CN110003294A - A kind of preparation method of copper cobalt nickel-scutelloside complex - Google Patents

Abstract

The present invention provides a method for preparing a copper-cobalt-nickel-baicalin complex, which comprises the following steps: dissolving a copper salt compound, or a cobalt salt compound, or a nickel salt compound in an aqueous sodium alginate solution to prepare a transition metal ion precursor solution; dissolve baicalin with a 4-12% triethylamine solution to obtain a baicalin solution; under magnetic stirring, dropwise add the precursor solution of transition metal ions to the triethylamine aqueous solution of baicalin, and carry out a complex reaction to obtain Precipitate the mixed solution; continue to stir the precipitation mixed solution until the reaction is complete, let it stand for a period of time, carry out suction filtration, and dry the precipitation to obtain finished products of copper, cobalt, and nickel-baicalin complexes, respectively. The invention has short reaction time, simple process, easy to obtain products, high yield and purity, stable properties and easy preservation, and has broad application prospects in medicine and animal feeding.

Description

A kind of preparation method of copper-cobalt-nickel-baicalin complex

technical field

The invention relates to the field of preparation of transition metal complexes, in particular to a preparation method of a copper-cobalt-nickel-baicalin complex.

Background technique

Baicalin (Baicalin) is a flavonoid-containing compound that exists in traditional Chinese medicine and has many pharmacological effects such as antibacterial, anti-inflammatory, antiviral, antihypertensive and diuretic, scavenging superoxide free radicals, and inhibiting lipase. In addition, some researchers have confirmed that baicalin has anti-inflammatory and anti-HIV-1 activities, and its in vitro anti-HIV-1 efficacy is relatively significant. Therefore, baicalin has become a popular anti-AIDS drug. In recent years, some people often chelate some pharmacologically active metal ions (such as zinc, copper, cobalt, iron, aluminum, manganese, etc.) with baicalin, in order to obtain complexes that can enhance the efficacy or produce new the purpose of pharmacological activity.

The synthesis of the existing transition metal-baicalin complex is usually by dissolving baicalin in an alkaline solution such as sodium hydroxide and sodium bicarbonate, and reacting with the aqueous solution of the transition metal salt under weak alkaline and heating conditions to generate Transition metal-baicalin complexes. This kind of synthetic method has the following problems: baicalin is unstable in alkaline solution, its structure is prone to deterioration, resulting in more by-products in the product, and the binding effect with transition metal ions is poor, and the yield is low; transition Metal ions are prone to precipitation in alkaline solutions, resulting in lower product purity; in addition, when transition metals are mixed with baicalin, it is easy to form a precipitated suspension, which is not easy to precipitate, resulting in excessive precipitation time, so that the yield of the complex product is relatively high. Low.

SUMMARY OF THE INVENTION

The main purpose of the present invention is to propose a preparation method and application of a (copper, cobalt, nickel)-baicalin complex, aiming to improve the precipitation speed, yield and purity of the obtained transition metal-baicalin complex.

In order to achieve the above object, the present invention proposes a preparation method of (copper, cobalt, nickel)-baicalin complex, and the preparation method of the (copper, cobalt, nickel)-baicalin complex comprises the following steps:

S1. Preparation of transition metal ion precursor solution: take copper salt compounds such as Cu(Ac) ₂ , CuCl ₂ , CuSO ₄ , Cu(NO ₃ ) ₂ , or cobalt salt compounds such as Co (Ac) ₂ , CoCl ₂ , CoSO ₄ , Co(NO ₃ ) ₂ , or nickel salts such as Ni (Ac) ₂ , NiCl ₂ , NiSO ₄ , Ni(NO ₃ ) ₂ are dissolved in sodium alginate aqueous solution to prepare transition metal ion precursor solution.

S2. Prepare the triethylamine aqueous solution of baicalin: take the baicalin powder and dissolve it with a 4-12% triethylamine aqueous solution to obtain a baicalin solution with a pH value of 7.1-8.2 containing triethylamine.

S3. The transition metal ion precursor solution obtained in S1 is slowly added dropwise to the triethylamine aqueous solution of baicalin obtained in S2 under magnetic stirring, and a complex reaction is carried out to immediately generate a colored complex precipitation mixture.

S4. Continue to stir the complex precipitation mixture obtained in S3 at room temperature for 2-3 h, and then let stand for 30-60 min; filter the precipitate with suction, wash it with triethylamine solution several times, and then wash it with distilled water several times, Finally, wash with 95% ethanol for several times to obtain copper, cobalt, nickel transition metal-baicalin complex products, and the products are dried under vacuum at 50-70 °C to prepare copper, cobalt, nickel transition metal-baicalin, respectively. Finished compound.

Preferably, the mass concentration of sodium alginate in S1 is 0.2-0.9%.

Preferably, the mass concentration of triethylamine contained in the triethylamine solution in S2 is 6-9%.

Preferably, the pH of the triethylamine-containing baicalin solution in S2 is 7.5.

Preferably, the molar ratio of baicalin and transition metal ions added in S3 is 1:1.2-1.6.

Preferably, the dropping rate of the transition metal ion precursor solution added to S3 is 1.0-2.5 mL/min.

Preferably, the stirring time in S4 is 2.5 h, the precipitation standing time is 30-60 min, and the vacuum drying temperature of the precipitated product is 65°C.

Preferably, the mass concentration of the triethylamine aqueous solution washed and precipitated in S4 is 3-6%.

In the technical solution of the present invention, the solvent used for dissolving baicalin is improved, and it is proposed to use triethylamine solution as the solvent, which is more efficient than existing alcoholic solvents or alkaline solutions such as sodium hydroxide and sodium bicarbonate. Good dissolving effect, baicalin can exist stably and completely dissolve in the triethylamine solution, which increases the concentration of baicalin participating in the complex reaction. At the same time, the pH of the baicalin solution is limited to dissociate the 5-position hydroxyl group in the baicalin molecule. It is (-O ^- ), which is more likely to have a coordination reaction with metal ions; at the same time, triethylamine does not participate in the coordination reaction and does not affect the molecular structure of metal-baicalin complexes. The sodium alginate added in the present invention is a kind of non-toxic food, which is widely used in the food industry and the medical field. The invention has high yield and purity, stable product properties and easy preservation, and has broad application prospects in medicine and animal feeding.

Description of drawings

Fig. 1 is the preparation process flow chart of the present invention.

Detailed ways

The structure and working principle of the present invention will be further explained below in conjunction with the accompanying drawings and specific embodiments:

As shown in Figure 1, the present invention provides a method for preparing a copper-cobalt-nickel transition metal-baicalin complex, which comprises the following steps:

S1. Prepare copper (cobalt, or nickel) ion precursor solution: take copper salt compounds such as Cu (Ac) ₂ , CuCl ₂ , CuSO ₄ , Cu(NO ₃ ) ₂ , or cobalt salt compounds such as Co (Ac) ₂ , CoCl _2. CoSO ₄ , Co(NO ₃ ) ₂ , or nickel salt compounds such as Ni (Ac) ₂ , NiCl ₂ , NiSO ₄ , Ni(NO ₃ ) ₂ are dissolved in 0.2-0.9% sodium alginate aqueous solution to prepare a transition metal ion precursor.

S2. Prepare the triethylamine aqueous solution of baicalin: take the baicalin powder and dissolve it with a 4-12% triethylamine aqueous solution to obtain a baicalin solution with a pH value of 7.1-8.2 containing triethylamine.

S3. The transition metal ion precursor solution obtained in S1 is slowly added dropwise to the triethylamine aqueous solution of baicalin obtained in S2 under magnetic stirring, and a complex reaction is carried out to immediately generate a colored complex precipitation mixture.

S4. Continue stirring the complex precipitate mixture obtained in S3 for 2-3 h at room temperature, and then let stand for 30-60 min; filter the precipitate with suction, wash it with 3%-6% triethylamine aqueous solution for several times, and then Wash with distilled water for several times, and finally wash with 95% ethanol for several times to obtain copper, cobalt, nickel transition metal-baicalin complex products, and dry the products under vacuum conditions at 50-70 ° C to obtain copper, cobalt, nickel The finished product of transition metal-baicalin complex.

Example 1

Take baicalin powder and dissolve it with 100mL of 4% triethylamine aqueous solution to make 6.7mmol of baicalin solution, the pH value of this solution is 7.1; under normal temperature stirring conditions, add dropwise to the above solution at a speed of 1 mL/min 8.04 mmol copper acetate solution (containing 0.2% sodium alginate), the precipitate is obtained; continue stirring at room temperature for 2 h, then let stand for 60 min, then filter, wash several times with an aqueous solution of 3% triethylamine by mass, and then use distilled water Washed 5 times, finally washed several times with 95% ethanol, and dried at 70°C under vacuum to obtain the copper-baicalin complex precipitated product.

The content of trace copper in the product was measured by atomic absorption spectrometry, and the yield and purity were calculated; the yield of the product was determined to be 98.72%, and the purity was 99.25%.

Example 2

Take baicalin powder and dissolve it with 100 mL of 12% triethylamine aqueous solution to make 6.7 mmol of baicalin solution, the pH value of this solution is 8.2; under stirring conditions at room temperature, add dropwise to the above solution at a speed of 2.5 mL/min 10.72 mmol copper sulfate solution (containing 0.9% sodium alginate) to obtain the precipitate; continue stirring at room temperature for 3 h, then stand for 30 min, filter, wash several times with 6% triethylamine aqueous solution by mass, and then wash with distilled water 5 times, and finally washed several times with 95% ethanol, and dried under vacuum at 50°C to obtain the copper-baicalin complex precipitated product.

The content of trace copper in the product was measured by atomic absorption spectrometry, and the yield and purity were calculated; the yield of the product was determined to be 99.03%, and the purity was 99.14%.

Example 3

The implementation steps of Example 3 are the same as those of Example 2, and other conditions are kept unchanged in Example 2, and copper acetate and copper sulfate can be replaced by 9.38 mmol copper chloride or copper nitrate respectively to prepare copper-baicalin complex precipitation. products, the purity of the products are 99.76% and 99.18% respectively.

Example 4

Take baicalin powder and dissolve it with 100 mL of 9% triethylamine aqueous solution to make 6.7 mmol of baicalin solution, and the pH value of this solution is 8.0; under normal temperature stirring conditions, add dropwise to the above solution at a speed of 2 mL/min 10.05 mmol cobalt nitrate solution (containing 0.5% sodium alginate) to obtain the precipitate; continue stirring at room temperature for 2.5 h, then let stand for 45 min, then filter, wash several times with 5% triethylamine aqueous solution by mass, and then use distilled water Washed 5 times, finally washed several times with 95% ethanol, and dried under vacuum at 60 °C to obtain the cobalt-baicalin complex precipitation product.

The content of trace copper in the product was measured by atomic absorption spectrometry, and the yield and purity were calculated. The product yield was determined to be 99.23%, and the purity was 99.46%.

Example 5

Take baicalin powder and dissolve it with 100 mL of 6% triethylamine aqueous solution to make 6.7 mmol of baicalin solution, the pH value of this solution is 7.5; under normal temperature stirring conditions, add dropwise to the above solution at a speed of 1.5 mL/min 8.71 mmol of cobalt chloride solution (containing 0.8% sodium alginate) to obtain the precipitate; continue to stir at room temperature for 2.6 h, then stand for 50 min, then filter, wash several times with 4% triethylamine aqueous solution, and then use Washed with distilled water for 5 times, finally washed with 95% ethanol for several times, and dried under vacuum at 65 °C to obtain the cobalt-baicalin complex precipitation product.

The content of trace copper in the product was measured by atomic absorption spectrometry, and the yield and purity were calculated; the yield of the product was determined to be 99.09%, and the purity was 99.03%.

Example 6

The implementation steps of Example 6 are the same as those of Example 5, and other conditions are kept unchanged in Example 5, and cobalt nitrate and cobalt chloride can be replaced by cobalt sulfate or cobalt acetate, respectively, to prepare a cobalt-baicalin complex precipitation product, The purities of its products are 99.34% and 99.15%, respectively.

Example 7

Take baicalin powder and dissolve it with 100 mL of 5% triethylamine aqueous solution to make 6.7 mmol of baicalin solution, the pH value of this solution is 7.3; under stirring conditions at room temperature, add dropwise to the above solution at a speed of 2.2 mL/min 8.71 mmol nickel nitrate solution (containing 0.3% sodium alginate) to obtain the precipitate; continue stirring at room temperature for 2 h, then let stand for 45 min, then filter, wash several times with 4% triethylamine aqueous solution by mass, and then use distilled water Washed 5 times, finally washed several times with 95% ethanol, and dried under vacuum at 60°C to obtain the nickel-baicalin complex precipitated product.

The content of trace nickel in the product was measured by atomic absorption spectrometry, and the yield and purity were calculated; the yield of the product was determined to be 99.41%, and the purity was 99.31%.

Example 8

Take baicalin powder and dissolve it with 100 mL of 8% triethylamine aqueous solution to make 6.7 mmol of baicalin solution, the pH value of this solution is 7.8; under stirring conditions at room temperature, add dropwise to the above solution at a speed of 1.8 mL/min 8.71 mmol nickel chloride solution (containing 0.5% sodium alginate), that is, to obtain the precipitation; continue stirring at room temperature for 3 h, then let stand for 35 min, then filter, wash several times with 4% triethylamine aqueous solution, and then use Washed with distilled water for 5 times, finally washed with 95% ethanol for several times, and dried under vacuum condition at 55°C to obtain the nickel-baicalin complex precipitated product.

The content of trace nickel in the product was measured by atomic absorption spectrometry, and the yield and purity were calculated; the yield of the product was determined to be 99.09%, and the purity was 99.27%.

Example 9

The implementation steps of Example 9 are the same as those of Example 8, and other conditions are kept unchanged in Example 8. Nickel nitrate and nickel chloride can be replaced by nickel sulfate or nickel acetate respectively to prepare a nickel-baicalin complex precipitation product, The purity of its products are 99.51% and 99.13% respectively.

Infrared spectrum analysis was performed on baicalin, the finished copper-baicalin complex prepared in Example 1, the finished cobalt-baicalin complex prepared in Example 5, and the finished nickel-baicalin complex prepared in Example 8, respectively. The results showed that the 4-position-C=O absorption peak of baicalin was at 1661.9cm ^-1 . After baicalin forms a complex with metal ions, the C=O of baicalin and the hydroxyl group (-OH) at the 5-position of baicalin will coordinate with the metal element, causing the electron cloud to transfer, which in turn leads to a red shift of the C=O absorption peak. The C=O absorption peaks in the baicalin molecule are all red-shifted from 1661.9cm ^-1 to 1622.52cm ^-1 (copper, cobalt), 1629.94cm ^-1 (nickel), illustrating the copper, cobalt, and nickel in Examples 1, 5, and 8 The ions formed stable complexes with baicalin, respectively.

The above-mentioned embodiments are only used to illustrate the technical solutions of the present invention, but not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand: The technical solutions described in the embodiments are modified, or some or all of the technical features thereof are equivalently replaced; and these modifications or replacements do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.

Claims (7)

1. a preparation method of copper-cobalt-nickel-baicalin complex, is characterized in that: it may further comprise the steps: S1. Preparation of copper, cobalt and nickel ion precursors: take copper salt compounds such as Cu(Ac) ₂ , CuCl ₂ , CuSO ₄ , Cu(NO ₃ ) ₂ , or cobalt salt compounds such as Co (Ac) ₂ , CoCl ₂ , CoSO _4. Co(NO ₃ ) ₂ , or nickel salts such as Ni (Ac) ₂ , NiCl ₂ , NiSO ₄ , Ni(NO ₃ ) ₂ are dissolved in an aqueous solution of sodium alginate to prepare a transition metal ion precursor solution; S2, prepare the triethylamine aqueous solution of baicalin: take baicalin powder and dissolve it with triethylamine aqueous solution to obtain the baicalin solution containing triethylamine with a pH value of 7.1～8.2; S3. The transition metal ion precursor solution obtained in S1 is slowly added dropwise to the triethylamine aqueous solution of baicalin in S2 under magnetic stirring, and a complex reaction is carried out to immediately generate a colored complex precipitation mixture; S4. Continue to stir the complex precipitation mixture obtained in S3 at room temperature, and then allow to stand; filter to obtain the precipitate, wash with triethylamine solution for several times, then wash with distilled water for several times, and finally wash with 95% ethanol For several times, copper, cobalt, nickel transition metal-baicalin complex products are obtained respectively, and the products are dried under vacuum conditions at 50-70° C. to prepare copper, cobalt, nickel transition metal-baicalin complex products. 2. The preparation method of copper-cobalt-nickel-baicalin complex according to claim 1, wherein the mass concentration of sodium alginate in S1 is 0.2-0.9%. 3. the preparation method of a kind of copper-cobalt-nickel-baicalin complex according to claim 1, is characterized in that: in S2, utilize triethylamine aqueous solution to dissolve baicalin, and the mass concentration of its triethylamine aqueous solution is 4%～ 12%, preferably 5% to 9%. 4 . The method for preparing a copper-cobalt-nickel-baicalin complex according to claim 3 , wherein the dropping rate of the copper (cobalt, or nickel) ion precursor solution in S3 is 1.0-2.5 mL/min. 5 . 5 . The method for preparing a copper-cobalt-nickel-baicalin complex according to claim 1 , wherein the molar ratio of baicalin to transition metal ions in S3 is 1:1.2-1.6. 6 . 6 . The method for preparing a copper-cobalt-nickel-baicalin complex according to claim 1 , wherein the precipitate is washed with an aqueous triethylamine solution in S4 , and the mass concentration of the aqueous triethylamine solution is 3 to 6%. 7 . 7. The preparation method of a copper-cobalt-nickel-baicalin complex according to claim 1, wherein the stirring time in S4 is 2 to 3 h, the precipitation standing time is 30 to 60 min, and the vacuum drying temperature It is 50～70 ℃.