of 2mg/cm²And (3) applying the skin moisturizing cream on a sample for absorption, and testing the skin moisture 15min, 30min and 60min after applying the sample.

Table 5 shows the quality control of stratum corneum water content (Mean ± SD, a.u.) for each sample at different times.

TABLE 5

Indicates significant difference from the base value (p < 0.05)

Table 6 shows the difference in stratum corneum hydration values (i.e., data at the time points tested-base value) for each sample at different times (Mean ± SD, a.u.).

TABLE 6

Test sample	15min	30min	60min
				Blank space	-0.39±1.04	-0.19±1.00	-0.35±0.90
Example 1	-2.12±5.03	-2.21±4.37	-2.26±3.15
				Example 3	10.51±3.64*	9.38±3.80*	9.03±5.15*
Example 5	9.86±3.09*	9.73±4.11*	9.53±3.77*
				Example 9	-4.00±5.82	-6.75±1.86*	-5.94±2.67*

Indicates significant difference from the base value (p < 0.05)

To simulate the conditions of use of the skin care products, the experiments were carried out using deionized water to dilute examples 1, 3, 5 and 9 so that the sum of the weight ratios of urea to betaine was 10%. The average of the blank spots on the left and right hand sides was also tested as a blank value against the sample.

As is clear from tables 5 and 6, the blank area was hardly changed from the base value at each time point within 1 hour of smearing the sample. The skin moisture content test values of the diluted samples of examples 1 and 9 were lower than the base value at each time point, and the decrease of the value of example 9 after 30min and 60min of smearing was statistically significant. It is worth mentioning that in example 1, after 10min of application, the attachment of fine crystals to the skin surface can be observed by naked eyes. The water content of the stratum corneum of the diluted samples in example 3 and example 5 after being smeared for 15min, 30min and 60min is obviously increased compared with the basic value, and the difference value has statistical significance.

The combination of the above experimental results shows that the urea-betaine is applied to the skin care product after being compounded, and compared with the single use of urea or betaine, the urea-betaine has obviously excellent moisturizing performance. The reasons for this may derive from: (1) the composition has higher precipitation resistance, and can promote urea and betaine to be effectively utilized by skin; (2) the composition is easy to keep liquid, and is beneficial to the penetration of the composition in the stratum corneum; (3) the composition has strong water holding capacity, and is helpful for resisting water diffusion loss of horny layer.

Examples 10 to 19: preparation of urea-containing compositions

Weighing appropriate amount of urea and betaine according to the weight shown in Table 7, adding into a sealed PET bottle with the specification of 200ml, weighing appropriate amount of deionized water, adding into the sealed PET bottle, sealing the sealed PET bottle, placing in a constant temperature shaking machine, and shaking at 38 deg.C for 60min at the frequency of 200 times/min. Cooling to room temperature for later use.

Table 7 shows the urea and betaine compositions of examples 10-19 and their immediate performance properties.

TABLE 7

Shaking time was 24 hours

The feed ratios and the properties of the preparations in examples 10 to 19 immediately after shaking and after cooling to room temperature are shown in Table 7. Examples 12-19 (water content from 20% to 80%) were all clear liquids after shaking at 38 ℃ for 60min, and no solid precipitated after cooling to room temperature. Example 11 shaking at 38 deg.C for 60min the solid did not dissolve completely, but after the shaking time was extended to 24h, the solid could dissolve completely to be a clear liquid, and no solid precipitated after cooling to room temperature. In example 10, the solid was not completely dissolved even after shaking at 38 ℃ for 24 hours, and the amount of precipitated solid increased after cooling to room temperature. The above experimental results show that when the weight ratio of urea to betaine is fixed to 4:6, a transparent clear liquid can be formed when the water content exceeds 15%, and no solid is precipitated after cooling to room temperature.

Test example 5: high temperature stability examination of examples 10-19

10g of the compositions of examples 10 to 19 were weighed and added to a petri dish. The petri dish was placed in an oven at 48 ℃ and heated for 168 hours, the petri dish was taken out of the oven and cooled to room temperature to observe the properties of the material body.

Table 8 shows the behavior of urea and betaine compositions of varying moisture content after drying at 48 ℃ for 168 hours.

TABLE 8

As shown in Table 8, examples 11-19 (varying from 15% to 80% moisture) all exhibited clear, flowable liquids after open heating at 48 ℃ for 168h, and no solids were observed to precipitate. The samples with higher water content can form a urea-betaine-water composition with approximate water content after dehydration and concentration, so that the samples with different initial water contents show similar properties after being dried at high temperature for a longer time. Example 10 did not form a clear solution completely, but a portion of the solid was still present. Therefore, after drying for 168 hours at 48 ℃, the phenomenon of obvious solid precipitation appears. The experimental results show that the uniform transparent liquid formed by dissolving urea-betaine in a proper amount of deionized water has better high-temperature crystallization resistance.

Test example 6: low temperature stability examination of examples 10-19

90g of the compositions of examples 10 to 19 were weighed into a sealed PET bottle and cooled in a refrigerator at 4 ℃ for 24 hours (h). And taking the PET sealed plastic bottle out of the refrigerator, and immediately observing the material body properties.

Table 9 shows the behavior of the urea-betaine compositions of examples 10 to 19 when cooled at 4 ℃ for 24 hours.

TABLE 9

As shown in Table 9, in example 10, since undissolved solid was present as seed crystals, a large amount of white solid was precipitated after cooling to 4 ℃. For examples 11-19 (water content 15% to 80%) all appeared as clear, flowable liquids without any solids precipitation after cooling at 4 ℃ for 24. The above experimental results show that the uniform transparent liquid dissolved in a proper amount of water after urea-betaine compounding has good low-temperature crystallization resistance.

Test example 7: freeze-thaw stability test of examples 10-19

Weighing 90g of the composition of examples 10-19, adding the composition into a PET sealed plastic bottle, placing the PET sealed plastic bottle into a refrigerator at the temperature of-18 ℃ for cooling for 24h, taking the PET sealed plastic bottle out of the refrigerator, and immediately observing the material body properties.

Table 10 shows the properties of the urea-betaine compositions of examples 10-19 after freezing at-18 ℃ for 24 hours and thawing at room temperature for 24 hours.

Watch 10

The properties of each sample after freezing at-18 ℃ for 24 hours and thawing at room temperature for 24 hours are summarized in Table 10. Example 10 after freezing to-18 ℃ a large amount of crystals precipitated as white smoothies, only a small amount of liquid was present, and a large amount of solid remained undissolved after thawing. Example 11 a clear, clear liquid after freezing coexists with a large amount of white solid, and a small amount of crystals remained undissolved after thawing (white dense granular solid). Examples 12-17 (water content from 20% to 60%) did not precipitate any solids, and appeared as clear liquids after both freezing and thawing. Example 18 after 24h of freezing, a small amount of solid in the clear liquid was found to precipitate, and the solid was completely dissolved after 24h of thawing at room temperature. Example 19 the ratio of solid to clear liquid after freezing was about the same, and the solid was completely thawed after thawing at room temperature upon standing. The results of the above experiments show that examples 12-17 (moisture content 20% -60%) have good freeze-thaw stability. And the sample with higher water content can partially show good anti-freezing performance of the drug with lower water content after the solute concentration is improved due to the crystallization of free water in the freezing process.

Claims

1. An aqueous composition comprising urea as an effective ingredient having moisturizing effect, wherein the composition further comprises betaine, and the weight ratio of the urea to the betaine is 1:99 to 85: 15.

2. The aqueous composition of claim 1, wherein the weight ratio of urea to betaine is from 3:7 to 1: 1.

3. The aqueous composition of claim 1, wherein the weight ratio of urea to betaine is 4: 6.

4. The aqueous composition of claim 1, wherein the composition has a water content of greater than 10% by weight.

5. Use of an aqueous composition according to claim 1 for skin moisturization.

6. Use of the aqueous composition according to claim 1 in a skin external preparation having a skin moisturizing effect.

7. The use of claim 6, wherein the external skin agent is selected from the group consisting of: face cleaning lotion, cosmetic water, lotion, cream and facial mask.

8. An external preparation for skin comprising the aqueous composition according to claim 1.

9. The external preparation for skin as claimed in claim 8, wherein the external preparation for skin comprises 0.001 to 20% by weight of the aqueous composition.