Cosmetic containing phloretin modified with tetraacetylglucoside and method for preparing the same

Abstract

The application provides a novel method for preparing a phloretin derivative. The method comprises modifying and grafting a hydroxyl group in p-hydroxyphenylpropionic acid in a raw material for synthesizing phloretin in advance, and then performing a synthesis reaction with phloroglucinol, i.e. m-benzene triol, to obtain a corresponding phloretin derivative, i.e. tetraacetyl glucoside modified phloretin. The derivative retains the antioxidant and anti-inflammatory properties of phloretin, and has good water solubility and skin absorption efficiency. Therefore, the obtained phloretin derivative can be widely applied to various forms of cosmetic products, and has excellent antioxidant and anti-inflammatory effects.

Description

Technical Field

[0001] The present invention relates to the field of cosmetics, in particular to cosmetics containing tetraacetyl glucoside-modified phloretin and a preparation method thereof. Background Art

[0002] Cosmetics are products that are applied to the surface of the human body by smearing or other similar methods to cleanse, maintain, or beautify the surface. Currently, there are many types of cosmetics on the market, among which those that relieve skin inflammation, provide antioxidants, and combat aging are the most popular among women.

[0003] Phloretin, also known as 2,4,6-trihydroxy-3-(4-hydroxyphenyl)propiophenone, is a natural flavonoid compound that is mainly found in the peels and root barks of juicy fruits such as apples and pears, as well as in the juices of various vegetables. Phloretin has whitening and acne-removing, anti-oxidant, and anti-inflammatory effects, and has been widely added to various cosmetics. However, when phloretin is added to the formula as a functional ingredient and directly applied to the surface of human skin, it easily forms a solid powder that adheres to the skin, which is likely to irritate the skin. In addition, the drug cannot effectively penetrate the skin surface and reach the blood circulation system, which greatly limits the skin anti-inflammatory effect of phloretin.

[0004] To this end, there are technical reports that formulate phloretin-containing preparations or compositions into thermosensitive gels, which maintain a semi-solid state during use, thereby prolonging the duration of phloretin's action on the human skin surface, increasing its absorption by the skin and exhibiting a good anti-inflammatory effect. However, gel products limit the diverse applications of phloretin.

[0005] In addition, phloretin has poor water solubility, and the absorption and utilization rate of phloretin by human skin is relatively low. Even if the preparation or composition containing phloretin is made into a thermosensitive gel to prolong the action time of phloretin on the surface of human skin, this cannot fundamentally improve the absorption efficiency of phloretin by human skin.

[0006] To this end, the present invention aims to improve the water solubility of phloretin derivatives and the absorption efficiency of phloretin derivatives by human skin by modifying phloretin, thereby enriching the application diversity of cosmetics containing phloretin derivatives and improving the skin inflammation relief, anti-oxidation and anti-aging effects of cosmetics containing phloretin derivatives. Summary of the Invention

[0007] In order to solve the above-mentioned problems existing in existing cosmetics containing phloretin, the present invention provides a novel tetraacetyl glucoside-modified phloretin derivative, a preparation method thereof, and cosmetics containing the phloretin derivative. Phloretin, namely 2,4,6-trihydroxy-3-(4-hydroxyphenyl)propiophenone, has antioxidant and anti-inflammatory properties mainly derived from the "2,4,6-trihydroxy" group therein, namely the phloretin group or phloretinol group. Therefore, in the process of modifying phloretin, in order to ensure the antioxidant and anti-inflammatory properties of the modified phloretin derivative, the "2,4,6-trihydroxy" group needs to be protected so that it is not changed. That is, the modified group should be grafted onto the hydroxyl group in the "4-hydroxyphenyl" group. However, in the phloretin molecule, the hydroxyl group in the "2,4,6-trihydroxy" group and the hydroxyl group in the "4-hydroxyphenyl" group are both phenolic hydroxyl groups, and their activities are relatively similar. Directly modifying and grafting the phloretin molecule can easily cause grafting modification on the hydroxyl group in "2,4,6-trihydroxy" and the hydroxyl group in "4-hydroxyphenyl" at the same time, which reduces the antioxidant and anti-inflammatory properties of the modified phloretin derivatives. In order to avoid this situation, the present invention provides a new method for preparing phloretin derivatives modified with tetraacetyl glucoside, by pre-modifying and grafting the hydroxyl group in p-hydroxyphenylpropionic acid in the raw material for synthesizing phloretin, and then performing a synthetic reaction with phloretinol, i.e., phloretinol, to obtain the corresponding phloretin derivatives. A method for preparing a phloretin derivative modified with tetraacetyl glucoside comprises the following steps:

[0008] (1) Glucose monohydrate is added to 3-5 times the molar amount of acetic anhydride, and 5-6 times the molar amount of triethylamine is added dropwise under ice-water bath conditions. After reacting for 2 hours, sufficient water is added to precipitate the product. After filtering, the filter cake is washed with water and then vacuum-dried to obtain pentaacetyl glucose; the dried pentaacetyl glucose is dissolved in dichloromethane, and hydrobromic acid 2.5-4 times the molar amount of pentaacetyl glucose is added dropwise at room temperature, wherein the hydrobromic acid is provided as a hydrobromic acid acetic acid solution with a mass concentration of 30%. After reacting for 1.5-3 hours, the mixture is poured into ice water, the aqueous phase is extracted with dichloromethane, the organic phases are combined, and the organic phases are quickly washed with saturated sodium bicarbonate solution and saturated brine to a pH value of 7, dried over anhydrous magnesium sulfate, and filtered. The filtrate is distilled under reduced pressure at room temperature to recover dichloromethane to obtain a white bromotetraacetyl glucose product.

[0009] (2) Sodium p-hydroxyphenylpropionate tetraacetyl glucoside

[0010] Aqueous solutions of sodium p-hydroxyphenylpropionate, sodium hydroxide and potassium iodide are added to a reaction vessel and stirred for reaction at room temperature, wherein the concentration of sodium p-hydroxyphenylpropionate is 0.2-0.5 mol / L, the concentration of sodium hydroxide is 20-50 g / L, and the concentration of potassium iodide is 1-3 g / L. Bromotetraacetyl glucose dissolved in acetone is then added dropwise to the reaction vessel. After stirring at room temperature for 6-8 hours, a solid is precipitated, namely sodium p-hydroxyphenylpropionate tetraacetyl glucoside. After filtration, the solid is washed with sodium hydroxide and deionized water to obtain solid sodium p-hydroxyphenylpropionate tetraacetyl glucoside.

[0011] (3) Sodium p-hydroxyphenylpropionic acid tetraacetyl glucoside, acetic acid, and phloroglucinol are dissolved in ethyl acetate solvent, and reacted for 4-8 hours under the catalytic action of boron trifluoride ether to obtain tetraacetyl glucoside-modified phloretin as shown in formula (I). After separation by distillation, the tetraacetyl glucoside-modified phloretin product can be obtained.

[0012]

[0013] The molar ratio of sodium p-hydroxyphenylpropionate tetraacetyl glucoside, acetic acid, and phloroglucinol is 1:(1.5-2):(1.5-2). In step (2), the ratio of the molar amount of the added tetraacetyl glucoside bromide to the molar amount of sodium p-hydroxyphenylpropionate is (1.2-1.5):1, thereby increasing the yield of sodium p-hydroxyphenylpropionate tetraacetyl glucoside.

[0014] Wherein, in step (3), the amount of the catalyst boron trifluoride etherate is 1-5 g based on the molar amount of sodium p-hydroxyphenylpropionic acid tetraacetyl glucoside.

[0015] The tetraacetyl glucoside-modified phloretin synthesized by the present invention retains the phloretinol group, ensuring the antioxidant and anti-inflammatory properties of the tetraacetyl glucoside-modified phloretin. Furthermore, the tetraacetyl glucoside group is grafted onto the phenolic hydroxyl group of the "4-hydroxyphenyl" group, improving the water solubility and skin absorption efficiency of the phloretin derivative. This allows the resulting phloretin derivative to be widely used in various cosmetic products and exhibits excellent antioxidant and anti-inflammatory properties.

[0016] A cosmetic containing tetraacetyl glucoside-modified phloretin, characterized in that the content of the tetraacetyl glucoside-modified phloretin is 1-3 wt.%.

[0017] Furthermore, the cosmetic is one of a nourishing cream, a facial mask, a facial cream, a lotion, an essence, a cream, and a patch.

[0018] Furthermore, the cosmetic is a nourishing cream, and the nourishing cream comprises the following components in the following weight percentages:

[0019] 1-3% tetraacetyl glucoside-modified phloretin, 1-2% hydrogenated lanolin, 0.5-2% polyoxyethylene sorbitan monostearate, 6-8% beeswax, 1-2% cetyl alcohol, 2-4% caprylic / capric triglyceride, 6-10% glycerol, 3-4% liquid paraffin, 0.1-0.5% triethanolamine, 0.1-0.2% flavor, and the balance deionized water.

[0020] Furthermore, the cosmetic is a facial mask, and the facial mask comprises the following components in the following weight percentages:

[0021] Tetraacetyl glucoside-modified phloretin 1-3%, carbomer 0.2-1%, triethanolamine 0.3-0.5%, ascorbic acid polypeptide 2-3%, palmitoyl pentapeptide-4 3-5%, glycerin 8-12%, hydroxypropyl methylcellulose 2-4%, propylene glycol 3-5%, hydrolyzed gelatin 2-4%, sorbitan sesquioleate 1-2%, hydrogenated lanolin 1-2%, caprylic / capric triglyceride 2-4%, deionized water balance. DETAILED DESCRIPTION

[0022] The following will illustrate the content of the present invention through specific examples, but these contents are not the entire content of the present invention. First, the tetraacetyl glucoside-modified phloretin of the present invention is prepared according to the following preparation method:

[0023] (1) Glucose monohydrate is added to 3 times the molar amount of acetic anhydride, and 5 times the molar amount of triethylamine is added dropwise under ice-water bath conditions. After reacting for 2 hours, sufficient water is added to precipitate the product. After filtering, the filter cake is washed with water and then vacuum-dried to obtain pentaacetyl glucose; the dried pentaacetyl glucose is dissolved in dichloromethane, and hydrobromic acid 3 times the molar amount of pentaacetyl glucose is added dropwise at room temperature, wherein the hydrobromic acid is provided as a hydrobromic acid-acetic acid solution with a mass concentration of 30%. After reacting for 2.5 hours, the mixture is poured into ice water, the aqueous phase is extracted with dichloromethane, the organic phases are combined, and the organic phases are quickly washed with saturated sodium bicarbonate solution and saturated salt water to a pH value of 7, dried over anhydrous magnesium sulfate, and filtered. The filtrate is distilled under reduced pressure at room temperature to recover dichloromethane to obtain a white bromotetraacetyl glucose product.

[0024] (2) Sodium p-hydroxyphenylpropionate tetraacetyl glucoside

[0025] Aqueous solutions of sodium p-hydroxyphenylpropionate, sodium hydroxide and potassium iodide are added to a reaction vessel and stirred for reaction at room temperature, wherein the concentration of sodium p-hydroxyphenylpropionate is 0.3 mol / L, the concentration of sodium hydroxide is 40 g / L, and the concentration of potassium iodide is 2 g / L. Bromotetraacetyl glucose dissolved in acetone is then added dropwise to the reaction vessel. After stirring and reacting at room temperature for 6 hours, a solid is precipitated, namely sodium p-hydroxyphenylpropionate tetraacetyl glucoside. After filtration, the solid is washed with sodium hydroxide and deionized water in turn to obtain solid sodium p-hydroxyphenylpropionate tetraacetyl glucoside.

[0026] (3) Sodium p-hydroxyphenylpropionic acid tetraacetyl glucoside, acetic acid, and phloroglucinol are dissolved in ethyl acetate solvent, and reacted for 5 hours under the catalytic action of boron trifluoride ether to obtain tetraacetyl glucoside-modified phloretin as shown in formula (I). After distillation and separation, the tetraacetyl glucoside-modified phloretin product can be obtained.

[0027]

[0028] The molar ratio of sodium p-hydroxyphenylpropionate tetraacetyl glucoside, acetic acid, and phloroglucinol is 1:1.5:1.5; in step (2), the ratio of the molar amount of the added tetraacetyl glucoside bromide to the molar amount of sodium p-hydroxyphenylpropionate is 1.3:1; in step (3), the amount of the catalyst boron trifluoride etherate used is 3 g based on 1 mole of sodium p-hydroxyphenylpropionate tetraacetyl glucoside.

[0029] Then, referring to the following component requirements, the prepared tetraacetyl glucoside-modified phloretin is added to the nourishing cream and facial mask products to prepare the corresponding nourishing cream and facial mask products.

[0030] The nutrient cream comprises the following components in the following weight percentages:

[0031] 1-3% tetraacetyl glucoside-modified phloretin, 1-2% hydrogenated lanolin, 0.5-2% polyoxyethylene sorbitan monostearate, 6-8% beeswax, 1-2% cetyl alcohol, 2-4% caprylic / capric triglyceride, 6-10% glycerol, 3-4% liquid paraffin, 0.1-0.5% triethanolamine, 0.1-0.2% flavor, and the balance deionized water.

[0032] The facial mask includes the following components in the following weight percentages:

[0033] Tetraacetyl glucoside-modified phloretin 1-3%, carbomer 0.2-1%, triethanolamine 0.3-0.5%, ascorbic acid polypeptide 2-3%, palmitoyl pentapeptide-4 3-5%, glycerin 8-12%, hydroxypropyl methylcellulose 2-4%, propylene glycol 3-5%, hydrolyzed gelatin 2-4%, sorbitan sesquioleate 1-2%, hydrogenated lanolin 1-2%, caprylic / capric triglyceride 2-4%, deionized water balance.

[0034] Specifically, the specific compositions and performance test results of the corresponding embodiments are given in Tables 1 and 2. The performance tests include antioxidant test, anti-inflammatory test and user experience evaluation.

[0035] The antioxidant test includes DPPH free radical inhibition rate, OH free radical inhibition rate and O 2- The anti-inflammatory activity was tested using a mouse ear swelling test. The corresponding nutrient cream and mask solution were directly applied to the red and swollen areas of the mouse ears. The application dosage was 100 mg / kg body weight based on the mass of tetraacetyl glucoside-modified phloretin, and the swelling inhibition rate was then calculated.

[0036] The criteria for user experience evaluation are:

[0037] 3 points: Comfortable, with good anti-inflammatory and antioxidant effects.

[0038] 2 points: relatively comfortable, with average anti-inflammatory and antioxidant effects.

[0039] 1 point: relatively comfortable, with no obvious anti-inflammatory and antioxidant effects.

[0040] 0 points: Uncomfortable, with no obvious anti-inflammatory and antioxidant effects.

[0041] Table 1

[0042]

[0043]

[0044] Table 2

[0045]

[0046]

[0047] As can be seen from Tables 1 and 2 above, the tetraacetyl glucoside-modified phloretin of the present invention exhibits excellent anti-inflammatory and antioxidant effects when applied to cosmetics. Furthermore, the user experience is comfortable and effective, demonstrating that the product has a high absorption rate on the skin surface and does not cause sensitivity irritation.

Claims

1. A method for preparing tetraacetyl glucoside-modified phloretin, comprising the following steps: (1) Preparation of brominated tetraacetyl glucose Glucose monohydrate is added to 3-5 times the molar amount of acetic anhydride, and 5-6 times the molar amount of triethylamine is added dropwise under ice-water bath. After reacting for 2 hours, sufficient water is added to precipitate the product, and the filter cake is filtered, washed with water, and then vacuum-dried to obtain pentaacetyl glucose; the dried pentaacetyl glucose is dissolved in dichloromethane, and hydrobromic acid in an amount of 2.5-4 times the molar amount of the pentaacetyl glucose is added dropwise at room temperature, wherein the hydrobromic acid is provided as a 30% by mass hydrobromic acid-acetic acid solution. After reacting for 1.5-3 hours, the mixture is poured into ice water, the aqueous phase is extracted with dichloromethane, the organic phases are combined, and the organic phases are quickly washed with saturated sodium bicarbonate solution and saturated brine respectively until the pH value is 7, dried over anhydrous magnesium sulfate, and filtered. The filtrate is distilled under reduced pressure at room temperature to recover the dichloromethane to obtain a white bromotetraacetyl glucose product; (2) Preparation of sodium p-hydroxyphenylpropionate tetraacetyl glucoside Aqueous solutions of sodium p-hydroxyphenylpropionate, sodium hydroxide, and potassium iodide are added to a reaction vessel and stirred for reaction at room temperature, wherein the concentration of sodium p-hydroxyphenylpropionate is 0.2-0.5 mol / L, the concentration of sodium hydroxide is 20-50 g / L, and the concentration of potassium iodide is 1-3 g / L. Bromotetraacetyl glucose dissolved in acetone is then added dropwise to the reaction vessel. After stirring and reacting at room temperature for 6-8 hours, a solid is precipitated, namely sodium p-hydroxyphenylpropionate tetraacetyl glucoside. After suction filtration, the solid is washed with sodium hydroxide and deionized water to obtain solid sodium p-hydroxyphenylpropionate tetraacetyl glucoside. (3) Preparation of tetraacetyl glucoside-modified phloretin Sodium p-hydroxyphenylpropionic acid tetraacetyl glucoside, acetic acid, and phloroglucinol are dissolved in ethyl acetate solvent, and reacted for 4-8 hours under the catalytic action of boron trifluoride etherate to obtain tetraacetyl glucoside-modified phloretin represented by formula (I), and after separation by distillation, a tetraacetyl glucoside-modified phloretin product can be obtained; The molar ratio of sodium p-hydroxyphenylpropionate tetraacetyl glucoside, acetic acid and phloroglucinol is 1:(1.5-2):(1.5-2).

2. The method for preparing tetraacetyl glucoside-modified phloretin according to claim 1, wherein: In step (2), the ratio of the molar amount of the added tetraacetyl glucose bromide to the molar amount of sodium p-hydroxyphenylpropionate is (1.2-1.5):

1.

3. The method for preparing tetraacetyl glucoside-modified phloretin according to claim 1, wherein: In step (3), the amount of the catalyst boron trifluoride etherate is 1-5 g based on 1 mole of sodium p-hydroxyphenylpropionic acid tetraacetyl glucoside.

4. A tetraacetyl glucoside-modified phloretin, characterized in that: The invention is prepared by the preparation method according to any one of claims 1 to 3.

5. A cosmetic containing the tetraacetyl glucoside-modified phloretin according to claim 4, characterized in that: The content of the tetraacetyl glucoside-modified phloretin is 1-3 wt.%.

6. The cosmetic according to claim 5, wherein The cosmetic is one of a nourishing cream, a facial mask, a facial cream, a moisturizing lotion, an essence, a cream, and a plaster.

7. The cosmetic according to claim 6, wherein The cosmetic is a nourishing cream, and the nourishing cream includes the following components in percentage by weight: 1-3% tetraacetyl glucoside-modified phloretin, 1-2% hydrogenated lanolin, 0.5-2% polyoxyethylene sorbitan monostearate, 6-8% beeswax, 1-2% cetyl alcohol, 2-4% caprylic / capric triglyceride, 6-10% glycerol, 3-4% liquid paraffin, 0.1-0.5% triethanolamine, 0.1-0.2% flavor, and the balance deionized water.

8. The cosmetic according to claim 6, wherein The cosmetic is a facial mask, and the facial mask comprises the following components in the following weight percentages: Tetraacetyl glucoside-modified phloretin 1-3%, carbomer 0.2-1%, triethanolamine 0.3-0.5%, ascorbic acid polypeptide 2-3%, palmitoyl pentapeptide-4 3-5%, glycerin 8-12%, hydroxypropyl methylcellulose 2-4%, propylene glycol 3-5%, hydrolyzed gelatin 2-4%, sorbitan sesquioleate 1-2%, hydrogenated lanolin 1-2%, caprylic / capric triglyceride 2-4%, deionized water balance.

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