Peroxide triglyceride rich in azelaic acid as well as preparation method and application of peroxide triglyceride

Abstract

The invention discloses peroxide triglyceride rich in azelaic acid as well as a preparation method and application of the peroxide triglyceride. The preparation method of the peroxide triglyceride rich in azelaic acid comprises the following steps: S1, mixing oleic acid and triglyceride, introducing mixed gas of ozone and oxygen under a stirring condition, and reacting at 20-30 DEG C for 8-14 hours to obtain an intermediate product; and S2, introducing oxygen into the intermediate product at 70-95 DEG C, and reacting for 6-10 hours to obtain the peroxide triglyceride rich in azelaic acid. According to the preparation technology disclosed by the invention, mutual dissolution of azelaic acid and oil is realized, and the prepared peroxide triglyceride rich in azelaic acid has the effect of relieving inflammation, and can be used for preventing and repairing light damage, reducing color sink, reducing generation of pigments and promoting fading of the pigments. The composition can also be used for barrier repair of other diseases such as atopic dermatitis, wound surfaces and the like and prevention of color subsidence; the air permeability is better, the usability is good, and basically no side effect exists.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to a peroxidized triglyceride rich in azelaic acid, and a preparation method and application thereof. Background Art

[0002] Photodamage is a series of skin reactions and diseases caused by exposure to ultraviolet radiation and other forms of light. It not only causes skin aging and aesthetic problems, but may also cause serious health problems, including acute photodamage (sunburn), chronic photodamage (including photoaging, polymorphic light eruption (PLE) and chronic actinic dermatitis (CAD)), etc. Sunburn is also known as solar dermatitis, solar edema or solar erythema. It is an acute and transient inflammatory reaction of the skin after ultraviolet radiation, manifested as erythema, blisters, swelling and pain. Ultraviolet rays include long-wave ultraviolet rays (UVA), medium-wave ultraviolet rays (UVB) and short-wave ultraviolet rays (UVC) according to different wavelengths. Among them, UVA and UVB have a direct effect on human skin and may cause tanning. UVA causes photooxidation of melanin, and UVB irradiation can stimulate skin melanocytes.

[0003] Plant oils and fats have multiple activities such as anti-inflammatory and antioxidant activities. In addition, they are green, environmentally friendly, safe to use, and easily absorbed by the skin. They can be further developed and utilized as ideal raw materials for natural sunscreens.

[0004] Azelaic acid is a natural dicarboxylic acid produced by Malassezia furfur. It is found in whole grains, rye, and barley. It can also be formed by chemical synthesis and fermentation. Azelaic acid shows hypopigmentation properties as a competitive inhibitor of tyrosinase. Azelaic acid can inhibit abnormal melanocyte activity and reduce pigmentation. It can also inhibit the production of reactive oxygen free radicals and exert anti-inflammatory effects. However, azelaic acid is insoluble in water and oil, and has the characteristics of poor solubility and high melting point.

[0005] Prior art CN 109180462 A discloses a method for preparing nonanoic acid and azelaic acid from oleic acid. Oleic acid and glacial acetic acid are subjected to ozone oxidation and oxidative cracking reactions, and the reactants are further extracted and purified to obtain nonanoic acid and azelaic acid with high purity, respectively; wherein the mass ratio of oleic acid to glacial acetic acid is 1:2-4.

[0006] Prior art CN 118084653 A relates to high-purity azelaic acid suitable for medical applications and a green synthesis method thereof. The method comprises the following steps: mixing oleic acid and glacial acetic acid, introducing ozone into the reactants to react the materials to obtain oleic acid ozonide; introducing oxygen into the obtained oleic acid ozonide, heating the materials to react, and obtaining an oxidative cracking product; extracting the obtained oxidative cracking product with hot water, crystallizing, filtering, and drying to obtain a crude product; and recrystallizing the crude product in a mixed solvent to obtain the final product azelaic acid.

[0007] The above two prior arts are both for obtaining pure product azelaic acid. The prepared azelaic acid is insoluble in water and oil, and has the characteristics of poor solubility and high melting point. Azelaic acid has been widely used in the treatment of acne, chloasma, rosacea, excessive pigmentation, etc., and the effective dose needs to be greater than 10%. The azelaic acid dosage forms currently used clinically include creams, gels, and syrups. High concentrations of azelaic acid cause a gritty feeling or easily cause demulsification. Creams are commonly used O / W types, and azelaic acid is mostly added as fine powder, which cannot be completely dissolved in the cream. In the reported preparations, the bioavailability of azelaic acid is reduced because the fine powder that cannot be completely dissolved by azelaic acid is dispersed in the matrix. In the gel of azelaic acid, in order to improve the solubility of azelaic acid, a large amount of oily ingredients or more solvents are generally added to the gel product, and too much solvent and oily products will lead to poor skin permeability, poor usability, and large side effects. Summary of the invention

[0008] The purpose of the present invention is to provide a peroxidized triglyceride rich in azelaic acid and a preparation method and application thereof, so as to solve the solubility problem of azelaic acid.

[0009] In order to achieve the above object, the present invention adopts the following technical solution: A method for preparing peroxidized triglyceride rich in azelaic acid comprises the following steps: S1. After mixing oleic acid and triglyceride, a mixed gas of ozone and oxygen is introduced under stirring, and the mixture is reacted at 20-30° C. for 8-14 hours to obtain an intermediate product; S2. Pass oxygen into the intermediate product at 70° C.-95° C. and react for 6-10 hours to obtain peroxidized triglyceride rich in azelaic acid.

[0010] In a preferred embodiment, the triglyceride is one or more of oleic acid triglyceride, dioleic acid palmitic acid triglyceride, dioleic acid stearic acid triglyceride, dioleic acid linoleic acid triglyceride, and linoleic acid triglyceride.

[0011] In a preferred embodiment, in step S1, the volume ratio of oleic acid to triglyceride is 5-20:80-95.

[0012] If the content of oleic acid is too much, the uniformity of the obtained product is poor and the preparation is turbid. If the amount of oleic acid is too little, the effective ingredient in the obtained product is less and the therapeutic effect is poor.

[0013] In a preferred embodiment, in step S1, in the mixed gas of ozone and oxygen, the volume ratio of ozone to oxygen is 3-5:95-97.

[0014] If the proportion of ozone is too low, the peroxidation efficiency will be reduced; if the proportion of ozone is too high, the uniformity of the prepared product will be poor.

[0015] In a preferred embodiment, in step S1, the introduction rate of the mixed gas of ozone and oxygen is 0.5-1.5 L / min.

[0016] In a preferred embodiment, in step S1, the peroxide value of the intermediate product is 200-280 meq / kg.

[0017] In a preferred embodiment, in step S1, the ozone absorption of the intermediate product is 80-144 mg / g.

[0018] In a preferred embodiment, in step S2, the oxygen ventilation volume is 0.2-0.7 L / kg.

[0019] In a preferred embodiment, in step S2, the content of azelaic acid in the peroxidized triglyceride rich in azelaic acid is 0.5-2.5 wt %.

[0020] In the step S2, the reaction temperature is controlled at 70°C-95°C. If the temperature is too high, the process cost is high and too many by-products will be produced. If the temperature is too low, the azelaic acid content is too low and the effect is poor.

[0021] Based on the same inventive concept, the present invention also claims protection for the azelaic acid-rich peroxidized triglyceride prepared by the preparation method.

[0022] Based on the same inventive concept, the present invention also claims to protect the use of the peroxidized triglyceride rich in azelaic acid in the preparation of drugs for treating or preventing acute photodamage and chronic photodamage.

[0023] Based on the same inventive concept, the present invention also claims to protect the use of the peroxidized triglyceride rich in azelaic acid in the preparation of barrier repair, anti-inflammatory, and pigmentation reducing drugs.

[0024] The present invention obtains a uniform system of peroxidized triglycerides rich in azelaic acid by mixing oleic acid and triglycerides for peroxidation and then performing oxidation treatment, thereby solving the solubility problem of azelaic acid in triglycerides and improving the bioavailability of azelaic acid. On the one hand, the present invention does not require the addition of glacial acetic acid, and the incomplete reaction of glacial acetic acid in the prior art has certain irritation to the skin; on the other hand, the peroxidized triglycerides rich in azelaic acid prepared by the present invention do not require additional purification steps, and a product with good therapeutic effect can be obtained by controlling appropriate reaction conditions.

[0025] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention provides a peroxidized triglyceride rich in azelaic acid, which can be used to prevent and treat photodamage and has a barrier repair effect.

[0026] 2. The preparation technology of the present invention realizes the mutual solubility of azelaic acid and oil. The prepared peroxidized triglyceride rich in azelaic acid has the effect of relieving inflammation and can be used for the prevention and repair of photodamage.

[0027] 3. The peroxidized triglyceride in the azelaic acid-rich peroxidized triglyceride prepared by the present invention has better air permeability, better usability and basically no side effects than the general oily components added to the gel.

[0028] 4. The peroxidized triglyceride rich in azelaic acid prepared by the present invention can reduce the generation of pigmentation, reduce the production of pigments, and promote the disappearance of pigments while resisting inflammation. It can also be used for barrier repair and prevention of pigmentation in other diseases such as atopic dermatitis and wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is the appearance of the azelaic acid-rich peroxidized triglyceride obtained in Example 6, which is clear, transparent, uniform and has good solubility; Figure 2 This is the appearance of the azelaic acid-rich peroxidized triglyceride obtained in Comparative Example 1, and it can be seen that the product is turbid and uneven; Figure 3 This is the appearance of the azelaic acid-rich peroxidized triglyceride obtained in Comparative Example 3, and it can be seen that the product is turbid and uneven; Figure 4 The liquid phase mass spectrometry is used to qualitatively detect the content of azelaic acid in Example 1; Figure 5 The content of azelaic acid in Example 1 was detected by high performance liquid chromatography; Figure 6 The content of azelaic acid in Examples 1, 2, 3, 4, 5, 6 and Comparative Examples 1 and 2 was detected by high performance liquid chromatography; Figure 7This is Example 4 for the treatment and observation of an acute light damage animal model; in the figure, A is an acute light damage model group, B is a peroxidized triglyceride group, C is azelaic acid gel group, and D is azelaic acid oil group; Figure 8 These are the reflective confocal microscopy results of each group used to treat the acute light damage animal model in Example 4. In the figure, A is the acute light damage model group, B is the azelaic acid gel group, C is the peroxidized triglyceride group, and D is the azelaic acid oil group. DETAILED DESCRIPTION

[0030] The present invention is not limited to the following specific embodiments. A person skilled in the art can implement the present invention in various other specific embodiments according to the contents disclosed in the present invention, or any simple changes or modifications made to the design structure and ideas of the present invention fall within the protection scope of the present invention. It should be noted that the embodiments and features in the embodiments of the present invention can be combined with each other without conflict.

[0031] Example 1

[0032] A method for preparing peroxidized triglyceride rich in azelaic acid comprises the following steps: Step 1: Mix 5 parts of oleic acid with 95 parts of oleic triglyceride, pass ozone / oxygen mixed gas into 350g of oleic acid and oleic triglyceride mixture at a flow rate of 1L / min, the ozone gas concentration in the mixed gas is 3% (v / v), stir at 400rpm, react at 20℃ for 8h, and obtain an intermediate containing peroxidized triglyceride and peroxidized oleic acid; the peroxide value of the intermediate at the end of the reaction should be 200meq / kg. The absorption of ozone is 80mg / g.

[0033] Step 2: The reaction temperature is 70°C, oxygen is introduced into the intermediate at an oxygen flow rate of 0.5 L / kg, and the reaction is carried out for 8 hours to finally prepare peroxidized triglyceride rich in azelaic acid.

[0034] Example 2

[0035] A method for preparing peroxidized triglyceride rich in azelaic acid comprises the following steps: Step 1: Mix 20 parts of oleic acid with 80 parts of dioleyl palmitic acid triglyceride, pass ozone / oxygen mixed gas into 350g of oleic acid and oleic acid triglyceride mixture at a flow rate of 1L / min, the ozone gas concentration in the mixed gas is 3% (v / v), stir at 400rpm, react at 20℃ for 8h, and obtain an intermediate containing peroxidized triglyceride and peroxidized oleic acid; the intermediate at the end of the reaction is the peroxide value should be 200meq / kg. The absorption of ozone is 80mg / g.

[0036] Step 2: The reaction temperature is 70°C, oxygen is introduced into the intermediate at an oxygen flow rate of 0.5 L / kg, and the reaction is carried out for 8 hours to finally prepare peroxidized triglyceride rich in azelaic acid.

[0037] Example 3

[0038] A method for preparing peroxidized triglyceride rich in azelaic acid comprises the following steps: Step 1: Mix 5 parts of oleic acid with 95 parts of dioleyl-stearate triglyceride, pass ozone / oxygen mixed gas into 350g of oleic acid and oleic triglyceride mixture at a flow rate of 1L / min, the ozone gas concentration in the mixed gas is 3% (v / v), stir at 400rpm, react at 20℃ for 14h, and obtain an intermediate containing peroxidized triglyceride and peroxidized oleic acid; the peroxide value of the intermediate at the end of the reaction should be 240meq / kg. The absorption of ozone is 120mg / g.

[0039] Step 2: The reaction temperature is 95°C, oxygen is introduced into the intermediate at an oxygen flow rate of 0.5 L / kg, and the reaction is carried out for 8 hours to finally prepare peroxidized triglyceride rich in azelaic acid.

[0040] Example 4

[0041] A method for preparing peroxidized triglyceride rich in azelaic acid comprises the following steps: Step 1: Mix 20 parts of oleic acid with 80 parts of triglyceride, pass ozone / oxygen mixed gas into 350g of oleic acid and oleic triglyceride mixture at a flow rate of 1L / min, the ozone gas concentration in the mixed gas is 5% (v / v), stir at 400rpm, react at 20℃ for 14h, and obtain an intermediate containing peroxidized triglyceride and peroxidized oleic acid; the peroxide value of the intermediate at the end of the reaction should be 280meq / kg. The absorption of ozone is 144mg / g.

[0042] Step 2: The reaction temperature is 95°C, oxygen is introduced into the intermediate at an oxygen flow rate of 0.5 L / kg, and the reaction is carried out for 8 hours to finally prepare peroxidized triglyceride rich in azelaic acid.

[0043] Example 5

[0044] A method for preparing peroxidized triglyceride rich in azelaic acid comprises the following steps: Step 1: Mix 5 parts of oleic acid with 95 parts of linoleic triglyceride, pass ozone / oxygen mixed gas into 350g of oleic acid and oleic triglyceride mixture at a flow rate of 1L / min, the ozone gas concentration in the mixed gas is 3% (v / v), stir at 400rpm, react at 20℃ for 14h, and obtain an intermediate containing peroxidized triglyceride and peroxidized oleic acid; the peroxide value of the intermediate at the end of the reaction should be 260meq / kg. The absorption of ozone is 130mg / g.

[0045] Step 2: The reaction temperature is 95°C, oxygen is introduced into the intermediate, the oxygen ventilation rate is 0.4 L / kg, and the reaction is carried out for 10 hours to finally prepare peroxidized triglyceride rich in azelaic acid.

[0046] Example 6

[0047] A method for preparing peroxidized triglyceride rich in azelaic acid comprises the following steps: Step 1: Mix 20 parts of oleic acid with 80 parts of dioleyl-linoleyl triglyceride, pass ozone / oxygen mixed gas into 350g of oleic acid and oleic triglyceride mixture at a flow rate of 1L / min, the ozone gas concentration in the mixed gas is 4% (v / v), stir at 400rpm, react at 20℃ for 14h, and obtain an intermediate containing peroxidized triglyceride and peroxidized oleic acid; the peroxide value of the intermediate at the end of the reaction should be 270meq / kg. The absorption of ozone is 135mg / g.

[0048] Step 2: The reaction temperature is 95°C, oxygen is introduced into the intermediate, and the oxygen ventilation rate is 0.6 L / kg. The reaction is carried out for 8 hours to finally prepare the peroxidized triglyceride rich in azelaic acid. The appearance of the obtained peroxidized triglyceride rich in azelaic acid is as follows: Figure 1 The appearance of the azelaic acid-rich peroxidized triglyceride obtained in Examples 1 to 5 is also clear and transparent without impurities. Figure 1 shown.

[0049] Comparative Example 1 A method for preparing an oil rich in azelaic acid peroxidized triglyceride comprises the following steps: Step 1: Mix 40 parts of oleic acid with 60 parts of triglyceride, pass ozone / oxygen mixed gas into 350g of oleic acid and oleic triglyceride mixture at a flow rate of 1L / min, the ozone gas concentration in the mixed gas is 3% (v / v), stir at 400rpm, react at 20℃ for 8h, and obtain an intermediate containing peroxidized triglyceride and peroxidized oleic acid; the peroxide value of the intermediate at the end of the reaction is 200meq / kg. The absorption of ozone is 80mg / g.

[0050] Step 2: Raise the reaction temperature to 70°C, introduce oxygen into the intermediate at an oxygen flow rate of 0.5 L / kg, and react for 8 hours to finally prepare azelaic acid-rich peroxidized triglyceride. The appearance of the obtained azelaic acid-rich peroxidized triglyceride is as follows: Figure 2 As shown, it is turbid and has poor solubility.

[0051] Comparative Example 2 A method for preparing an oil rich in azelaic acid peroxidized triglyceride comprises the following steps: Step 1: Mix 2 parts of oleic acid with 98 parts of triglyceride, pass ozone / oxygen mixed gas into 350g of oleic acid and oleic triglyceride mixture at a flow rate of 1L / min, the ozone gas concentration in the mixed gas is 3% (v / v), stir at 400rpm, react at 20℃ for 8h, and obtain an intermediate containing peroxidized triglyceride and peroxidized oleic acid; the peroxide value of the intermediate at the end of the reaction is 200meq / kg. The absorption of ozone is 80mg / g.

[0052] Step 2: Raise the reaction temperature to 70°C, introduce oxygen into the intermediate at an oxygen flow rate of 0.5 L / kg, and react for 8 hours to finally prepare azelaic acid-rich peroxidized triglyceride.

[0053] Comparative Example 3 A method for preparing an oil rich in azelaic acid peroxidized triglyceride comprises the following steps: Step 1: Pass an ozone / oxygen mixed gas into 350g of triglyceride at a flow rate of 1L / min, the ozone concentration in the mixed gas is 3% (v / v), stir at 400rpm, react at 20℃ for 8h, and prepare peroxidized triglyceride with a peroxide value of 200 meq / kg. The absorption of ozone is 80mg / g.

[0054] Step 2: Raise the reaction temperature to 70°C, introduce oxygen into the intermediate at an oxygen flow rate of 0.5 L / kg, and react for 8 hours to finally prepare peroxidized triglyceride.

[0055] Step 3: 0.5 parts of azelaic acid and 99.5 parts of peroxidized triglyceride were mixed at a speed of 300 rpm and a stirring temperature of 95°C to finally prepare a peroxidized triglyceride oil containing azelaic acid. The appearance of the obtained peroxidized triglyceride rich in azelaic acid is as follows: Figure 3 As shown, it is turbid and has poor solubility.

[0056] Comparative Example 4 A method for preparing an oil rich in azelaic acid peroxidized triglyceride comprises the following steps: Step 1: Mix 5 parts of oleic acid with 95 parts of triglyceride, pass ozone / oxygen mixed gas into 350g of oleic acid and oleic triglyceride mixture at a flow rate of 1L / min, the ozone gas concentration in the mixed gas is 3% (v / v), stir at 400rpm, react at 20℃ for 8h, and obtain an intermediate containing peroxidized triglyceride and peroxidized oleic acid; the peroxide value of the intermediate at the end of the reaction should be 200meq / kg. The absorption of ozone is 80mg / g.

[0057] Step 2: The reaction temperature is 100° C., oxygen is introduced into the intermediate at an oxygen flow rate of 0.5 L / kg, and the reaction is carried out for 8 hours to finally prepare peroxidized triglyceride rich in azelaic acid.

[0058] The prepared peroxidized triglyceride rich in azelaic acid was subjected to qualitative and quantitative detection of azelaic acid, and the operation steps were as follows: 1. Qualitative detection of azelaic acid by liquid mass spectrometry The samples prepared in Example 6 were qualitatively tested by Shimadzu LCMS-8040 triple quadrupole liquid-mass spectrometry system. The chromatographic column used was WomdaSil C18 (250 mm × 4.6 mm, 5 um). The mobile phase A was 0.1% formic acid aqueous solution, the mobile phase B was acetonitrile, the mobile phase flow rate was 1 ml / min, the injection volume was 10 ul, the column temperature was 40°C, and the gradient elution program was as shown in Table 1. The ion source was ESI, and the MRM parameters were as shown in Table 2. The sample was extracted with boiling water, and the water layer was diluted with 50% methanol water for sample analysis. The test results were as shown in Table 1. Figure 4 shown.

[0059] Table 1 Gradient elution time program

[0060] Table 2 MRM parameters

[0061] Figure 4 It is shown that azelaic acid exists in the azelaic acid-rich peroxidized triglyceride prepared in Example 1. Likewise, azelaic acid also exists in the azelaic acid-rich peroxidized triglyceride prepared in Examples 2-6.

[0062] 2. Liquid phase quantitative detection A Shimadzu LC-20A liquid chromatograph (UV-visible detector SPD-16, chromatographic column WondaSil C18-WR, 5μm, 4.6×150mm) was used, the mobile phase flow rate was 1ml / min, and gradient elution was adopted. The elution program is detailed in Table 3 below. The column temperature was 30°C, and azelaic acid had a maximum absorption peak at a detection wavelength of 215nm. Mobile phase: Phase A 50mmol / L sodium dihydrogen phosphate, PH 3; Phase B acetonitrile. The sample was dissolved in isopropanol and 20µl was injected. The azelaic acid content in Examples 1, 2, 3, 4, 5, 6 and Comparative Examples 1 and 2 was quantitatively detected respectively. The detection results of peroxidized triglycerides rich in azelaic acid in Example 1 are shown as follows. Figure 5 shown.

[0063] Table 3 Gradient elution time program

[0064] The azelaic acid content in Examples 1, 2, 3, 4, 5, 6 and Comparative Examples 1 and 2 is as follows: Figure 6 As shown. Comparative Example 4 produced a large amount of by-products due to the high temperature, resulting in a low azelaic acid content of only 0.181%, which is much lower than Example 1. The azelaic acid content of Comparative Examples 2 and 4 is low, and the therapeutic effect is worse than that of Example 1. 2. Animal Experiments on Acute Light Damage

[0065] The prepared azelaic acid-rich peroxidized triglyceride was subjected to an acute light damage animal experiment as follows: 2.1 Purpose of the experiment To study the therapeutic effect of azelaic acid-rich peroxidized triglyceride on acute photodamage, a guinea pig model of acute photodamage induced by ultraviolet light was established to explore its therapeutic effect on photodamage.

[0066] 2.2 Experimental methods (1) Research subjects and groups: 16 male guinea pigs, 6-8 weeks old (250-350 g), were randomly divided into 4 groups, namely, UVB model group, azelaic acid oil group, and peroxidized triglyceride group, with 4 guinea pigs in each group. The light, temperature (24±1℃), humidity and other feeding conditions of the experimental guinea pigs in each group were the same.

[0067] (2) Modeling method: The guinea pigs were shaved on their backs, with an area of ​​4 cm × 5 cm. A broad-spectrum UVB phototherapy device (PL-S 9W / 12) was used to irradiate the hair removal area on the backs of the experimental guinea pigs in each group. The daily irradiation dose was 3.75 J / cm2, the irradiation intensity was 12 mW / cm2, the irradiation time was 5 min, and the distance between the light source and the shaved area was about 15 cm. The irradiation was performed once a day, and the naked eye observation for 2 consecutive days indicated that the modeling was successful.

[0068] (3) Intervention method: After successful modeling, drugs were applied to the back irradiated area once a day for 5 consecutive days. The azelaic acid oil group was applied with the oil prepared in Example 4, the peroxidized triglyceride group was applied with the oil prepared in Comparative Example 3, and the azelaic acid gel group was treated with Finacea azelaic acid gel (30 g, azelaic acid content 15%, w / w). The UVB model group did not receive any treatment.

[0069] 2.3 Experimental Results The experimental results are as follows Figure 7 As shown in the figure, A is the acute light damage model group (UVB model group), B is the peroxidized triglyceride group, C is the azelaic acid gel group, and D is the azelaic acid oil group. In the UVB model group, obvious erythema, scabs, and scales were seen in the irradiated area on the back of the guinea pigs. Compared with the model group, the azelaic acid oil group recovered faster, the scabs on the back of the experimental animals were reduced, and the inflammation subsided significantly. The azelaic acid gel group was relieved compared with the model group, but recovered worse than the azelaic acid oil group.

[0070] like Figure 8 The results of reflective confocal microscopy showed that in the figure, A was the acute light damage model group (UVB model group), B was the azelaic acid gel group, C was the peroxidized triglyceride group, and D was the azelaic acid oil group. The epidermis in the UVB model group was thickened, and more inflammatory cells were seen infiltrating the superficial dermis in the dermis. Compared with the UVB model group, the peroxidized triglyceride group and the azelaic acid oil group had less edema and inflammatory cell infiltration in the dermal papillary layer. However, the effect of the azelaic acid oil group was significantly better than that of the peroxidized triglyceride group and the azelaic acid gel group. 3. Clinical application observation experiment

[0071] This experiment aims to observe whether azelaic acid oil and azelaic acid gel have protective and therapeutic effects on acute photodamage induced by simulated sunlight exposure.

[0072] Ten healthy female volunteers were recruited, and each volunteer signed an informed consent form. Inclusion criteria: no systemic disease or skin disease; no systemic treatment or local skin treatment; no history of photosensitivity; The minimum erythema dose of each volunteer was measured before the start of the test. The following operations were performed on 4 parts of the volunteer's back: Part 1 was smeared with azelaic acid oil (Example 4), Part 2 was smeared with azelaic acid gel (Finacea Azelaic Acid Gel, 30g, azelaic acid content 15%, w / w), Part 3 was only irradiated with a solar simulator without applying the test sample, and Part 4 was neither irradiated nor applied with the test sample. Each irradiated part was irradiated once a day for 5 consecutive days. The EI value was measured by a narrow-band reflectance spectrophotometer before the start of the test and after the last irradiation. Each part was tested three times and the average value was taken.

[0073] The EI value reflects the degree of erythema of the skin. Before the test, the EI value fluctuated between 184.15 and 200. After the study, the EI values ​​of sites 1-3 increased significantly, especially sites 2 and 3. They increased from 200 and 175.4 before treatment to 561.12 and 523.12 respectively. Site 1 increased less, from 197.23 before treatment to 452.12. It was also observed that the pigmentation of site 2 was more significant than that of site 1.

[0074] This shows that azelaic acid oil has a protective effect on the skin in simulating acute photodamage induced by sunlight exposure, while also being able to reduce pigmentation.

[0075] It should be noted that the above embodiments are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the embodiments here. Any obvious changes or modifications derived from the technical solution of the present invention are still within the scope of protection of the present invention.

Claims

1. A method for preparing peroxidized triglyceride rich in azelaic acid, characterized in that: The following steps are involved: S1. After mixing oleic acid and triglyceride, a mixed gas of ozone and oxygen is introduced under stirring, and the mixture is reacted at 20-30° C. for 8-14 hours to obtain an intermediate product; S2. Pass oxygen into the intermediate product at 70° C.-95° C. and react for 6-10 hours to obtain peroxidized triglyceride rich in azelaic acid.

2. The preparation method according to claim 1, characterized in that: The triglyceride is one or more of oleic acid triglyceride, dioleic acid palmitic acid triglyceride, dioleic acid stearic acid triglyceride, dioleic acid linoleic acid triglyceride, and linoleic acid triglyceride.

3. The preparation method according to claim 1, characterized in that: In the step S1, the volume ratio of oleic acid to triglyceride is 5-20:80-95.

4. The preparation method according to claim 1, characterized in that: In step S1, in the mixed gas of ozone and oxygen, the volume ratio of ozone to oxygen is 3-5:95-97.

5. The preparation method according to claim 1, characterized in that: In the step S1, the introduction rate of the mixed gas of ozone and oxygen is 0.5-1.5 L / min.

6. The preparation method according to claim 1, characterized in that: In the step S1, the peroxide value of the intermediate product is 200-280 meq / kg; the ozone absorption of the intermediate product is 80-144 mg / g.

7. The preparation method according to claim 1, characterized in that: In step S2, the oxygen ventilation volume is 0.2-0.7 L / kg.

8. The preparation method according to any one of claims 1 to 7, characterized in that: The content of azelaic acid in the peroxidized triglyceride rich in azelaic acid is 0.5-2.5wt%.

9. A peroxidized triglyceride rich in azelaic acid prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the peroxidized triglyceride rich in azelaic acid according to claim 9 in the preparation of a drug for treating or preventing acute photodamage, chronic photodamage, barrier repair, anti-inflammation or reducing pigmentation.

Images