阅读说明：本技术 一种染料木素钯螯合物及其制备方法与应用 (Genistein palladium chelate as well as preparation method and application thereof ) 是由 杨成雄 张宇旋 李立威 毛学荣 于 2018-10-24 设计创作，主要内容包括：本发明公开了一种染料木素钯螯合物,其具有以下结构：<Image he="286" wi="382" file="100004_DEST_PATH_DEST_PATH_IMAGE002.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>,所述的染料木素钯螯合物的制备方法,包括以下步骤：S1、配制染料木素溶液；S2、配制含钯离子的溶液；S3、将S1和S2得到的溶液反应得到所述染料木素钯螯合物。本发明所述染料木素钯螯合物在乙醇等溶剂中有良好的溶解性,相比染料木素具有更强的抗抗肿瘤等医疗功能,可广泛使用于医药产品中,满足人们日益增长的医疗保健的需求,制备方法操作简单,反应条件温和,原料成本低廉,产品后处理简单、得到的产物收率高,可达85%,纯度可高达98%,是一种制备染料木素钯螯合物的新方法。(The invention discloses a genistein palladium chelate, which has the following structure: the preparation method of the genistein palladium chelate comprises the following steps: s1, preparing a genistein solution; s2, preparing a solution containing palladium ions; s3, and reacting the solution obtained from S1 and S2 to obtain the genistein palladium chelate. The genistein palladium chelate disclosed by the invention has good solubility in solvents such as ethanol, has stronger medical functions such as anti-tumor and the like compared with genistein, can be widely used in medical products, meets the increasing medical health care requirements of people, and has the advantages of simple preparation method operation, mild reaction conditions, low raw material cost, and product post-treatmentSimple process, high yield up to 85% and high purity up to 98%, and is a new method for preparing genistein palladium chelate.)

1. A genistein palladium chelate characterized by the following structure:

2. the method for preparing the genistein palladium chelate according to claim 1, characterized by comprising the following steps:

s1, preparing a genistein solution;

s2, preparing a solution containing palladium ions;

s3, and reacting the solution obtained from S1 and S2 to obtain the genistein palladium chelate.

3. The method for preparing the genistein palladium chelate according to claim 2, characterized in that a solvent used for preparing the genistein solution is an organic solvent or a mixed solvent of the organic solvent and water, and the organic solvent is one or more of an alcohol solvent, a sulfone solvent, a halogenated hydrocarbon solvent, an ester solvent, an ether solvent and a ketone solvent;

wherein the alcohol solvent is one or more of methanol, ethanol, propanol, isopropanol, butanol, pentanol, decanol, n-dodecanol, cyclopentanol, cyclohexanol, benzyl alcohol, and phenethyl alcohol;

the sulfone solvent is one or more of dimethyl sulfoxide, dimethyl sulfone, sulfolane and 2, 4-dimethyl sulfolane;

the halogenated hydrocarbon solvent is one or more of dichloromethane, trichloromethane and carbon tetrachloride;

the ester solvent is one or two of ethyl acetate and methyl acetate;

the ether solvent is one or more of diethyl ether, methyl ethyl ether, methyl tert-butyl ether, dipropyl ether, dibutyl ether, 1, 4-dioxane and tetrahydrofuran;

the ketone solvent is one or two of acetone and methyl ethyl ketone;

the mass percentage of the organic solvent in the mixed solution is 40% ~ 99%.

4. The method for preparing the genistein palladium chelate according to claim 2, characterized in that a catalyst is added in the process of preparing the genistein solution at S1, the catalyst is one or more of DMAP, sodium methoxide, potassium ethoxide, pyridine, potassium tert-butoxide, lithium diisopropylamide and lithium hexamethyldisilazide, and the molar ratio of the catalyst to the genistein is (0.0001 ~ 0.5.5): 1.

5. The method for preparing the genistein palladium chelate according to claim 4, characterized in that the molar ratio of the catalyst amount to the genistein is (0.001 ~ 0.2.2): 1.

6. The method for preparing the genistein palladium chelate according to claim 2, wherein in S1, the solvent is heated at 10-90 ℃ during the preparation of the genistein solution.

7. The method for preparing the genistein palladium chelate according to claim 3, wherein the same solvent is used for S2 and S1, and the palladium source used for preparing the solution containing palladium ions in S2 is one or both of palladium chloride and palladium sulfate.

8. The method for preparing the palladium chelate of genistein according to claim 2, characterized in that the molar ratio of genistein in the genistein solution to palladium source in the palladium ion-containing solution is (1 ~ 10): 10, and the reaction of genistein with palladium source in S3 is carried out under heating at 10-90 ℃.

9. The method for preparing the genistein palladium chelate according to claim 2, characterized by comprising the following steps:

t1, adding a solvent and a catalyst into a three-mouth glass bottle containing genistein, heating and stirring to prepare a solution A for later use;

t2, adding a palladium-containing compound into a solvent, and stirring to dissolve the palladium-containing compound to prepare a solution B for later use;

and T3, taking a constant-pressure dropping filter funnel, adding the solution B, opening a piston, dropwise adding the solution B into the solution A while stirring for reaction, filtering after the reaction is finished, and drying filter residues to obtain the genistein palladium chelate.

10. The use of a genistein palladium chelate according to claim 1 in the preparation of an anti-tumor medicament.

Technical Field

The invention relates to the technical field of preparation of medical products, in particular to a genistein palladium chelate with an anti-tumor effect, and a preparation method and application thereof.

Background

Genistein (Genistein), also known as Genistein, 5,7, 4' -trihydroxyisoflavone, is an active ingredient mainly extracted from leguminous plants such as soybean, clover, kudzu root, sophora flower, sophora fruit, Genistein and subprostrate sophora, is a natural tyrosine kinase and a soybean metabolite, and is called phytoestrogen. Genistein is one of isoflavone compounds with the highest active function, is a single component, is a non-estrogen compound, has dual regulation effects of estrogen and antiestrogen, and can be widely applied in the fields of pharmacy, health products and the like. The study proves that the genistein has the following effects:

(one) have estrogen and antiestrogen properties;

(II) has an anti-oxidation effect;

(III) the activity of tyrosine protein kinase (PTK) can be inhibited;

(IV) the activity of the topologic purchased enzyme II can be inhibited;

(V) inhibiting cell cycle: stopping the cells at G2/M phase; induction of tumor cell apoptosis: by up-regulating and down-regulating the apoptosis-promoting gene and the corresponding anti-apoptosis gene, the apoptosis of tumor cells is promoted, thereby preventing and limiting the occurrence of tumors, and the anti-apoptosis gene has the effects of inducing programmed cell death, improving the anti-cancer efficacy, inhibiting angiogenesis and the like.

The summary of pharmacological activity of genistein records that genistein has obvious physiological activities of reducing blood fat, resisting cancer, resisting tumor, preventing and treating osteoporosis, resisting oxidation, resisting atherosclerosis, having estrogen-like effect and the like, so that the genistein is widely applied to the fields of pharmacy, health care products and the like. In recent years, genistein has become a hot spot of research of scholars at home and abroad. The genistein has weak lipophilicity and hydrophilicity, so the genistein influences the absorption of the genistein in the body, has low bioavailability by direct oral administration, has strong first-pass effect, is difficult to achieve the aim of preventing and treating diseases clinically, and limits the clinical application of the genistein.

Palladium is a member of the platinum group VIII of the fifth period, is a silvery white transition metal, is relatively soft, has good ductility and plasticity, and can be forged, calendered and drawn. Palladium is an indispensable key material in high-tech fields such as aerospace, aviation, navigation, weapons and nuclear energy and the like and in automobile manufacturing industry, and is also an investment variety which is not neglected in the international precious metal investment market. The palladium is fused with ruthenium, iridium, silver, gold, copper and the like to form an alloy, the resistivity, the hardness and the strength of the palladium can be improved, and the palladium is used for manufacturing precision resistors, jewelry and the like. Palladium is mainly used as a catalyst in chemistry, but the application of the palladium in the aspect of medicines is less reported.

Disclosure of Invention

The invention aims to provide a genistein palladium chelate as well as a preparation method and application thereof, which can improve the problems. Compared with genistein, the genistein palladium chelate provided by the invention has stronger anti-tumor functions and the like. In addition, the preparation method is simple to operate, mild in reaction conditions and low in raw material cost, and is a novel method for preparing the genistein palladium chelate.

A genistein palladium chelate having the structure:

。

a preparation method of a genistein palladium chelate comprises the following steps:

s1, preparing a genistein solution;

s2, preparing a solution containing palladium ions;

s3, and reacting the solution obtained from S1 and S2 to obtain the genistein palladium chelate.

The solvent used for preparing the genistein solution is an organic solvent or a mixed solvent of the organic solvent and water, wherein the organic solvent is one or more of an alcohol solvent, a sulfone solvent, a halogenated hydrocarbon solvent, an ester solvent, an ether solvent and a ketone solvent;

wherein the alcohol solvent is one or more of methanol, ethanol, propanol, isopropanol, butanol, pentanol, decanol, n-dodecanol, cyclopentanol, cyclohexanol, benzyl alcohol, and phenethyl alcohol;

the sulfone solvent is one or more of dimethyl sulfoxide, dimethyl sulfone, sulfolane and 2, 4-dimethyl sulfolane;

the halogenated hydrocarbon solvent is one or more of dichloromethane, trichloromethane and carbon tetrachloride;

the ester solvent is one or two of ethyl acetate and methyl acetate;

the ether solvent is one or more of diethyl ether, methyl ethyl ether, methyl tert-butyl ether, dipropyl ether, dibutyl ether, 1, 4-dioxane and tetrahydrofuran;

the ketone solvent is one or two of acetone and methyl ethyl ketone;

the mass percentage of the organic solvent in the mixed solution is 40% ~ 99%.

Adding a catalyst during the preparation of the genistein solution in S1, wherein the catalyst is one or more of DMAP, sodium methoxide, potassium ethoxide, pyridine, potassium tert-butoxide, lithium diisopropylamide and lithium hexamethyldisilazide, and the molar ratio of the catalyst to the genistein is (0.0001 ~ 0.5.5): 1, preferably (0.001 ~ 0.2.2): 1.

In S1, the solvent is heated at 10-90 deg.C, preferably 10-70 deg.C in the process of preparing genistein solution.

S2 and S1 use the same solvent, and the palladium source used for preparing the solution containing palladium ions in S2 is one or two of palladium chloride and palladium sulfate.

The molar ratio of genistein to palladium source in the solution containing palladium ions in the genistein solution is (1 ~ 10): 10, preferably (2 ~ 8): 10, for example 3.7:10, 5.2:10 or 7.2: 10. the reaction of genistein with palladium source in S3 is carried out under heating at a temperature of 10-90 ℃.

A preparation method of a genistein palladium chelate comprises the following steps:

t1, adding a solvent and a catalyst into a three-mouth glass bottle containing genistein, heating and stirring to prepare a solution A for later use;

t2, adding a palladium-containing compound into a solvent, and stirring to dissolve the palladium-containing compound to prepare a solution B for later use;

and T3, taking a constant-pressure dropping filter funnel, adding the solution B, opening a piston, dropwise adding the solution B into the solution A while stirring for reaction, filtering after the reaction is finished, and drying filter residues to obtain the genistein palladium chelate.

An application of genistein palladium chelate in preparing antineoplastic medicine is disclosed.

The invention has the beneficial effects that:

1) the genistein palladium chelate disclosed by the invention has good solubility in solvents such as ethanol and the like, can be prepared into tablets, capsules, oral liquid, injection and the like, has stronger medical functions such as anti-tumor and the like compared with genistein, can be widely used in medical products, and meets the increasing medical and health-care requirements of people.

2) The preparation method disclosed by the invention is simple to operate, mild in reaction conditions, low in raw material cost, simple in product post-treatment, high in product yield which can reach 85%, and high in purity which can reach 98%, and is a novel method for preparing the genistein palladium chelate.

Drawings

FIG. 1 is an X-ray diffraction pattern of genistein according to the present invention;

FIG. 2 is an X-ray diffraction pattern of a genistein palladium complex prepared according to example 1 of the present invention;

FIG. 3 is an infrared spectrum of genistein;

FIG. 4 is an infrared spectrum of genistein palladium compound prepared in example 1 of the present invention.

Detailed Description

The compounds of the present invention, methods for their preparation and their use are described in further detail in the following examples. The following examples are merely illustrative and explanatory of the present invention and should not be construed as limiting the scope of the invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.

Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.