CN109970800A - A kind of bismuth-baicalin complex and its preparation method and application - Google Patents

Abstract

The invention discloses a bismuth-baicalin complex, a preparation method and application thereof, and relates to the technical field of veterinary medicine. The general molecular formula of the bismuth-baicalin complex is (C ₂₁ H ₁₇ O ₁₁ )(NO ₃ )Bi·4H ₂ O, and the bismuth-baicalin complex has the structure shown in structural formula (1). The preparation method of the bismuth-baicalin complex includes the following steps: dissolving the bismuth salt in a glycerol solution to obtain a bismuth ion precursor solution; adding the bismuth ion precursor dropwise to the baicalin solution of pH 7-9, and reacting The bismuth-baicalin complex was obtained. The invention aims to prepare a new metal-baicalin complex with higher biological activity than baicalin, and the metal-baicalin complex can be used for treating piglet diarrhea.

Description

A kind of bismuth-baicalin complex and its preparation method and application

technical field

The invention relates to the technical field of veterinary drugs, in particular to a bismuth-baicalin complex and a preparation method and application thereof.

Background technique

The most common method to treat piglet diarrhea is to use antibiotics, but the bacteria have strong drug resistance, and the long-term use of antibiotics has poor therapeutic effect. There are currently treatments for piglet diarrhea using Chinese herbal medicines, such as baicalin.

Baicalin is the main active ingredient of Scutellaria baicalensis. It is a flavonoid compound with good antibacterial and anti-inflammatory effects. It can relieve the symptoms of poisonous blood during bacterial infection, and has a protective and repairing effect on various organs in the body. The antibacterial test in vitro and in vivo confirmed that baicalin has good antibacterial effect on Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Using baicalin to treat piglet diarrhea, the therapeutic effect is obvious. It has been reported in the literature that baicalin can coordinate to synthesize complexes with copper (II), zinc (II), and aluminum (III), and after baicalin forms complexes with the above metal ions, the original biological activity has been improved to varying degrees. . But not all metal ions can be combined with baicalin to enhance its biological activity. It is of great significance for piglet breeding to find new baicalin drugs for the treatment of piglet diarrhea.

SUMMARY OF THE INVENTION

The main purpose of the present invention is to propose a bismuth-baicalin complex and its preparation method and application, aiming to prepare a new metal-baicalin complex with higher biological activity than baicalin. Baicalin complex can be used to treat piglet diarrhea.

In order to achieve the above purpose, the present invention proposes a bismuth-baicalin complex, and the general molecular formula of the bismuth-baicalin complex is (C ₂₁ H ₁₇ O ₁₁ )(NO ₃ )Bi·4H ₂ O, so The bismuth-baicalin complex has the structure shown in structural formula (1).

Structural formula (1):

In order to achieve the above purpose, the present invention proposes a preparation method of a bismuth-baicalin complex for synthesizing the above-mentioned bismuth-baicalin complex, and the preparation method of the bismuth-baicalin complex comprises the following steps:

Dissolving the bismuth salt in the glycerol solution to obtain the bismuth ion precursor solution;

The bismuth ion precursor is added dropwise to the baicalin solution of pH 7-9 to react to obtain a bismuth-baicalin complex.

Optionally, the bismuth salt is dissolved in the glycerol solution, and in the step of obtaining the bismuth ion precursor solution,

The bismuth salt is bismuth nitrate; and/or,

The glycerol solution is an aqueous solution of glycerol.

Optionally, in the step of dissolving the bismuth salt in the glycerol solution to obtain a bismuth ion precursor solution, the mass concentration of the bismuth salt in the bismuth ion precursor solution is 10-25%.

Optionally, in the step of dissolving the bismuth salt in the glycerol solution to obtain the bismuth ion precursor solution, the mass concentration of the glycerol solution is 30-60%.

Optionally, the bismuth ion precursor is added dropwise to the baicalin solution of pH 7-9, and the step of reacting to obtain the bismuth-baicalin complex further includes:

Dissolving baicalin in an aqueous solution of triethylamine to obtain a baicalin solution with pH 7-9, wherein, in the aqueous solution of triethylamine, the mass concentration of triethylamine is 0.8-1.5%.

Optionally, the bismuth ion precursor is added dropwise to a baicalin solution of pH 7-9, and in the step of reacting to obtain a bismuth-baicalin complex, the molar ratio of baicalin to bismuth ion is 1: (1.1-1.6 ).

Optionally, the bismuth ion precursor is added dropwise to a baicalin solution with a pH of 7-9, and the steps of reacting to obtain a bismuth-baicalin complex include:

The bismuth ion precursor solution is added dropwise to the baicalin solution with pH 7-9 at a dropping rate of 1.2-2.4 mL/min, and stirring is continued for 60-120 min to obtain a mixed solution;

After the mixed solution is allowed to stand for 2 to 4 hours, the precipitate is obtained by filtration;

The precipitate is washed with distilled water and 60% ethanol in sequence, and then dried under vacuum at 40-60° C. to obtain a bismuth-baicalin complex.

Optionally, the bismuth ion precursor solution is added dropwise to the baicalin solution of pH 7-9 at a dropping rate of 1.2-2.4 mL/min, and stirring is continued for 60-120 min, and the step of obtaining the mixed solution is at a temperature of 25-45 °C. conditions.

In addition, the present invention also proposes the application of the above-mentioned bismuth-baicalin complex in the treatment of piglet diarrhea.

In the technical scheme of the present invention, through in-depth research on the spatial structure of baicalin, various metal ions and the coordination ability of bismuth with different valences, it is proposed that the bismuth-baicalin complex synthesized by the coordination of trivalent bismuth and baicalin has more advantages than baicalin. Glycoside has better stability, higher efficacy and antioxidant activity than baicalin, and has the effect of bismuth, which can be better utilized by piglets and has good bacteriostatic effect, which also opens up the development and utilization of bismuth element. wider space. In addition, based on the solubility characteristics of bismuth salt and baicalin, a certain concentration of glycerin solution was selected as the solvent for dissolving bismuth salt, which improved the solubility of bismuth salt, promoted the reaction to proceed in a forward direction, and effectively improved the yield, and glycerol would not participate in the complexing reaction. The production of by-products is avoided; and the pH of the baicalin solution is controlled to prevent the baicalin from being damaged by strong acid or strong base, thereby avoiding the occurrence of side reactions and effectively improving the product purity.

Description of drawings

In order to explain the embodiments of the present invention or the technical solutions in the prior art more clearly, the following briefly introduces the accompanying drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only For some embodiments of the present invention, for those of ordinary skill in the art, other related drawings can also be obtained according to these drawings without creative effort.

Fig. 1 is the schematic flow sheet of an embodiment of the preparation method of the bismuth-baicalin complex proposed by the present invention;

Fig. 2 is the infrared absorption spectrogram of baicalin;

3 is an infrared spectrum diagram of the bismuth-baicalin complex prepared in Example 1.

The realization, functional characteristics and advantages of the present invention will be further described with reference to the accompanying drawings in conjunction with the embodiments.

Detailed ways

In order to make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not indicated in the examples, it is carried out according to the conventional conditions or the conditions suggested by the manufacturer. The reagents or instruments used without the manufacturer's indication are conventional products that can be purchased from the market.

The antibacterial test in vitro and in vivo confirmed that baicalin has good antibacterial effect on Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Using baicalin to treat piglet diarrhea, the therapeutic effect is obvious. It has been reported in the literature that baicalin can coordinate to synthesize complexes with copper (II), zinc (II), and aluminum (III), and after baicalin forms complexes with the above metal ions, the original biological activity has been improved to varying degrees. . But not all metal ions can be combined with baicalin to enhance its biological activity. It is of great significance for piglet breeding to find new baicalin drugs for the treatment of piglet diarrhea.

Therefore, the present invention proposes a bismuth-baicalin complex, the general molecular formula of the bismuth-baicalin complex is (C ₂₁ H ₁₇ O ₁₁ )(NO ₃ )Bi·4H ₂ O, the bismuth-baicalin complex is The baicalin complex has the structure shown in structural formula (1).

Structural formula (1):

Bismuth salt is a low-toxicity or toxic substance, which has the effect of physiological activation. After oral administration of bismuth-containing drugs, a protective film can be formed on the wound surface of the gastric mucosa to reduce the stimulation of food to the gastric mucosa; bismuth and hydrogen sulfide in pig intestines. Combined, insoluble bismuth sulfide is formed on the intestinal mucosa, which slows down intestinal peristalsis, has astringent, gastric mucosa protection and antibacterial effects, thereby preventing piglet diarrhea and protecting animal growth and production. Through in-depth research on the spatial structure of baicalin, various metal ions and the coordination ability of bismuth with different valences, the inventor found that under certain conditions, trivalent bismuth can coordinate with baicalin to synthesize a complex with the above structure. The bismuth-baicalin complex with the above structure has stable properties, has higher efficacy and antioxidant activity than baicalin, and has the effect of bismuth, which can be better utilized by the piglet body and improve the nutrition of animals. Substance digestibility and utilization rate, inhibit the growth of pathogenic bacteria, and open up a broader space for the development and utilization of bismuth element.

In addition, the synthesis of the existing metal-baicalin complex is usually by dissolving baicalin in an alkaline solution such as sodium hydroxide, sodium bicarbonate or a 60% ethanol solution, under alkaline and heating conditions, with metal The aqueous solution of the salt reacts to form the metal-baicalin complex. But these synthetic methods have the following problems: baicalin is unstable in alkaline solution, its structure is prone to deterioration, and metal ions are prone to precipitation in alkaline solution, resulting in more by-products in the product and low purity; Scutellaria baicalensis The glycosides are insoluble in water and slightly soluble in alcohol. When the above synthesis method is used, baicalin cannot be completely dissolved, and less baicalin participates in the reaction, resulting in lower product yield; moreover, most bismuth salts are insoluble in water or easily hydrolyzed. , can not be made into an aqueous solution, and can not be used to prepare bismuth-baicalin complexes.

In view of this, the present invention proposes a preparation method of a bismuth-baicalin complex for preparing the above-mentioned bismuth-baicalin complex. The preparation method has simple process, easy control, high yield and good product purity. With reference to the schematic flowchart of an embodiment of the preparation method of bismuth-baicalin complex proposed in FIG. 1, the preparation method of bismuth-baicalin complex includes the following steps:

Step S10, dissolving the bismuth salt in the glycerol solution to obtain a bismuth ion precursor solution.

Most bismuth salts are insoluble in water or easily hydrolyzed, especially bismuth nitrate. When dissolved in water, they will hydrolyze to form basic salt precipitates that are insoluble in water, such as BiONO ₃ , Bi ₂ O ₂ (OH)NO ₃ and Bi ₆ O ₄ (OH) ₄ (NO ₃ ) ₆ ·H ₂ O, so that it is difficult to form a complex with baicalin, thereby affecting the preparation of bismuth-baicalin complexes, and the bismuth salt will not precipitate in the solution containing glycerol, It is favorable for the subsequent complex reaction between bismuth ions and baicalin molecules to improve the reaction yield. Moreover, glycerol molecules do not participate in the complex reaction, and no by-products are generated, which affects the product purity. Therefore, in this embodiment, a glycerol solution is selected as a solvent, and a bismuth salt is dissolved to prepare a bismuth ion precursor solution for reacting with the baicalin solution. The molar mass fraction of the bismuth salt in the bismuth ion precursor solution is 10-25%.

In addition, in this embodiment, the glycerol solution is an aqueous solution of glycerol. In the glycerol solution, the ratio of glycerol to water will affect the solubility of the bismuth salt in the solution. Based on this, in this embodiment, the mass concentration of glycerol in the glycerol solution is controlled to be 30-60%. Under this condition, the bismuth salt is It can be fully dissolved, which is beneficial to improve the reaction yield.

Further, the bismuth salt can be any bismuth salt soluble in glycerol solution, and wherein, the dissolving effect of bismuth nitrate is the best, and it is easier to react with baicalin. Therefore, in the present embodiment, the bismuth salt is preferably nitric acid. Bismuth (Bi(NO ₃ ) ₃ ·5H ₂ O).

In step S20, the bismuth ion precursor is added dropwise to the baicalin solution of pH 7-9 to react to obtain a bismuth-baicalin complex.

In this embodiment, the bismuth ion precursor is added dropwise to a baicalin solution with pH 7-9, and the bismuth ion and baicalin undergo a complex reaction to form a bismuth-baicalin complex.

Under the condition of pH 7-9, the structure of baicalin is not easy to be deteriorated, and the bismuth ion will not produce precipitation, so it is easier to cooperate with the reaction, which is beneficial to improve the reaction yield and product purity.

At the same time, when baicalin is excessive, baicalin molecules will polymerize through hydrogen bonds to form a colloidal solution, thereby causing the precipitation to be difficult to crystallize out, not only reducing the yield, but also not easy to follow up the reaction process, therefore, in the present embodiment, The molar ratio of baicalin to bismuth salt metal ion is 1:(1.1-1.6).

During specific implementation, step S20 can be realized by the following steps:

In step S210, the bismuth ion precursor solution is added dropwise to the baicalin solution of pH 7-9 at a dropping rate of 1.2-2.4 mL/min, and stirring is continued for 60-120 min to obtain a mixed solution.

Wherein, step S210 is performed under a temperature condition of 25-45°C. Under this condition, the speed of the coordination reaction can be accelerated, and the reaction can proceed forward. And because the combination of bismuth ions and baicalin will form complex precipitates, by controlling the dropping speed and constant stirring, the precipitates can be formed at a moderate speed, and the distribution is not aggregated, so that the reaction can be fully carried out.

In step S220, after the mixed solution is allowed to stand for 2-4 hours, the precipitate is filtered.

After sufficient standing, filtration can be carried out to make the precipitation sufficient and improve the yield of the precipitate. The filtration is for solid-liquid separation. In addition to filtration, suction filtration, centrifugation and other methods can also be used.

In step S230, the precipitate is washed with distilled water and 60% ethanol in sequence, and then dried in vacuum at 40-60° C. to obtain a bismuth-baicalin complex.

In addition, since different solvents will affect the solubility of baicalin and the stability of baicalin, thereby affecting the yield and product purity of the subsequent complexing reaction, in this embodiment, before step S20, it may also include preparing pH 7-9 The steps of the baicalin solution:

Step S100: Dissolving baicalin in an aqueous solution of triethylamine to obtain a baicalin solution with pH 7-9, wherein, in the aqueous solution of triethylamine, the mass concentration of triethylamine is 0.8-1.5%.

Compared with strong alkali solution and 60% ethanol solution, in the aqueous solution of triethylamine with mass concentration of 0.8 to 1.5%, baicalin is not only stable in properties, not easy to deteriorate, reduces the generation of by-products, improves the yield, and The hydroxyl group in the baicalin molecule is easy to dissociate, which is beneficial to the combination of baicalin and bismuth ions, thereby promoting the reaction to proceed in the positive direction and effectively improving the yield.

It should be noted that there is no sequence between step S100 and step S10, and step S100 may be performed before, after or at the same time as step S10.

The preparation method provided by the invention is simple in process, easy to control, and the yield of the finished baicalin-bismuth complex product can reach 99.23-99.81%, and the purity can reach 99.32-99.89%.

In addition, the present invention also proposes the application of the above-mentioned bismuth-baicalin complex in the treatment of piglet diarrhea.

The antibacterial test in vitro and in vivo confirmed that baicalin has good antibacterial effect on Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Bismuth salt is a low-toxicity or toxic substance, which has the effect of physiological activation. After oral administration of bismuth-containing drugs, a protective film can be formed on the wound surface of the gastric mucosa to reduce the stimulation of food to the gastric mucosa. The bismuth-baicalin complex formed by bismuth salt and baicalin has stable properties, and its in vitro inhibitory effect on drug-resistant and sensitive porcine-derived Escherichia coli is obviously better than that of baicalin, and has the efficacy of bismuth salt itself, which can be used for It can treat piglet diarrhea, inhibit the growth of pathogenic bacteria, improve the digestibility and utilization rate of nutrients in animals, and is beneficial to the growth of piglets. The application mode can be directly taken as a therapeutic drug, and the dosage is 50-100 mg/kg.bw per day for 3-5 days; it can also be used as an additive for preparing piglet feed, veterinary medicine or premix.

The technical solutions of the present invention will be described in further detail below with reference to the specific embodiments and the accompanying drawings. It should be understood that the following embodiments are only used to explain the present invention and are not intended to limit the present invention.

Example 1

Put 8.04mmol Bi(NO ₃ ) ₃ ·5H ₂ O (3.9g) in a 100ml small beaker, add 30% glycerol solution, stir and dissolve to obtain 10% bismuth ion precursor solution;

6.7mmol of baicalin was placed in a 250ml three-necked flask, 100ml of 0.8% triethylamine solution was added, mixed and stirred to obtain a baicalin solution with a pH of 7;

At 25°C, the above-mentioned bismuth ion precursor solution was slowly added dropwise to the three-necked flask containing the baicalin solution through the addition funnel at a speed of 1.2 ml/min. Under stirring, the bismuth ion and baicalin appeared immediately after the complex reaction occurred. The complex was precipitated, and after the dropwise addition was completed, stirring was continued for 60 min at 25°C, and the reaction was performed to obtain a precipitation mixture;

After the precipitation mixture was allowed to stand for 3 hours, the precipitation was obtained by filtration. The precipitation was washed with distilled water and 60% ethanol solution for 3-5 times in turn, and then dried under vacuum at 40 °C to obtain an orange baicalin-bismuth complex product. .

The content of bismuth in the product was measured by Inductively Coupled Plasma-Emission Spectroscopy (ICP-OES), the calculated yield was 99.51%, and the product purity was 99.89%.

Example 2

Weigh 10.72mmol Bi(NO ₃ ) ₃ ·5H ₂ O (5.2g) in a 100ml small beaker, add 55% glycerol solution, stir and dissolve to obtain 20.8% bismuth ion precursor solution;

6.7mmol of baicalin was placed in a 250ml three-necked flask, 100ml of 1.5% triethylamine solution was added, mixed and stirred to obtain a baicalin solution with a pH of 9;

At 45 ° C, the above-mentioned bismuth ion precursor solution was slowly added dropwise to the three-necked flask containing the baicalin solution through the addition funnel at a speed of 2.4ml/min. Under stirring, the bismuth ion and baicalin appeared immediately after the complex reaction occurred. Precipitation, after the dropwise addition is completed, continue stirring at 45 ° C for 120 min, and the reaction is to obtain a compound solution;

After standing for 4 hours, the compound solution was filtered to obtain the precipitate. The precipitate was washed with distilled water and 60% ethanol solution for 3-5 times, and then dried under vacuum at 55°C to obtain an orange bismuth-baicalin complex product.

The content of bismuth in the product was measured by Inductively Coupled Plasma-Emission Spectroscopy (ICP-OES), the calculated yield was 99.69%, and the product purity was 99.92%.

Example 3

Weigh 9.38mmol Bi(NO ₃ ) ₃ ·5H ₂ O (4.55g) into a 100ml small beaker, add it to 45% glycerol solution, stir to dissolve, and obtain 22.75% bismuth ion precursor solution;

6.7mmol of baicalin was placed in a 250ml three-necked flask, 100ml of 1.0% triethylamine solution was added, mixed and stirred to obtain a baicalin solution with a pH of 8.3;

At 35°C, the above-mentioned bismuth ion precursor solution was slowly added dropwise into the three-necked flask containing the baicalin solution through the addition funnel at a speed of 2.0 ml/min, and under stirring, the bismuth ion and baicalin appeared immediately after the complex reaction occurred. Precipitation, after the dropwise addition is completed, continue stirring at 45 ° C for 90 min, and the reaction is to obtain a compound solution;

After standing for 2 hours, the compound solution was filtered to obtain the precipitate, which was washed 3-5 times with distilled water and 60% ethanol solution in turn, and then dried under vacuum at 60°C to obtain an orange bismuth-baicalin complex product.

The content of bismuth in the product was measured by inductively coupled plasma-optical emission spectrometry (ICP-OES), the calculated yield was 99.54%, and the product purity was 99.78%.

Example 4

Weigh 10.05mmolBi(NO ₃ ) ₃ ·5H ₂ O (4.874g) into a 100ml small beaker, add 40% glycerol solution, stir to dissolve, and obtain 25% bismuth ion precursor solution;

6.7mmol of baicalin was placed in a 250ml three-necked flask, 100ml of 1.2% triethylamine was added, mixed and stirred to obtain a baicalin solution with a pH of 8.6;

At 30°C, the above-mentioned bismuth ion precursor solution was slowly added dropwise to the three-necked flask containing the baicalin solution through the addition funnel at a speed of 1.5 ml/min. Under stirring, the bismuth ion and baicalin appeared immediately after the complex reaction occurred. Precipitation, after the dropwise addition is completed, continue stirring at 30 ° C for 80 min, and the reaction is to obtain a compound solution;

After standing for 4 hours, the complex solution was filtered to obtain the precipitate, which was washed with distilled water and 60% ethanol solution for 3-5 times, and then dried under vacuum at 50°C to obtain an orange bismuth-baicalin complex product.

The content of bismuth in the product was measured by inductively coupled plasma-optical emission spectrometry (ICP-OES), the calculated yield was 99.78%, and the product purity was 99.86%.

Example 5

Weigh 8.71mmol Bi(NO ₃ ) ₃ ·5H ₂ O (4.224g) in a 100ml small beaker, add 60% glycerol solution, stir to dissolve, and obtain 16.9% bismuth ion precursor solution;

6.7mmol of baicalin was placed in a 250ml three-necked flask, 100ml of 1.1% triethylamine was added, mixed and stirred to obtain a baicalin solution with a pH of 8.4;

At 40 ° C, the above-mentioned bismuth ion precursor solution was slowly added dropwise to the three-necked flask containing the baicalin solution through the addition funnel at a speed of 1.8 ml/min. Under stirring, the bismuth ion and baicalin appeared immediately after the complex reaction occurred. Precipitation, after the dropwise addition is completed, continue to stir at 40 ° C for 100 min, and react to obtain a compound solution;

After the compound solution was left standing for 2.5 hours, the precipitate was obtained by filtration. The precipitate was washed with distilled water and 60% ethanol solution for 3-5 times in turn, and then dried under vacuum at 60°C to obtain an orange bismuth-baicalin complex product. .

The content of bismuth in the product was measured by Inductively Coupled Plasma-Emission Spectroscopy (ICP-OES), the calculated yield was 99.63%, and the product purity was 99.72%.

Example 6

Put 7.37mmol Bi(NO ₃ ) ₃ ·5H ₂ O (7.37g) in a 100ml small beaker, add 48% glycerol solution, stir and dissolve to obtain 24.56% bismuth ion precursor solution;

6.7mmol of baicalin was placed in a 250ml three-necked flask, 30ml of 0.9% triethylamine solution was added, mixed and stirred to obtain a baicalin solution with a pH of 8.1;

At 28°C, the above-mentioned bismuth ion precursor solution was slowly added dropwise into the three-necked flask containing the baicalin solution through the addition funnel at a speed of 1.6 ml/min. Under stirring, the bismuth ion and baicalin appeared immediately after the complex reaction occurred. Precipitation, after the dropwise addition is completed, continue stirring at 28 ° C for 120 min, the reaction is to obtain a compound solution;

After the complex solution was allowed to stand for 3.5 hours, the precipitate was obtained by filtration. The precipitate was washed 3-5 times with distilled water and 60% ethanol solution in turn, and then dried under vacuum at 40°C to obtain an orange cerium-baicalin complex product. .

The content of cerium in the product was measured by inductively coupled plasma-optical emission spectrometry (ICP-OES), the calculated yield was 99.54%, and the product purity was 99.87%.

The antibacterial effects of the bismuth-baicalin complex finished products prepared in the above-mentioned examples were respectively tested.

Select 20 serotype-identified porcine pathogenic Escherichia coli and Escherichia coli standard strain ATCC25922. The minimum inhibitory concentration (MIC) in vitro of Escherichia coli was determined by the 96-well plate dilution method, and the minimum inhibitory concentration in vitro of baicalin and the bismuth-baicalin complex products prepared in each example against 21 strains of porcine Escherichia coli As shown in Table 1.

Table 1 MIC value of baicalin and bismuth-baicalin against Escherichia coli (μg/mL)

It can be seen from the above table that the in vitro bacteriostatic effect of the bismuth-baicalin complex prepared in each example on drug-resistant and sensitive porcine-derived Escherichia coli is significantly better than that of baicalin. It is indicated that the bismuth-baicalin complex prepared by the present invention can be used as a high-efficiency and low-toxic medicine for treating diarrhea of early weaned piglets.

Infrared spectrum analysis was performed on baicalin and the product prepared in Example 1, respectively, as shown in Figure 2 and Figure 3.

The C=O absorption peak at the 4th position of baicalin in Fig. 2 is at 1661.9 cm ^-1 , and the C=O absorption peak at the 4th position in Fig. 3 is red-shifted to 1617.98 cm ^-1 , indicating that the C=O absorption peak at the 4th position of baicalin is at 1661.9 cm -1 . O and the hydroxyl group on the 5th position are coordinated with the bismuth ion together, and the electron cloud density is reduced, indicating that the bismuth ion and baicalin in the product prepared by the preparation method of the present invention form a stable complex.

The above are only preferred embodiments of the present invention, and are not intended to limit the scope of the present invention. For those skilled in the art, the present invention may have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the scope of patent protection of the present invention.

Claims (10)

1. A bismuth-baicalin complex, characterized in that, the general molecular formula of the bismuth-baicalin complex is (C ₂₁ H ₁₇ O ₁₁ )(NO ₃ )Bi·4H ₂ O, and the bismuth- The baicalin complex has the structure shown in structural formula (1). Structural formula (1): 2. a preparation method of bismuth-baicalin complex as claimed in claim 1, is characterized in that, comprises the following steps: Dissolving the bismuth salt in the glycerol solution to obtain the bismuth ion precursor solution; The bismuth ion precursor is added dropwise to the baicalin solution of pH 7-9 to react to obtain a bismuth-baicalin complex. 3. the preparation method of bismuth-baicalin complex as claimed in claim 2, is characterized in that, bismuth salt is dissolved in glycerol solution, in the step of obtaining bismuth ion precursor solution, The bismuth salt is bismuth nitrate; and/or, The glycerol solution is an aqueous solution of glycerol. 4. the preparation method of bismuth-baicalin complex as claimed in claim 2, it is characterised in that the bismuth salt is dissolved in the glycerol solution, in the step of obtaining a bismuth ion precursor solution, described in the bismuth ion precursor solution The mass concentration of the bismuth salt is 10-25%. 5. the preparation method of bismuth-baicalin complex as claimed in claim 2, is characterized in that, bismuth salt is dissolved in glycerol solution, in the step of obtaining bismuth ion precursor solution, the mass concentration of described glycerol solution is 30 ~60%. 6. the preparation method of bismuth-baicalin complex as claimed in claim 2, is characterized in that, described bismuth ion precursor is added dropwise in the baicalin solution of pH7～9, reacts to obtain bismuth-baicalin complex The steps also include: Dissolving baicalin in an aqueous solution of triethylamine to obtain a baicalin solution with pH 7-9, wherein, in the aqueous solution of triethylamine, the mass concentration of triethylamine is 0.8-1.5%. 7. the preparation method of bismuth-baicalin complex as claimed in claim 2, is characterized in that, described bismuth ion precursor is added dropwise in the baicalin solution of pH7～9, reacts to obtain bismuth-baicalin complex In the step of , the molar ratio of baicalin and bismuth ion is 1:(1.1～1.6). 8. the preparation method of bismuth-baicalin complex as claimed in claim 2, is characterized in that, described bismuth ion precursor is added dropwise to the baicalin solution of pH7～9, reacts to obtain bismuth-baicalin complex The steps include: The bismuth ion precursor solution is added dropwise to the baicalin solution with pH 7-9 at a dropping rate of 1.2-2.4 mL/min, and stirring is continued for 60-120 min to obtain a mixed solution; After the mixed solution is allowed to stand for 2 to 4 hours, the precipitate is obtained by filtration; The precipitate is washed with distilled water and 60% ethanol in sequence, and then dried under vacuum at 40-60° C. to obtain a bismuth-baicalin complex. 9 . The preparation method of bismuth-baicalin complex according to claim 8 , wherein the bismuth ion precursor solution is added dropwise to the baicalin solution of pH 7 to 9 at a rate of addition of 1.2 to 2.4 mL/min. 10 . During the process, continue stirring for 60-120 min, and the step of obtaining the mixed solution is carried out at a temperature of 25-45 °C. 10. An application of the bismuth-baicalin complex as claimed in claim 1 in the treatment of piglet diarrhea.