Composition for resisting skin hypoxia and application thereof

Abstract

The invention relates to a composition for resisting skin hypoxia and application thereof. The composition is prepared from sea buckthorn fruit oil, natural vegetable fat and water-soluble components, the palmitoleic acid content of the sea buckthorn fruit oil is greater than 4mg / mL. In the hypoxia state of the skin, by smearing the traditional Chinese medicine composition on the surface of the skin, HIF-1alpha is activated, the oxygen uptake capacity of skin epidermis cells is improved, the effects of increasing the oxygen content of the skin, resisting inflammation, relieving, moisturizing and nourishing are achieved, and the adverse effect of hypoxia on the skin state is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of skin care products, and particularly relates to a composition for resisting skin hypoxia and application thereof. Background Art

[0002] The problem of skin hypoxia is widely present in people's daily lives and in the occurrence and development of related diseases. When the oxygen content in the external environment where skin cells are located is insufficient, the normal function of epidermal cells will be affected, such as stagnation of cell growth and differentiation, abnormal metabolism and acid-base balance, etc. Skin hypoxia is usually caused by skin vascular dysfunction. Skin blood flow accounts for about 8.5% of the total body blood flow. The blood supply enters the dermis through the subcutaneous tissue and forms a vascular network, providing oxygen, nutrition, blood storage and participating in body temperature regulation for the skin. Changes in the external environment and insufficient oxygen supply capacity of the skin's microvessels cause the skin to be in a state of hypoxia, leading to inflammation, damage or necrosis of skin tissue, further destroying the skin's vascular oxygen supply capacity and skin oxygen homeostasis.

[0003] In daily life, the skin may be in a state of mild hypoxia due to long periods of sitting, lying down, restricted clothing or being at high altitudes; severe skin hypoxia may lead to the occurrence of some hypoxia-related skin diseases.

[0004] Mild skin hypoxia can affect the health of the skin. For example, the low oxygen environment in high altitude areas reduces the oxygen saturation of the human blood, causing the skin to be in a state of hypoxia, which damages the health of the skin and increases the incidence of skin diseases. In addition, under hypoxic conditions, the strength and density of the skin's blood vessels decrease, causing the skin to lose elasticity; the integrity of the blood vessel walls is damaged, and tissue fluid extravasation accumulates, aggravating skin pigmentation and making the skin more sensitive; the fluidity of the skin's blood decreases under hypoxic conditions, and the ability to remove metabolic waste decreases, causing the skin to become dull.

[0005] Severe skin hypoxia can lead to skin diseases. For example, pressure sores (also known as pressure ulcers or pressure injuries) occur due to long-term compression of local bony protrusions of human tissue, which leads to blood flow obstruction and produces skin epidermal hypoxia and deep skin tissue necrosis. Diabetic patients have lesions in the blood vessels and nerve tissues of the feet beyond the ankle joint, leading to insufficient blood supply to the feet, paresthesia, and symptoms such as ulcers and infections, forming diabetic foot, which is also closely related to skin hypoxia. For example, the cause of livedo reticularis is the continuous pathological expansion and contraction of skin blood vessels, which leads to lesions of the vascular wall, accumulation of hypoxic blood in the local venous plexus, and prominence of the vascular structure, forming red-blue or violet reticular livedo on the skin surface. Congestive dermatitis is also related to skin hypoxia. Microvascular lesions hinder the delivery of oxygen and nutrients to the skin epidermis, leading to skin inflammation.

[0006] Therefore, solving the problem of skin hypoxia is crucial to relieve various skin diseases and keep the skin healthy and beautiful. However, the current means of dealing with skin hypoxia are still very limited. Treatments such as oxygen inhalation and hyperbaric oxygen mainly solve the problem of systemic hypoxia in the human body, but cannot directly and quickly deal with skin epidermal hypoxia. In addition, there are problems such as inconvenience in use and high cost. Summary of the invention

[0007] The technical problem to be solved by the present invention is to provide a composition for resisting skin hypoxia and its application. When the skin is in a state of hypoxia, the composition is applied to the skin surface to activate hypoxia-inducible factor-1α (HIF-1α), thereby improving the oxygen uptake capacity of skin epidermal cells, thereby increasing the oxygen content of the skin, resisting inflammation, soothing, moisturizing and nourishing, and improving the adverse effects of hypoxia on the skin condition.

[0008] The invention provides a composition for resisting skin hypoxia, comprising seabuckthorn fruit oil, natural plant oil and water-soluble components; the palmitoleic acid content of the seabuckthorn fruit oil is greater than 4 mg / mL.

[0009] The seabuckthorn fruit oil contains a variety of unsaturated fatty acids and vitamins, especially rich in C16:1 (Omega-7) palmitoleic acid, which can increase the intracellular oxygen content of skin epidermal cells under hypoxic conditions by upregulating the cell HIF-1α transcription factor, thereby improving the vitality of skin cells.

[0010] The C16:1 (Omega-7) palmitoleic acid content of the seabuckthorn fruit oil should be greater than 4 mg / mL, and the determination method is methyl esterification derivatization followed by gas chromatography-mass spectrometry. In brief summary, firstly, a mixed solvent of chloroform and methanol in a ratio of 2:1 (v / v) is used to extract lipids in the seabuckthorn fruit oil sample. Then, a certain concentration of boron trifluoride methanol (BF3-CH3OH) solution is added to the lipid extract and heated, and the lipid undergoes an esterification reaction under the catalysis of boron trifluoride methanol to generate low-polarity fatty acid methyl esters. Then, the n-hexane liquid-liquid extraction method is used for extraction, enrichment, and injection into a gas chromatography-mass spectrometer for analysis. Quantitative analysis is performed using the internal standard method using tridecanoic acid as the internal standard.

[0011] The seabuckthorn fruit oil is a light yellow clear oily liquid obtained by supercritical extraction of seabuckthorn fruit, centrifugation to obtain the upper oil portion, and then decolorization by activated white earth adsorption and removal of impurities.

[0012] Preferably, the natural plant oil comprises one or more of corn germ oil, algae oil, meadowfoam seed oil, moringa seed oil, and peony seed oil.

[0013] Preferably, the water-soluble component includes one or more of oat kernel powder, olive leaf extract, tetrahydrocurcumin, salvia miltiorrhiza root extract, and sulphanol.

[0014] The present invention selects and screens a series of natural plant oils and water-soluble components with anti-inflammatory and soothing effects and mixes them with seabuckthorn fruit oil to form an oily or watery dosage form according to actual application needs.

[0015] According to some embodiments of the present invention, natural plant oils such as corn germ oil, algae oil, meadowfoam seed oil, moringa seed oil, and peony seed oil contain a variety of unsaturated fatty acids, especially oleic acid, linoleic acid, linolenic acid, and docosahexaenoic acid (DHA). These oils can inhibit the secretion of inflammatory factors in epidermal cells under hypoxic conditions, promote epidermal cell migration and proliferation activity, and improve skin barrier function, thereby helping the skin to resist inflammation, soothe, moisturize, and nourish under hypoxic conditions. It is particularly suitable for use in oily anti-skin hypoxia preparations.

[0016] According to some embodiments of the present invention, oat kernel powder is rich in β-glucan, olive leaf extract is rich in oleuropein, curcumin isolated from the rhizome of the ginger plant turmeric (curcuma longa) is hydrogenated, salvia root extract is rich in tanshinone and salvianolic acid, and sulmoside is rich in various skin ceramides. These water-soluble or water-dispersible ingredients can be anti-inflammatory and soothing, inhibit bacteria and relieve itching, and promote the recovery of skin barrier function under skin hypoxia conditions. They are particularly suitable for use in water-based anti-skin hypoxia preparations.

[0017] Preferably, in terms of mass percentage, the composition comprises: 1%-10% seabuckthorn fruit oil, 0-90% natural plant oil and 0-40% water-soluble components.

[0018] More preferably, in terms of mass percentage, the composition comprises: 1%-10% seabuckthorn fruit oil, 0%-89.9% corn germ oil, 0%-6.5% seaweed oil, 0%-55% meadowfoam seed oil, 0%-5% moringa seed oil, 0%-50% peony seed oil, 0%-7% oat kernel powder, 0%-32% olive leaf extract, 0%-1% tetrahydrocurcumin, 0%-2.8% salvia miltiorrhiza root extract, and 0%-0.2% succinate.

[0019] More preferably, the mass percentage of the corn germ oil is 1%-85%.

[0020] More preferably, the mass percentage of the algae oil is 1%-5%.

[0021] More preferably, the mass percentage of the meadowfoam seed oil is 1%-30%.

[0022] More preferably, the mass percentage of the Moringa seed oil is 1%-5%.

[0023] More preferably, the mass percentage of the peony seed oil is 1%-40%.

[0024] More preferably, the mass percentage of the oat kernel fine powder is 1%-7%.

[0025] More preferably, the mass percentage of the olive leaf extract is 1%-25%.

[0026] More preferably, the mass percentage of the tetrahydrocurcumin is 0.1%-1%.

[0027] More preferably, the mass percentage of the Salvia miltiorrhiza root extract is 0.1%-2.8%.

[0028] More preferably, the mass percentage of sulbutamide is 0.1%-0.2%.

[0029] The invention provides application of a composition for resisting skin hypoxia in preparing a product for resisting skin hypoxia.

[0030] Preferably, the product includes one of functional skin care products, external skin medicines, medical devices, and chemical preparations.

[0031] Preferably, the functional skin care products include but are not limited to skin care oils and skin care lotions.

[0032] Preferably, the skin external medicine includes but is not limited to external ointment.

[0033] Preferably, the medical device includes but is not limited to medical hydrogel.

[0034] Furthermore, the product also includes other commonly used auxiliary ingredients.

[0035] When measuring the oxygen content in skin epidermal cells in vitro, Hydrogen peroxide detection kit detection. In brief, take two 6-well plates of HaCat cells in the logarithmic growth phase, add 2 mL of culture medium to each well, and culture them in normal oxygen and hypoxic incubators for 24 hours respectively. Then take out the cells and add 1:500 diluted The oxygen probe was returned to the cell culture incubator for incubation for 1 hour. After the incubation, the cells were taken out, the cells were enzymatically hydrolyzed with collagenase to suspend them, the cells were collected and the probes remaining in the cells were washed according to the instructions of the kit, and then the CytoFLEX flow cytometer was used to analyze the intensity of the fluorescence probe luminescence and the number of cells in the epidermal cells. The stronger the fluorescence, the lower the intracellular oxygen content, and the weaker the fluorescence, the higher the intracellular oxygen content. Therefore, the more cells with strong fluorescence, the more severe the degree of cell hypoxia; the fewer cells with strong fluorescence, the milder the degree of cell hypoxia. Under normal oxygen culture conditions, the percentage of cells emitting strong fluorescence should be less than 25%.

[0036] The DCFH-DA staining method was used to determine the intracellular ROS level. In short, HaCat cells were treated with 2,4-diphenylsulfonephenol (DBSPs) at a concentration of 125 μg / mL under normal oxygen and hypoxic culture conditions for 48 hours. After rinsing twice with PBS, the DCFH-DA probe was added to the cells and incubated at 37°C for 30 minutes according to the kit instructions. After observing the cells under a fluorescent inverted microscope, the fluorescence intensity was measured using a microplate reader. The higher the fluorescence intensity, the higher the intracellular ROS level; the lower the fluorescence intensity, the lower the intracellular ROS level. The composition preparation of the present invention can simultaneously increase the skin ROS to a normal level by increasing the skin oxygen content to a normal level when the skin is hypoxic, resulting in a decrease in skin ROS, without causing excessive accumulation of ROS. Under normal oxygen culture conditions, the fluorescence intensity density value of ROS should be around 40.

[0037] The hypoxic state after applying pressure to the skin was simulated by a magnetic mouse animal model. In short, after shaving the hair on the back of the C57BL / 6 mice, two cylindrical magnets with a magnetic force of 800Gs, a diameter of 10 mm, and a thickness of 3 mm were used to clamp the mouse back skin for 1-2 hours and then removed. The skin hypoxia state caused by pressure damage was simulated. By applying a preparation containing the composition on the back skin of the mouse, the hypoxia caused by the magnetic pressure on the back skin of the mouse was reduced, and the skin damage caused by it was alleviated.

[0038] When measuring skin oxygen content in vivo, a TCM4 transcutaneous oxygen partial pressure detector is used to detect the oxygen content of mouse or human skin. In simple terms, use 75% alcohol to clean the skin surface, stick the fixing ring to the skin surface, drip 5 drops of electrode liquid into the fixing ring, and then screw the transcutaneous oxygen partial pressure / transcutaneous carbon dioxide partial pressure combined electrode into the fixing ring and start monitoring. The higher the oxygen partial pressure, the higher the skin oxygen content; the lower the oxygen partial pressure (pO2), the lower the skin oxygen content. The normal pO2 of human and mouse skin is about 80-100mmHg. When the skin is hypoxic due to external pressure, the skin pO2 drops to 30-60mmHg.

[0039] When assessing the risk of human skin pressure injury (pressure sore) caused by hypoxia, the SEM Scanner pressure injury risk tester is used for measurement. In simple terms, when pressure injury (pressure sore) just causes hypoxia in skin tissue, skin cell damage begins, and skin erythema and wounds cannot be observed with the naked eye at this time. Increased subepidermal moisture (SEM) is one of the earliest signs of skin cell damage or even death. Therefore, SEM is a biomarker for skin pressure injury risk. When the SEM Scanner probe is placed close to the surface of human skin, the instrument will identify SEM and report it as SEMδ(Δ) value. SEMδ(Δ) value ≥ 0.6 indicates an increased risk of ruptured skin pressure injury. Thus, the SEM Scanner can distinguish between healthy skin tissue and damaged skin tissue, providing an objective and specific pressure injury risk measurement. When the skin is severely compressed and the degree of hypoxia is high, its SEMδ(Δ) value is higher; when the skin is relieved from pressure and the degree of hypoxia is reduced, its SEMδ(Δ) value decreases accordingly.

[0040] Under hypoxic conditions, after HIF-1α is activated and stably expressed by sea buckthorn oil, it will regulate a series of downstream target genes and improve the oxygen uptake capacity of epidermal cells. At the same time, other target genes related to inflammation will also be upregulated by HIF-1α, such as IL-1β, IL-6, IL-8, etc. If only HIF-1α is activated without inhibiting the expression of related inflammatory factors, it may cause inflammation of the skin and aggravate skin problems caused by hypoxia. Therefore, it is necessary to add other ingredients with anti-inflammatory and soothing effects to form a composition with sea buckthorn oil in a certain ratio, so as to increase the oxygen content of skin epidermal cells while inhibiting inflammatory factors such as IL-1β, IL-6, IL-8, and prevent skin inflammation.

[0041] The real-time fluorescence quantitative PCR (RT-qPCR) method was used to determine the HIF-1α gene expression of HaCat cells under hypoxic culture conditions to evaluate the degree of activation of HIF-1α by the composition. The primer sequences of HIF-1α were: 5'ATT TTG GCA GCA ACGACA CA 3', 5'TGC AGG GTC AGC ACT ACT TC 3'. Compared with adding less or no composition, the gene expression of HIF-1α increased when the cells to which the composition was added were cultured under hypoxia, indicating that the composition activated HIF-1α. Compared with the hypoxic control group (no composition was added), the composition should increase the gene expression of HIF-1α in skin cells by 25%-50%.

[0042] The ELISA method was used to determine the expression of inflammatory factors such as IL-1β, IL-6, IL-8 in the supernatant of the HaCat cell culture medium under hypoxic culture conditions to evaluate the anti-inflammatory ability of the composition. Compared with adding less or no composition, when the cells with the addition of the composition were cultured in hypoxia, the expression of inflammatory factors such as IL-1β, IL-6, IL-8 in the supernatant of the cell culture medium was lower, indicating that the composition inhibited skin inflammation. Compared with the hypoxic control group (no composition was added), the composition should inhibit the expression of inflammatory factors by 20%-30%.

[0043] The RT-qPCR method was used to determine the gene expression of skin barrier-related proteins such as Involucrin (IVL), Loricrin (LOR) and Filaggrin (FLG) in HaCat cells under hypoxic culture conditions to evaluate the repair effect of the composition on the skin barrier. The sequence of the IVL primer is: 5'TGA GCA GAG CCT CTA CTT GAG 3', 5'ACA CTC ACT GAT TCA GCT TCA A 3'; the sequence of the LOR primer is: 5'GCA AAT CCT TCA TGT CTTAAC C 3', 5'AAA CCA AAG AGG CTA AAC AGC 3'; the sequence of the FLG primer is: 5'AGA GGA GGA AGGCAG GGA T 3', 5'TGG TGT GGC TGT GAT GGT AC 3'. Compared with cells with little or no addition of the composition, when the cells with the composition added are cultured in hypoxia, the gene expression of IVL, LOR and FLG is higher, indicating that the composition enhances the skin barrier function. Compared with the hypoxic control group (no addition of any composition), the composition should increase the expression of skin barrier function genes by 25%-50%.

[0044] The cell scratch method was used to determine the percentage of HaCat cell scratch recovery under oxygen culture conditions, and to evaluate the migration and proliferation activity of HaCat cells under oxygen culture conditions. Compared with adding less or no composition, the cell scratch repair rate was higher when the cells with the composition added were cultured in hypoxia, indicating that the composition improved the migration and proliferation activity of epidermal cells. Compared with the hypoxic control group (no composition added), the composition should increase the viability of skin cells by 35%-50%.

[0045] The Braden pressure sore scoring standard is used to evaluate whether the improvement of the subject's skin hypoxia state before and after the use of the composition-containing preparation is related to the disappearance of the objective risk of pressure injury (pressure sore). The Braden pressure sore scoring standard is an important tool for clinically evaluating the objective factors of the risk of pressure sores in patients. This scoring standard comprehensively evaluates the possibility and risk of pressure sores from multiple dimensions such as perception ability, moisture level of skin and contact objects. The lower the Braden pressure sore score, the more and more serious the objective factors of the patient's risk of pressure sores; the higher the Braden pressure sore score, the fewer and milder the objective factors of the patient's risk of pressure sores. The risk of pressure sores usually increases during surgery and postoperative bed rest and rehabilitation. An increase in the Braden score indicates that the objective factors of the patient's risk of pressure sores increase. The anti-skin hypoxia composition of the present invention can improve the skin hypoxia state and prevent the risk of pressure injury when the Braden score does not change, that is, when the objective factors that cause pressure injury still exist.

[0046] The moisture content of the stratum corneum, the transepidermal water loss rate and the hemoglobin content are used to evaluate the efficacy of the composition-containing preparation on the skin moisturizing, repairing and soothing of the subjects. Based on the principle of capacitance test, the moisture content of the stratum corneum of human skin is measured by the significant difference in the dielectric constants of water and other substances. According to the different moisture content of the stratum corneum of the skin, the capacitance value of the skin is different, and its parameters can represent the moisture content of the skin. The larger the value of the moisture content of the stratum corneum, the higher the moisture content of the stratum corneum. Based on Fick's diffusion law, the skin barrier function is reflected by collecting the moisture emitted from the skin surface. The smaller the transepidermal water loss value, the better the skin barrier function. The hemoglobin content is determined based on the light reflected by the skin. For hemoglobin measurement, two specific wavelengths (green: 568nm and red: 660nm) are used, corresponding to the spectral absorption peak of hemoglobin, and avoiding the influence of other colors (such as bilirubin). The above data were measured using the skin moisture test probe Corneometer CM825, the skin transepidermal water loss rate probe VapoMeter, and the skin hemoglobin test probe Mexameter MX18. Under hypoxic conditions, the water content of the skin increased by 15%-65%, the transepidermal water loss rate decreased by 31%-46%, and the hemoglobin content decreased by 18%-27% after using the composition preparation, indicating that the composition has the effects of moisturizing, repairing and soothing the skin under hypoxic conditions.

[0047] Beneficial Effects

[0048] (1) The present invention uses seabuckthorn fruit oil rich in C16:1 (Omega-7) palmitoleic acid to improve the oxygen uptake capacity of epidermal cells by activating HIF-1α. The present invention limits the minimum content of palmitoleic acid in seabuckthorn fruit oil to ensure that it can effectively activate HIF-1α. At the same time, excessive activation of HIF-1α will cause inflammatory response and generate excess reactive oxygen species (ROS). Therefore, the proportion of seabuckthorn fruit oil in the composition is limited so that the composition can moderately activate HIF-1α and maintain the cellular oxygen content at a normal level;

[0049] (2) While activating HIF-1α, downstream inflammatory factor target genes will also be activated. The present invention adds natural plant oils and plant extracts, ceramide and other skin anti-inflammatory soothing ingredients that have the effect of inhibiting inflammatory factors, so that the composition can activate HIF-1α and increase the oxygen content of cells without causing negative effects such as skin inflammation.

[0050] (3) The natural plant oils, plant extracts and ceramides added to the composition of the present invention not only have anti-inflammatory effects, but can also cooperate with seabuckthorn oil to better enhance the skin barrier function, deeply moisturize, prevent and improve skin damage caused by hypoxia, and make the skin appear natural and healthy;

[0051] (4) The anti-skin hypoxia composition provided by the present invention can be prepared into skin external products by reasonable compatibility and further adding relevant matrix or excipients, including but not limited to aqueous solutions, oils, lotions, powders, tablets, capsules, facial masks, emulsions, creams, gels, etc., which can be better adapted to different application scenarios. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 It was shown that the proportion of hypoxic cells increased under hypoxic conditions, and the composition (Example 1) significantly reduced the proportion of hypoxic cells.

[0053] Figure 2 It shows that the cell scratch recovery activity is reduced under hypoxic conditions, and the composition (Example 1) significantly improves the cell scratch recovery activity. DETAILED DESCRIPTION

[0054] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall within the scope limited by the appended claims of the application equally.

[0055] Example

[0056] Example 1

[0057] This embodiment provides a skin care oil and a preparation method thereof:

[0058] Phase A: pentaerythritol tetra(di-tert-butyl hydroxyhydrocinnamate) 0.1%, algae oil (triolein) 3.0%;

[0059] Phase B: 80.9% corn (ZEA MAYS) germ oil, 10.0% sea buckthorn (HIPPOPHAE RHAMNOIDES) fruit oil, 3.0% LIMNANTHES ALBA seed oil, 1.0% moringa (MORINGA OLEIFERA) seed oil, 2.0% peony (PAEONIA SUFFRUTICOSA) seed oil.

[0060] The preparation process of the above skin care oil is:

[0061] Mix phase A and heat to 75℃ until dissolved until transparent and uniform without particles. After cooling to 45℃, add phase B ingredients one by one and stir thoroughly.

[0062] Example 2

[0063] This embodiment provides a skin care lotion and a preparation method thereof:

[0064] Phase A: water 67.994%, glycerol 3.5%, carbomer 0.3%;

[0065] Phase B: Glyceryl Stearate, PEG-100 Stearate 3.5%, Cetearyl Alcohol 0.5%, Hippophae Rhamnoides Fruit Oil 1%, Zea Mays Germ Oil 0.5%, Triolein (Algae Oil) 1%, Limnanthes Alba Seed Oil 0.5%, Moringa Oleifera Seed Oil 0.5%, Peony Seed Oil 0.5%, Jojoba Seed Oil 2%, Caprylic / Capric Triglyceride 8%;

[0066] Phase C: 0.5% p-hydroxyacetophenone, 0.5% hexylene glycol;

[0067] Phase D: 1,3-propylene glycol 3%, oat (AVENA SATIVA) kernel powder 2%;

[0068] Phase E: water 1%, sodium hydroxide 0.006%;

[0069] Phase F: 1,3-propanediol 2%, tetrahydrocurcumin 0.3%;

[0070] Phase G: 0.1% sulfothiorine, 0.3% olive (OLEA EUROPAEA) leaf extract, 0.5% salvia miltiorrhiza (SALVIAMILTIORRHIZA) root extract.

[0071] The preparation process of the above-mentioned skin care emulsion is:

[0072] Pre-mix 1) Phase C, heat to 75-80°C and dissolve until transparent, set aside;

[0073] Pre-mix 2) D phase, homogenize until uniform, and set aside;

[0074] Pre-mix 3) Phase E and dissolve until transparent and free of particles, set aside;

[0075] Pre-mix 4) phase F and heat to 65-70°C to dissolve until transparent, set aside;

[0076] Phase A is homogenized and dispersed until uniform. Phase A and phase B are heated to 80°C. Phase B is added to phase A while stirring. Homogenize at 9000rpm for 3min. Cool down to 70-75°C, add phases C and D, and homogenize at 8000rpm for 2min. Cool down to 65-70°C, add phases E and F while stirring. Continue to cool down to 50-55°C, add phase G one by one, and stir evenly. Finally, cool down to 35-38°C and discharge.

[0077] Notes: Sumoxiu = water, 1,3-propylene glycol, caprylic / capric triglyceride, PEG-40 hydrogenated castor oil, 1,2-pentylene glycol / hydrogenated lecithin, ceramide NP, ceramide NS / ceramide NG, triethylhexanoin, ceramide AP, phytosphingosine, cholesterol, vetiver root extract, ceramide EOP.

[0078] Example 3

[0079] This embodiment provides an external ointment and a preparation method thereof:

[0080] Phase A: water 54.09%, glycerol 3.5%, carbomer 0.5%;

[0081] Phase B: Glyceryl Stearate, PEG-100 Stearate 5%, Cetearyl Alcohol 2%, Hippophae Rhamnoides Fruit Oil 1%, Zea Mays Germ Oil 1%, Triolein (Algae Oil) 3%, Limnanthes Alba Seed Oil 3%, Moringa Oleifera Seed Oil 2%, Peony Seed Oil 3%, Jojoba Seed Oil 2%, Caprylic / Capric Triglyceride 8%;

[0082] Phase C: 0.5% p-hydroxyacetophenone, 0.5% hexylene glycol;

[0083] Phase D: 1,3-propylene glycol 3%, oat (AVENA SATIVA) kernel powder 2%;

[0084] Phase E: water 1%, sodium hydroxide 0.01%;

[0085] Phase F: 1,3-propanediol 2%, tetrahydrocurcumin 0.3%;

[0086] Phase G: Sulfamidine 0.1%, olive (OLEA EUROPAEA) leaf extract 1.5%, salvia miltiorrhiza (SALVIAMILTIORRHIZA) root extract 1%;

[0087] The preparation process of the above-mentioned external ointment is:

[0088] Pre-mix 1) Phase C, heat to 75-80°C and dissolve until transparent, set aside;

[0089] Pre-mix 2) D phase, homogenize until uniform, and set aside;

[0090] Pre-mix 3) Phase E and dissolve until transparent and free of particles, set aside;

[0091] Pre-mix 4) phase F and heat to 65-70°C to dissolve until transparent, set aside;

[0092] Phase A is homogenized and dispersed until uniform. Phase A and phase B are heated to 80°C. Phase B is added to phase A while stirring. Homogenize at 9000rpm for 3min. Cool down to 70-75°C, add phases C and D, and homogenize at 8000rpm for 2min. Cool down to 65-70°C, add phases E and F while stirring. Continue to cool down to 50-55°C, add phase G one by one, and stir evenly. Finally, cool down to 35-38°C and discharge.

[0093] Notes: Sumoxiu = water, 1,3-propylene glycol, caprylic / capric triglyceride, PEG-40 hydrogenated castor oil, 1,2-pentylene glycol / hydrogenated lecithin, ceramide NP, ceramide NS / ceramide NG, triethylhexanoin, ceramide AP, phytosphingosine, cholesterol, vetiver root extract, ceramide EOP.

[0094] Example 4

[0095] This embodiment provides a medical hydrogel and a preparation method thereof:

[0096] Phase A: water 86.682%, glycerol 2.4%, carbomer 0.5%;

[0097] Phase B: 0.5% p-hydroxyacetophenone, 0.5% hexylene glycol;

[0098] Phase C: 1,3-propylene glycol 3%, oat (AVENA SATIVA) kernel powder 1%;

[0099] Phase D: water 1%, sodium hydroxide 0.012%;

[0100] Phase E: Hippophae Rhamnoides fruit oil 1%, Zea mays germ oil 0.001%, triolein (algae oil) 0.001%, Limnanthes Alba seed oil 0.001%, Moringa Oleifera seed oil 0.001%, Peony seed oil 0.001%;

[0101] Phase F: 1,3-propanediol 2%, tetrahydrocurcumin 0.3%;

[0102] Phase G: 0.1% sulfothiorine, 0.3% olive (OLEA EUROPAEA) leaf extract, 0.5% salvia miltiorrhiza (SALVIAMILTIORRHIZA) root extract.

[0103] The preparation process of the above-mentioned medical hydrogel is:

[0104] Pre-mix 1) Phase B, heat to 75-80°C and dissolve until transparent, set aside;

[0105] Pre-mix 2) phase C and dissolve it evenly for later use;

[0106] Pre-mix 3) D phase, homogenize until uniform, and set aside;

[0107] Pre-mix 4) phase F and heat to 65-70°C to dissolve until transparent, set aside;

[0108] Phase A is homogenized and dispersed until uniform, then heated to 80℃, kept warm for 10 minutes, cooled to 70-75℃, and added phases B and C to phase A while stirring, and stirred evenly; continued to cool to 65-70℃, and added phase D while stirring, and stirred evenly; continued to cool to 50-55℃, added phases E and F, and then added phase G one by one, and stirred evenly; continued to cool to 35-38℃, and discharged

[0109] Notes: Sumoxiu = water, 1,3-propylene glycol, caprylic / capric triglyceride, PEG-40 hydrogenated castor oil, 1,2-pentylene glycol / hydrogenated lecithin, ceramide NP, ceramide NS / ceramide NG, triethylhexanoin, ceramide AP, phytosphingosine, cholesterol, vetiver root extract, ceramide EOP.

[0110] Comparative Example

[0111] Comparative Example 1

[0112] This comparative example is a comparative example of Example 1. The skin care oil of this comparative example is different from the skin care oil of Example 1 mainly in that the content of palmitoleic acid in the seabuckthorn fruit oil added to the skin care oil of this comparative example is less than 4 mg / mL. The purpose of setting this comparative example is to investigate whether the composition can effectively resist skin hypoxia when the content of palmitoleic acid in the seabuckthorn fruit oil is less than 4 mg / mL.

[0113] Comparative Example 2

[0114] This comparative example is a comparative example of Example 2. The main difference between the skin care lotion of this comparative example and the skin care lotion of Example 2 is that the mass percentage of sea buckthorn fruit oil added to the skin care lotion of this comparative example is 0.5%. The purpose of setting this comparative example is to examine whether the composition can effectively resist skin hypoxia when the mass percentage of sea buckthorn fruit oil in the composition is less than 1%.

[0115] Comparative Example 3

[0116] This comparative example is a comparative example of Example 3. The main difference between the topical ointment of this comparative example and the topical ointment of Example 3 is that the mass percentage of seabuckthorn fruit oil added to the topical ointment of this comparative example is 12%. The purpose of setting this comparative example is to examine whether the composition can effectively resist skin hypoxia without causing negative effects such as skin inflammation when the mass percentage of seabuckthorn fruit oil in the composition is greater than 10%.

[0117] Comparative Example 4

[0118] This comparative example is a comparative example of Example 4. The main difference between the medical hydrogel of this comparative example and the medical hydrogel of Example 4 is that corn germ oil, algae oil, meadowfoam seed oil, moringa seed oil, peony seed oil, oat kernel powder, olive leaf extract, tetrahydrocurcumin, salvia root extract, and sulmoides are not added to the medical hydrogel of this comparative example. The purpose of setting this comparative example is to investigate whether the composition can effectively resist skin hypoxia without causing negative effects such as skin inflammation when corn germ oil, algae oil, meadowfoam seed oil, moringa seed oil, peony seed oil, oat kernel powder, olive leaf extract, tetrahydrocurcumin, salvia root extract, and sulmoides are lacking in the composition.

[0119] Anti-hypoxia efficacy experiment

[0120] Determination of cell oxygen content: A 6-well plate full of keratinocyte HaCat cells was taken and divided into two groups, "Example Group" and "Comparative Example Group", with 3 wells in each group and 2 mL of culture medium in each well. 20 uL of DMSO dissolved with 10% (by mass percentage) of the composition of Examples 1-4 was added to each well of the Example Group, and 20 μL of DMSO dissolved with 10% (by mass percentage) of the composition of Comparative Examples 1-4 was added to the Comparative Example Group. Then, after culturing in a hypoxic incubator at 10% oxygen concentration for 24 hours, the cells were taken out and a 1:500 dilution of The oxygen probe was returned to the cell culture incubator for incubation for 1 hour. After the incubation, the cells were taken out, the cells were enzymatically hydrolyzed with collagenase to suspend them, the cells were collected and the probes remaining in the cells were washed according to the kit instructions, and then the CytoFLEX flow cytometer was used to analyze the intensity of the fluorescence probe luminescence in the epidermal cells and the number of cells. The stronger the fluorescence, the lower the intracellular oxygen content, and the weaker the fluorescence, the higher the intracellular oxygen content. Therefore, the more cells with strong fluorescence, the more serious the degree of cell hypoxia; the fewer cells with strong fluorescence, the milder the degree of cell hypoxia. At the same time, a 6-well plate of HaCat cells of keratinocytes in the logarithmic growth phase was set and placed in a normal oxygen concentration cell culture incubator as a "normal oxygen control group", and then a 6-well plate of HaCat cells of keratinocytes in the logarithmic growth phase was placed in a hypoxic cell culture incubator as a "hypoxia control group", without adding the composition, and the rest of the operations were the same as above, respectively compared with the "Example" group and the "Comparative Example" group.

[0121] Cell viability assay: Take a 6-well plate full of keratinocyte HaCat cells and divide it into two groups, "Example Group" and "Comparative Example Group", with 3 wells in each group and 2 mL of culture medium in each well. Use a pipette tip to make a scratch in each of the 6 wells according to the diameter direction, take pictures under a microscope and calculate the average width of the scratch in each well as the "initial scratch width". Then, 20uL of DMSO dissolved with 10% (by mass percentage) of the composition of Examples 1-4 was added to each well of the Example Group, and 20μL of DMSO dissolved with 10% (by mass percentage) of the composition of Comparative Examples 1-4 was added to the Comparative Example Group. Then, in a hypoxic incubator, after culturing for 24 hours at different oxygen concentrations of 10%, the cells were taken out and then taken pictures under a microscope to calculate the average width of the scratch in each well as the "24-hour scratch width". At the same time, a 6-well plate full of keratinocyte HaCat cells was set up and placed in a normal oxygen concentration cell culture incubator as a "normal oxygen control group", and another 6-well plate full of keratinocyte HaCat cells was set up and placed in a hypoxic cell culture incubator as a "hypoxia control group". No composition was added, and the rest of the operations were the same as above, and compared with the "Example" group and the "Comparative Example" group, respectively. The cell scratch recovery rate was calculated by the formula: scratch recovery rate = (initial scratch width - scratch width after 24 hours) / initial scratch width * 100%. The higher the scratch recovery rate, the higher the improvement of the epidermal cell migration and proliferation activity by the composition.

[0122] Determination of cellular HIF-1α gene and barrier-related genes (IVL, LOR and FLG): Take a 6-well plate of keratinocyte HaCat cells in the logarithmic growth phase and divide it into two groups, "Example Group" and "Comparative Example Group", with 3 wells in each group and 2mL of culture medium in each well. 20uL of DMSO dissolved with 10% (by mass percentage) of the composition of Examples 1-4 was added to each well of the Example Group, and 20μL of DMSO dissolved with 10% (by mass percentage) of the composition of Comparative Examples 1-4 was added to the Comparative Example Group, and then cultured in a hypoxic incubator at an oxygen concentration of 10% for 24 hours. After taking out the cells, use a cell scraper to collect the cells from the well plate into a 1.5mL centrifuge tube, and then use an RNA extraction kit to extract the cellular RNA, quantify it and reverse transcribe it into a template DNA, and then use a PCR-specific 384-well plate to add the template DNA, primers, and SYBR according to the system of 10uL per well. TMGreen dye and deionized water, and then measured and analyzed with a CFX Opus real-time fluorescence quantitative PCR instrument. At the same time, a 6-well plate of HaCat cells of a keratinocyte cell line in the logarithmic growth phase was set up and placed in a normal oxygen concentration cell culture box as a "normal oxygen control group", and then a 6-well plate of HaCat cells of a keratinocyte cell line in the logarithmic growth phase was placed in a hypoxic cell culture box as a "hypoxia control group". No composition was added, and the rest of the operations were the same as above, and compared with the "Example" group and the "Comparative Example" group, respectively. The gene expression level of the normal oxygen control group was set to 1, and the gene expression levels of the hypoxia control group, the example group, and the comparative example group relative to the control group were calculated. The higher the relative gene expression level, the higher the level of activation of the HIF-1α gene and barrier-related genes.

[0123] Cellular ROS determination: Take a 6-well plate of HaCat cells of keratinocyte cell line in the logarithmic growth phase and divide it into two groups, "Example Group" and "Comparative Example Group", with 3 wells in each group and 2mL culture medium in each well. 20uL of DMSO dissolved with 10% (by mass percentage) of the composition of Example 1-4 was added to each well of the Example Group, and 20μL of DMSO dissolved with 10% (by mass percentage) of the composition of Comparative Example 1-4 was added to the Comparative Example Group. DBSPs (125μg / mL) were added to each well, and then cultured in a hypoxic incubator at 10% oxygen concentration for 48 hours. After taking out the cells and rinsing them twice with PBS, the DCFH-DA probe was added to the cells, and incubated at 37°C for 30min according to the instructions of the kit. After observing the cells under a fluorescent inverted microscope, the fluorescence intensity was measured using an ELISA instrument. At the same time, a 6-well plate of keratinocyte HaCat cells in the logarithmic growth phase was set up and placed in a normal oxygen concentration cell culture incubator as a "normal oxygen control group", and then a 6-well plate of keratinocyte HaCat cells in the logarithmic growth phase was placed in a hypoxic cell culture incubator as a "hypoxia control group". No composition was added, and the rest of the operations were the same as above, and compared with the "Example" group and the "Comparative Example" group, respectively.

[0124] Determination of cellular inflammatory factors: Take a 6-well plate of HaCat cells, a keratinocyte cell line in the logarithmic growth phase, and divide it into two groups, "Example Group" and "Comparative Example Group", with 3 wells in each group and 2mL culture medium in each well. 20uL of DMSO dissolved in 10% (by mass percentage) of the composition of Example 1-4 was added to each well of the Example Group, and 20μL of DMSO dissolved in 10% (by mass percentage) of the composition of Comparative Example 1-4 was added to the Comparative Example Group. Lipopolysaccharide (LPS) at a concentration of 1X (2μL / mL) was added to each well, and then cultured in a hypoxic incubator at 10% oxygen concentration for 48 hours. After taking out the cells, centrifuge and take the supernatant, and measure the expression of inflammatory factors such as IL-1β, IL-6, and IL-8 in a microplate reader according to the instructions of the ELISA kit. At the same time, a 6-well plate of keratinocyte HaCat cells in the logarithmic growth phase was set up and placed in a normal oxygen concentration cell culture incubator as a "normal oxygen control group", and then a 6-well plate of keratinocyte HaCat cells in the logarithmic growth phase was placed in a hypoxic cell culture incubator as a "hypoxia control group". No composition was added, and the rest of the operations were the same as above, and compared with the "Example" group and the "Comparative Example" group, respectively.

[0125] Determination of oxygen partial pressure in the skin of the pressure injury mouse model: 16 female mice of the C57BL / 6 strain were shaved on the back and divided into four groups, namely, the "normal control group" (no treatment), the "magnetic control group" (no application of any preparation, magnetic pressure injury simulation), the "example group" (the composition preparation of Examples 1-4 was applied to the back skin and then magnetic pressure was applied) and the "comparative example group" (the composition preparation of Comparative Examples 1-4 was applied to the back skin and then magnetic pressure was applied). After 30 minutes after the composition preparation was applied, two cylindrical magnets with a magnetic force of 800Gs, a diameter of 10 mm, and a thickness of 3 mm were used to clamp the mouse back skin for 1-2 hours by magnetic attraction and then removed to simulate the skin hypoxia caused by pressure injury. By applying the composition preparation on the back skin of the mouse in advance, the hypoxia caused by the magnetic pressure on the back skin of the mouse is reduced, and the skin damage caused thereby is alleviated. After removing the magnet, the oxygen content of the mouse skin is detected by a TCM4 transcutaneous oxygen partial pressure detector. First, clean the mouse skin surface with 75% alcohol, then stick the fixing ring to the skin surface, drip 5 drops of electrode liquid into the fixing ring, and then screw the transcutaneous oxygen partial pressure / transcutaneous carbon dioxide partial pressure combined electrode into the fixing ring and fix it before starting monitoring. The higher the oxygen partial pressure, the higher the oxygen content of the skin; the lower the oxygen partial pressure (pO2), the lower the oxygen content of the skin. The normal pO2 of mouse skin is about 80-100mmHg. When the skin is hypoxic due to external pressure, the skin pO2 drops to a level of 30-60mmHg. By comparing the "normal control group", "magnetic control group", "example group" and "comparative example group", the anti-hypoxia ability of the composition on mouse skin was observed.

[0126] Determination of skin injury recovery time in pressure injury mouse model: Before and after magnetic treatment of mouse skin, the DermLite DL4 dermatoscope was used to observe the back skin of the above mice once a day. When the mouse skin recovered to the state before magnetic treatment, the number of days from the magnetic treatment was recorded as the skin recovery time of pressure injury mouse model. The shorter the time, the faster the mouse skin recovered; the longer the time, the slower the mouse skin recovered.

[0127] Comparative experimental results

[0128] The results of intracellular oxygen, reactive oxygen species and vitality experiments are shown in Table 1.

[0129] Table 1

[0130]

[0131] The results shown in Table 1 show that when the content of palmitoleic acid in seabuckthorn fruit oil is lower than 4 mg / mL (Comparative Example 1), or the mass percentage of seabuckthorn fruit oil in the composition is lower than 1% (Comparative Example 2), the composition cannot increase intracellular oxygen; when the mass percentage of seabuckthorn fruit oil in the composition is higher than 10% (Comparative Example 3), or the composition lacks other ingredients except seabuckthorn fruit oil (Comparative Example 4), the composition over-activates intracellular oxygen and produces excess active oxygen, and cell viability decreases.

[0132] The experimental results of cellular HIF-1α gene, skin barrier-related genes and inflammatory factor expression (all expressed as relative expression levels to the “hypoxia control group”) are shown in Table 2.

[0133] Table 2

[0134]

[0135]

[0136] The results shown in Table 2 indicate that when the content of palmitoleic acid in seabuckthorn fruit oil is lower than 4 mg / mL (Comparative Example 1), or the mass percentage of seabuckthorn fruit oil in the composition is lower than 1% (Comparative Example 2), the composition cannot activate HIF-1α; when the mass percentage of seabuckthorn fruit oil in the composition is higher than 10% (Comparative Example 3), or the composition lacks other ingredients except seabuckthorn fruit oil (Comparative Example 4), the composition over-activates HIF-1α, produces inflammatory factors, and the expression of skin barrier-related genes decreases.

[0137] The results of the mouse experiment are shown in Table 3.

[0138] Table 3

[0139] Experimental Project <![CDATA[Skin oxygen partial pressure (pO2, mmHg)]]> Skin injury recovery time (days) Example 1 99 2 Example 2 82 3 Example 3 84 2 Example 4 92 3 Comparative Example 1 42 7 Comparative Example 2 48 6 Comparative Example 3 39 7 Comparative Example 4 46 8

[0140] The results shown in Table 3 indicate that when the content of palmitoleic acid in seabuckthorn fruit oil is lower than 4 mg / mL (Comparative Example 1), or the mass percentage of seabuckthorn fruit oil in the composition is lower than 1% (Comparative Example 2), the composition cannot increase the oxygen partial pressure of mouse skin; when the mass percentage of seabuckthorn fruit oil in the composition is higher than 10% (Comparative Example 3), or the composition lacks other ingredients except seabuckthorn fruit oil (Comparative Example 4), the composition excessively increases the oxygen partial pressure of mouse skin, or prolongs the recovery time of skin damage.

[0141] Application Examples

[0142] Application Example 1

[0143] This application example is a specific application of Example 1.

[0144] The stability test shows that the skin care oil described in Example 1 has no obvious color change under various temperature conditions (-18°C, 5°C, 25°C, 40°C, 45°C, 50°C) within 12 weeks, and the state is normal; in terms of odor, there is a slight oily smell after high temperature of 40°C, 45°C, 50°C and light exposure for 4-12 weeks, which is evaluated to be within the normal acceptable range, and the overall stability is good.

[0145] The safety patch test showed that among the 30 subjects, one grade 1 adverse reaction occurred, which was a mild, transient symptom that disappeared after 5 minutes. The remaining 29 subjects had no adverse reactions, indicating that the skin care oil is mild.

[0146] At Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, 30 subjects at high risk of pressure sores (SEM value greater than or equal to 0.6 or Braden score less than or equal to 12 points) used skin care oil 4 times a day on the pressure area of ​​the coccyx, 0.4 mL each time, with an interval of 4 hours between each application. The pO2 and SEM values ​​of the used areas were tested before and 1-2 weeks after use. The results showed that pO2 increased by 21% after 1 week of using the skin care oil, and increased by 28% after 2 weeks of using the skin care oil; the SEM value decreased by 25% after 1 week of using the skin care oil, and decreased by 42% after 2 weeks of using the skin care oil. This shows that the skin care oil effectively increases the skin oxygen content of the pressure area of ​​patients with pressure sores and reduces the risk of pressure sores.

[0147] Application Example 2

[0148] This application example is a specific application of Example 2.

[0149] The stability test shows that the skin care lotion described in Example 2 has no abnormal state and odor under various temperature conditions (-18°C, 5°C, 25°C, 40°C, 45°C, 50°C) within 12 weeks; the color slightly turns yellow after high temperature of 40°C, 45°C, 50°C and light exposure for 4-12 weeks, which is assessed to be within the normal acceptable range and has good overall stability.

[0150] The safety patch test showed that there were no adverse reactions among the 30 subjects, indicating that the skin care lotion is mild.

[0151] The bandage compression method was used to simulate the skin compression state on the arms of 30 healthy subjects. After compression, the implementers were asked to use skin care lotion once a day in the morning and evening. The pO2, skin water content, transepidermal water loss rate and skin hemoglobin content of the subjects' arms were tested before compression, before use after compression, and 30 minutes, 2 hours and 2 weeks after use. The results showed that pO2 increased by 16%, 19% and 22% respectively after using the skin care lotion 30 minutes, 2 hours and 2 weeks compared with before use after compression, and reached the normal level before compression 2 hours after use. After using the skin care lotion 30 minutes, 2 hours and 2 weeks compared with before use after compression, the skin water content increased by 16%, 44% and 65% respectively; after using the skin care lotion 30 minutes, 2 hours and 2 weeks compared with before use after compression, the transepidermal water loss rate decreased by 37%, 31% and 46% respectively; after using the skin care lotion 30 minutes, 2 hours and 2 weeks compared with before use after compression, the skin hemoglobin content decreased by 18% and 27% respectively after using the skin care lotion 30 minutes and 2 hours compared with before use after compression. This suggests that the lotion effectively increases the oxygen content of the skin in stressed areas and has the effect of moisturizing, repairing and soothing the skin.

[0152] The results of the sensory experience evaluation questionnaire of the subjects on the use of skin care lotion are shown in Table 4.

[0153] Table 4

[0154]

[0155]

[0156] The results in Table 4 show that after using the skin care lotion, the subjects felt that their skin was more moisturized, soothing, and delicate, their skin was softer, and the product was mild and non-irritating.

[0157] In summary, the composition of the present invention, when the skin is in a state of hypoxia, can activate HIF-1α by being applied to the skin surface, thereby improving the oxygen uptake capacity of skin epidermal cells, thereby playing the role of increasing skin oxygen content, anti-inflammatory, soothing, moisturizing and nourishing, and improving the adverse effects of hypoxia on skin condition.

Claims

1. A composition for resisting skin hypoxia, characterized in that: The composition comprises seabuckthorn fruit oil, natural plant oil and water-soluble components; the palmitoleic acid content of the seabuckthorn fruit oil is greater than 4 mg / mL.

2. The composition for resisting skin hypoxia according to claim 1, characterized in that: The natural plant oils and fats include one or more of corn germ oil, seaweed oil, meadowfoam seed oil, moringa seed oil, and peony seed oil.

3. The composition for resisting skin hypoxia according to claim 1, characterized in that: The water-soluble ingredients include one or more of oat kernel powder, olive leaf extract, tetrahydrocurcumin, salvia miltiorrhiza root extract and sulphanol.

4. The composition for resisting skin hypoxia according to claim 1, characterized in that: In terms of mass percentage, the composition comprises: 1%-10% seabuckthorn fruit oil, 0-90% natural plant oil and 0-40% water-soluble components.

5. The composition for resisting skin hypoxia according to claim 4, characterized in that: In terms of mass percentage, the composition comprises: 1%-10% seabuckthorn fruit oil, 0%-89.9% corn germ oil, 0%-6.5% seaweed oil, 0%-55% meadowfoam seed oil, 0%-5% moringa seed oil, 0%-50% peony seed oil, 0%-7% oat kernel powder, 0%-32% olive leaf extract, 0%-1% tetrahydrocurcumin, 0%-2.8% salvia miltiorrhiza root extract, and 0%-0.2% succinate.

6. Use of the anti-skin hypoxia composition according to any one of claims 1 to 5 in the preparation of an anti-skin hypoxia product.

7. The use according to claim 6, characterized in that: The product includes one of functional skin care products, external skin medicines, medical devices, and chemical preparations.

8. The use according to claim 6, characterized in that: The product may also include other commonly used auxiliary ingredients.

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