4-butylresorcinol cyclodextrin inclusion compound as well as preparation method and application thereof

Abstract

The invention provides a 4-butylresorcinol cyclodextrin inclusion compound as well as a preparation method and application thereof. The inclusion compound is prepared from the following raw materials in parts by weight: 10 to 15 parts of 4-butylresorcinol, 40 to 50 parts of modified hydroxypropyl-beta-cyclodextrin and 260 to 350 parts of ethanol. The preparation method of the modified hydroxypropyl-beta-cyclodextrin comprises the following steps: (1) carrying out ammonia gas blasting treatment on hydroxypropyl-beta-cyclodextrin, so as to obtain pretreated hydroxypropyl-beta-cyclodextrin; (2) putting the pretreated hydroxypropyl-beta-cyclodextrin, pyrrolidone carboxylic acid and water into a reaction kettle, then adding an EDC / NHS solution, heating, stirring and cooling to obtain a reaction solution; and (3) dialyzing the reaction liquid with deionized water, and then freeze-drying. Compared with the traditional formula, the cyclodextrin adopted by the invention is less, and the prepared 4-butylresorcinol cyclodextrin inclusion compound has higher inclusion rate and stability, and has higher application prospect in the field of cosmetics.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and in particular to a 4-butylresorcinol cyclodextrin inclusion compound, a preparation method and an application thereof. Background Art

[0002] 4-Butylresorcinol is a phenolic compound with multiple biological activities, widely used in medicine and cosmetics. For skin whitening, it effectively inhibits tyrosinase activity, blocking a key step in melanin synthesis, thereby reducing dark spots and brightening the skin tone. Its effectiveness is superior to traditional ingredients like arbutin, while being less irritating.

[0003] 4-Butylresorcinol-cyclodextrin inclusion complexes are supramolecular complexes formed by embedding 4-butylresorcinol into the hydrophobic cavity of cyclodextrins (such as hydroxypropyl-β-cyclodextrin). This complex significantly improves the solubility, stability, and bioavailability of 4-butylresorcinol. In cosmetics, this inclusion complex serves as a highly effective whitening agent, inhibiting tyrosinase activity and reducing melanin production. The inclusion of cyclodextrin also reduces skin irritation and prolongs the sustained release of the active ingredient, making it suitable for products such as spot-lightening serums and lotions. Furthermore, the inclusion of cyclodextrins addresses the susceptibility of 4-butylresorcinol to oxidative degradation, expanding its application in temperature-sensitive formulations.

[0004] Patent application number 202210702739.1 discloses an inclusion compound and its preparation method, as well as an external-use preparation and its preparation method. The provided inclusion compound comprises a host molecule and a guest molecule encapsulated in the host molecule; the host molecule comprises sulfobutyl-β-cyclodextrin, hydroxypropyl-γ-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxymethylated-β-cyclodextrin, amino-β-cyclodextrin, or methylated-β-cyclodextrin; the guest molecule comprises hydroquinone, resorcinol, phenylethyl resorcinol, hexyl resorcinol, 4-butyl resorcinol, 4-isobutyl resorcinol, isobutylamidothiazolyl resorcinol, or phloroglucinol; the molar ratio of host molecule to guest molecule is 1:1.1-3. The inclusion compound has a low content of host molecule, and the guest molecule has good stability, capable of maintaining a certain release rate to avoid burst release, and can effectively exert the efficacy of the guest molecule.

[0005] In the current 4-butylresorcinol-cyclodextrin inclusion complex, the molar ratio of 4-butylresorcinol to cyclodextrin is generally between 1:1 and 1:4. However, a higher content of cyclodextrin will reduce the ductility of the prepared essences, emulsions and other cosmetics, thereby affecting the performance and may affect the release efficiency of 4-butylresorcinol. However, if the amount of cyclodextrin added is small, its inclusion rate and stability will be affected. Summary of the Invention

[0006] The present invention aims to provide a 4-butylresorcinol-cyclodextrin inclusion compound, a preparation method and an application thereof. The cyclodextrin used is less than that in traditional formulas, and the prepared 4-butylresorcinol-cyclodextrin inclusion compound has a high inclusion rate and stability, and has a high application prospect in the field of cosmetics.

[0007] To achieve the above objectives, the present invention is implemented through the following technical solutions: A 4-butylresorcinol-cyclodextrin inclusion compound comprises the following raw materials in parts by weight: 10-15 parts of 4-butylresorcinol, 40-50 parts of modified hydroxypropyl-β-cyclodextrin, and 260-350 parts of ethanol.

[0008] Preferably, the preparation method of the modified hydroxypropyl-β-cyclodextrin comprises the following steps: (1) subjecting hydroxypropyl-β-cyclodextrin to ammonia explosion treatment to obtain pretreated hydroxypropyl-β-cyclodextrin; (2) Pretreated hydroxypropyl-β-cyclodextrin, pyrrolidone carboxylic acid, and water were placed in a reaction kettle, and then EDC / NHS solution was added. The temperature was raised to 55-60°C and stirred for 10-16 hours. The mixture was cooled to room temperature to obtain a reaction solution. (3) The reaction solution was dialyzed with deionized water and then freeze-dried to obtain modified hydroxypropyl-β-cyclodextrin.

[0009] Preferably, in step (1), when the ammonia explosion treatment is performed, the pressure is 1.6-1.9 MPa, the temperature is 90-95° C., and the time is 30-40 min.

[0010] Preferably, in step (2), the mass ratio of the pretreated hydroxypropyl-β-cyclodextrin to pyrrolidone carboxylic acid is 18-35:1.

[0011] Preferably, the mass ratio of the pretreated hydroxypropyl-β-cyclodextrin to pyrrolidone carboxylic acid is 25-27:1.

[0012] Preferably, in step (2), the molar ratio of EDC to NHS in the EDC / NHS solution is 1:1 to 1:4; The concentration of the EDC / NHS solution is 10-20 mg / mL; The mass volume ratio of the pyrrolidone carboxylic acid to the EDC / NHS solution is 1 g: 6-10 mL.

[0013] Preferably, the raw materials of the 4-butylresorcinol cyclodextrin inclusion compound further include 0.3-0.7 parts of polyethylene glycol, and the molecular weight of the polyethylene glycol is 200-300.

[0014] As a general inventive concept, the present invention also provides a method for preparing a 4-butylresorcinol cyclodextrin inclusion compound, comprising the following steps: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir to dissolve, add the remaining raw materials, and homogenize using a microfluidizer to obtain a mixed solution; S2. Spray-drying the mixed solution to obtain the 4-butylresorcinol-cyclodextrin inclusion compound.

[0015] Preferably, in step S1, the pressure of the homogenization treatment is 10,000-20,000 psi, and the number of homogenization treatments is 3-5 times; In step S2, the spray drying temperature is 82-88°C.

[0016] As a general inventive concept, the present invention also provides a 4-butylresorcinol-cyclodextrin inclusion compound or the use of the 4-butylresorcinol-cyclodextrin inclusion compound prepared by the above preparation method in cosmetics.

[0017] The beneficial effects of the present invention are: The present invention modifies hydroxypropyl-β-cyclodextrin by first performing an ammonia explosion treatment. This operation expands the cyclodextrin cavity, increasing its volume and enabling it to better accommodate the guest molecule 4-butylresorcinol. Simultaneously, after the ammonia explosion, amino groups are introduced into the hydroxypropyl-β-cyclodextrin. This, on the one hand, enhances the interaction between the cyclodextrin cavity and 4-butylresorcinol, strengthening the inclusion of 4-butylresorcinol. On the other hand, some amino groups react with pyrrolidone carboxylic acid, binding to the hydroxyl groups on hydroxypropyl-β-cyclodextrin and strengthening the binding of pyrrolidone carboxylic acid to hydroxypropyl-β-cyclodextrin. The present invention, through research, modifies pretreated hydroxypropyl-β-cyclodextrin with an appropriate amount of pyrrolidone carboxylic acid. The pyrrolidone carboxylic acid may condense with the pretreated hydroxypropyl-β-cyclodextrin via the carboxyl groups (under the catalysis of EDC / NHS), further improving the overall inclusion rate of hydroxypropyl-β-cyclodextrin for 4-butylresorcinol.

[0018] Furthermore, when preparing the 4-butylresorcinol cyclodextrin inclusion compound, the present invention introduces an appropriate amount of low molecular weight polyethylene glycol, which can further improve the inclusion rate of the 4-butylresorcinol cyclodextrin inclusion compound.

[0019] The present invention appropriately modifies hydroxypropyl-β-cyclodextrin and selectively combines an appropriate amount of polyethylene glycol. When preparing a 4-butylresorcinol-cyclodextrin inclusion compound, less cyclodextrin is used than in a traditional formula. The prepared 4-butylresorcinol-cyclodextrin inclusion compound has a high inclusion rate and stability, can effectively and stably exert its whitening, brightening and spot-lightening effects, and has high application prospects in the field of cosmetics. DETAILED DESCRIPTION

[0020] To make the objectives, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0021] A first aspect of the present invention provides a 4-butylresorcinol-cyclodextrin inclusion compound comprising the following raw materials in parts by weight: 10-15 parts of 4-butylresorcinol, 40-50 parts of modified hydroxypropyl-β-cyclodextrin, and 260-350 parts of ethanol.

[0022] The preparation method of modified hydroxypropyl-β-cyclodextrin comprises the following steps: (1) subjecting hydroxypropyl-β-cyclodextrin to ammonia explosion treatment to obtain pretreated hydroxypropyl-β-cyclodextrin; (2) Pretreated hydroxypropyl-β-cyclodextrin, pyrrolidone carboxylic acid, and water were placed in a reaction kettle, and then EDC / NHS solution was added. The temperature was raised to 55-60°C and stirred for 10-16 hours. The mixture was cooled to room temperature to obtain a reaction solution. (3) The reaction solution was dialyzed with deionized water and then freeze-dried to obtain modified hydroxypropyl-β-cyclodextrin.

[0023] The present invention uses ammonia explosion treatment to expand the cyclodextrin cavity, increasing the cavity volume, thereby better accommodating the guest molecule 4-butylresorcinol. It can also introduce amino groups into hydroxypropyl-β-cyclodextrin. On the one hand, it can enhance the interaction between the cyclodextrin cavity and 4-butylresorcinol and strengthen the inclusion of 4-butylresorcinol. At the same time, some amino groups will react with pyrrolidone carboxylic acid, strengthening the binding of pyrrolidone carboxylic acid and hydroxypropyl-β-cyclodextrin. The inventors of the present invention have found that by modifying the pretreated hydroxypropyl-β-cyclodextrin with an appropriate amount of pyrrolidone carboxylic acid, the overall inclusion rate of hydroxypropyl-β-cyclodextrin for 4-butylresorcinol can be further improved.

[0024] In the present invention, preferably, in step (1), when the ammonia explosion treatment is performed, the pressure is 1.6-1.9 MPa, the temperature is 90-95° C., and the time is 30-40 min.

[0025] In the present invention, preferably, in step (2), the mass ratio of the pretreated hydroxypropyl-β-cyclodextrin to pyrrolidone carboxylic acid is 18 to 35:1. When preparing modified hydroxypropyl-β-cyclodextrin, if the pretreated hydroxypropyl-β-cyclodextrin and pyrrolidone carboxylic acid are too large or too small, the inclusion rate of the 4-butylresorcinol cyclodextrin inclusion complex will be affected.

[0026] More preferably, the mass ratio of the pretreated hydroxypropyl-β-cyclodextrin to pyrrolidone carboxylic acid is 25-27:1.

[0027] In the present invention, preferably, in step (2), the molar ratio of EDC to NHS in the EDC / NHS solution is 1:1 to 1:4; The concentration of the EDC / NHS solution is 10-20 mg / mL; The mass volume ratio of the pyrrolidone carboxylic acid to the EDC / NHS solution is 1 g: 6-10 mL.

[0028] In the present invention, preferably, the raw materials of the 4-butylresorcinol cyclodextrin inclusion compound further include 0.3 to 0.7 parts of polyethylene glycol, and the molecular weight of the polyethylene glycol is 200 to 300.

[0029] A second aspect of the present invention provides a method for preparing the above-mentioned 4-butylresorcinol cyclodextrin inclusion compound, comprising the following steps:

[0030] S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir to dissolve, add the remaining raw materials, and homogenize using a microfluidizer to obtain a mixed solution; S2. Spray-drying the mixed solution to obtain the 4-butylresorcinol-cyclodextrin inclusion compound.

[0031] Preferably, in step S1, the pressure of the homogenization treatment is 10,000-20,000 psi, and the number of homogenization treatments is 3-5 times; In the present invention, preferably, in step S2, the spray drying temperature is 82-88°C.

[0032] A third aspect of the present invention provides a use of the above-mentioned 4-butylresorcinol-cyclodextrin inclusion compound or the 4-butylresorcinol-cyclodextrin inclusion compound prepared by the above-mentioned preparation method in cosmetics.

[0033] This cosmetic contains a 4-butylresorcinol cyclodextrin inclusion complex, which effectively whitens, brightens, and reduces dark spots. The cosmetic can be applied to any part of the human body by at least applying, spraying, or similar methods. Specifically, the cosmetic can be an essence, cream, lotion, mask, sunscreen, or the like.

[0034] Cosmetics prepared using the 4-butylresorcinol cyclodextrin inclusion complex of the present invention may further contain other ingredients, such as moisturizers, antioxidants, emulsifiers, thickeners, preservatives, sunscreens, whitening agents, pH adjusters, flavors, pigments, plant extracts, etc. Those skilled in the art can select appropriate ingredients based on actual needs.

[0035] The present invention will be described in detail below through examples.

[0036] Example 1: A 4-butylresorcinol-cyclodextrin inclusion compound comprises the following raw materials in parts by weight: 12 parts of 4-butylresorcinol, 45 parts of modified hydroxypropyl-β-cyclodextrin, and 300 parts of ethanol.

[0037] The preparation method of modified hydroxypropyl-β-cyclodextrin comprises the following steps: (1) subjecting hydroxypropyl-β-cyclodextrin to ammonia explosion treatment at a pressure of 1.7 MPa, a temperature of 90°C, and a time of 35 min to obtain pretreated hydroxypropyl-β-cyclodextrin; (2) 255 g of pretreated hydroxypropyl-β-cyclodextrin, 10 g of pyrrolidone carboxylic acid, and 2500 mL of water were placed in a reactor, and then 80 mL of EDC / NHS solution was added. The mixture was heated to 60 °C and stirred for 12 h, and then cooled to room temperature to obtain a reaction solution. The molar ratio of EDC to NHS in the EDC / NHS solution was 1:2, and the concentration of the EDC / NHS solution was 10 mg / mL. (3) The reaction solution was dialyzed with deionized water and then freeze-dried to obtain modified hydroxypropyl-β-cyclodextrin.

[0038] The preparation method of the 4-butylresorcinol cyclodextrin inclusion compound in this embodiment comprises the following steps: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir to dissolve, add 4-butylresorcinol, and homogenize using a microfluidizer to obtain a mixed solution; wherein the homogenization pressure is 20,000 psi and the number of homogenization times is 3; S2. spray-drying the mixed solution at a temperature of 85° C. to obtain a 4-butylresorcinol cyclodextrin inclusion complex.

[0039] Example 2: A 4-butylresorcinol cyclodextrin inclusion compound comprises the following raw materials in parts by weight: 13.5 parts of 4-butylresorcinol, 45 parts of modified hydroxypropyl-β-cyclodextrin, and 320 parts of ethanol.

[0040] The preparation method of modified hydroxypropyl-β-cyclodextrin comprises the following steps: (1) subjecting hydroxypropyl-β-cyclodextrin to ammonia explosion treatment at a pressure of 1.9 MPa, a temperature of 90°C, and a time of 30 min to obtain pretreated hydroxypropyl-β-cyclodextrin; (2) 270 g of pretreated hydroxypropyl-β-cyclodextrin, 10 g of pyrrolidone carboxylic acid, and 2500 mL of water were placed in a reactor, and then 100 mL of EDC / NHS solution was added. The mixture was heated to 60 °C and stirred for 12 h, and then cooled to room temperature to obtain a reaction solution. The molar ratio of EDC to NHS in the EDC / NHS solution was 1:2, and the concentration of the EDC / NHS solution was 10 mg / mL. (3) The reaction solution was dialyzed with deionized water and then freeze-dried to obtain modified hydroxypropyl-β-cyclodextrin.

[0041] The preparation method of the 4-butylresorcinol cyclodextrin inclusion compound in this embodiment comprises the following steps: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir to dissolve, add 4-butylresorcinol, and homogenize using a microfluidizer to obtain a mixed solution; wherein the homogenization pressure is 20,000 psi and the number of homogenization times is 3; S2. spray-drying the mixed solution at a temperature of 82-88° C. to obtain a 4-butylresorcinol cyclodextrin inclusion complex.

[0042] Example 3: A 4-butylresorcinol-cyclodextrin inclusion compound comprises the following raw materials in parts by weight: 10 parts of 4-butylresorcinol, 40 parts of modified hydroxypropyl-β-cyclodextrin, and 260 parts of ethanol.

[0043] The preparation method of modified hydroxypropyl-β-cyclodextrin comprises the following steps: (1) Hydroxypropyl-β-cyclodextrin was subjected to ammonia explosion treatment at a pressure of 1.7 MPa, a temperature of 95°C, and a time of 32 min to obtain pretreated hydroxypropyl-β-cyclodextrin; (2) 250 g of pretreated hydroxypropyl-β-cyclodextrin, 10 g of pyrrolidone carboxylic acid, and 2500 mL of water were placed in a reactor, and then 100 mL of EDC / NHS solution was added. The mixture was heated to 55 °C and stirred for 16 h, and then cooled to room temperature to obtain a reaction solution. The molar ratio of EDC to NHS in the EDC / NHS solution was 1:1, and the concentration of the EDC / NHS solution was 10 mg / mL. (3) The reaction solution was dialyzed with deionized water and then freeze-dried to obtain modified hydroxypropyl-β-cyclodextrin.

[0044] The preparation method of the 4-butylresorcinol cyclodextrin inclusion compound in this embodiment comprises the following steps: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir to dissolve, add 4-butylresorcinol, and homogenize using a microfluidizer to obtain a mixed solution; wherein the homogenization pressure is 20,000 psi and the number of homogenization times is 3; S2. spray-drying the mixed solution at a temperature of 82° C. to obtain a 4-butylresorcinol cyclodextrin inclusion complex.

[0045] Example 4: A 4-butylresorcinol-cyclodextrin inclusion compound comprises the following raw materials in parts by weight: 15 parts of 4-butylresorcinol, 50 parts of modified hydroxypropyl-β-cyclodextrin, and 350 parts of ethanol.

[0046] The preparation method of modified hydroxypropyl-β-cyclodextrin comprises the following steps: (1) subjecting hydroxypropyl-β-cyclodextrin to ammonia explosion treatment at a pressure of 1.6 MPa, a temperature of 95°C, and a time of 40 min to obtain pretreated hydroxypropyl-β-cyclodextrin; (2) 270 g of pretreated hydroxypropyl-β-cyclodextrin, 10 g of pyrrolidone carboxylic acid, and 2500 mL of water were placed in a reactor, and then 60 mL of EDC / NHS solution was added. The mixture was heated to 60 °C and stirred for 13 h, and then cooled to room temperature to obtain a reaction solution. The molar ratio of EDC to NHS in the EDC / NHS solution was 1:2, and the concentration of the EDC / NHS solution was 20 mg / mL. (3) The reaction solution was dialyzed with deionized water and then freeze-dried to obtain modified hydroxypropyl-β-cyclodextrin.

[0047] The preparation method of the 4-butylresorcinol cyclodextrin inclusion compound in this embodiment comprises the following steps: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir and dissolve, add 4-butylresorcinol, and homogenize using a microfluidizer to obtain a mixed solution; wherein the homogenization pressure is 10,000 psi and the number of homogenization times is 5; S2. spray-drying the mixed solution at a temperature of 88° C. to obtain a 4-butylresorcinol cyclodextrin inclusion complex.

[0048] Example 5: A 4-butylresorcinol-cyclodextrin inclusion compound comprises the following raw materials in parts by weight: 12 parts of 4-butylresorcinol, 43 parts of modified hydroxypropyl-β-cyclodextrin, and 280 parts of ethanol.

[0049] The preparation method of modified hydroxypropyl-β-cyclodextrin comprises the following steps: (1) subjecting hydroxypropyl-β-cyclodextrin to ammonia explosion treatment at a pressure of 1.9 MPa, a temperature of 92°C, and a time of 35 min to obtain pretreated hydroxypropyl-β-cyclodextrin; (2) 265 g of pretreated hydroxypropyl-β-cyclodextrin, 10 g of pyrrolidone carboxylic acid, and 2500 mL of water were placed in a reactor, and then 80 mL of EDC / NHS solution was added. The mixture was heated to 60 °C and stirred for 10 h, and then cooled to room temperature to obtain a reaction solution. The molar ratio of EDC to NHS in the EDC / NHS solution was 1:4, and the concentration of the EDC / NHS solution was 20 mg / mL. (3) The reaction solution was dialyzed with deionized water and then freeze-dried to obtain modified hydroxypropyl-β-cyclodextrin.

[0050] The preparation method of the 4-butylresorcinol cyclodextrin inclusion compound in this embodiment comprises the following steps: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir and dissolve, add 4-butylresorcinol, and homogenize using a microfluidizer to obtain a mixed solution; wherein the homogenization pressure is 10,000 psi and the number of homogenization times is 5; S2. spray-drying the mixed solution at a temperature of 85° C. to obtain a 4-butylresorcinol cyclodextrin inclusion complex.

[0051] Example 6: A 4-butylresorcinol cyclodextrin inclusion complex, which is different from Example 5 in that when preparing the modified hydroxypropyl-β-cyclodextrin, the amount of pretreated hydroxypropyl-β-cyclodextrin added is 180 g.

[0052] Example 7: A 4-butylresorcinol cyclodextrin inclusion compound, which is different from Example 5 in that when preparing the modified hydroxypropyl-β-cyclodextrin, the amount of pretreated hydroxypropyl-β-cyclodextrin added is 350 g.

[0053] Example 8: A 4-butylresorcinol cyclodextrin inclusion compound comprises the following raw materials in parts by weight: 12 parts of 4-butylresorcinol, 0.7 parts of polyethylene glycol 200, 43 parts of modified hydroxypropyl-β-cyclodextrin, and 280 parts of ethanol.

[0054] The preparation method of modified hydroxypropyl-β-cyclodextrin is the same as that in Example 5.

[0055] The preparation method of the 4-butylresorcinol cyclodextrin inclusion compound in this embodiment comprises the following steps: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir and dissolve, add 4-butylresorcinol and polyethylene glycol 200, and homogenize using a microfluidizer to obtain a mixed solution; wherein the homogenization pressure is 10,000 psi and the number of homogenization times is 5; S2. spray-drying the mixed solution at a temperature of 85° C. to obtain a 4-butylresorcinol cyclodextrin inclusion complex.

[0056] Example 9: A 4-butylresorcinol cyclodextrin inclusion compound comprises the following raw materials in parts by weight: 12 parts of 4-butylresorcinol, 0.45 parts of polyethylene glycol 200, 43 parts of modified hydroxypropyl-β-cyclodextrin, and 280 parts of ethanol.

[0057] The preparation method of modified hydroxypropyl-β-cyclodextrin is the same as that in Example 5.

[0058] The preparation method of the 4-butylresorcinol cyclodextrin inclusion compound in this embodiment comprises the following steps: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir and dissolve, add 4-butylresorcinol and polyethylene glycol 200, and homogenize using a microfluidizer to obtain a mixed solution; wherein the homogenization pressure is 10,000 psi and the number of homogenization times is 5; S2. spray-drying the mixed solution at a temperature of 85° C. to obtain a 4-butylresorcinol cyclodextrin inclusion complex.

[0059] Example 10: A 4-butylresorcinol cyclodextrin inclusion compound comprises the following raw materials in parts by weight: 12 parts of 4-butylresorcinol, 0.3 parts of polyethylene glycol 300, 43 parts of modified hydroxypropyl-β-cyclodextrin, and 280 parts of ethanol.

[0060] The preparation method of modified hydroxypropyl-β-cyclodextrin is the same as that in Example 5.

[0061] The preparation method of the 4-butylresorcinol cyclodextrin inclusion compound in this embodiment comprises the following steps: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir and dissolve, add 4-butylresorcinol and polyethylene glycol 300, and homogenize using a microfluidizer to obtain a mixed solution; wherein the homogenization pressure is 10,000 psi and the number of homogenization times is 5; S2. spray-drying the mixed solution at a temperature of 85° C. to obtain a 4-butylresorcinol cyclodextrin inclusion complex.

[0062] Comparative Example 1: The method is basically the same as Example 5, except that the modified hydroxypropyl-β-cyclodextrin is replaced by hydroxypropyl-β-cyclodextrin.

[0063] Comparative Example 2: The method is basically the same as Example 5, except that the modified hydroxypropyl-β-cyclodextrin is replaced by the pretreated hydroxypropyl-β-cyclodextrin prepared in step (1).

[0064] Comparative Example 3: The method is basically the same as Example 5, except that the modified hydroxypropyl-β-cyclodextrin is replaced by pyrrolidone carboxylic acid modified hydroxypropyl-β-cyclodextrin.

[0065] The preparation method of pyrrolidone carboxylic acid modified hydroxypropyl-β-cyclodextrin comprises the following steps: (1) 265 g of hydroxypropyl-β-cyclodextrin, 10 g of pyrrolidone carboxylic acid, and 2500 mL of water were placed in a reactor, and then 80 mL of EDC / NHS solution was added. The mixture was heated to 60°C and stirred for 10 h, and then cooled to room temperature to obtain a reaction solution. The molar ratio of EDC to NHS in the EDC / NHS solution was 1:4, and the concentration of the EDC / NHS solution was 20 mg / mL. (2) The reaction solution was dialyzed with deionized water and then freeze-dried to obtain pyrrolidone carboxylic acid-modified hydroxypropyl-β-cyclodextrin.

[0066] Comparative Example 4: The method is basically the same as Example 5, except that when preparing the modified hydroxypropyl-β-cyclodextrin, the amount of pretreated hydroxypropyl-β-cyclodextrin added is 100 g.

[0067] Comparative Example 5: The method is basically the same as Example 5, except that when preparing the modified hydroxypropyl-β-cyclodextrin, the amount of pretreated hydroxypropyl-β-cyclodextrin added is 700 g.

[0068] Comparative Example 6: The same as Example 8, except that 0.7 parts of polyethylene glycol 200 are replaced by 2 parts of polyethylene glycol 1000.

[0069] Performance testing: 1. Determine the inclusion rate and stability of the 4-butylresorcinol cyclodextrin inclusion complexes in Examples 1 to 10 and Comparative Examples 1 to 6.

[0070] When testing the inclusion rate, the weighed 4-butylresorcinol cyclodextrin inclusion complex was eluted with ether. After the ether evaporated, the solid was weighed, diluted to a fixed volume with methanol, and passed through a microporous filter membrane with a pore size of 0.45 μm. After obtaining the filtrate, the inclusion rate was determined by HPLC.

[0071] To test stability, the 4-butylresorcinol-cyclodextrin inclusion complexes of Examples 1-10 and Comparative Examples 1-6 were placed in an environment of 40°C±2°C and 75%RH±5%RH for 3 months. The inclusion rate was then tested according to the above method. A higher inclusion rate indicates greater stability. The 4-butylresorcinol-cyclodextrin inclusion complexes were also observed for discoloration, indicating instability.

[0072] The specific test structure is shown in Table 1.

[0073] Table 1:

[0074] As shown in Table 1, the inclusion rates of the 4-butylresorcinol cyclodextrin inclusion complexes prepared in Examples 1-10 can reach over 97%, and they are highly stable. A comparison of Examples 5 and 6-7 shows that when preparing modified hydroxypropyl-β-cyclodextrin, the overall inclusion rate is higher when the mass ratio of pretreated hydroxypropyl-β-cyclodextrin to pyrrolidone carboxylic acid is 25-27:1. A comparison of Examples 5 and 8-10 shows that the addition of polyethylene glycol 200 or polyethylene glycol 300 to the 4-butylresorcinol cyclodextrin inclusion complexes significantly improves the inclusion rate.

[0075] By comparing Example 5 with Comparative Example 1, it can be seen that if no modification is performed on hydroxypropyl-β-cyclodextrin, the inclusion rate of the 4-butylresorcinol cyclodextrin inclusion complex is low, and the stability is also significantly reduced. By comparing Example 5 with Comparative Examples 2 to 3, it can be seen that the modification of hydroxypropyl-β-cyclodextrin with pyrrolidone carboxylic acid or the ammonia explosion treatment has a positive effect on improving the inclusion rate and stability of the 4-butylresorcinol cyclodextrin inclusion complex. By comparing Example 5 with Comparative Examples 4 to 5, it can be seen that when preparing modified hydroxypropyl-β-cyclodextrin, if the ratio of pretreated hydroxypropyl-β-cyclodextrin to pyrrolidone carboxylic acid is too large or too small, the inclusion rate of the 4-butylresorcinol cyclodextrin inclusion complex will be affected, especially when the amount of pyrrolidone carboxylic acid added relative to hydroxypropyl-β-cyclodextrin is too much, the inclusion rate is more significantly reduced, and the stability will also be reduced.

[0076] From the comparison between Example 5 and Comparative Example 6, it can be seen that if the molecular weight of the added polyethylene glycol is too large and the added mass is too much, the inclusion rate will be reduced.

[0077] 2. A facial cream was prepared using the 4-butylresorcinol cyclodextrin inclusion complex in Examples 1 to 10 and Comparative Examples 1 to 6. The facial cream comprised the following ingredients in percentage by weight: 2% 4-butylresorcinol cyclodextrin inclusion complex, 12% white meadowfoam seed oil, 1% ammonium acryloyldimethyltaurate / VP copolymer, 1% allantoin, 2% lecithin, 4.5% glycerol, 2% coconut oil caprylate / caprate, 3% butylene glycol, 2% caprylic / capric triglyceride, 0.3% ethylhexylglycerin, 0.02% sodium bisulfite, and the balance was deionized water. The preparation method was a conventional method for preparing a facial cream.

[0078] The whitening and brightening effects of the facial creams prepared with the 4-butylresorcinol cyclodextrin inclusion compounds in Examples 1 to 10 and Comparative Examples 1 to 6 were tested, and the subjects provided feedback after use.

[0079] Test population: 96 female subjects aged 25 to 35 years old, all of whom had dull skin problems, were randomly divided into 16 groups, with 6 people in each group.

[0080] Test method: After cleansing their faces in the morning and evening, and using a uniform toner, 16 groups of female subjects respectively applied the creams of Examples 1 to 10 and Comparative Examples 1 to 6 on their faces; the dosage was 2 g each time, twice a day (once in the morning and once in the evening), for 45 consecutive days. The satisfaction rating range was 0 to 10, with a full score of 10. The satisfaction rating results (average values) are shown in Table 2.

[0081] During the test, the subjects shall not use any cosmetics, medicines or health products that may affect the results; during the test, they shall not use samples with the same efficacy as the test samples; during the test, they shall not use other cosmetics or personal care products except the test samples.

[0082] In addition, the cream was placed at room temperature and sealed for 2 years to observe the color change of the cream.

[0083] Table 2:

[0084] As can be seen from Table 2, the facial cream prepared using the 4-butylresorcinol cyclodextrin inclusion compound in the embodiment of the present invention has excellent whitening and spot-lightening and skin-lightening effects, while the facial cream prepared using the 4-butylresorcinol cyclodextrin inclusion compound in the comparative example has an effect worse than that of the embodiment.

[0085] From the perspective of long-term stability, for the 4-butylresorcinol cyclodextrin inclusion complex used, if no modification is performed on the hydroxypropyl-β-cyclodextrin or if the hydroxypropyl-β-cyclodextrin is only modified with pyrrolidone carboxylic acid or subjected to ammonia explosion treatment, the stability of the resulting cream will deteriorate. Moreover, if the amount of pyrrolidone carboxylic acid added relative to hydroxypropyl-β-cyclodextrin is too large, the stability of the cream will also deteriorate.

[0086] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A 4-butylresorcinol cyclodextrin inclusion compound, characterized in that: The invention comprises the following raw materials in parts by weight: 10-15 parts of 4-butylresorcinol, 40-50 parts of modified hydroxypropyl-β-cyclodextrin and 260-350 parts of ethanol.

2. The 4-butylresorcinol cyclodextrin inclusion compound according to claim 1, wherein The preparation method of the modified hydroxypropyl-β-cyclodextrin comprises the following steps: (1) subjecting hydroxypropyl-β-cyclodextrin to ammonia explosion treatment to obtain pretreated hydroxypropyl-β-cyclodextrin; (2) Pretreated hydroxypropyl-β-cyclodextrin, pyrrolidone carboxylic acid, and water were placed in a reaction kettle, and then EDC / NHS solution was added. The temperature was raised to 55-60°C and stirred for 10-16 hours. The mixture was cooled to room temperature to obtain a reaction solution. (3) The reaction solution was dialyzed with deionized water and then freeze-dried to obtain modified hydroxypropyl-β-cyclodextrin.

3. The 4-butylresorcinol cyclodextrin inclusion compound according to claim 2, wherein In step (1), when performing ammonia explosion treatment, the pressure is 1.6-1.9 MPa, the temperature is 90-95°C, and the time is 30-40 min.

4. The 4-butylresorcinol cyclodextrin inclusion compound according to claim 2, wherein In step (2), the mass ratio of the pretreated hydroxypropyl-β-cyclodextrin to pyrrolidone carboxylic acid is 18-35:

1.

5. The 4-butylresorcinol cyclodextrin inclusion compound according to claim 4, characterized in that The mass ratio of the pretreated hydroxypropyl-β-cyclodextrin to pyrrolidone carboxylic acid is 25-27:

1.

6. The 4-butylresorcinol cyclodextrin inclusion compound according to claim 2, wherein In step (2), the molar ratio of EDC to NHS in the EDC / NHS solution is 1:1 to 1:4; The concentration of the EDC / NHS solution is 10-20 mg / mL; The mass volume ratio of the pyrrolidone carboxylic acid to the EDC / NHS solution is 1 g: 6-10 mL.

7. The 4-butylresorcinol cyclodextrin inclusion compound according to claim 1, wherein The raw materials of the 4-butylresorcinol cyclodextrin inclusion compound further include 0.3-0.7 parts of polyethylene glycol, and the molecular weight of the polyethylene glycol is 200-300.

8. A method for preparing the 4-butylresorcinol-cyclodextrin inclusion compound according to any one of claims 1 to 7, characterized in that: The following steps are involved: S1. Place modified hydroxypropyl-β-cyclodextrin in ethanol, stir to dissolve, add the remaining raw materials, and homogenize using a microfluidizer to obtain a mixed solution; S2. Spray-drying the mixed solution to obtain the 4-butylresorcinol-cyclodextrin inclusion compound.

9. The method for preparing the 4-butylresorcinol cyclodextrin inclusion compound according to claim 8, wherein: In step S1, the pressure of the homogenization process is 10,000 to 20,000 psi, and the number of homogenization processes is 3 to 5 times; In step S2, the spray drying temperature is 82-88°C.

10. Use of the 4-butylresorcinol-cyclodextrin inclusion compound according to any one of claims 1 to 7 or the 4-butylresorcinol-cyclodextrin inclusion compound prepared by the preparation method according to any one of claims 8 to 9 in cosmetics.

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