阅读说明：本技术 制备丝柏油醇金属化合物及复合物的方法 (Method for preparing cypress oleyl alcohol metal compound and compound ) 是由 宋吉青 刘家磊 何文清 于 2020-06-16 设计创作，主要内容包括：本发明提供一种制备丝柏油醇金属化合物或丝柏油醇铵化合物的方法,包括：将丝柏油醇溶于水溶性有机溶剂,得到丝柏油醇浓度为6~25mol/L的丝柏油醇溶液；将所得丝柏油醇溶液与水溶性金属盐或铵盐的水溶液在室温下充分混合反应,所述的水溶性金属盐选自常温下溶解度不低于35g/100ml的金属盐,或所述的水溶性金属盐或铵盐的水溶液浓度常温下不低于25%；所述的水溶性金属盐或铵盐的水溶液进一步优选所述水溶性金属盐在30~50℃下的饱和溶液；控制所述的水溶性金属盐或铵盐与所述的丝柏油醇的摩尔比在1：0.9~5,制备得到丝柏油醇金属化合物或丝柏油醇铵化合物溶液。本发明的方法可以根本性地改善丝柏油醇遇光易分解的不稳定特性,避免使用酸溶液造成的废水环境污染负荷及其处理成本。(The present invention provides a method for preparing a cypress oil alcohol metal compound or an ammonium cypress oil alcohol compound, comprising: dissolving cypress oil alcohol in a water-soluble organic solvent to obtain a cypress oil alcohol solution with the cypress oil alcohol concentration of 6-25 mol/L; fully mixing the obtained cypress oil alcohol solution with an aqueous solution of water-soluble metal salt or ammonium salt at room temperature for reaction, wherein the water-soluble metal salt is selected from metal salt with solubility not lower than 35g/100ml at normal temperature, or the concentration of the aqueous solution of the water-soluble metal salt or ammonium salt is not lower than 25% at normal temperature; the water solution of the water-soluble metal salt or the ammonium salt is preferably a saturated solution of the water-soluble metal salt at the temperature of 30-50 ℃; controlling the molar ratio of the water-soluble metal salt or ammonium salt to the cypress oleyl alcohol to be 1: 0.9-5, and preparing the cypress oil alcohol metal compound or cypress oil alcohol ammonium compound solution. The method of the invention can radically improve the unstable characteristic of the hinokitiol which is easy to decompose in light, and avoid the environmental pollution load of the waste water and the treatment cost thereof caused by using acid solution.)

1. A method of preparing a cypress oil alcohol metal compound or an ammonium cypress oil alcohol compound, comprising:

1) dissolving cypress oil alcohol in a water-soluble organic solvent to obtain a cypress oil alcohol solution with the cypress oil alcohol concentration of 6-25 mol/L;

2) fully mixing the cypress oil alcohol solution obtained in the step 1) with an aqueous solution of water-soluble metal salt or ammonium salt at room temperature for reaction, wherein the water-soluble metal salt is selected from metal salts with solubility not lower than 35g/100ml at normal temperature, and the concentration of the aqueous solution of the water-soluble metal salt or ammonium salt is 5.4-125 mol/L; the water solution of the water-soluble metal salt or the ammonium salt is preferably a saturated solution of the water-soluble metal salt at the temperature of 30-50 ℃; controlling the molar ratio of the water-soluble metal salt or ammonium salt to the cypress oil alcohol to be 1: 0.9-5, and preparing to obtain a cypress oil alcohol metal compound or a cypress oil alcohol ammonium compound solution.

2. The method of claim 1, wherein 2) said intimately mixing is by subjecting said solution of cypress oil alcohol to shear homogenization after rapidly mixing with said aqueous solution of water-soluble metal or ammonium salt; more preferably, the continuous shearing and homogenizing are carried out for 20-60 minutes; preferably, the rapid mixing is mixing of the two solutions under high shear homogenization, or via relative spray mixing.

3. The method of claim 1, wherein 1) said cypress oleyl alcohol is dissolved in a water-soluble organic solvent, then mixed with ionized water and dispersed thoroughly to obtain said cypress oleyl alcohol solution as a stable cypress oleyl alcohol suspension self-emulsifying solution; 2) the full mixing reaction is to rapidly mix the cypress oil alcohol solution obtained in the step 1) with the water solution of the water-soluble metal salt or the ammonium salt in a high-speed shearing and homogenizing state, and then continuously shear and homogenize for 20-60 minutes.

4. The method of claim 1, wherein 1) said cypress oleyl alcohol is dissolved in a water-soluble organic solvent, then 0.01% to 5% of a viscous auxiliary substance aqueous solution is added and fully dispersed, and the obtained cypress oleyl alcohol solution is a cypress oleyl alcohol suspension self-emulsifying solution; 2) the full mixing reaction is to rapidly mix the cypress oil alcohol solution obtained in the step 1) with the water solution of the water-soluble metal salt or the ammonium salt in a high-speed shearing and homogenizing state, and then continuously shear and homogenize for 20-60 minutes.

5. The method of claim 1, wherein 1) the step of dissolving cypress oleyl alcohol in a water-soluble organic solvent to obtain a cypress oleyl alcohol solution; 2) the fully mixing reaction is to perform relative spraying and mixing on the cypress oil alcohol solution obtained in the step 1) and the water solution of the water-soluble metal salt or the ammonium salt, and then continuously shear and homogenize the solution obtained after spraying for 20-60 minutes.

6. A method of making a compound containing a cypress oil alcohol compound, comprising:

dissolving cypress oleyl alcohol in a water-soluble organic solvent to obtain a cypress oleyl alcohol solution with the cypress oleyl alcohol concentration of 6-25 mol/L;

fully mixing and reacting the cypress oil alcohol solution obtained in the step one with an aqueous solution of water-soluble metal salt or ammonium salt at room temperature, wherein the water-soluble metal salt is selected from metal salts with the solubility of not less than 35g/100ml at normal temperature, and the concentration of the aqueous solution of the water-soluble metal salt or ammonium salt is 5.4-125 mol/L; the water solution of the water-soluble metal salt or the ammonium salt is preferably a saturated solution of the water-soluble metal salt at the temperature of 30-50 ℃; controlling the molar ratio of the water-soluble metal salt or ammonium salt to the cypress oleyl alcohol to be 1: 0.9-5, preparing a cypress oil alcohol compound solution; performing conventional crystallization, separation, cleaning and drying to obtain cypress oil alcohol compound crystals;

thirdly, physically coating and modifying the crystal of the cypress oil alcohol compound obtained in the second step by using a water-soluble viscosity auxiliary substance to obtain a compound containing the cypress oil alcohol compound; the viscosity auxiliary substance is selected from 1 or more than 2 of sodium alginate, polysaccharide, beta-cyclodextrin, sodium carboxymethylcellulose (CMC-Na) (modified cellulose), starch sodium phosphate (modified starch), chitosan, xanthan gum, arabic gum, sesbania gum and carrageenan.

7. The method of any one of claims 1 or 6, wherein said cypress oil alcohol solution is a suspended self-emulsifying solution of cypress oil alcohol, which is obtained by dissolving the cypress oil alcohol in a water-soluble organic solvent, further adding deionized water, mixing and fully dispersing.

8. The method of any one of claims 1 or 6, wherein said cypress oil alcohol is dissolved in a water-soluble organic solvent, and then a 0.01% to 5% aqueous solution of a viscosity auxiliary substance is further added thereto and sufficiently dispersed, so that said cypress oil alcohol solution is a cypress oil alcohol suspension self-emulsifying solution.

9. The method of claim 6 wherein (c) said intimately mixing is carried out by rapidly mixing said solution of cypress oil alcohol with said aqueous solution of water-soluble metal or ammonium salt followed by continuous shear homogenization; more preferably, the continuous shearing and homogenizing are carried out for 20-60 minutes; preferably, the rapid mixing is mixing of the two solutions under high shear homogenization, or via relative spray mixing.

10. The method of claim 6, wherein said physical encapsulation modification is accomplished by any one of:

uniformly mixing the viscosity auxiliary substance water solution and the cypress oil alcohol compound crystal, wherein the weight ratio of the viscosity auxiliary substance to the cypress oil alcohol compound crystal is 0.01-1.2: 30, and then recrystallizing, cleaning and drying to obtain the compound containing the cypress oil alcohol compound;

alternatively, the first and second electrodes may be,

and cleaning the cypress oil alcohol compound crystal by using 0.01% -5% viscosity auxiliary substance aqueous solution at 0-5 ℃ to obtain the compound containing the cypress oil alcohol compound.

Technical Field

The invention relates to a preparation method of an organic compound, in particular to a method for preparing a cypress oleyl alcohol metal compound and a compound.

Background

Cupressol, also known as Hinokitiol or Hinokitiol (Hinokitiol), has excellent broad-spectrum antibacterial property, moisture retention property and pest repellent effect, and is a highly safe raw material component for preparing antibacterial agents and insect repellents. The cypress oleyl alcohol has the functions of broad-spectrum antibiosis and mildew resistance, inhibiting ALDH activity and self-renewal capacity in glioma stem cells, inhibiting in vitro carcinogenicity, inhibiting tyrosinase, inhibiting ethylene generation by plants, endowing cell activity and the like, and is applied to the development of various products such as medicine development, sanitary products, cosmetics, hair nourishing and hair growth, food preservation and the like.

The minimum inhibitory concentration of the cypress oleyl alcohol to bacteria is 10-100ppm, and the cypress oleyl alcohol has fragrant smell and good effect. The cypress oleyl alcohol can kill bacteria and mould in the air, prevent pathogenic bodies from invading human bodies, inhibit pathogenic infection of the human bodies and has remarkable inhibition effect on staphylococcus aureus (MRSA).

Recent research results show that cypress oleyl alcohol can reduce Nrf2 expression in glioma stem cells in a dose-dependent manner, inhibit colon cancer cell growth, also can reduce mRNA and protein expression of DNMT1 and UHRF1, increase TET1 expression by enhancing 5hmC levels in HCT-116 cells, and can reduce methylation status and restore mRNA expression of MGMT, CHST10 and BTG4 genes. In addition, cypress oil alcohol has attracted much attention in the field of inhibiting viral activity and antiviral action.

Cupressol has strong inhibiting effect on tyrosinase diphenol enzyme, and with dopa as substrate, 0.3 μmol/l Cupressol concentration (IC 50) can reduce enzyme activity by 50%, so as to inhibit freckle, chloasma, and cyasma. It has the function activity of inhibiting tyrosinase activity without causing permanent enzyme inactivation, and is applied to the aspects of beauty and whitening.

The molecular formula of the cypress oleyl alcohol is C₁₀H₁₂O₂Molecular weight is 164.20, melting point is 51-52 ℃, white or light yellow crystal is obtained by distillation refining or absolute ethyl alcohol recrystallization,is difficult to dissolve in water, is easy to decompose when meeting light, is corrosive to metal, is not high temperature resistant, is easy to decompose after melting, and has special odor. The strong antibacterial and antiviral activity of the cypress oleyl alcohol enables the cypress oleyl alcohol to be widely applied to the fields of medicines, cosmetics, food preservation and the like. But the convenience of the wide application is seriously influenced by the properties of visible light decomposition, heat instability, difficult water dissolution, strong corrosiveness to metal and the like.

Disclosure of Invention

The invention aims to provide a preparation method of a cypress oleyl alcohol metal compound, which is used for radically improving the unstable characteristic that cypress oleyl alcohol is easy to decompose when meeting light and avoiding the environmental pollution load of waste water and the treatment cost caused by using an acid solution.

The above object of the present invention is achieved by the following technical solutions:

first, there is provided a method for preparing a cypress oil alcohol metal compound or an ammonium cypress oil alcohol compound, comprising:

1) dissolving cypress oleyl alcohol in a water-soluble organic solvent to obtain a cypress oleyl alcohol solution;

2) fully mixing and reacting the cypress oil alcohol solution obtained in the step 1) with an aqueous solution of water-soluble metal salt or ammonium salt at room temperature, and controlling the molar ratio of the water-soluble metal salt or ammonium salt to the cypress oil alcohol to be 1: 0.9-5, and preparing the cypress oil alcohol metal compound or cypress oil alcohol ammonium compound solution.

In order to improve the uniformity of the cypress oil alcohol solution participating in the combination reaction and improve the efficiency of the combination reaction, in a preferable scheme of the invention, 1) the cypress oil alcohol is dissolved in a water-soluble organic solvent, and then deionized water is further added for mixing and fully dispersing, so that the obtained cypress oil alcohol solution is a cypress oil alcohol suspension self-emulsifying solution.

In order to improve the stability of the cypress oil alcohol solution participating in the combination reaction, in another preferable scheme of the invention, 1) the cypress oil alcohol is dissolved in a water-soluble organic solvent, and then a viscosity auxiliary substance aqueous solution with the concentration of 0.01-5% is further added for full dispersion, so that the obtained cypress oil alcohol solution is a cypress oil alcohol suspension self-emulsifying solution.

The viscosity auxiliary substance is preferably selected from 1 or more than 2 of sodium alginate, polysaccharide, beta-cyclodextrin, sodium carboxymethylcellulose (CMC-Na) (modified cellulose), starch sodium phosphate (modified starch), chitosan, xanthan gum, arabic gum, sesbania gum and carrageenan.

In order to enable the cypress oil alcohol and the metal ion to be evenly and fully combined, in the preferable scheme of the invention, 2) the full mixing reaction is that the cypress oil alcohol solution and the water solution of the water-soluble metal salt or the ammonium salt are quickly mixed and then continuously subjected to shearing homogenization; more preferably, the shearing is continued for 20 to 60 minutes.

In order to further improve the uniformity and sufficiency of the combination reaction, in a more preferred embodiment of the present invention, the rapid mixing is mixing the two solutions under a high shear homogeneous state, or by relative spray mixing.

In a preferred embodiment of the present invention, 1) the cypress oleyl alcohol is dissolved in a water-soluble organic solvent, and then added with ionized water to be mixed and fully dispersed, so that the obtained cypress oleyl alcohol solution is a stable cypress oleyl alcohol suspension self-emulsifying solution; 2) the full mixing reaction is to rapidly mix the cypress oil alcohol solution obtained in the step 1) with the water solution of the water-soluble metal salt or the ammonium salt in a high-speed shearing and homogenizing state, and then continuously shear and homogenize for 20-60 minutes.

In another preferred embodiment of the present invention, 1) the cypress oleyl alcohol is dissolved in a water-soluble organic solvent, and then a viscosity auxiliary substance aqueous solution with a concentration of 0.01% to 5% is added to fully disperse, so as to obtain the cypress oleyl alcohol solution which is a suspension self-emulsifying solution of cypress oleyl alcohol; 2) the full mixing reaction is to rapidly mix the cypress oil alcohol solution obtained in the step 1) with the water solution of the water-soluble metal salt or the ammonium salt in a high-speed shearing and homogenizing state, and then continuously shear and homogenize for 20-60 minutes.

In still another preferred embodiment of the present invention, 1) cypress oleyl alcohol is dissolved in a water-soluble organic solvent to obtain a cypress oleyl alcohol solution; 2) the fully mixing reaction is to perform relative spraying and mixing on the cypress oil alcohol solution obtained in the step 1) and the water solution of the water-soluble metal salt or the ammonium salt, and then continuously shear and homogenize the solution obtained after spraying for 20-60 minutes.

In a preferable scheme of the invention, the method further comprises the steps of cooling and crystallizing the cypress oil alcohol metal compound or the cypress oil alcohol ammonium compound solution in the step 2) at the temperature of-2-5 ℃, washing and drying the separated crystal with deionized water at the temperature of 0-5 ℃ to obtain the cypress oil alcohol metal compound crystal or the cypress oil alcohol ammonium compound crystal.

On this basis, the present invention also provides a method for producing a compound containing a cypress oil alcohol compound, comprising:

dissolving cypress oleyl alcohol in a water-soluble organic solvent to obtain a cypress oleyl alcohol solution;

fully mixing and reacting the obtained cypress oil alcohol solution and a water solution of water-soluble metal salt or ammonium salt at room temperature, and controlling the molar ratio of the water-soluble metal salt or ammonium salt to the cypress oil alcohol to be 1: 0.9-5 to prepare a cypress oil alcohol compound solution; performing conventional crystallization, separation, cleaning and drying to obtain cypress oil alcohol compound crystals;

and thirdly, physically coating and modifying the crystal of the cypress oil alcohol compound obtained in the step two by using a water-soluble viscosity auxiliary substance to obtain a compound containing the cypress oil alcohol compound.

In the preferable preparation method of the compound, in order to improve the uniformity of the cypress oil alcohol solution participating in the combination reaction and improve the efficiency of the combination reaction, the cypress oil alcohol is dissolved in the water-soluble organic solvent, and then the deionized water is further added for mixing and fully dispersing, so that the obtained cypress oil alcohol solution is a cypress oil alcohol suspension self-emulsifying solution.

In the preferable preparation method of the compound, in order to improve the stability of the cypress oil alcohol solution participating in the chemical combination reaction, firstly, the cypress oil alcohol is dissolved in a water-soluble organic solvent, and then, a viscosity auxiliary substance aqueous solution with the concentration of 0.01-5% is further added for full dispersion, so that the obtained cypress oil alcohol solution is a cypress oil alcohol suspension self-emulsifying solution.

In the preferable preparation method of the compound, in order to enable the cypress oil alcohol and the metal ions to be uniformly and fully combined, the fully mixing reaction is that the cypress oil alcohol solution and the water solution of the water-soluble metal salt or ammonium salt are quickly mixed and then continuously sheared and homogenized; more preferably, the shearing is continued for 20 to 60 minutes.

In the preferred method for preparing the compound of the present invention, in order to further improve the uniformity and sufficiency of the combination reaction, the rapid mixing is that the two solutions are mixed under a high-speed shearing homogeneous state or are mixed by relative spraying.

In the method for preparing the compound, the physical coating modification is to improve the instability of the cypress oil alcohol compound in light decomposition and high temperature resistance, improve the water-soluble dispersion of the cypress oil alcohol compound, and endow the cypress oil alcohol metal compound with slow release functional activity by utilizing the coating absorption effect of water-soluble viscosity auxiliary substances. The method can be specifically completed in any one of the following modes:

and uniformly mixing the viscosity auxiliary substance water solution and the cypress oil alcohol compound crystal, wherein the weight ratio of the viscosity auxiliary substance to the cypress oil alcohol compound crystal is 0.01-1.2: 30, and then recrystallizing, cleaning and drying to obtain the cypress oil alcohol compound-containing compound.

Alternatively, the first and second electrodes may be,

and cleaning the cypress oil alcohol compound crystal by using 0.01% -5% viscosity auxiliary substance aqueous solution at 0-5 ℃ to obtain the compound containing the cypress oil alcohol compound.

The viscosity auxiliary substance is used for ensuring the stability of the cypress oleyl alcohol turbid solution and promoting the water solubility of the cypress oleyl alcohol metal compound, and is preferably any combination of 1 or more than 2 of sodium alginate, polysaccharide, beta-cyclodextrin, sodium carboxymethylcellulose (CMC-Na) (modified cellulose), sodium starch phosphate (modified starch), chitosan, xanthan gum, arabic gum, sesbania gum and carrageenan, and is not limited to the selection of the raw materials.

In a preferable scheme of the invention, the water-soluble metal salt is selected from metal salts with solubility not lower than 35g/100ml at normal temperature, or the concentration of the water-soluble metal salt or the aqueous solution of ammonium salt is not lower than 25% at normal temperature; the water solution of the water-soluble metal salt or the ammonium salt is preferably a saturated solution of the water-soluble metal salt at a temperature of 30-50 ℃.

In a preferred embodiment of the present invention, the water-soluble metal salt is selected from inorganic acid metal salts or organic acid metal salts having high water solubility, and the inorganic acid metal salt is selected from a combination of one or more of nitrate, chloride, sulfate, sulfite, phosphate, phosphite, hypophosphite, citrate and carbonate; the organic acid metal salt is selected from one or a composition of more than two of formate, acetate, propionate, succinate, tartrate or malate; and do not constitute a limitation on the choice of starting materials for the salt compounds.

In a more preferred embodiment of the present invention, the metal salt is a salt compound of one or more of Na, Ni, K, Mg, Ca, Cu, Zn, Ag, Mn, Fe having a valence of 2 or 3, Li, Be, Ba, Cr, Co, Mo, Pt, or Pd.

In a preferred embodiment of the present invention, the water-soluble organic solvent is selected from any one of ethanol, methanol, and acetone;

in the preferable scheme of the invention, the cypress oil alcohol is dissolved in a cypress oil alcohol solution obtained by a water-soluble organic solvent, and the concentration of the cypress oil alcohol is 6-25 mol/L; the concentration of the water-soluble metal salt or ammonium salt aqueous solution is 5.4-125 mol/L.

Compared with the prior art, the method for preparing the cypress oil alcohol metal compound or the cypress oil alcohol ammonium compound greatly reduces the use amount of the organic solvent and the water used in the combination process, and further can effectively reduce the separation loss caused by difficult crystallization of the cypress oil alcohol metal compound in the combination solution. In the preferable scheme of the invention, the combination process of directly mixing the high-concentration water-soluble organic solvent solution of the cypress oleyl alcohol and the aqueous solution of the metal salt or the ammonium salt in a spraying mode is adopted, so that the water for suspension self-emulsification and dispersion of the cypress oleyl alcohol is reduced, the cypress oleyl alcohol metal crystalline compound can be quickly obtained, the separation loss caused by difficult crystallization is greatly reduced, and meanwhile, the technical support is provided for recycling the organic solvent and reducing energy consumption. In addition, in the method for preparing the compound, the instability of light decomposition and non-high temperature resistance of the cypress oil alcohol metal compound can be further improved by compounding the water-soluble viscosity auxiliary substance, the water-soluble dispersion of the cypress oil alcohol metal compound is improved, and the slow-release functional activity is endowed to the cypress oil alcohol metal compound by utilizing the wrapping and holding effect of the water-soluble viscosity auxiliary substance. In addition, the preparation method does not use inorganic acid and organic acid solution in the chemical combination process, thereby avoiding the environmental problems of acid solution wastewater treatment, pollution load and the like.

Detailed Description

The method for producing the cypress oleyl alcohol metal compound of the present invention is described in the following preferred examples.