WO2021218129A1

WO2021218129A1 - Copper @ rhubarb anthraquinone metal organic framework composite and use thereof

Info

Publication number: WO2021218129A1
Application number: PCT/CN2020/131025
Authority: WO
Inventors: 肖计生; 苏小滢; 刘四军
Original assignee: 广州中医药大学(广州中医药研究院)
Priority date: 2020-04-29
Filing date: 2020-11-24
Publication date: 2021-11-04
Also published as: CN111494226B; CN111494226A

Abstract

Disclosed are a copper @ rhubarb anthraquinone metal organic framework composite and the use thereof. The copper @ rhubarb anthraquinone metal organic framework composite comprises the following components in parts by mass: 1-600 parts of a rhubarb anthraquinone compound and 1-1200 parts of an alkaline copper salt. The copper @ rhubarb anthraquinone metal organic framework composite has both physical and chemical sunscreen functions, has a good anti-ultraviolet damage effect, can remarkably protect skin, and can be used as an additive ingredient in sunscreen and makeup. In addition, the copper @ rhubarb anthraquinone metal organic framework composite is synthesized with the rhubarb anthraquinone compound, which is a natural Chinese herbal ingredient, as a raw material, thereby reducing the problem caused by the permeation of general chemical sunscreen ingredients into the human body in terms of safety.

Description

Copper@大黄anthraquinone metal organic framework composite and application thereof

Technical field

The invention relates to the technical field of sunscreen materials, in particular to a copper@大黄anthraquinone metal organic framework composite and its application.

Background technique

In order to resist ultraviolet radiation, various sunscreen materials are currently on the market, but these sunscreen materials have a single sunscreen approach and have certain limitations. For example, chemical sunscreen agents are mainly organic substances such as benzophenones and benzotriazoles. It has problems such as intradermal penetration, skin irritation, phototoxicity, etc.; physical sunscreens that reflect or scatter ultraviolet radiation, mainly _{inorganic substances such as TiO 2} , ZnO, etc., will affect the secretion of sebaceous glands and sweat glands after use, and pose safety hazards such as inhalation . The development of natural Chinese medicine sunscreen has better safety, and has dual sun protection and anti-oxidation properties, and has broad development prospects.

Metal ions and chemical components of traditional Chinese medicine often change or enhance their activities such as anti-oxidation and anti-tumor. Combining the effective components of traditional Chinese medicine with metal ions can play the role of synergy between the two and produce new functions. It is to improve traditional Chinese medicine. An effective way of chemical activity. Copper is an important trace element, which is necessary for the activity of certain enzymes. It also has important physiological functions such as affecting iron metabolism, participating in and maintaining hematopoietic function; it can also protect body cells from damage by superoxide anion. Oxide dismutase catalyzes the reaction to scavenge free radicals and so on. Rhubarb, a traditional Chinese medicine in my country, is derived from the dried roots and rhizomes of Polygonaceae plant Rheum palmatum, Tanggutehuang or medicinal rhubarb. It tastes bitter and cold in nature. Its main active ingredients are anthraquinones such as emodin, rhein, Aloe-emodin, etc., its pharmacological effects include anti-tumor, regulation of gastrointestinal function, anti-pathogenic microorganisms, anti-oxidation, and strong absorption of ultraviolet rays due to its chemical conjugated system structure. It has good application value. Consider using it as a sunscreen. However, it has not been found that the copper@大黄-like anthraquinone metal organic framework compound has the effect of anti-ultraviolet radiation, can significantly protect the skin from sunburn, and can be used as a sunscreen material.

Summary of the invention

The purpose of the present invention is to overcome the shortcomings of the prior art and provide a copper@大黄anthraquinone metal organic framework composite and its application.

In order to achieve the above objectives, the technical solutions adopted by the present invention are as follows:

A copper@rhubarb anthraquinone metal organic framework composite, comprising the following components by mass: 1-600 parts of rhubarb anthraquinone compound and 1-1200 parts of basic copper salt.

The present invention uses alkaline copper salt and natural Chinese medicine component rhubarb anthraquinone compound as raw materials to synthesize copper@大黄anthraquinone metal organic framework compound. The compound has the dual functions of physical and chemical sun protection and has good anti-ultraviolet damage. effect.

Preferably, the copper@大黄anthraquinone metal-organic framework composite includes the following components by mass: 1 part of a rhubarb anthraquinone compound and 1 part of an alkaline copper salt, and the yield of the copper@大黄anthraquinone metal-organic framework composite is relatively high.

Preferably, the rhubarb anthraquinone compound includes at least one of emodin, rhein, and aloe-emodin.

Preferably, the alkaline copper salt includes at least one of copper acetate monohydrate, copper acetate anhydrous, copper nitrate anhydrous, and copper nitrate hexahydrate.

The present invention also provides a preparation method of the copper@大黄anthraquinone metal-organic framework composite. The rhubarb anthraquinone compound and the alkaline copper salt are respectively fully dissolved in an organic solvent, and the reaction is stirred in a condensing reflux device, and the reaction product is collected by centrifugation , Using N,N'-dimethylformamide and ethanol to wash the reaction product multiple times to obtain the copper@大黄anthraquinone metal organic framework complex.

The method for synthesizing the copper@大黄anthraquinone metal-organic framework compound of the present invention has simple operation, and the prepared copper@大黄anthraquinone metal-organic framework compound has a crystal particle structure and a chemical conjugated system structure so that it has both physics and chemistry The dual role of sunscreen, has a good anti-ultraviolet damage effect, can significantly protect the skin. In addition, the present invention uses the natural Chinese medicine component rhubarb anthraquinone compound as a raw material for synthesis, which reduces the safety problems caused by the penetration of general chemical sunscreen ingredients into the human body.

Preferably, in the above preparation method, the reaction temperature is 25°C-°C, the reaction time is 8-24h, and the stirring speed is 250-500rpm, where, when the reaction temperature is 60°C, the reaction time is 16h, and the stirring speed At 360 rpm, the particle size of the obtained product is more uniform.

Preferably, the organic solvent includes at least one of N,N'-dimethylformamide and pyridine.

The present invention also provides the application of the above-mentioned copper@大黄anthraquinone metal-organic framework compound or the copper@大黄anthraquinone metal-organic framework compound prepared according to the above method in sunscreen products.

The present invention also provides a sunscreen cosmetic, which contains the above-mentioned copper@大黄anthraquinone metal-organic framework compound or the copper@大黄anthraquinone metal-organic framework compound prepared according to the above-mentioned method.

The copper@大黄anthraquinone metal organic framework compound of the present invention has a very significant anti-UVB effect, can protect the skin from damage, is a good anti-UV radiation damage material, and can be used as an additive component for sunscreen and color cosmetics .

Compared with the prior art, the beneficial effects of the present invention are:

1. At the level of material physics and chemistry, the emodin anthraquinone conjugated system has a strong ultraviolet absorption effect. The copper@大黄anthraquinone metal organic framework composite nano-particles of the present invention are uniform and have a certain effect of reflecting ultraviolet rays; the present invention The rhubarb anthraquinone compound is a natural medicine ingredient, which reduces the safety problems caused by the penetration of general chemical sunscreen ingredients into the human body;

2. The copper@大黄anthraquinone metal organic framework complex of the present invention has a very significant anti-UVB effect and can protect the skin from damage. Under the same administration concentration, the protective effect on animals, mice and pigs is consistent, and excellent For the protective effect of ZnO and TiO _2.

Description of the drawings

Figure 1 shows the hydrogen nuclear magnetic resonance spectrum ¹ H-NMR spectrum (A), X-ray powder diffraction spectrum (B), transmission electron microscope spectrum (C), and ultraviolet absorption spectrum (D) of the copper@emodin metal organic framework complex.

Figure 2 shows the blank group (Con), ultraviolet radiation group (UVB), glycerol matrix group (Gly), zinc oxide group (ZnO), titanium dioxide group (TiO ₂ ), emodin group (Emodin) and The skin changes of the Copper@Emodin metal organic framework complex group (Cu@Emodin).

Figure 3 shows the mouse blank group (Con), ultraviolet radiation group (UVB), glycerin matrix group (Gly), zinc oxide group (ZnO), titanium dioxide group (TiO ₂ ), emodin group (Emodin), copper@大黄素Statistical comparison of skin paraffin section staining and epidermal thickness in the metal organic framework complex group (Cu@Emodin) (n=3, *p<0.05, **p<0.01, ***p<0.001 vs UVB group.#p<0.05,##p<0.01vs Cu@Emodin group).

Figure 4 shows the blank group (Con), ultraviolet radiation group (UVB), glycerin matrix group (Gly), zinc oxide group (ZnO), titanium dioxide group (TiO ₂ ), and emodin group (Emodin) after the second day of ultraviolet irradiation for piglets. ), the skin changes of the copper@emodin metal organic framework complex group (Cu@Emodin) (n=6).

Figure 5 shows the piglet blank group (Con), ultraviolet radiation group (UVB), glycerin matrix group (Gly), zinc oxide group (ZnO), titanium dioxide group (TiO ₂ ), emodin group (Emodin), copper@大黄素Statistical comparison of skin paraffin section staining and epidermal thickness in the metal-organic framework complex group (Cu@Emodin) (n=6, *p<0.05, **p<0.01, ***p<0.001 vs UVB group.#p<0.05,##p<0.01vs Cu@Emodin group).

Detailed ways

In order to better illustrate the objectives, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments. Those skilled in the art should understand that the specific embodiments described herein are only used to explain the present invention, but not to limit the present invention.

In the examples, the experimental methods used are conventional methods unless otherwise specified, and the materials and reagents used, unless otherwise specified, can be obtained from commercial sources.

Example 1

The copper@emodin metal organic framework composite of this embodiment is made of raw materials including the following parts by mass: 1 part of emodin and 1 part of copper acetate monohydrate.

The preparation method of the copper@emodin metal organic framework composite of this embodiment is specifically as follows: respectively fully dissolve emodin and copper acetate monohydrate in N,N'-dimethylformamide, and heat at 60°C in a condensing reflux device. , Stirring at 350rpm for 16h, centrifugation to collect the reaction product, using N,N'-dimethylformamide and ethanol to wash the reaction product multiple times to obtain the copper@大黄素metal organic framework complex (Cu@ Emodin). The resulting product has the largest recovery rate and uniform particle size.

(1) Physical and chemical characterization of Cu@Emodin

The ^{structure of Cu@Emodin in Example 1 was characterized by 1} H-NMR, X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and ultraviolet spectrophotometer (UV). The results are shown in Figure 1. .

In Figure 1, A is the 1H-NMR spectrum of Cu@Emodin and Emodin, δ6.58～7.47 (1H, s) is the hydrogen peak on the emodin anthraquinone core ring, δ2.41(3H, -CH ₃ ) It is the methyl peak; from the peak position of Cu@Emodin, it is consistent with the peak range of emodin, indicating that the product Cu@Emodin retains the anthraquinone ring structure, retains the conjugated system, and has good UV absorption capacity;

In Figure 1, B is the X-ray powder diffraction pattern of Cu@Emodin, indicating that the synthetic substance has a certain crystal structure and has a good physical effect of ultraviolet reflection;

In Figure 1, C is the TEM spectrum of Cu@Emodin. It can be seen that the polyhedral structure of the synthetic material is clear, and the particle size is 250-350nm;

In Figure 1, D is _{the UV (200-600nm) absorption spectrum of ZnO, TiO 2} and Cu@Emodin. Compare the UV absorption peak position and absorption of the same amount (50μg/ml) of Cu@Emodin, ZnO and TiO ₂ Cu@Emodin has a good absorption band value for both UVA and UVB bands, which is even more advantageous.

(2) Animal experiment

(2.1) Use Balb/c mice for anti-UV test

Experimental groups: There are blank group (Con), ultraviolet radiation group (UVB), glycerin matrix group (Gly), zinc oxide group (ZnO), titanium dioxide group (TiO ₂ ), emodin group (Emodin), and copper@大黄 respectively Element metal organic framework composite group (Cu@Emodin). Animals were anesthetized and the spare skin was uniformly applied to the skin of the administration group, and the administration area except the blank group was irradiated under a UV lamp. Observe and record skin appearance changes every day (see Figure 2). Three days later, the skins of each group were sacrificed, fixed, sliced, stained with hematoxylin and eosin (HE), and skin thickness changes were observed (see Figure 3).

It can be seen from Figure 2 that the UVB group and Gly group have the most severe skin damage. The _{erythema, roughness, and wrinkles of the ZnO group, TiO 2} group and Emodin group are lighter, and the damage is lighter; and the skin condition of the Cu@Emodin group is relatively good. Individual erythema appears, with slight roughness, which is not much different from normal skin.

Figure 3 shows the skin thickness staining and statistical results of the skin thickness of each group. As a whole, it can be seen that the Cu@Emodin group has the best protection against sunburn.

(2.2) Use Bama Xiang pig for anti-UV test

Experimental groups: There are blank group (Con), ultraviolet radiation group (UVB), glycerin matrix group (Gly), zinc oxide group (ZnO), titanium dioxide group (TiO ₂ ), emodin group (Emodin), copper@大黄Element metal organic framework composite group (Cu@Emodin). Animals were anesthetized and the spare skin was uniformly applied to the skin of the administration group, and the administration area except the blank group was irradiated under a UV lamp. The skin appearance changes on the second day were recorded (see Figure 4), and the skins of each group were sacrificed two days later, fixed, sliced, stained with hematoxylin and eosin (HE), and the skin thickness changes were observed (see Figure 5).

Figure 4 shows that the skin of the UVB group and the Gly group is the most swollen and the most severely damaged. The ZnO group and the TiO ₂ group have relatively lighter erythema; while the Cu@Emodin group has relatively good skin condition, and there is no obvious damage compared with the normal group.

Figure 5 shows the epidermal thickness staining of each group and the statistical results of epidermal thickness. As a whole, it can be seen that the Cu@Emodin group does not thicken the epidermis and has the best effect on skin sunburn protection.

In summary, the Cu@Emodin of the present invention can achieve the following effects:

(1) On the physical and chemical level of materials, the emodin anthraquinone conjugated system has a strong UV absorption effect, and the uniform nano-particle appearance of Cu@Emodin has a certain effect of reflecting ultraviolet rays; and the raw material rhubarb anthraquinone compound is a natural medicine ingredient , Has better safety, which shows that the Cu@Emodin is a good anti-ultraviolet radiation damage material, and can be used as an additive component for sunscreen and makeup;

(2) Cu@Emodin has a very significant anti-UVB effect and protects the skin from damage. Under the same concentration, the protective effect on animals, mice and piglets is the same, and is better than that of ZnO and TiO ₂ .

In the present invention, the copper acetate monohydrate of Example 1 can be replaced with copper nitrate hexahydrate or other alkaline copper salts, and emodin can be replaced with rhein anthraquinone compounds such as rhein and aloe-emodin. N, N '-Dimethylformamide is replaced with pyridine, and the prepared copper@大黄anthraquinone metal organic framework compound also has good safety, dual sun protection and UV radiation resistance characteristics, and has broad development prospects. It can be used For the preparation of sunscreen products.

The ratio of emodin and copper acetate monohydrate in Example 1 can be appropriately adjusted within a certain range: 1-600 parts by mass of emodin and 1-1200 parts by mass of copper acetate monohydrate to prepare copper@大黄素金属organic framework For the composite, the crystal powder diffraction and ultraviolet absorption of the obtained product are not much different, but the different ratios of emodin and copper acetate monohydrate are selected, and the yield of the final product is significantly different, among which, 1 part by mass of emodin and 1 part by mass of copper acetate monohydrate In parts by mass, the yield of the product is the largest.

The process parameters of Example 1 can also be adjusted appropriately within a certain range: the reaction temperature is 25°C-80°C, the reaction time is 8-24h, and the stirring speed is 250-500rmp, where, when the reaction temperature is 60°C, the reaction When the time is 16h and the stirring speed is 360rpm, the particle size of the product obtained is more uniform.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit the protection scope of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that, The technical solution of the present invention can be modified or equivalently replaced without departing from the essence and scope of the technical solution of the present invention.

Claims

A copper@大黄anthraquinone metal organic framework composite, which is characterized in that it comprises the following components by mass: 1-600 parts of rhubarb anthraquinone compound and 1-1200 parts of basic copper salt.
The copper@rhubarb anthraquinone metal organic framework complex according to claim 1, wherein the rhubarb anthraquinone compound comprises at least one of emodin, rhein, and aloe-emodin.
The copper@大黄anthraquinone metal organic framework composite of claim 1 or 2, wherein the alkaline copper salt comprises copper acetate monohydrate, copper acetate anhydrous, copper nitrate anhydrous, copper nitrate hexahydrate At least one of them.
The preparation method of copper@rhubarb anthraquinone metal-organic framework composite according to any one of claims 1 to 3, characterized in that the rhubarb anthraquinone compound and the basic copper salt are fully dissolved in an organic solvent, and then refluxed after condensing and refluxing. The reaction is stirred in the device, the reaction product is collected by centrifugation, and the reaction product is washed multiple times with N,N'-dimethylformamide and ethanol to obtain the copper@大黄anthraquinone metal organic framework composite.
The method for preparing the copper@rhubarb anthraquinone metal organic framework composite according to claim 4, wherein the reaction temperature is 25° C.-80° C., the reaction time is 8-24 h, and the stirring speed is 250-500 rpm.
The method for preparing the copper@rhubarb anthraquinone metal organic framework complex according to claim 4, wherein the organic solvent comprises at least one of N,N'-dimethylformamide and pyridine.
The copper@大黄anthraquinone metal-organic framework composite according to any one of claims 1 to 3 or the copper@大黄anthraquinone metal-organic framework compound prepared according to any one of claims 4-6 is used in sunscreen products application.
A sunscreen cosmetic, which is characterized in that it contains the copper@大黄anthraquinone metal organic framework complex according to any one of claims 1-3 or the copper@大黄anthraquinone prepared by the method according to any one of claims 4-6 Metal organic framework complex.