Citrate composition of silver as well as preparation method and application of citrate composition

Abstract

The invention belongs to the technical field of antibacterial agents, and particularly relates to a citrate composition of silver and a preparation method and application thereof. The preparation method of the silver citrate composition provided by the invention comprises the following steps: mixing silver carbonate and a citric acid aqueous solution, and carrying out double decomposition reaction to obtain the silver citrate composition, the pH value of the citric acid aqueous solution is 1-5, and the molar ratio of citric acid in the silver citrate aqueous solution to silver element in silver carbonate is greater than or equal to 1: 2. By limiting the pH value of the citric acid aqueous solution and the dosage ratio of the citric acid to the silver carbonate, the citric acid aqueous solution and the silver carbonate are directly mixed under the conditions of normal temperature and normal pressure, so that the citrate composition of silver can be efficiently prepared, the preparation process is simple and easy to operate, and industrial production can be conveniently realized.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of antibacterial agents, and particularly relates to a silver citrate composition and a preparation method and application thereof. BACKGROUND

[0002] At present, there are many antibacterial materials containing silver in the field of antibacterial agents, mainly including nano-silver and silver compounds; among them, nano-silver is widely used due to its broad spectrum and strong antibacterial activity, such as fabrics, pharmaceutical preparations (such as gynecological suppositories and lotions), water purification, etc.; however, nano-silver has cytotoxicity, liver and tissue accumulation, biological barrier penetration and long-term exposure risk; in addition, nano-silver is easy to oxidize with oxygen in the air under ultraviolet or strong light irradiation during preparation, storage and use, forming brown or black precipitates, which are difficult to clean or remove, and the experience is poor.

[0003] Silver compounds are also very excellent antibacterial agents, with a wide antibacterial spectrum, especially in eliminating resistant strains of Staphylococcus aureus, Pneumococcus and Pseudomonas aeruginosa. Silver compounds have the advantages of easy dissolution and easy removal, but because silver ions are precipitated by many anions at neutral pH, the stability of the formula containing surfactants and / or lower quality water is severely limited, because trace amounts of chloride ions in the surfactant or water will easily cause the precipitation of silver chloride, resulting in turbidity of the formula and possible loss of antibacterial activity; its instability has become a bottleneck limiting its application.

[0004] In order to overcome this instability, researchers have studied citric acid dihydrogen silver in the form of anion "complexation", such silver compounds have the quick-acting property of organic bactericides and the safety and durability of inorganic silver antibacterial agents, and are effective against a wide variety of microorganisms including bacteria, viruses and fungi, and therefore can be used as useful antibacterial agents or antiviral agents.

[0005] The prior art uses a silver electrode to prepare a solution containing silver citrate by electrolysis, and the method for preparing a silver citrate solution containing citric acid dihydrogen silver by electrolysis is to immerse a silver plate as an electrode plate into a citric acid solution and pass direct current therethrough; as the reaction proceeds, water is also electrolyzed on the surface of the electrode, and tiny bubbles cover the surface of the electrode, making it difficult for current to flow, resulting in a decrease in the production capacity of citric acid dihydrogen silver; it takes as long as 144 hours to obtain a citric acid dihydrogen silver solution with a silver ion concentration of 2400 ppm, and the production efficiency is extremely low, making it difficult to realize industrial mass production.

[0006] In view of the problems existing in the preparation method of the silver citrate composition, a simple and efficient preparation method of the silver citrate composition is urgently needed. SUMMARY

[0007] Therefore, the application provides a silver citrate composition, a preparation method and application thereof.

[0008] To solve the above technical problems, the application provides a preparation method of a silver citrate composition, comprising the following steps: mixing silver carbonate and a citric acid aqueous solution to perform a double decomposition reaction to obtain the silver citrate composition; The pH value of the citric acid aqueous solution is 1-5, and the molar ratio of citric acid in the silver citrate aqueous solution to silver in the silver carbonate is greater than or equal to 1:2.

[0009] Preferably, the pH value of the citric acid aqueous solution is 1-4.

[0010] Preferably, the method for adjusting the pH value of the citric acid aqueous solution comprises adjusting the concentration of the citric acid aqueous solution or adding an acid solution to the citric acid aqueous solution.

[0011] Preferably, the acid solution comprises one or more of nitric acid aqueous solution, acetic acid aqueous solution and glacial acetic acid.

[0012] Preferably, the molar ratio of citric acid in the silver citrate aqueous solution to silver in the silver carbonate is greater than or equal to 0.94:1.

[0013] Preferably, the temperature of the double decomposition reaction is 20-50 DEG C, and the time is less than 48 hours.

[0014] Preferably, the mixing method comprises one or more of stirring, oscillation and ultrasonic.

[0015] Preferably, the mixing and the double decomposition reaction are both performed in a light-proof condition.

[0016] The application further provides a silver citrate composition prepared by the preparation method. The mass concentration of silver in the silver citrate composition is 0.001-16.5 g / L.

[0017] The application further provides application of the silver citrate composition as an antibacterial agent, bacteriostatic agent or antiviral agent.

[0018] The application provides a preparation method of a silver citrate composition, comprising the following steps: mixing silver carbonate and a citric acid aqueous solution, and performing a double decomposition reaction to obtain the silver citrate composition; the pH value of the citric acid aqueous solution is 1-5, and the molar ratio of citric acid in the silver citrate aqueous solution to silver in the silver carbonate is greater than or equal to 1:2. DETAILED DESCRIPTION

[0019] The application provides a preparation method of a silver citrate composition, comprising the following steps: mixing silver carbonate and a citric acid aqueous solution, and performing a double decomposition reaction to obtain the silver citrate composition; The pH value of the citric acid aqueous solution is 1-5, and the molar ratio of citric acid in the silver citrate aqueous solution to silver in the silver carbonate is greater than or equal to 1:2.

[0020] As a specific embodiment of the application, the pH value of the citric acid aqueous solution can be 1-4, and can be specifically 1.09, 1.34, 1.8, 2, 2.5, 3, 3.5 or 4. As a specific embodiment of the application, the preparation step of the citric acid aqueous solution can comprise: dissolving anhydrous citric acid or citric acid hydrate in water to obtain the citric acid aqueous solution; the water can be deionized water, distilled water or double-distilled water; the application does not have special requirements for the dissolving, as long as complete dissolution can be achieved. As a specific embodiment of the application, the way of adjusting the pH value of the citric acid aqueous solution can comprise: adjusting the concentration of the citric acid aqueous solution or adding an acid liquid to the citric acid aqueous solution; the acid liquid can comprise one or more of a nitric acid aqueous solution, an acetic acid aqueous solution and glacial acetic acid, and can be specifically a nitric acid aqueous solution, an acetic acid aqueous solution or glacial acetic acid. The application does not have special requirements for the mass concentration and amount of the acid liquid, as long as the required pH value can be achieved.

[0021] As a specific embodiment of the application, the molar ratio of citric acid in the silver citrate aqueous solution to silver in the silver carbonate can be greater than or equal to 1:2, and can also be greater than or equal to 0.94:1, and can be specifically 0.94:1, 1.09:1, 1.64:1, 1.82:1, 2:1, 2.19:1 or 6.57:1.

[0022] As a specific embodiment of the present application, the mixing can be adding silver carbonate into the aqueous solution of citric acid; the mixing mode can include one or more of stirring, oscillation and ultrasonic, and the present application does not have special limitation on the conditions of the stirring, oscillation and ultrasonic, as long as uniform mixing can be achieved. As a specific embodiment of the present application, the mixing can be carried out in the dark to avoid discoloration of silver carbonate and generation of silver oxide when exposed to light.

[0023] As a specific embodiment of the present application, the temperature of the metathesis reaction can be 15-50℃, and can also be 35-45℃, and can be specifically 25℃, 30℃, 35℃, 40℃, 45℃ or 50℃; the time of the metathesis reaction can be 48h or less, and can also be 5-26h, and can be specifically 6h, 20h, 22h, 24h or 26h.

[0024] As a specific embodiment of the present application, the metathesis reaction can be accompanied by stirring, and the present application does not have special limitation on the stirring, as long as sufficient reaction can be ensured. As a specific embodiment of the present application, the metathesis reaction can be carried out in the dark to avoid discoloration of silver carbonate and generation of silver oxide when exposed to light.

[0025] As a specific embodiment of the present application, the metathesis reaction can further include filtering or centrifuging the system after the metathesis reaction. The present application does not have special requirement on the filtering or centrifuging, and the conventional mode in the art can be used. The present application can remove the unreacted silver carbonate through filtering or centrifuging.

[0026] The present application also provides a silver citrate composition prepared by the preparation method described in the above technical solution, which includes dihydrogen silver citrate and / or hydrogen disilver citrate; the mass concentration of silver ions in the silver citrate composition is 0.001-16.5g / L, can be 1-13g / L, and can also be 4-10g / L, and can be specifically 1.05g / L, 1.28g / L, 1.36g / L, 4.89g / L or 16.5g / L.

[0027] The present application also provides the application of the silver citrate composition described in the above technical solution as an antibacterial agent, bacteriostatic agent or antiviral agent. As a specific embodiment of the present application, the silver citrate composition can be used alone or in combination with other substances when used as an antibacterial agent or antiviral agent.

[0028] In order to further illustrate the present application, the technical solutions provided by the present application are described in detail below in combination with examples, but they should not be understood as limiting the scope of protection of the present application.

[0029] Example 1 Under the condition of avoiding light, 180 mg (0.65 mmol) of silver carbonate was added into 100 mL of aqueous citric acid solution with different pH values, and stirred uniformly at a rotation speed of 200 rpm. The metathesis reaction was continued for 24 h at room temperature (about 22°C) under the condition of avoiding light (with stirring). The filtrate was obtained by filtration, and a silver citrate composition was obtained.

[0030] The pH value of the silver citrate composition was detected, and the silver citrate composition was mixed with a sodium chloride solution with a mass concentration of 16.5 mg / mL in equal volume. Whether a precipitate appeared was observed, and the specific results are listed in Table 1.

[0031] Table 1 Results of preparing silver citrate compositions by different concentrations of aqueous citric acid solution

[0032] As can be seen from the results in Table 1, with the increase of the concentration of the aqueous citric acid solution, the pH value of the silver citrate composition has a decreasing trend, the remaining precipitate amount after adding the same silver carbonate gradually decreases, and the silver element content in the silver citrate composition gradually increases. At the same time, no precipitate appears after the prepared silver citrate composition is mixed with the sodium chloride solution, indicating that the silver citrate composition has good chloride ion tolerance.

[0033] Example 2 Under the condition of avoiding light, different amounts of silver carbonate solid powder were added into 100 mL of aqueous citric acid solution with a mass concentration of 5 mg / mL, and stirred uniformly at a rotation speed of 400 rpm. The metathesis reaction was continued for 5 h at room temperature (about 22°C) under the condition of avoiding light (with magnetic stirring). Whether the silver carbonate was completely reacted was judged by observing the remaining precipitate. The results are shown in Table 2. The system after the metathesis reaction was filtered, and the filtrate was obtained to obtain a silver citrate composition. The silver citrate composition was mixed with a sodium chloride solution with a mass concentration of 16.5 mg / mL in equal volume, and whether a precipitate appeared was observed. The results are listed in Table 2.

[0034] Table 2 Results of preparing silver citrate compositions by different amounts of silver carbonate

[0035] As can be seen from the results of Table 2, when the amount of citric acid is fixed at 5 mg / mL, 50 mg of silver carbonate can be completely dissolved, and almost all of 200 mg of silver carbonate can be dissolved, but when 350 mg of silver carbonate is added, a large amount of silver carbonate cannot be dissolved, indicating that the reaction system is saturated. However, with the increase of the amount of silver carbonate, the pH value of the silver citrate composition has a trend of increasing, which indirectly reflects the increase of the amount of dissolved silver carbonate. At the same time, no precipitate is observed after the soluble silver salt solution (silver citrate composition) is mixed with a sodium chloride solution, indicating that the soluble silver salt has good resistance to chloride ions.

[0036] Example 3 Under the condition of light shielding, 180 mg of silver carbonate solid was added into 100 mL of a citric acid aqueous solution with a mass concentration of 5 mg / mL, and stirred uniformly at a rotation speed of 400 rpm. Then, the double decomposition reaction (with stirring) was carried out at room temperature (about 22°C), 45°C and 35°C, respectively, under the condition of light shielding, and the solid disappearance time was observed and recorded in Table 3. In addition, 350 mg of silver carbonate was added into 100 mL of a 5 mg / mL citric acid solution, and heated and stirred at 45°C, and the solid disappearance time was observed. The system after the double decomposition reaction was filtered, and the filtrate was obtained to obtain a silver citrate composition. The silver citrate composition was mixed with a 16.5 mg / mL sodium chloride solution in equal volume, and whether a precipitate was observed was observed.

[0037] Table 3 Results of preparing silver citrate composition at different reaction temperatures

[0038] As can be seen from the results of Table 3, with the increase of the reaction temperature, the precipitation disappearance, that is, the complete reaction time is shortened, but the increase of the reaction temperature does not significantly increase the amount of soluble silver carbonate. At the same time, no precipitate is observed after the soluble silver salt solution (silver citrate composition) is mixed with a sodium chloride solution, indicating that the soluble silver salt has good resistance to chloride ions.

[0039] Example 4 Under the condition of light shielding, 2 g of anhydrous citric acid was dissolved in 10 mL of deionized water to obtain a citric acid aqueous solution. Then, 720 mg of silver carbonate was added into the citric acid aqueous solution, and stirred (double decomposition reaction) at 45°C and 400 rpm under the condition of light shielding for 6 h. Then, the supernatant was obtained by centrifugation at 3000 rpm for 10 min to obtain a silver citrate composition. The content of soluble silver element in the supernatant was detected by an inductively coupled plasma mass spectrometer. The specific results are shown in Table 4.

[0040] Dissolve 6 g of anhydrous citric acid in 10 mL of deionized water to obtain a citric acid aqueous solution under light shielding condition; add silver carbonate 2.16 g to the citric acid aqueous solution, and stir (double decomposition reaction) at 45 °C and 400 rpm under light shielding for 6 h; centrifuge at 3000 rpm for 10 min to obtain the supernatant to obtain a silver citrate composition; detect the content of soluble silver element in the supernatant by inductively coupled plasma mass spectrometry; and the specific results are shown in Table 4.

[0041] Table 4 Results of silver citrate dosage challenge experiment

[0042] As can be seen from the results in Table 4, with the increase of the concentration of the citric acid aqueous solution, the concentration of the obtained soluble silver citrate is significantly increased. The saturated solubility of citric acid is about 59.2% (20 °C) or 64.3% (30 °C), i.e. about 0.6 g / mL, therefore, in this experiment, the soluble silver citrate is generated by using a nearly saturated citric acid solution, and the results show that the content of soluble silver atoms can be as high as 16.5 g / L.

[0043] Comparative Example 1 Dissolve 1.4 g of citric acid monohydrate and 1.0 g of trisodium citrate dihydrate in 100 mL of distilled water to obtain a citric acid buffer solution with a pH value of 4.0. Add 1.0 g of silver nitrate to the above citric acid buffer solution under the condition of magnetic stirring at 600 rpm; mix 0.75 g of sodium citrate dihydrate and 0.18 g of sodium citrate dibasic hydrate (each two molecules of sodium citrate dibasic contain 3 molecules of water) together, and then add the mixture to the above citric acid buffer solution containing silver nitrate under stirring; continue to stir for 3 h. Filter the above solution using filter paper with a pore size of 40 μm, transfer the filtrate to a beaker, and store it at room temperature under light shielding; collect the precipitate, dry it in an oven at 50 °C for 1 h, and then dry it in a vacuum drying oven under reduced pressure overnight to obtain a mixture of silver citrate dihydrate and silver citrate dibasic (silver citrate composition solid powder).

[0044] According to the above method, two batches of silver citrate composition solid powder were prepared. Add 100 mg of silver citrate composition solid powder to 100 mL of distilled water, stir, and stand for 1 h; then filter the solution using filter paper with a pore size of 40 μm, collect the insoluble substance and the filtrate, dry the insoluble substance, accurately weigh it, and record the data; and detect the content of silver ions in the filtrate, and the results are shown in Table 5.

[0045] Table 5 Detection results of two batches of silver citrate composition samples prepared by the method of Comparative Example 1

[0046] From the results of Table 5, the soluble silver salt content in the citrate composition of silver obtained from different batches varies greatly, the silver content detection results of batch samples have poor reproducibility, and the content is low. In addition, the obtained silver salt powder is easy to be oxidized into gray substances, resulting in an increase in insoluble substances.

[0047] Comparative Example 2 Under light-proof conditions, 50 mg or 150 mg of silver oxide solid was weighed and added to 100 mL of a 5 mg / mL mass concentration citric acid aqueous solution, and heating and stirring was continued under light-proof conditions at 45°C, and whether the solid disappeared and the disappearance time was observed.

[0048] It was found that after heating and stirring at 45°C for 24 h, only a small amount of solid was dissolved, and a large amount of black solid insoluble substance remained, indicating that the preparation of soluble silver citrate salt from silver oxide as the silver source has low efficiency.

[0049] Test Example 1 The chloride ion tolerance performance of silver nitrate solution and the silver citrate composition prepared by the present application was tested according to the following method: Sodium chloride solutions with mass concentrations of 8.25 mg / L and 16.5 mg / L were prepared respectively for standby; an appropriate amount of silver nitrate was dissolved with distilled water to prepare silver nitrate solutions with silver ion mass concentrations of 300 mg / L and 600 mg / L; and the silver citrate composition prepared in Example 4 was used to prepare soluble silver citrate salt solutions with different concentrations; and the solutions were mixed with different concentrations of sodium chloride according to a volume ratio of 1:1, and whether a precipitate appeared was observed, and the specific results are shown in Tables 6 and 7.

[0050] Table 6 Chloride ion tolerance results of silver nitrate solution

[0051] Table 7 Chloride ion tolerance results of silver citrate solution

[0052] From the results of Tables 6 and 7, after mixing silver nitrate solutions with different concentrations with sodium chloride solutions with different concentrations, a large amount of white precipitate appeared, indicating that the silver nitrate solution has poor tolerance to chloride ions; after mixing soluble silver citrate salt solutions with different concentrations with sodium chloride solutions with different concentrations, the solutions are still clear and transparent, indicating that the silver citrate prepared by the present application has good chloride ion tolerance.

[0053] Although the above examples have made a detailed description of the present application, it is only a part of the examples of the present application, but not all the examples, and other examples can be obtained according to the present examples without creativity, which all belong to the protection scope of the present application.

Claims

1. A method for preparing a silver citrate composition, characterized in that: The following steps are involved: mixing silver carbonate and an aqueous citric acid solution and performing a double decomposition reaction to obtain a silver citrate composition; The pH value of the citric acid aqueous solution is 1-5, and the molar ratio of citric acid in the silver citrate aqueous solution to silver element in silver carbonate is greater than or equal to 1:

2.

2. The preparation method according to claim 1, characterized in that The pH value of the citric acid aqueous solution is 1-4.

3. The preparation method according to claim 2, characterized in that The pH value of the citric acid aqueous solution is adjusted in the following manner: adjusting the concentration of the citric acid aqueous solution or adding acid to the citric acid aqueous solution.

4. The preparation method according to claim 3, characterized in that The acid solution includes one or more of a nitric acid aqueous solution, an acetic acid aqueous solution and glacial acetic acid.

5. The preparation method according to claim 1, characterized in that The molar ratio of citric acid in the silver citrate aqueous solution to silver element in silver carbonate is greater than or equal to 0.94:

1.

6. The preparation method according to any one of claims 1 to 5, characterized in that The temperature of the metathesis reaction is 20-50° C., and the time is less than 48 hours.

7. The preparation method according to any one of claims 1 to 5, characterized in that The mixing method includes one or more of stirring, shaking and ultrasound.

8. The preparation method according to claim 1, characterized in that The mixing and metathesis reactions are both carried out under light-proof conditions.

9. The silver citrate composition prepared by the preparation method according to any one of claims 1 to 8, characterized in that: including silver dihydrogen citrate and / or disilver hydrogen citrate; The mass concentration of silver element in the silver citrate composition is 0.001-16.5 g / L.

10. Use of the silver citrate composition according to claim 9 as an antibacterial agent, bacteriostatic agent or antiviral agent.

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