Ceramide liposome and application thereof

Abstract

The invention relates to the field of cosmetics, and discloses ceramide liposome and application thereof.The ceramide liposome is prepared from, by mass, 1.5-3 parts of ceramide NP, 1-3 parts of octyldodecanol, 0.5-2 parts of caprylic / capric triglyceride, 11-18 parts of hydrogenated lecithin, 2-6 parts of sucrose stearate, 3-7 parts of polyglycerol-10 oleate and 25-35 parts of glycerinum, and the balance is water. 0.5-8 parts of 1, 2-pentanediol, and the balance of water. The ceramide liposome provided by the invention has good stability at least at 40 DEG C, is not easy to cause lactic acid pricking pain and allergy after being smeared on skin, and can be used for sensitive skin; the skin care product can reduce skin transdermal moisture loss, maintain skin cutin moisture, reduce skin heme content, improve skin gloss, relieve skin dryness, relieve skin redness and improve skin fineness, and has the effects of moisturizing, repairing and relieving.

Description

Technical Field

[0001] The invention belongs to the field of cosmetics, and specifically relates to a ceramide liposome and an application thereof. Background Art

[0002] Ceramide (CER), also known as brain amide and N-acylsphingosine, is a common structural unit of (neuro)sphingolipids. It has physiological functions such as maintaining skin barrier, moisturizing, anti-aging, and anti-allergy. Therefore, it has attracted a lot of research and attention in the fields of medicine and cosmetics. However, ceramide has a high melting point, low solubility, and is easy to crystallize or flocculate from cosmetic formulas, which not only affects the stability of the formula, but also reduces the utilization rate of ceramide, greatly limiting its application.

[0003] Liposomes are composed of amphiphilic molecules such as phospholipids. They are bilayer closed vesicles that spontaneously form in aqueous solutions. They are similar to the bilayer of skin keratin and have good skin affinity. The application of liquid crystal liposomes encapsulating ceramide in cosmetics can promote the penetration of ceramide through the epidermis and produce sufficient accumulation in the corresponding parts, achieving the effects of efficient moisturizing, skin repair, anti-oxidation, and anti-aging. They are widely used in the fields of medicine and cosmetics. However, ceramide liposomes have poor stability at high temperatures, which affects their functions of maintaining skin barrier and moisturizing. In order to solve the problem of instability, preservatives are often added to cosmetics containing ceramide liposomes, but cosmetics containing preservatives are more irritating to the skin. It is necessary to continue to develop ceramide liposomes with good stability. Summary of the invention

[0004] The purpose of the present invention is to overcome the problem of poor stability of ceramide liposomes at high temperatures in the prior art, and to provide a ceramide liposome and an application thereof.

[0005] In order to achieve the above object, the first aspect of the present invention provides a ceramide liposome, which is prepared from the following components based on 100 parts by mass: 1.5-3 parts of ceramide NP, 1-3 parts of octyldodecanol, 0.5-2 parts of caprylic capric triglyceride, 11-18 parts of hydrogenated lecithin, 2-6 parts of sucrose stearate, 3-7 parts of polyglycerol-10 oleate, 25-35 parts of glycerol, 0.5-8 parts of 1,2-pentanediol, and the rest is water; The preparation method of the ceramide liposome comprises: firstly mixing the ceramide NP, caprylic capric triglyceride, hydrogenated lecithin, sucrose stearate, polyglycerol-10 oleate and glycerol, then adding 1,2-pentanediol, octyldodecanol and water, and finally homogenizing; The homogenization conditions include: the first homogenization pressure is 20000-28000psi, and the discharge temperature is 60-70°C; the second homogenization pressure is 15000-22000psi; the third homogenization pressure is 12000-20000psi; the fourth homogenization pressure is 10000-15000psi; the discharge temperature gradient decreases, and the discharge temperature difference between two adjacent homogenizations is 13-17°C.

[0006] The second aspect of the present invention provides the use of the ceramide liposomes described in the first aspect of the present invention in promoting skin moisturizing, repairing skin and soothing skin.

[0007] The third aspect of the present invention provides a cosmetic containing the ceramide liposomes described in the first aspect of the present invention.

[0008] Through the above technical scheme, the ceramide liposomes provided by the present invention have good stability at least at 40°C. When applied to the skin, they are not prone to lactic acid stinging and allergies, and can be used for sensitive skin; they can reduce skin transepidermal water loss, maintain skin keratin moisture, reduce skin hemoglobin content, improve skin gloss, relieve skin dryness, relieve skin redness and improve skin fineness, have moisturizing, repairing and soothing effects, and are especially suitable for sensitive skin. DETAILED DESCRIPTION

[0009] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0010] The first aspect of the present invention provides a ceramide liposome, which is prepared from the following components based on 100 parts by mass: 1.5-3 parts of ceramide NP, 1-3 parts of octyldodecanol, 0.5-2 parts of caprylic capric triglyceride, 11-18 parts of hydrogenated lecithin, 2-6 parts of sucrose stearate, 3-7 parts of polyglycerol-10 oleate, 25-35 parts of glycerol, 0.5-8 parts of 1,2-pentanediol, and the rest is water; The preparation method of the ceramide liposome comprises: firstly mixing the ceramide NP, caprylic capric triglyceride, hydrogenated lecithin, sucrose stearate, polyglycerol-10 oleate and glycerol, then adding 1,2-pentanediol, octyldodecanol and water to mix, and finally homogenizing. The inventor of the present invention has found that the stability of the prepared liposome is improved by combining the formula with a specific preparation method, and the liposome can also have good moisturizing, repairing and soothing effects.

[0011] The inventors have also found through research that controlling the number of homogenization cycles and gradient cooling can further improve the stability of the obtained liposomes at high temperatures.

[0012] In the present invention, taking into account the stability, production cost and production efficiency of the obtained liposomes, preferably, the homogenization conditions include: the first homogenization pressure is 20000-28000 psi, the discharge temperature is 60-70°C (for example, it can be any value among 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, any range composed of any two of the above values, and any value in any range); the second homogenization pressure is 15000-22000 psi; the third homogenization pressure is 12000-20000 psi; the fourth homogenization pressure is 10000-15000 psi; the discharge temperature gradient decreases, and the discharge temperature difference between two adjacent homogenizations is 13-17°C (for example, it can be any value among 13°C, 14°C, 15°C, 16°C, 17°C, any range composed of any two of the above values, and any value in any range). The homogenization can be performed in a conventional high-pressure homogenizer.

[0013] More preferably, the discharge temperature of the second homogenization is 52-57°C.

[0014] More preferably, the discharge temperature of the third homogenization is 38-42°C; More preferably, the discharge temperature of the fourth homogenization is 23-27°C.

[0015] Lecithin is a natural mixture of diglycerides of stearic acid, palmitic acid and oleic acid, which is connected to the choline ester of phosphoric acid (commonly known as phosphatidylcholine). Hydrogenated lecithin is the product of controlled hydrogenation of lecithin. It is a stable emulsifier and moisturizer with strong hydrophilicity and moisturizing properties, and has a strong affinity for skin and mucous membranes. Polyglycerol-10 oleate is an ester compound generated by the reaction of glycerol and oleic acid. In the present invention, it can not only play an antibacterial role, but also can be compounded with other ingredients to improve skin affinity and transdermal properties. The inventors of the present invention also unexpectedly found that after ceramide NP is compounded with hydrogenated lecithin and polyglycerol-10 oleate in a specific ratio, the particle size distribution of the resulting liposome is more uniform and the stability is further improved.

[0016] In the present invention, preferably, the mass ratio of ceramide, hydrogenated lecithin and polyglycerol-10 oleate is 1:(6-8):(1.5-5). More preferably, the mass ratio of ceramide, hydrogenated lecithin and polyglycerol-10 oleate is 1:(7-8):(1.5-3).

[0017] In the present invention, preferably, the amount of ceramide NP is 1.8-2.2 parts by weight. Ceramide NP, also known as ceramide 3, English name CERAMIDE NP, molecular formula C 36 H 71 NO4, molecular weight 582.0, is composed of hydroxyl-free fatty acids and phytosphingosine and is commercially available.

[0018] In the present invention, preferably, the amount of octyl dodecanol used is 1.8-2.4 parts by mass.

[0019] In the present invention, preferably, the amount of caprylic capric triglyceride is 0.9-1.2 parts by mass.

[0020] In the present invention, preferably, the amount of 1,2-pentanediol used is 1-3 parts by mass.

[0021] In the present invention, the mixing temperature can be independently 65-80°C, for example, it can be any value among 65°C, 68°C, 71°C, 74°C, 77°C, 80°C, any range composed of any two of the above values, and any value in any range, more preferably 68-77°C.

[0022] The mixing can dissolve the components in the mixed system, and the mass of the undissolved matter accounts for less than 5% of the added amount of the component.

[0023] The second aspect of the present invention provides the use of the ceramide liposomes described in the first aspect of the present invention in promoting skin moisturizing, repairing skin and soothing skin.

[0024] In some specific embodiments, the skin can be any skin type, especially sensitive skin. Sensitive skin is a highly intolerant skin condition, which is easily irritated by various factors and produces subjective symptoms such as stinging, burning, tightness, itching and other multifactorial syndromes. The skin appearance is normal or accompanied by mild desquamation, erythema and dryness; it can be skin of any part, preferably facial skin.

[0025] In some specific embodiments, the application includes at least one of reducing transepidermal water loss, maintaining skin keratin moisture, reducing skin hemoglobin content, improving skin gloss, alleviating skin dryness, alleviating skin redness, and improving skin smoothness.

[0026] The third aspect of the present invention provides a cosmetic comprising the ceramide liposome according to the first aspect of the present invention.

[0027] The cosmetics at least include daily chemical industrial products that are spread on any part of the human body surface (skin, hair, nails, lips, etc.) by rubbing, spraying or similar methods to achieve the purposes of cleaning, removing bad odors, skin care, beauty and modification. Specifically, they may include but are not limited to lotions and creams, such as hand cream, face cream, skin care water, etc.

[0028] The cosmetics may further include other ingredients, such as thickeners, emulsifiers, preservatives, moisturizers (such as hyaluronic acid, sodium hyaluronate, propylene glycol, butylene glycol, panthenol, etc.), antioxidants (such as vitamin E, vitamin C), preservatives (such as parabens), active ingredients (such as retinol, nicotine amide), occlusives (such as petrolatum, lanolin, cetyl alcohol, mineral oil, silicone derivatives, etc.), soothing agents (such as allantoin, urea, various plant extracts (Centella asiatica, Portulaca oleracea, bisabolol, dipotassium glycyrrhizinate, whitening ingredients (such as niacinamide, arbutin, vitamin C, phenylethyl resorcinol, tranexamic acid, glutathione, kojic acid, etc.), anti-aging ingredients (such as retinol), anti-acne ingredients (such as azelaic acid, salicylic acid, fruit acid, etc.), etc. Those skilled in the art may select appropriate ingredients according to actual needs.

[0029] In the present invention, the cosmetic can be prepared by mixing the liposome provided by the present invention with other ingredients in the cosmetic.

[0030] The present invention will be described in detail below by way of examples. The present invention generally and / or specifically describes the materials and test methods used in the tests. In the following examples, unless otherwise specified, % represents wt%, i.e., weight percentage. The reagents or instruments used without indicating the manufacturer are all conventional reagent products that can be obtained commercially.

[0031] Example 1 Weigh ceramide NP, caprylic capric triglyceride, hydrogenated lecithin, sucrose stearate, and polyglycerol-10 oleate, add glycerol solvent, dissolve in a 75°C constant temperature water bath, and stir for 15 min after complete dissolution; Add the prescribed amount of 75°C 1,2-pentanediol, octyldodecanol and water in sequence at a uniform speed, stirring while adding, and quickly mix to obtain colostrum; The colostrum was treated with high-pressure homogenization, and the number of homogenization cycles was 4 times. The first homogenization pressure was 24000psi and the discharge temperature was 65°C; the second homogenization pressure was 20000psi and the discharge temperature was 55°C; the third homogenization pressure was 18000psi and the discharge temperature was 40°C; the fourth homogenization pressure was 12000psi and the discharge temperature was 25°C.

[0032] Example 2 The method of Example 1 is followed, except that the formulation is different, see Table 1.

[0033] Example 3 The method of Example 1 is followed, except that the formulation is different, see Table 1.

[0034] Table 1

[0035] Comparative Example 1 The method of Example 1 was followed, except that only two homogenizations were performed, and the pressure of the first homogenization was set to 24,000 psi, and the discharge temperature was set to 65°C; the pressure of the second homogenization was set to 20,000 psi, and the discharge temperature was set to 25°C.

[0036] Comparative Example 2 The method of Example 1 was followed, except that hydrogenated lecithin was replaced by lecithin.

[0037] Comparative Example 3 The method of Example 1 was followed, except that hydrogenated lecithin was not added and 19 parts of polyglycerol-10 oleate was added.

[0038] Comparative Example 4 The method of Example 1 was followed, except that polyglycerol-10 oleate was replaced by polyglycerol-6 oleate.

[0039] Comparative Examples 5-6 The method of Example 1 is followed, except that the formula is different, see Table 2 for details.

[0040] Table 2

[0041] Test Example 1 The stability of the samples of each example and comparative example was measured.

[0042] The samples of each embodiment and comparative example were placed in a suitable clean container and stored under different conditions for 28 days. Five bottles of each sample were placed at 35° C. After 28 days, the product particle size (1wt% dispersed liquid) and dispersion (1wt% concentration dispersed liquid) were tested to evaluate the stability. The test results are detailed in Table 3.

[0043] The particle size and PDI value of liposomes were measured by ZetaSizer Nano ZS (Malvern Panalytical, Malvern, UK) and the measurement was repeated three times at room temperature of 25 °C.

[0044] Table 3

[0045] The experimenters also observed that as the time of being placed at high temperature increased, the colors of Examples 2-3 changed, and the resulting products also showed obvious stratification. The stratification time of Example 3 was earlier, indicating that the combination of hydrogenated lecithin and other ingredients can improve the stability of liposomes.

[0046] The results of Comparative Example 4 show that although the particle size distribution of the liposomes prepared using the polyglycerol-10 oleate analog is smaller, the stability during long-term storage is still poor.

[0047] In Comparative Example 1, reducing the number of homogenization times can significantly reduce the stability of the liposomes, and the particle size distribution is uneven, which is not conducive to the further preparation of cosmetics such as emulsions and creams by liposomes.

[0048] In Comparative Examples 5 and 6, when the ratio of ceramide NP, hydrogenated lecithin and polyglycerol-10 oleate is too large or too small, the long-term stability of the prepared liposomes is poor.

[0049] Test Example 2 The liposomes obtained in Example 1 with the best stability were selected to test their moisturizing, repairing and soothing effects.

[0050] 1. Test plan Eleven women were selected as subjects; (1) Inclusion criteria: Healthy female, aged 18-60 years old; sensitive skin; dull and dry facial skin; facial redness, redness score is 3-6; Corneometer stratum corneum moisture content <60 cu; Tewameter test skin moisture loss value >15g / h / m 2 ; Be able to cooperate well with the tester and maintain a regular life during the test; Be able to read and understand all the contents of the informed consent form and voluntarily sign the informed consent form; During the test, the subjects will not use any cosmetics, drugs or health products that may affect the results; will not use samples with the same efficacy as the test samples; will not use other cosmetics or personal care products except the test samples during the test; are not currently participating in and will not participate in any other research involving the test area during the study; and will not undergo any medical beauty projects during the test.

[0051] (2) Environmental conditions: The test environment conditions during the entire test process are controlled as follows: temperature 20-22°C, humidity 40-60%RH.

[0052] (3) Sample usage: Use on the face twice a day for 28 consecutive days. After cleansing in the morning and evening, use your usual lotion and essence, take an appropriate amount of the liposome dispersion obtained in Example 1 and evenly apply it on the entire face, and gently massage until it is completely absorbed.

[0053] (4) Test time: The following tests were performed on the 0th day when the sample was not used, and on the 7th, 14th and 28th days after the sample was used: (5) Skin test items, see the table below: Table 4-1

[0054] (6) Dermatologist evaluation Conduct efficacy assessment: Skin redness: 0 means no redness at all, 9 means very redness; Dry skin: 0 points represent very moist skin, 9 points represent very dry skin; Glossiness: 0 points represent very glossy, 9 points represent very dull; Skin smoothness: 0 points represent very smooth, 9 points represent very rough; Skin smoothness: 0 points represent very smooth skin, 9 points represent very rough skin.

[0055] (7) Lactic acid sting assessment Take 50 μL of 10% lactic acid solution and drop it on a single-layer non-woven fabric with a diameter of 0.8 cm. Apply the non-woven fabric to the nasolabial groove on either side of the subject, and use distilled water as a control on the other side. The researcher asked the subject about the tingling sensation at 2.5 minutes and 5 minutes, and scored according to the "4-point method" in Table 1. Those with a cumulative tingling sensation of ≥3 points on the lactic acid side relative to the distilled water side are considered to have lactic acid tingling and can be judged as sensitive skin. Method reference: He Li. Chinese Guidelines for Clinical Diagnosis and Treatment of Sensitive Skin (2024 Edition) [J / OL]. Chinese Journal of Dermatology and Venereology.

[0056] The lactic acid sting rating scale is as follows: 0 points, no tingling sensation; 1 point, slight tingling sensation; 2 points, moderate tingling sensation, tolerable; 3 points, severe tingling sensation, unbearable.

[0057] Note: If the score of the subject on the lactic acid side reaches 3 points at any time during the test, the experiment can be terminated and the subject will be judged as having lactic acid stinging.

[0058] Specific test plan: Table 4-2

[0059] (8) Data analysis Statistical analysis software SPSS was used to perform statistical analysis of the data and calculate the mean, standard deviation, and rate of change of each parameter at each time point.

[0060] Change rate = [(value after use - value before use) / value before use] × 100%

[0061] (II) Test results (1) Skin keratin moisture content test results Table 5-1

[0062] (2) Transepidermal Water Loss (TEWL) value (Tewameter TM Hex) Table 5-2

[0063] (3) Skin hemoglobin EI value test results Table 5-3

[0064] (4) Skin color (red-green) value a* value test results Table 5-4

[0065] (5) Skin color (yellow-blue) value b* value test results Table 5-5

[0066] (6) Dermatologist evaluation score test results Table 5-6

[0067] (7) Lactic acid stinging score test results Table 5-7

[0068] During the experiment, no adverse reactions were observed.

[0069] The above experimental results show that as the use time increases, the moisture content of the stratum corneum of the subjects' skin gradually increases, and the increase is obvious; the water loss is gradually alleviated, and the moisturizing and repairing effects are obvious; the skin hemoglobin content is reduced, indicating that it has a soothing effect; the evaluation results of dermatologists show that it has the effect of relieving skin redness, relieving skin dryness, improving skin gloss and smoothness, and can also significantly improve the skin's delicateness. The ceramide-containing liposomes also have a whitening effect.

[0070] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A ceramide liposome, characterized in that: The ceramide liposome is prepared from the following components based on 100 parts by mass: 1.5-3 parts of ceramide NP, 1-3 parts of octyldodecanol, 0.5-2 parts of caprylic capric triglyceride, 11-18 parts of hydrogenated lecithin, 2-6 parts of sucrose stearate, 3-7 parts of polyglycerol-10 oleate, 25-35 parts of glycerol, 0.5-8 parts of 1,2-pentanediol, and the rest is water; The preparation method of the ceramide liposome comprises: firstly mixing the ceramide NP, caprylic capric triglyceride, hydrogenated lecithin, sucrose stearate, polyglycerol-10 oleate and glycerol, then adding 1,2-pentanediol, octyldodecanol and water, and finally homogenizing; The homogenization conditions include: the first homogenization pressure is 20000-28000psi, and the discharge temperature is 60-70°C; the second homogenization pressure is 15000-22000psi; the third homogenization pressure is 12000-20000psi; the fourth homogenization pressure is 10000-15000psi; the discharge temperature gradient decreases, and the discharge temperature difference between two adjacent homogenizations is 13-17°C.

2. The ceramide liposome according to claim 1, wherein The mass ratio of the ceramide, hydrogenated lecithin and polyglycerol-10 oleate is 1:(6-8):(1.5-5).

3. The ceramide liposome according to claim 1 or 2, wherein The mass ratio of the ceramide, hydrogenated lecithin and polyglycerol-10 oleate is 1:(7-8):(1.5-3).

4. The ceramide liposome according to claim 1 or 2, wherein The amount of ceramide NP used is 1.8-2.2 parts by weight.

5. The ceramide liposome according to claim 1 or 2, wherein The usage of the octyl dodecanol is 1.8-2.4 parts by mass.

6. The ceramide liposome according to claim 1 or 2, wherein The usage of caprylic capric triglyceride is 0.9-1.2 parts by weight.

7. The ceramide liposome according to claim 1 or 2, wherein The amount of 1,2-pentanediol used is 1-3 parts by mass.

8. The ceramide liposome according to claim 1 or 2, wherein The discharge temperature of the second homogenization is 52-57°C; Preferably, the discharge temperature of the third homogenization is 38-42°C; Preferably, the discharge temperature of the fourth homogenization is 23-27°C.

9. Use of the ceramide liposome according to any one of claims 1 to 8 in promoting skin moisturizing, repairing skin and soothing skin.

10. A cosmetic comprising the ceramide liposome according to any one of claims 1 to 8.

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