WO2021057391A1 - 一种组合物及其在制备护理熬夜者皮肤产品中的应用 - Google Patents

一种组合物及其在制备护理熬夜者皮肤产品中的应用 Download PDF

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WO2021057391A1
WO2021057391A1 PCT/CN2020/112457 CN2020112457W WO2021057391A1 WO 2021057391 A1 WO2021057391 A1 WO 2021057391A1 CN 2020112457 W CN2020112457 W CN 2020112457W WO 2021057391 A1 WO2021057391 A1 WO 2021057391A1
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skin
test
composition
skin care
care product
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PCT/CN2020/112457
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English (en)
French (fr)
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戴跃锋
颜少慰
何广文
钱景茹
徐筱群
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湖南御家化妆品制造有限公司
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Priority to US17/763,918 priority Critical patent/US20220347086A1/en
Priority to JP2022519546A priority patent/JP7448642B2/ja
Publication of WO2021057391A1 publication Critical patent/WO2021057391A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/345—Alcohols containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • A61K8/466—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfonic acid derivatives; Salts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/645—Proteins of vegetable origin; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • the invention relates to the technical field of skin care products, in particular to a composition and its application in the preparation of products for caring the skin of people who stay up late.
  • Rough skin late at night is an important stage for the skin to repair itself. But in the process of staying up late, the energy originally used to maintain cell metabolism, self-repair and renewal is consumed by the mechanism of staying up late, and the body does not have more energy to participate in cell repair. Therefore, the speed of skin aging will accelerate, and the skin will easily become rough.
  • Dull skin tone Because skin cells do not repair and renew themselves in time, it leads to cell decay. In the process of cell decay, some inflammatory factors will be released. Inflammatory factors will activate melanocytes, thereby causing melanocytes to produce melanin. Eventually lead to skin pigmentation. The decay and death of skin cells, if they are not renewed in time, the tissue structure of the skin will be damaged, which will cause the skin to lose its luster and cause dull skin.
  • the night is a physiological rest time for the human body, and it is also an important time for the repair and metabolism of various organisms.
  • the repair and metabolism of the organism are disordered due to staying up late.
  • the metabolic products cannot be eliminated from the body in time, and the metabolic products in the blood increase, and the local The blood circulation is not smooth, causing dark circles and bags under the eyes aggravated in the orbital area where the skin is relatively thin.
  • the technical problem to be solved by the present invention is to provide a composition and its application in the preparation of products for caring for the skin of people who stay up late.
  • the composition of the present invention has good moisturizing and moisturizing effects, and can restore skin luster and promote Cellular energy synthesis.
  • composition provided by the present invention includes the following components by mass:
  • the skin conditioner A includes the following mass fractions:
  • the skin conditioner B includes the following mass fractions:
  • the balance is water.
  • the preservatives in the skin conditioner A are phenoxyethanol and ethylhexylglycerol, and the mass ratio of the two is 1:1.
  • the stabilizer in the skin conditioner A is sodium metabisulfite.
  • the preservatives in the skin conditioner B are sorbic acid and phenoxyethanol, and the mass ratio of the two is 1:3.
  • the sodium hyaluronate is composed of components with the following mass fractions:
  • the composition is composed of the following components by mass:
  • the composition is composed of the following components by mass:
  • the composition is composed of the following components by mass:
  • the present invention takes the state of staying up late as the research object, and prepares the composition on the background of skin biological rhythm mechanism and skin repair.
  • skin conditioner B containing biological rhythm peptides
  • the circadian clock genes of the skin promote the repair and proliferation of keratinocytes, promote the synthesis of vitamin D, and activate the conversion of vitamin D to activate the skin.
  • Skin conditioner B rich in glycoprotein, glutamic acid, valine, and threonine to promote sugar degradation and mitochondrial respiration, ensuring that the ATP of skin cells is at a high level throughout the day, and there is sufficient energy supply during the day
  • Cells are used to resist external unfavorable factors; to ensure adequate energy supply when skin cells need to be repaired at night; and adenosine is added to directly supplement the energy required by the cells.
  • Skin repair add hyaluronic acid (containing 2.1 million, 1.3 million, hydrolyzed hyaluronic acid) and adenosine, debug a combination of hydrating and moisturizing from the three dimensions of cell repair, stratum corneum hydration, and epidermal hydration.
  • Xia Xuepi lotus bulb extract with powerful cell repairing effect inhibits the proliferation of melanocytes, reduces the production of melanin, and avoids the dull skin caused by melanin deposition.
  • the components in the composition of the present invention cooperate with each other, promote each other, and play a good synergistic effect.
  • composition of the present invention is used in the preparation of skin care products for caring for the skin of people who stay up late.
  • the functions of the skin care product include: moisturizing and moisturizing, restoring skin luster, and promoting cell energy synthesis.
  • the invention also provides a skin care product for caring for the skin of people who stay up late, including the composition of the invention.
  • the mass fraction of the composition is 1% to 7.5%.
  • the mass fraction of the composition is 1%, 2.3%, and 7.5%.
  • the skin care products of the present invention include:
  • the humectant is glycerin and 1,3 butanediol, and the mass ratio of the glycerin and 1,3 butanediol is 1:1;
  • the penetration enhancer is pentanediol
  • the keratin softener is hydroxyethylpiperazine ethane sulfonic acid
  • the preservative is PHL.
  • the skin care product of the present invention is composed of components with the following mass fractions:
  • the skin conditioner A includes the following mass fractions:
  • the skin conditioner B includes the following mass fractions:
  • the balance is water.
  • the cosmetic is composed of the following components:
  • the cosmetic is composed of the following components:
  • the cosmetic is composed of the following components:
  • the skin care products of the present invention are lotions, lotions, creams, facial masks, essences, gels and the like.
  • the preparation method of the skin care product of the present invention includes:
  • the composition provided by the present invention includes adenosine, Xia Xuelian bulb extract, sodium hyaluronate, skin conditioner A containing glycoprotein and amino acid, and skin conditioner B containing glutamine ethyl imidazole.
  • Each component cooperates with each other and promotes each other, so as to achieve good moisturizing and moisturizing, restore skin luster, and promote cell energy synthesis.
  • the composition can be used to prepare cosmetics and can improve a series of skin problems of people who stay up late.
  • Figure 1 shows the effect of each sample on the energy synthesis of cells
  • Figure 2 shows the instant replenishment effect of each sample
  • Figure 3 shows the long-term moisturizing effect of each sample
  • Figure 4 shows the short-term effects of each sample on the loss of skin water dispersion
  • Figure 5 shows the long-term effects of each sample on the loss of skin water dispersion
  • Figure 6 shows the effect of each sample on skin gloss.
  • the present invention provides a composition and its application in the preparation of products for caring for the skin of people who stay up late.
  • Those skilled in the art can learn from the content of this article and appropriately improve the process parameters.
  • all similar replacements and modifications are obvious to those skilled in the art, and they are all deemed to be included in the present invention.
  • the method and application of the present invention have been described through the preferred embodiments. It is obvious that relevant personnel can modify or appropriately change and combine the methods and applications herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention.
  • Invent technology is obvious that relevant personnel can modify or appropriately change and combine the methods and applications herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention.
  • test materials used in the present invention are all common commercially available products, all of which can be purchased in the market.
  • composition of the skin conditioner A used is:
  • composition of the skin conditioner B used is:
  • the Xia Xuepi lotus bulb extract is extracted from the dormant Xia Xuepi lotus bulb as a raw material, and the main active ingredient is abscisic acid.
  • the composition of the Xia Xuelian lotus bulb extract used in the present invention is:
  • the sodium hyaluronate is also called tri-molecule hyaluronic acid, and its composition is:
  • the used skin conditioner A, skin conditioner B and Xia Xuepilian bulb extract are all purchased from the market, and the trade names are in order And IBR
  • the physiological activity of skin tissue is strictly controlled by biological rhythms.
  • skin cells are mainly dedicated to the skin's natural defenses (resistance to UV, anti-pollution, etc.); at night, they focus on cell repair and metabolism.
  • skin clock genes such as CLOCK and PERIOD-1, are related to the proliferation of keratinocytes, fibroblasts and melanocytes. Irregular biological rhythms will change the periodic activation of circadian clock genes, leading to changes in skin physiological metabolism.
  • the present invention measures the efficacy of the composition from four aspects: cell energy change, hydrating effect, skin loss of water dispersion, and improvement of skin gloss.
  • Adenosine 5'-triphosphate is the most basic carrier for energy exchange in organisms, and changes in its content are directly related to the energy metabolism of various organs. As the most important energy molecule, ATP plays an important role in various physiological and pathological processes of cells. Changes in ATP levels can affect cell function. Normally, ATP levels will decrease when cells are in apoptosis, necrosis, or in some toxic state. The decrease of ATP level during apoptosis usually coincides with the decrease of mitochondrial membrane potential.
  • the ATP content determination kit can be used to detect ATP levels in cells.
  • sample to be tested is diluted with DMEM medium, the concentration after dilution is 0.1%, and the sample is prepared 10ml.
  • -Keratinocyte collection and processing After the cells are collected, centrifuge to remove the medium, add 0.5ml of double distilled water, and mix well. Place the cell aqueous solution in the wastewater for 10 minutes, vortex and mix for 1 minute; centrifuge at 4000 rpm for 10 minutes, and take the supernatant for testing.
  • Substrate liquid 1 is powder, add 10ml of distilled water to dissolve when using, and heat to dissolve in boiling water
  • Substrate liquid 2 is liquid, use it directly
  • Reagent 3 Accelerator, add the diluent to the powder to form a solution when in use
  • Reagent 5 Chromogenic agent, add liquid A to liquid B when using, mix well and wait for use
  • -ATP Increase(%) (ATP n -ATP 0 )/ATP 0 ⁇ 100% (where ATP n is the cell energy of each test sample, and ATP 0 is the cell energy of the blank sample)
  • Examples 1 to 3 can significantly increase cell energy, indicating that the composition of the present invention has a significant effect in improving cell energy; p ⁇ 0.05;
  • Examples 1 to 3 Compared with Comparative Example 3, Examples 1 to 3 have more significant effects in improving cell energy, indicating that the composition of the present invention has better effects with the same content of active ingredients, indicating that the composition of the present invention has a reasonable and appropriate ratio.
  • Example 3 the effect of Example 3 is the most significant, indicating that the ratio and concentration are the most appropriate, and the effect of the obtained sample is significantly different from that of other groups, p ⁇ 0.05.
  • German CK company multifunctional skin tester model Corneometer CM825MDD,
  • the capacitance method is used to test the moisture content of the stratum corneum of human skin. Its principle is based on the significant difference between the dielectric constants of water and other substances. According to the skin moisture content, the measured skin capacitance values are different, and the observation parameters can be Represents skin moisture value.
  • test environment temperature is 22 ⁇ 1°C
  • humidity is 50 ⁇ 5%
  • real-time dynamic detection is carried out
  • -Test volunteers at least 30 effective volunteers, aged between 16-65 years old (except pregnant or lactating women); the basic value of the capacitance method for skin moisture determination of the forearm test area is between 15-100; no serious Systemic diseases, those who have no immunodeficiency or autoimmune diseases; those who have no history of severe allergies to skin care cosmetics; those who have not used hormone drugs and immunosuppressants in the past month; those who have not participated in other clinical trials; Trial drugs and complete information; all volunteers should fill out an informed consent form before the test.
  • Preparation before the test Do not use any products (cosmetics or topical drugs) 2-3 days before the test site. Before the experiment, subjects need to agree to clean their hands and forearms for internal testing, and air dry them naturally. After cleaning, the subject's hands and forearms were measured and the measurement area was marked. Before the formal test, you should sit quietly in a room that meets the standards for at least 30 minutes, without drinking water, with the forearms exposed, and place in the test state, and stay relaxed.
  • Test process In the experiment, 3 ⁇ 3cm 2 test areas are marked on the inner sides of the left and right arms, and multiple areas can be marked on the same arm, with an interval of 1cm.
  • the test product and the blank control are randomly distributed on the left and right arms.
  • Use the probe Corneometer CM825 MDD to measure the skin moisture content of the test area and the control area. Each area was measured 15 times in parallel. Measure the blank value of each test area first, and then inject the sample into the membrane cloth at an amount of 0.072ml sample/cm 2 , and apply it to the test area for 20 minutes. Take off the mask cloth after 20 minutes, and test the moisture content of the skin in this area after 10 minutes, which is the moisture content of the skin at 30 minutes. After measuring 1 hour, 2 hours, the skin moisture content of the test area and the blank control area (measured at this time during verification), the test of the same volunteer was completed by the same measurement staff.
  • the subjects applied the test sample in the same area every day according to the above test method, and tested the moisture content of the skin on the 14th and 28th day without applying the test sample.
  • Test data According to the design of the experiment, the skin moisture content of each time period is measured separately, and the increase of the skin moisture content at each time point is calculated.
  • Example-1 From the point of view of the instant hydrating effect, the basic formula of Control Sample-1 has a certain hydrating effect, and the increase in water content is 108.1%. In Example-1, the moisture content of the skin increased to 169.0% at 30 minutes, and the hydrating effect was still about 1755.5% at 120 minutes. The instant hydrating effect was obvious and the duration was longer.
  • Examples 1 to 3 can significantly improve the moisturizing effect (long-acting, instant), indicating that the composition of the present invention has a significant effect in the ability of moisturizing (long-acting, instant); p ⁇ 0.05;
  • Examples 1 to 3 Compared with Comparative Example 3, Examples 1 to 3 have more significant effects in hydrating (long-acting, instant), indicating that the composition of the present invention has better effects under the same active ingredient content, indicating that the composition of the present invention is reasonable and appropriate.
  • Example 3 the effect of Example 3 is the most significant, indicating that the ratio and concentration are the most appropriate, and the effect of the obtained sample is significantly different from that of other groups, p ⁇ 0.05.
  • Two sets of temperature and humidity sensors are used to measure the water vapor pressure gradient formed by the water loss of the stratum corneum at different bright spots near the epidermis (within about 1 cm), and directly measure the amount of water emitted through the skin.
  • the TEWL value is an important indicator of the quality of the skin barrier. The lower the TEWL value of the skin, the better the barrier function of the skin, and vice versa.
  • test environment temperature is 22 ⁇ 1°C
  • humidity is 50 ⁇ 5%
  • real-time dynamic detection is carried out
  • -Test volunteers at least 30 effective volunteers, aged between 16-65 years (except pregnant or lactating women); no serious system disease, no immune deficiency or autoimmune disease; no previous use of skin care cosmetics Those with a history of severe allergies; those who have not used hormone drugs and immunosuppressive agents in the past month; those who have not participated in other clinical trials; those who have used the test drugs as required and the information is complete; all volunteers should fill out an informed consent form before the test.
  • Preparation before the test Do not use any products (cosmetics or topical drugs) 2-3 days before the test site. Before the experiment, subjects need to agree to clean their hands and forearms for internal testing, and air dry them naturally. After cleaning, the subject's hands and forearms were measured and the measurement area was marked. Before the formal test, you should sit quietly in a room that meets the standards for at least 30 minutes, without drinking water, with the forearms exposed, and place in the test state, and stay relaxed.
  • Test process In the experiment, 3 ⁇ 3cm 2 test areas are marked on the inner sides of the left and right arms, and multiple areas can be marked on the same arm, with an interval of 1cm.
  • the test product and the blank control are randomly distributed on the left and right arms.
  • the probe Tewameter TM300 was used to measure the skin water loss of the test area and the control area. Each area was measured 15 times in parallel. Measure the blank value of each test area first, and then inject the sample into the membrane cloth at an amount of 0.072ml sample/cm 2 , and apply it to the test area for 20 minutes. Take off the mask cloth after 20 minutes, and test the water loss of the skin in this area after 10 minutes, which is the water loss of the skin at 30 minutes. After measuring 1 hour and 2 hours respectively, the skin water loss of the test area and the blank control area were measured. The test of the same volunteer was completed by the same measurement staff.
  • the subjects apply the test sample in the same area every day according to the above test method, and test the water loss TEWL of the skin on the 14th and 28th day without applying the test sample. .
  • Test data According to the design of the experiment, the skin loss of water dispersion was measured at each time period, and the reduction of the skin loss of water at each time point was calculated. The greater the reduction in skin loss of water dispersion, the better the effect of skin barrier repair.
  • Example-1 From the results of the long-lasting skin loss of water dispersion, the use of Example-1 for 28 days has reduced the skin loss of water loss of 18.93%, that is, the skin loss of water loss is constantly increasing. The reduction reflects that the barrier function of the skin has been effectively repaired.
  • Examples 1 to 3 can significantly improve the moisturizing effect (long-acting, instant), indicating that the composition of the present invention has a significant effect in moisturizing (long-acting, instant) ability; p ⁇ 0.05;
  • Examples 1 to 3 Compared with Comparative Example 2, Examples 1 to 3 have more significant effects in terms of moisturizing (long-lasting, instant), indicating that the composition of the present invention is more reasonable, and each component is indispensable, and the mutual cooperation produces a significant synergistic effect.
  • Examples 1 to 3 Compared with Comparative Example 3, Examples 1 to 3 have more significant effects in terms of moisturizing (long-lasting, instant), indicating that the composition of the present invention has better effects with the same content of active ingredients, indicating that the composition of the present invention has a reasonable and appropriate ratio.
  • Example 3 the effect of Example 3 is the most significant, indicating that the ratio and concentration are the most appropriate, and the effect of the obtained sample is significantly different from that of other groups, p ⁇ 0.05.
  • the skin surface gloss is reflected by the direct reflection and scattered reflection of the light irradiated on the skin surface.
  • a beam of parallel white light generated by the LED at the tip of the probe passes through a flat reflector and then strikes the skin surface at an angle of 60°.
  • a part of the light is directly reflected at the same angle and then passes through a flat reflector to a receiving sensor.
  • Another part of the light is scattered by the skin surface and then received by another sensor.
  • the skin gloss test probe GL200 can not only test the light directly reflected by the skin related to the gloss, but also the light scattered by the skin.
  • test environment temperature is 22 ⁇ 1°C
  • humidity is 50 ⁇ 5%
  • real-time dynamic detection is carried out
  • -Test volunteers at least 30 effective volunteers, aged between 16-65 years (except pregnant or breastfeeding women); the basic value of the capacitance method for skin moisture determination of the forearm test area is between 15-100; none Severe systemic diseases, no immunodeficiency or autoimmune diseases; no previous history of severe allergies to skin care cosmetics; no use of hormone drugs or immunosuppressants in the past month; no other clinical trials; use according to regulations
  • the tested drug and the data are complete; all volunteers should fill in the informed consent form before the test.
  • Preparation before the test Do not use any products (cosmetics or topical drugs) 2-3 days before the test site. Before the experiment, subjects need to agree to clean their hands and forearms for internal testing, and air dry them naturally. After cleaning, the subject's hands and forearms were measured and the measurement area was marked. Before the formal test, you should sit quietly in a room that meets the standards for at least 30 minutes, without drinking water, with the forearms exposed, and place in the test state, and stay relaxed.
  • Test process In the experiment, 3 ⁇ 3cm 2 test areas are marked on the inner sides of the left and right arms, and multiple areas can be marked on the same arm, with an interval of 1cm.
  • the test product and the blank control are randomly distributed on the left and right arms.
  • the GL200 probe was used to measure the gloss of the skin in the test area and the control area. Each area was measured 15 times in parallel. First measure the blank value of each test area and record it as G 0 , and then inject the sample into the membrane cloth according to the amount of 0.072ml sample/cm 2, and apply it to the test area for 20 minutes. After 20 minutes, remove the mask cloth and massage until the sample is completely absorbed.
  • the subject applied the test sample in the same area every day according to the above test method, and tested the skin gloss G n of the corresponding area on the 14th and 28th day without applying the test sample.
  • Test data According to the design of the experiment, the skin gloss at each time point was measured, and the increase in skin gloss at each time point was calculated.
  • Examples 1 to 3 can significantly improve skin gloss, indicating that the composition of the present invention has a significant effect in improving skin gloss; p ⁇ 0.05;
  • Examples 1 to 3 Compared with Comparative Example 3, Examples 1 to 3 have more significant effects in improving skin gloss, indicating that the composition of the present invention has better effects with the same content of active ingredients, indicating that the composition of the present invention has a reasonable and appropriate ratio.
  • Example 3 the effect of Example 3 is the most significant, indicating that the ratio and concentration are the most appropriate, and the effect of the obtained sample is significantly different from that of other groups, p ⁇ 0.05.

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Abstract

涉及护肤品技术领域，尤其涉及一种组合物及其在制备皮肤护理的产品中的应用。提供的组合物包括腺苷、夏雪片莲鳞茎提取物、透明质酸钠、含有糖蛋白、氨基酸的皮肤调理剂A以及含有谷氨酰胺基乙基咪唑的皮肤调理剂B。各组分相互配合，相互促进，从而实现了良好的补水保湿、恢复皮肤光泽、促进细胞能量合成。将该组合物用于制备化妆品，能够改善熬夜者肌肤的一系列问题。

Description

一种组合物及其在制备护理熬夜者皮肤产品中的应用 技术领域
本发明涉及护肤品技术领域，尤其涉及一种组合物及其在制备护理熬夜者皮肤的产品中的应用。
背景技术
现代社会，出于生活和工作的种种因素，人们的入睡时间越来越晚。中国医师协会睡眠医学专业委员发布的《2018中国睡眠指数》报告显示，3/4的“90后”是在晚上11点后入睡，1/3是在凌晨1点入睡，晚睡晚起的“猫头鹰型”和晚睡早起的“蜂鸟型”作息占到六成以上。经常熬夜，不但会导致人们抵抗力下降，记忆力减退，还会直接表现在皮肤上来。
熬夜造成的皮肤的问题主要包括：
1、皮肤油脂分泌过多：熬夜会影响人体正常的内分泌，导致皮肤的新陈代谢出现紊乱，表征为皮脂腺收到刺激，从而导致大量的油脂产生，如果清洗不及时的话，就容易因为油脂过多造成毛孔堵塞，从而造成痘痘和粉刺的生成。
2、皮肤干燥：当皮肤的皮脂腺功能正常时，皮脂腺分泌的皮脂覆盖在皮肤的表面，从而减少皮肤水分的散失；当长期熬夜后内分泌紊乱造成皮肤的皮脂分泌较少时，皮肤的水分散失量会加大，皮肤的水分含量下降加快，从而导致皮肤的干燥加剧。
3、皮肤粗糙：深夜是皮肤进行自我修复的重要阶段。但是熬夜过程中，原本用于维持细胞进行新陈代谢，自我修复及更新的能量被用于熬夜的机理消耗，机体没有更多的能量参与细胞修复。因此皮肤衰老速度会加快，皮肤容易变得粗糙。
4、肤色暗沉：由于皮肤细胞没有及时地进行自我修复及更新，导致细胞的衰亡，细胞衰亡的过程中会释放出一些炎症因子，炎症因子会将黑色素细胞活化，从而使黑色素细胞生成黑色素，最终导致皮肤色素的沉着。皮肤细胞的衰亡，如果没有及时得到更新，皮肤的组织结构将会受损，从而导致皮肤失去光泽，造成皮肤暗沉。
5、黑眼圈及眼部浮肿
夜晚是人体生理的休息时间，也是各种机体的修复和代谢的重要时间，熬夜导致的机体的修复和代谢出现紊乱，代谢后的产物没能及时地排除体外，血液中的代谢产物增多，局部的血液循环不畅，在皮肤比较薄的眼眶区域，造成黑眼圈和眼袋加重。
目前，针对熬夜皮肤的护理的护肤品种类较少，有些组方以补水保湿或促进血液循环，加快新陈代谢为主；而另一些组方以中草药提取物为活性成分，但具体的功效并不明确。可见，目前有限的用于熬夜皮肤或者局部如眼眶护理的产品，并没有从熬夜对皮肤的伤害的机理出发。
发明内容
有鉴于此，本发明要解决的技术问题在于提供一种组合物及其在制备护理熬夜者皮肤的产品中的应用，本发明的组合物具有良好的补水保湿效果，并且能够恢复皮肤光泽、促进细胞能量合成。
本发明提供的组合物，包括如下质量份的组分：
Figure PCTCN2020112457-appb-000001
所述皮肤调理剂A包括如下质量分数的：
Figure PCTCN2020112457-appb-000002
所述皮肤调理剂B包括如下质量分数的：
谷氨酰胺基乙基咪唑     1％
防腐剂                 0.4％
余量为水。
所述皮肤调理剂A中的防腐剂为苯氧乙醇和乙基己基甘油，二者的质量比为1：1。
所述皮肤调理剂A中稳定剂为焦亚硫酸钠。
皮肤调理剂B中的防腐剂为山梨酸和苯氧乙醇，二者的质量比为1:3。
本发明中，所述透明质酸钠由如下质量分数的组分组成：
分子量为210万的透明质酸钠     14.6％；
分子量为130万的透明质酸钠     23.6％；
水解透明质酸钠                61.8％。
一些实施例中，所述的组合物由如下质量份的组分组成：
Figure PCTCN2020112457-appb-000003
一些实施例中，所述的组合物由如下质量份的组分组成：
Figure PCTCN2020112457-appb-000004
一些实施例中，所述的组合物由如下质量份的组分组成：
Figure PCTCN2020112457-appb-000005
本发明以熬夜皮肤的状态为研究对象，以皮肤的生物节律机理和皮肤修复为背景制备组合物。在皮肤的生物节律调整方面：以皮肤调理剂B(含有生物节律肽)对皮肤的生物钟基因进行调节，促进角质细胞的的修复及增殖， 促进维生素D的合成，激活维生素D转化从而激活皮肤的屏障能力；采用富含糖蛋白、谷氨酸、缬氨酸、苏氨酸的皮肤调理剂B促进糖降解和线粒体呼吸，确保皮肤细胞的ATP整天处于高水平，日间有足够的能量供给细胞用于抵御外界不利因素；确保夜间皮肤细胞需要修复时，有足够的能量供给；并添加腺苷，直接补充细胞所需要的能量。皮肤修复方面：添加透明质酸(含有210万、130万、水解透明质酸)和腺苷，调试出从细胞修复、角质层补水、表皮锁水三个维度进行补水保湿的组合，并添加具有强效细胞修复功效的夏雪片莲鳞茎提取物，抑制黑色素细胞的增殖，减少黑色素的生成，避免黑色素沉积导致的皮肤暗沉。本发明组合物中各组分相互配合，相互促进，起到了良好的增效协同作用。
本发明所述的组合物在制备护理熬夜者皮肤的护肤品中的应用。
所述护肤品的功能包括：补水保湿、恢复皮肤光泽、促进细胞能量合成。
本发明还提供了一种护理熬夜者皮肤的护肤品，包括本发明所述的组合物。
本发明所述的护肤品中，所述的组合物的质量分数为1％～7.5％。
一些具体实施例中，所述组合物的质量分数为1％、2.3％、7.5％。
本发明所述的护肤品包括：
Figure PCTCN2020112457-appb-000006
本发明所述的护肤品中，
所述保湿剂为甘油和1,3丁二醇，所述甘油和1,3丁二醇的质量比为1：1；
所述促渗剂为戊二醇；
所述角质软化剂为羟乙基哌嗪乙烷磺酸；
所述防腐剂为PHL。
本发明所述的护肤品由如下质量分数的组分组成：
Figure PCTCN2020112457-appb-000007
Figure PCTCN2020112457-appb-000008
所述皮肤调理剂A包括如下质量分数的：
Figure PCTCN2020112457-appb-000009
所述皮肤调理剂B包括如下质量分数的：
谷氨酰胺基乙基咪唑     1％
防腐剂                 0.4％
余量为水。
一些实施例中，所述化妆品由如下组分组成：
Figure PCTCN2020112457-appb-000010
Figure PCTCN2020112457-appb-000011
一些实施例中，所述化妆品由如下组分组成：
Figure PCTCN2020112457-appb-000012
一些实施例中，所述化妆品由如下组分组成：
Figure PCTCN2020112457-appb-000013
本发明所述护肤品为化妆水、乳液、膏霜、面膜、精华、凝胶等。
本发明所述护肤品的制备方法，包括：
将羟乙基哌嗪乙烷磺酸、透明质酸钠、腺苷，加入去离子水加热至75℃ ～80℃，250～300r/min搅拌溶解20min；
加入甘油、1,3-丁二醇、戊二醇，温度控制为65～75℃，300r/min搅拌溶解15min；
加入夏雪片莲鳞茎提取物、皮肤调理剂A、皮肤调理剂B和PHL，温度控制35～45℃，100r/min搅拌15min，然后冷却至室温制得护肤品。
本发明提供的组合物包括腺苷、夏雪片莲鳞茎提取物、透明质酸钠、含有糖蛋白、氨基酸的皮肤调理剂A以及含有谷氨酰胺基乙基咪唑的皮肤调理剂B。各组分相互配合，相互促进，从而实现了良好的补水保湿、恢复皮肤光泽、促进细胞能量合成。将该组合物用于制备化妆品，能够改善熬夜者肌肤的一系列问题。
附图说明
图1示各样品对细胞的能量合成量的影响；
图2示各样品的即时补水效果；
图3示各样品的长效补水效果；
图4示各样品对皮肤水分散失量的短期效果；
图5示各样品对皮肤水分散失量的长期效果；
图6示各样品对皮肤光泽度的影响。
具体实施方式
本发明提供了一种组合物及其在制备护理熬夜者皮肤的产品中的应用，本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文的方法和应用进行改动或适当变更与组合，来实现和应用本发明技术。
本发明采用的试材皆为普通市售品，皆可于市场购得。
如下实施例中，所采用的皮肤调理剂A的组成为：
Figure PCTCN2020112457-appb-000014
Figure PCTCN2020112457-appb-000015
所采用的皮肤调理剂B的组成为：
Figure PCTCN2020112457-appb-000016
其中谷氨酰氨基乙基咪唑的结构式为:
Figure PCTCN2020112457-appb-000017
所述夏雪片莲鳞茎提取物，以休眠期的夏雪片莲鳞茎为原材料进行提取，主要的活性成分为脱落酸，本发明采用的夏雪片莲鳞茎提取物的组成为：
Figure PCTCN2020112457-appb-000018
所述透明质酸钠又称为三分子玻尿酸，其组成为：
分子量为210万的透明质酸钠   14.6％；
分子量为130万的透明质酸钠   23.6％；
水解透明质酸钠              61.8％。
本发明实施例中，所采用的皮肤调理剂A、皮肤调理剂B和夏雪片莲鳞茎提取物皆购自市场，商品名依次为
Figure PCTCN2020112457-appb-000019
和IBR
Figure PCTCN2020112457-appb-000020
下面结合实施例，进一步阐述本发明：
实施例
各组配方如表1：
表1各组配方含量(％)
Figure PCTCN2020112457-appb-000021
按照配方配比称取羟乙基哌嗪磺酸、透明质酸钠、腺苷，加入去离子水加热至75-80℃，以250-300r/min,搅拌20min,直至溶解透明；
按照配方配比加入甘油、1,3-丁二醇、戊二醇，温度控制为65-75℃，以300r/min，搅拌15min,直至所有添加物全部溶解；
按照配比称取夏雪片莲鳞茎提取物、皮肤调理剂A、皮肤调理剂B和PHL,温度控制45℃以下，以100r/min，搅拌15min,静置恢复到室温即可。
功效评测
皮肤组织的生理活性由生物节律严格控制。在日间，皮肤细胞主要致力于皮肤的天然防御(抵抗UV、抗污染等)；在夜间着重于细胞的修复和代谢。研究发现，皮肤生物钟基因，如：CLOCK和PERIOD-1，与角质形成细胞、成纤维细胞和黑色素细胞等的增殖活动相关。不规律的生物节律会使得生物钟基因的周期性激活被改变，从而导致皮肤生理代谢的变化。皮肤的生理代谢出现变化后，日间皮肤抵御外界不利因素的能力下降，将导致皮肤受到的 损伤加大；夜间皮肤细胞进行自我修复的能力将变弱，最终导致皮肤的屏障受损，表征为皮肤的水分含量不断降低，水分散失量加大，皮肤的光泽度不断下降。皮肤细胞的损伤也将导致细胞合成的ATP含量不断下降。本发明从细胞能量变化、补水效果、皮肤水分散失量以及皮肤光泽度改善四个方面来衡量组合物的功效。
1)细胞能量的增加量
三磷酸腺苷(adenosine 5’-triphosphate,ATP)是生物体内能量装换最基本的载体，其含量的变化直接关系到各器官的能量代谢。ATP作为最重要的能量分子在细胞的各种生理、病理过程中起着重要的作用。ATP水平的改变会影响细胞的功能。通常细胞在凋亡、坏死或处于一些毒性状态下，ATP水平会下降。在细胞凋亡时ATP水平的下降通常和线粒体的膜电位下降同时发生。ATP含量测定试剂盒可以用于检测细胞内的ATP水平。
实验仪器：酶标仪、水浴锅、移液枪、离心机、96孔板、ATP含量检测试剂盒
实验材料:角质形成细胞，DMEM，FBS，DPBS
实验方法：
1.将角质形成细胞消化后，利用DMEM培基分散细胞，利用Hemacytometer来计数细胞，然后利用DMEM来稀释细胞，稀释到浓度为5×10 4cells/ml。
2.稀释后的细胞溶液分别接种到培养皿中。
3.在37℃，5％CO 2的培养箱中培养24小时。
4.待测样品准备：待测样品用DMEM培基稀释，稀释后浓度分别为0.1％，样品均准备10ml。
5.细胞培养24小时后，观察细胞是否完全贴壁生长，如果细胞完全贴壁生长的话，将原培基移除，用DPBS洗涤。
6.将DPBS移除之后，分别加入前面准备好的含有0.1％待测样品的培养基.
7.样品加入之后，放入37℃，5％CO 2的培养箱中培养48小时。
-角质形成细胞收集及处理：细胞收集后，离心去掉培养基，加入0.5ml双蒸馏水，混合均匀。将细胞水溶液放置于废水中加热煮10分钟，漩涡混匀 1分钟；4000rpm条件下离心10分钟，取上清液待测。
-具体试剂及操作步骤如下：
实验试剂：
试剂一：底物液1为粉体，使用时加10ml蒸馏水溶解，沸水中加热溶解
试剂二：底物液2为液体，直接使用
试剂三：促进剂，使用时将稀释液加入到粉剂中配置成溶液
试剂四：沉淀剂
试剂五：显色剂，使用时将甲液加入到乙液中，混合均匀后待用
试剂六：终止剂
ATP标准品：用DDW配置成1mMATP标准品溶液
检测体系配制：
表2检测体系
Figure PCTCN2020112457-appb-000022
混合均匀，室温中静置反应5分钟，分别从各待测样管、对照管、标准管和空白管中移取200μL样品到96孔板上，于630nm波长处测试吸光度。
因此可得到各测试样品细胞的ATP的含量为：ATP含量(μmol)＝[(A 测定管-A对照管)/(A标准管-A空白)]×标准品浓度×稀释倍数
-各测试样品的细胞能量的增长量：
-ATP Increase(％)＝(ATP n-ATP 0)/ATP 0×100％(其中ATP n为各测试样品的细胞能量，ATP 0为空白样的细胞能量)
实验结果：
表3专利组合促进细胞的能量合成量
  细胞能量的增长量(％)
对照样-1 12.47
对照样-2 78.35
对照样-3 102.40
实例样-1 146.62
实例样-2 120.37
实例样-3 164.32
实验结果：通过细胞的能量的测试结果可知，对照样-1几乎没有促进细胞能量增长的功效，随着促进细胞能量的物质的添加，实例样1～3可以将细胞的能量提升120.37％～164.32％。细胞能量的提升有助于受损的皮肤状态的修复。经统计学分析：
相对于对比例1，实施例1～3能够显著的提高细胞能量，说明本发明的组合物在提高细胞能量方面存在显著的功效；p<0.05；
相对于对比例2，实施例1～3在提高细胞能量方面的效果更显著，说明本发明的组合物组成更加合理，各组分缺一不可，相互配合产生了显著的增效协同作用；
相对于对比例3，实施例1～3在提高细胞能量方面效果更显著，说明同等有效成分含量下，本发明组合物效果更好，说明本发明组合物的配比合理得当。
各样品中，实施例3的效果最为显著，说明该配比及浓度最为适宜，所得样品的效果与其他各组皆产生了显著差异，p<0.05。
2)皮肤的即时及长效补水效果
-测试仪器：德国CK公司多功能皮肤测试仪，型号Corneometer CM825MDD，
-测试原理：采用电容法测试人体皮肤角质层的水分含量，它的原理是基于水和其他物质的介电常数差异显著，按照皮肤含水量不同，测得皮肤的电容值不同，其观测参数可代表皮肤水分值。
-测试环境：测试环境温度为22±1℃，湿度为50±5％，并且进行实时动态检测；
-测试志愿者：有效志愿者至少30人，年龄在16-65岁之间(妊娠或哺乳期妇女除外)；前臂测试区域电容法皮肤水分测定意义的基础值在15-100之间；无严重系统疾病，无免疫缺陷或自身免疫性疾病者；既往对护肤类化妆品无严重过敏史者；近一个月内未曾使用激素类药物及免疫抑制剂者；未参加其他临床试验者；按规定使用受试药物且资料齐全；测试前所有自愿者应填写知情同意书。
-测试步骤：
测试前准备：受试部位前2-3天不能使用任何产品(化妆品或外用药品)。实验前，受试者需要同意清洁双手前臂内测，自然风干。清洁后受试者双手前臂内测做好测量区域标记。正式测试前应在符合标准房间内静坐至少30min，不能喝水，前臂暴露，呈测试状态放置，保持放松。
测试过程：实验中左右手臂内侧标记3×3cm 2试验区域，同一手臂可以标记多个区域，区域间隔1cm。测试产品和空白对照均随机分布在左右手臂上。使用探头Corneometer CM825 MDD进行受试区域和对照区域的皮肤水分含量测量。每个区域依照平行测定15次。先测量各测试区域的空白值，然后按0.072ml样品/cm 2的用量，将样品注入到膜布中，并敷在试验区内，时间为20分钟。20分钟后揭掉面膜布，10分钟后测试该区域皮肤水分含量，即为30分钟时皮肤的水分含量。之后分别测量1小时，2小时，受试区域和空白对照区域的皮肤含水量(验证时按此时间测定)，同一个志愿者的测试由同一个测量人员完成。
对于长效补水的测试，受试者每天在同一区域按照上述测试方法自行进行涂抹测试样品，并在第14、28天时在不涂抹待测样品的情况下，测试皮肤的水分含量。
测试数据：按实验的设计分别测得各时间段的皮肤水分含量，并计算各个时间点的皮肤水分含量的增加量。
Figure PCTCN2020112457-appb-000023
实验结果：
2.1)即时补水结果
表4即时补水效果
Figure PCTCN2020112457-appb-000024
结果：从即时的补水效果来看，对照样-1为基础配方具有一定的补水效果，水分含量增加量为108.1％。实例样-1在30分钟时皮肤的水分含量增加到169.0％，120分钟时补水效果仍有175.5％左右，即时补水效果明显，持续时间较长。
2.2)长效补水效果
表5长效补水效果
Figure PCTCN2020112457-appb-000025
结果：从长效的补水效果来看，持续的使用专利样的话，皮肤的水分含量会有一个增长的过程，在28天时皮肤的水分含量增长约18.02％。同时也侧面的反应了皮肤的屏障功能得到修复，使皮肤的水分含量得到提升。
相对于对比例1实施例1～3能够显著的提高补水效果(长效、即时)，说明本发明的组合物在补水(长效、即时)能力方面存在显著的功效；p<0.05；
相对于对比例2，实施例1～3在补水(长效、即时)方面的效果更显著，说明本发明的组合物组成更加合理，各组分缺一不可，相互配合产生了显著的增效协同作用；
相对于对比例3，实施例1～3在补水(长效、即时)方面效果更显著，说明同等有效成分含量下，本发明组合物效果更好，说明本发明组合物的配比合理得当。
各样品中，实施例3的效果最为显著，说明该配比及浓度最为适宜，所得样品的效果与其他各组皆产生了显著差异，p<0.05。
3)皮肤的屏障修复效果(TEWL值)
-测试仪器：德国CK公司多功能皮肤测试仪，探头型号Tewameter TM300，
-测试原理：FICK菲克扩散定律：dm/dt＝D.A.dp/dx。通过两组温度、湿度传感器测定近表皮(约1cm内)由角质层水分散失在不同亮点形成的水蒸气压梯度，直接测出经皮散发的水分量。TEWL值是皮肤屏障好坏的一个重要标志，皮肤的TEWL值越低，说明皮肤的屏障功能越好，反之越差。
-测试环境：测试环境温度为22±1℃，湿度为50±5％，并且进行实时动态检测；
-测试志愿者：有效志愿者至少30人，年龄在16-65岁之间(妊娠或哺乳期妇女除外)；无严重系统疾病，无免疫缺陷或自身免疫性疾病者；既往对护肤类化妆品无严重过敏史者；近一个月内未曾使用激素类药物及免疫抑制剂者；未参加其他临床试验者；按规定使用受试药物且资料齐全；测试前所有自愿者应填写知情同意书。
-测试步骤：
测试前准备：受试部位前2-3天不能使用任何产品(化妆品或外用药品)。实验前，受试者需要同意清洁双手前臂内测，自然风干。清洁后受试者双手前臂内测做好测量区域标记。正式测试前应在符合标准房间内静坐至少30min，不能喝水，前臂暴露，呈测试状态放置，保持放松。
测试过程：实验中左右手臂内侧标记3×3cm 2试验区域，同一手臂可以标记多个区域，区域间隔1cm。测试产品和空白对照均随机分布在左右手臂上。使用探头Tewameter TM300进行受试区域和对照区域的皮肤水分散失量测量。每个区域依照平行测定15次。先测量各测试区域的空白值，然后按0.072ml样品/cm 2的用量，将样品注入到膜布中，并敷在试验区内，时间为20分钟。20分钟后揭掉面膜布，10分钟后测试该区域皮肤水分散失含量，即为30分钟时皮肤的水分散失量。之后分别测量1小时，2小时，受试区域和空白对照区域的皮肤水分散失量，同一个志愿者的测试由同一个测量人员完成。
对于长效的屏障修复的测试，受试者每天在同一区域按照上述测试方法自行进行涂抹测试样品，并在第14、28天时在不涂抹待测样品的情况下，测试皮肤的水分散失量TEWL。
测试数据：按实验的设计分别测得各时间段的皮肤水分散失量，并计算各个时间点的皮肤水分散失量的减少量。皮肤水分散失量的减少量越大，皮肤屏障修复的效果越好。
Figure PCTCN2020112457-appb-000026
实验结果：
3.1)即时屏障修复效果
表6即时皮肤水分散失量的减少量
Figure PCTCN2020112457-appb-000027
结果：从皮肤水分散失量的减少量来看，对照样-1为基础样具有一定的降低皮肤水分散失量的效果，30分钟时，皮肤的水分散失量的减少为4.62％，专利样的皮肤的水分散失量的减少量达到11.53％，显著降低了皮肤的水分散 失量，体现了皮肤屏障的修复的效果。
3.2)长效屏障修复效果
表7长效皮肤水分散失量的减少量
Figure PCTCN2020112457-appb-000028
结果：从长效的皮肤水分散失量的减少量的结果来看，持续28天实例样-1的使用，使得皮肤的水分散失量的减少量达到18.93％，即皮肤的水分散失量在不断的减少，体现了皮肤的屏障功能得到了有效的修复。
相对于对比例1实施例1～3能够显著的提高保湿效果(长效、即时)，说明本发明的组合物在保湿(长效、即时)能力方面存在显著的功效；p<0.05；
相对于对比例2，实施例1～3在保湿(长效、即时)方面的效果更显著，说明本发明的组合物组成更加合理，各组分缺一不可，相互配合产生了显著的增效协同作用；
相对于对比例3，实施例1～3在保湿(长效、即时)方面效果更显著，说明同等有效成分含量下，本发明组合物效果更好，说明本发明组合物的配比合理得当。
各样品中，实施例3的效果最为显著，说明该配比及浓度最为适宜，所得样品的效果与其他各组皆产生了显著差异，p<0.05。
4)皮肤光泽度的改善
-测试仪器：德国CK公司多功能皮肤测试仪，型号GL200
-测试机理：
皮肤表面光泽度是由照射到皮肤表面的光的直接反射和散反射来反映的。在探头顶端由LED产生的一束平行白光通过一个平面反射镜后以60°角 射向皮肤表面，一部分光以同样角度被直接反射后通过一个平面反射镜射向一个接收传感器。另一部分光被皮肤表面散射后被另一个传感器接收。这样皮肤光泽度测试探头GL200不仅能测试与光泽度有关的被皮肤直接反射的光，也能够测试被皮肤散射的光。
-测试环境：测试环境温度为22±1℃，湿度为50±5％，并且进行实时动态检测；
-测试志愿者：有效志愿者至少30人，年龄在16-65岁之间(妊娠或浦乳期妇女除外)；前臂测试区域电容法皮肤水分测定意义的基础值在15-100之间；无严重系统疾病，无免疫缺陷或自身免疫性疾病者；既往对护肤类化妆品无严重过敏史者；近一个月内未曾使用激素类药物及免疫抑制剂者；未参加其他临床试验者；按规定使用受试药物且资料齐全；测试前所有自愿者应填写知情同意书。
-测试步骤：
测试前准备：受试部位前2-3天不能使用任何产品(化妆品或外用药品)。实验前，受试者需要同意清洁双手前臂内测，自然风干。清洁后受试者双手前臂内测做好测量区域标记。正式测试前应在符合标准房间内静坐至少30min，不能喝水，前臂暴露，呈测试状态放置，保持放松。
测试过程：实验中左右手臂内侧标记3×3cm 2试验区域，同一手臂可以标记多个区域，区域间隔1cm。测试产品和空白对照均随机分布在左右手臂上。使用探头GL200进行受试区域和对照区域的皮肤的光泽度进行测量。每个区域依照平行测定15次。先测量各测试区域的空白值记为G 0，然后按0.072ml样品/cm 2的用量，将样品注入到膜布中，并敷在试验区内，时间为20分钟。20分钟后揭掉面膜布，按摩至样品完全吸收即可。受试者每天在同一区域按照上述测试方法自行进行涂抹测试样品，并在第14、28天时在不涂抹待测样品的情况下，测试相应区域皮肤的光泽度G n。
测试数据：按实验的设计分别测得各时间点皮肤的光泽度，并计算各个时间点的皮肤光泽度的增加量。
皮肤光泽度的增加量(％)＝(G n-G 0)/G 0×100％
实验结果：
表8肤光泽度的增加量
Figure PCTCN2020112457-appb-000029
实验结果：从皮肤光泽度的增加量的结果来看，持续28天实例样-1的使用，使得皮肤的光泽度提升13.68％，即皮肤的光泽度得到有效提升，体现了皮肤的屏障功能得到了有效的修复。
相对于对比例1实施例1～3能够显著的提高皮肤光泽度，说明本发明的组合物在提高皮肤光泽度方面存在显著的功效；p<0.05；
相对于对比例2，实施例1～3在提高皮肤光泽度方面的效果更显著，说明本发明的组合物组成更加合理，各组分缺一不可，相互配合产生了显著的增效协同作用；
相对于对比例3，实施例1～3在提高皮肤光泽度方面效果更显著，说明同等有效成分含量下，本发明组合物效果更好，说明本发明组合物的配比合理得当。
各样品中，实施例3的效果最为显著，说明该配比及浓度最为适宜，所得样品的效果与其他各组皆产生了显著差异，p<0.05。
以上仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。

Claims (10)

  1. 一种组合物，包括如下质量份的组分：
    Figure PCTCN2020112457-appb-100001
    所述皮肤调理剂A包括如下质量分数的：
    Figure PCTCN2020112457-appb-100002
    所述皮肤调理剂B包括如下质量分数的：
    谷氨酰胺基乙基咪唑     1％
    防腐剂                 0.4％
    余量为水。
  2. 根据权利要求1所述的组合物，其特征在于，所述透明质酸钠由如下质量分数的组分组成：
    分子量为210万的透明质酸钠     14.6％；
    分子量为130万的透明质酸钠     23.6％；
    水解透明质酸钠                61.8％。
  3. 权利要求1或2所述的组合物在制备护理熬夜者皮肤的护肤品中的应用。
  4. 根据权利要求3所述的应用，其特征在于，所述护肤品的功能包括：补水保湿、恢复皮肤光泽、促进细胞能量合成。
  5. 一种护理熬夜者皮肤的护肤品，其特征在于，包括权利要求1或2所 述的组合物。
  6. 根据权利要求5所述的护肤品，其特征在于，权利要求1或2所述的组合物的质量分数为1％～7.5％。
  7. 根据权利要求5所述的护肤品，其特征在于，包括：
    Figure PCTCN2020112457-appb-100003
  8. 根据权利要求7所述的护肤品，其特征在于，
    所述保湿剂为甘油和1,3丁二醇，所述甘油和1,3丁二醇的质量比为1：1；
    所述促渗剂为戊二醇；
    所述角质软化剂为羟乙基哌嗪乙烷磺酸；
    所述防腐剂为PHL。
  9. 根据权利要求7所述的护肤品，其特征在于，由如下质量分数的组分组成：
    Figure PCTCN2020112457-appb-100004
    所述皮肤调理剂A包括如下质量分数的：
    Figure PCTCN2020112457-appb-100005
    Figure PCTCN2020112457-appb-100006
    所述皮肤调理剂B包括如下质量分数的：
    谷氨酰胺基乙基咪唑      1％
    防腐剂                  0.4％
    余量为水。
  10. 权利要求5～9任一项所述的护肤品的制备方法，包括：
    将羟乙基哌嗪乙烷磺酸、透明质酸钠、腺苷，加入去离子水加热至75℃～80℃，250～300r/min搅拌溶解20min；
    加入甘油、1,3-丁二醇、戊二醇，温度控制为65～75℃，300r/min搅拌溶解15min；
    加入夏雪片莲鳞茎提取物、皮肤调理剂A、皮肤调理剂B和PHL，温度控制35～45℃，100r/min搅拌15min，然后冷却至室温制得护肤品。
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