阅读说明：本技术 一种兽用聚维酮碘溶液及其制备方法 (Povidone iodine solution for livestock and preparation method thereof ) 是由 高平 陈振威 李云 梁金兰 刘为和 于 2021-02-04 设计创作，主要内容包括：本发明公开了一种兽用聚维酮碘溶液及其制备方法,属于消毒剂技术领域。该一种兽用聚维酮碘溶液按照质量百分比由以下成分组成：聚维酮碘8-12％、聚维酮0.8-1.2％、阳离子聚合多肽1.5-4％、苹果酸0.1-0.15％、磷酸氢二钠0.03-0.08％、磷酸二氢钠0.16-0.22％、碘酸钾0.2-0.3％、碘化钾0.3-0.5％和余量水。制备方法包括：将聚维酮碘、聚维酮、阳离子聚合多肽、苹果酸加入水中溶解得混合物1；将磷酸氢二钠、磷酸二氢钠、碘酸钾、碘化钾加入水中溶解得混合物2；混合物1与混合物2混合,加水至定量得。本产品杀菌效果好,稳定性明显提高,有效碘含量增加,不易产生耐药,安全性高。(The invention discloses a povidone iodine solution for livestock and a preparation method thereof, belonging to the technical field of disinfectants. The povidone iodine solution for livestock comprises the following components in percentage by mass: 8-12% of povidone iodine, 0.8-1.2% of povidone, 1.5-4% of cationic polymerized polypeptide, 0.1-0.15% of malic acid, 0.03-0.08% of disodium hydrogen phosphate, 0.16-0.22% of sodium dihydrogen phosphate, 0.2-0.3% of potassium iodate, 0.3-0.5% of potassium iodide and the balance of water. The preparation method comprises the following steps: dissolving povidone iodine, povidone, cationic polymerized polypeptide and malic acid in water to obtain a mixture 1; adding disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium iodate and potassium iodide into water to dissolve to obtain a mixture 2; mixing the mixture 1 and the mixture 2, and adding water to a certain amount to obtain the product. The product has good sterilization effect, obviously improved stability, increased effective iodine content, difficult generation of drug resistance and high safety.)

1. The povidone-iodine solution for livestock is characterized by comprising the following components in percentage by mass:

8-12% of povidone iodine, 0.8-1.2% of povidone, 1.5-4% of cationic polymerized polypeptide, 0.1-0.15% of malic acid, 0.03-0.08% of disodium hydrogen phosphate, 0.16-0.22% of sodium dihydrogen phosphate, 0.2-0.3% of potassium iodate, 0.3-0.5% of potassium iodide and the balance of water.

2. The povidone-iodine solution for veterinary use as claimed in claim 1, wherein the mass ratio of povidone-iodine, povidone, cationic polymerized polypeptide and malic acid is 9-11:0.9-1.1:2.5-3.5: 0.11-0.13.

3. The povidone-iodine solution for veterinary use as claimed in claim 2, wherein the mass ratio of povidone-iodine, povidone, cationic polymerized polypeptide and malic acid is 10:1:3: 0.12.

4. The povidone-iodine solution for veterinary use as claimed in claim 1, which consists of the following components in percentage by mass: povidone iodine 10%, povidone 1%, cationic polymerized polypeptide 3%, malic acid 0.12%, disodium hydrogen phosphate 0.06%, sodium dihydrogen phosphate 0.2%, potassium iodate 0.25%, potassium iodide 0.4% and balance water.

5. Povidone-iodine solution for veterinary use according to claim 1, wherein the povidone is K300, the water is sterile water and the cationic polymeric polypeptide is selected from at least one of polylysine, polyarginine or polyglutamic acid, preferably polyglutamic acid.

6. A process for the preparation of povidone-iodine solutions for veterinary use as claimed in any of claims 1 to 5, which comprises the following steps:

(1) adding povidone iodine, povidone, cationic polymerization polypeptide and malic acid in the formula dosage into water, and stirring and dissolving to obtain a mixture 1;

(2) adding disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium iodate and potassium iodide into water according to the formula dosage, and stirring and dissolving to obtain a mixture 2;

(3) and mixing the mixture 1 and the mixture 2 to obtain a mixture 3, and adding water to a certain amount to obtain the povidone-iodine solution for livestock.

7. The preparation method according to claim 6, wherein in the step (1), the mass ratio of the total mass of the povidone-iodine, the povidone, the cationic polymerized polypeptide, the malic acid and the water is as follows: 1:3.5-7.5.

8. The method according to claim 6, wherein the temperature for the agitation dissolution in the step (1) is 17 to 24 ℃.

9. The method according to claim 6, wherein in the step (2), the ratio of the total mass of the disodium hydrogen phosphate, the sodium dihydrogen phosphate, the potassium iodate and the potassium iodide to the mass of the water is: 1:9-15.

10. The method according to claim 6, wherein the temperature for the agitation dissolution in the step (2) is 30 to 40 ℃.

Technical Field

The invention belongs to the technical field of disinfectants, and particularly relates to a povidone iodine solution for livestock and a preparation method thereof.

Background

Povidone iodine (PVP-I), also known as povidone iodine, is a complex of elemental iodine and 1-vinyl-2-pyrrolidone (PVP) homopolymer. The molecular structure of povidone iodine is a unique and stable structural form, and is mainly a stable complex formed by polyvinylpyrrolidone and iodine elements by means of hydrogen bonds and other attractive forces. The polyvinylpyrrolidone (PV P) belongs to a nonionic surfactant, is easily dissolved in water, and iodine elements are complexed with the surfactant, so that the solubility of the iodine elements is improved. In addition, the iodine element is combined on the inner side of the spiral structure of the polyvinylpyrrolidone, so that the stability of the iodine element is greatly enhanced. Meanwhile, the coating structure enables povidone iodine to slowly release iodide ions when povidone iodine is used, and the effect is durable. The stability of povidone-iodine is greatly affected by temperature. Povidone iodine is unstable under light conditions, and the stronger the light intensity, the faster the decomposition and the poorer the stability, so the povidone iodine should be stored away from light.

The povidone iodine solution is used as a high-efficiency low-toxicity disinfectant, has good killing effect on bacteria, spores, viruses and fungi, and particularly has good killing effect on viruses and bacterial propagules. Under the concentration of 15ppm, the compound can kill propagules of various bacteria within 1 minute, takes longer time for killing tubercle bacillus, 1.5 hours for killing fungi and longer time for spore. The product has strong bactericidal effect under acidic condition, and weak bactericidal effect under alkaline condition. The povidone iodine solution can be used for drinking water disinfection of chickens, ducks and geese, pig disinfection in pigsties, environmental disinfection, aquaculture and the like. The povidone iodine for the aquatic products can be used for disinfecting aquaculture water and aquaculture appliances, the povidone iodine is decomposed quickly due to the nature of visible light decomposition, the drug effect of the povidone iodine is greatly influenced by organic matters, and the water environment is complex, so that the development of a povidone iodine preparation with good environmental tolerance and slow decomposition is necessary.

Chinese patent application 201810732602.4 discloses a povidone-iodine solution and a preparation method thereof. The povidone iodine solution provided by the invention consists of povidone iodine, monopotassium phosphate, dipotassium phosphate, potassium iodate, glycerol, aloe polysaccharide zinc and sodium citrate. In addition, the invention also particularly discloses a preparation method of the aloe polysaccharide zinc, which comprises the steps of extracting aloe with absolute ethyl alcohol, carrying out ultrasonic extraction and ultrafiltration to obtain aloe polysaccharide concentrated solution, then mixing with zinc acetate, and then carrying out heating, reaction and dialysis. The povidone iodine solution prepared by the invention has the advantages of high stability, obvious sterilization effect and lasting effect.

Chinese patent application 201911238041.3 discloses a safe broad-spectrum povidone-iodine preparation and a preparation method and application thereof, wherein each 1000g of the safe broad-spectrum povidone-iodine preparation contains the following raw materials in parts by weight: 10-15.5g of polyvinylpyrrolidone, 5.5-7.5g of refined iodine, 1.8-8.3g of potassium iodide, 0.01-3g of potassium iodate, 0.01-1.25g of surfactant, 2-8g of pH regulator and the balance of water; the weight ratio of the polyvinylpyrrolidone to the effective iodine is (1.6-3.6): 1. The safe broad-spectrum povidone iodine preparation with proper oral dose can not cause poisoning and digestive tract injury, can be used for preventing and treating diseases of animals, reducing abuse of antibiotics and improving food safety of human.

At present, the povidone iodine solution still has the problems of fast decomposition under low concentration by light and improved stability, and is easy to cause drug resistance of floras when being used in the field of cultivation, so that the safety needs to be further improved, the drug resistance of the floras is reduced, and the disinfection and sterilization effects are further improved.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a povidone iodine solution which has good sterilization effect and higher stability and is difficult to form drug resistance.

In order to achieve the purpose, the technical scheme of the invention is as follows:

firstly, the invention provides a povidone iodine solution for animals, which comprises the following components in percentage by mass:

8-12% of povidone iodine, 0.8-1.2% of povidone, 1.5-4% of cationic polymerized polypeptide, 0.1-0.15% of malic acid, 0.03-0.08% of disodium hydrogen phosphate, 0.16-0.22% of sodium dihydrogen phosphate, 0.2-0.3% of potassium iodate, 0.3-0.5% of potassium iodide and the balance of water.

Preferably, the mass ratio of the povidone iodine, the povidone, the cationic polymerized polypeptide and the malic acid is 9-11:0.9-1.1:2.5-3.5:0.11-0.13, and more preferably 10:1:3: 0.12.

As the most preferred embodiment of the invention, the povidone iodine solution for livestock comprises the following components in percentage by mass: povidone iodine 10%, povidone 1%, cationic polymerized polypeptide 3%, malic acid 0.12%, disodium hydrogen phosphate 0.06%, sodium dihydrogen phosphate 0.2%, potassium iodate 0.25%, potassium iodide 0.4% and balance water.

Preferably, the povidone is K300.

Preferably, the water is sterilized water.

Preferably, the cationic polymeric polypeptide is at least one selected from polylysine, polyarginine, or polyglutamic acid, and more preferably polyglutamic acid.

Secondly, the invention provides a preparation method of the povidone iodine solution for livestock, which comprises the following steps:

(1) adding povidone iodine, povidone, cationic polymerization polypeptide and malic acid in the formula dosage into water, and stirring and dissolving to obtain a mixture 1;

(2) adding disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium iodate and potassium iodide into water according to the formula dosage, and stirring and dissolving to obtain a mixture 2;

(3) and mixing the mixture 1 and the mixture 2 to obtain a mixture 3, and adding water to a certain amount to obtain the povidone-iodine solution for livestock.

Preferably, in the step (1), the mass ratio of the total mass of the povidone iodine, the povidone, the cationic polymerized polypeptide and the malic acid to the water is as follows: 1:3.5-7.5.

Preferably, in the step (1), the temperature for stirring and dissolving is 17 to 24 ℃, and more preferably 18 ℃.

Preferably, in the step (2), the mass ratio of the total mass of the disodium hydrogen phosphate, the sodium dihydrogen phosphate, the potassium iodate and the potassium iodide to the water is as follows: 1:9-15.

Preferably, in the step (2), the temperature for stirring and dissolving is 30 to 40 ℃, and more preferably 32 ℃.

The invention has the beneficial effects that:

(1) the cationic polymerization polypeptide, the multi-use povidone, the malic acid and the povidone iodine have good synergistic sterilization effect, and through proportion optimization, the product of the invention has good sterilization effect, obviously improved stability, stabilized iodine molecules and increased effective iodine content;

(2) the stress reaction can be reduced in the culture application, the skin and the mucosa of animals are not damaged, the culture medium can be used for disinfecting the skin and the water body in the culture process for a long time, the safety is high, and the drug resistance is not easy to generate;

(3) the method for preparing the povidone iodine solution meets the national standard, is simple and easy to operate, and can be used for industrial production.

Detailed Description

The present invention will be further explained with reference to specific examples in order to make the technical means, the technical features, the technical objectives and the effects of the present invention easier to understand, but the following examples are only preferred embodiments of the present invention, and not all embodiments of the present invention. Based on the embodiments in the implementation, other embodiments obtained by those skilled in the art without any creative efforts belong to the protection scope of the present invention. In the following examples, unless otherwise specified, all the procedures used were conventional, all the equipment used were conventional, and all the starting materials used were commercially available.

The povidone iodine is purchased from Chuangchuangmeike technology Limited, and the effective iodine (I) is 9.0-12.0%.

The povidone K300 is purchased from new-open-source medical science and technology group ltd, boai, K value: 27.0-32.0.

The polyglutamic acid CAS:25513-46-6, purchased from indigenous reagents, cat # P0004585, and has a molecular weight of about thirty thousand.

Examples 1 to 5

Preparing a povidone iodine solution for livestock according to the following steps:

(1) adding povidone iodine, povidone, polyglutamic acid and malic acid in the formula dosage into 60g of sterilized water, and stirring at 18 ℃ until the povidone iodine, the povidone, the polyglutamic acid and the malic acid are completely dissolved to obtain a mixture 1;

(2) adding the disodium hydrogen phosphate, the sodium dihydrogen phosphate, the potassium iodate and the potassium iodide into 10g of sterilized water according to the formula dosage, and stirring at the temperature of 32 ℃ until the disodium hydrogen phosphate, the sodium dihydrogen phosphate, the potassium iodate and the potassium iodide are completely dissolved to obtain a mixture 2;

(3) and (3) mixing the mixture 1 and the mixture 2 to obtain a mixture 3, adding water to 100g, and uniformly stirring to obtain the povidone iodine solution for livestock.

The formulations of examples 1-5 are shown in Table 1, below:

table 1.

Comparative example 1

Unlike example 1, no povidone was added, and the rest was the same.

Comparative example 2

The same as in example 1, except that malic acid was not added.

Comparative example 3

The same as in example 1, except that polyglutamic acid was not added.

Comparative example 4

In contrast to example 1, the malic acid was replaced with the same amount of citric acid, and the rest was the same.

Comparative examples 5 to 6

In contrast to example 1, the formulations of comparative examples 5 to 6 are shown in the following table:

table 2.

Comparative example 7

Unlike example 1, comparative example 7 was prepared by the following method:

adding povidone iodine, povidone, polyglutamic acid, malic acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium iodate and potassium iodide into 100g of sterilized water according to the formula dosage, and stirring at 32 ℃ until the povidone iodine solution for livestock is completely dissolved to obtain the povidone iodine solution for livestock.

Result detection

1. Iodine content test

Taking the samples of the above examples and comparative examples, the effective iodine content and the free iodine content are determined, and the detection results are shown in the following table:

table 3.

It can be seen that the products of the examples of the application have low free iodine content and good stability, and the products of the comparative examples have higher free iodine content.

2. Stability detection

The samples of the above examples and comparative examples were taken and left at 40 ℃. + -. 2 ℃ and a relative humidity of 75%. + -. 5% for 12 months. Samples are taken once at the end of the 6 th month and 12 th month of the test period, the content of available iodine and the pH value are detected, and the stability of the samples is determined. The results of the measurements are shown in the following table:

TABLE 4 test results in 6 months

TABLE 5 test results of 12 months

	Effective iodine content%	Free iodine content,%)	pH
				Example 1	9.88	0.324	5.2
Example 2	8.93	0.328	5.0
				Example 3	10.56	0.458	5.2
Example 4	7.95	0.295	4.9
				Example 5	11.43	0.576	5.1
Comparative example 1	9.15	0.785	2.4
				Comparative example 2	9.65	0.769	2.2
Comparative example 3	9.85	0.728	2.4
				Comparative example 4	9.68	0.775	3.2
Comparative example 5	7.92	0.436	3.6
				Comparative example 6	15.21	0.732	3.9
Comparative example 7	9.68	0.518	4.4

It can be seen that the product of the examples of the present application has little change in available iodine content and good storage stability after being left for 12 months.

3. In vitro bacteriostasis test

3.1 E.coli (isolated from a piggery and not previously used with a similar disinfectant) was uniformly spread on an LB agar plate, paper pieces (filter paper was prepared into 2 cm-diameter paper pieces by a puncher and sterilized at 120 ℃ for 2 hours) were immersed in the disinfectant solutions obtained by diluting the products of examples and comparative examples by 10 times, respectively (the paper pieces were completely soaked in the disinfectant solutions) to obtain paper pieces, the paper pieces were attached to the plate, cultured at 37 ℃ for 35 hours, the results were observed, and the size of the zone of inhibition was recorded.

Table 6.

3.2 evenly coating staphylococcus aureus (separated from a piggery and not used with similar disinfectant before) on an LB agar plate, respectively soaking paper sheets (the filter paper is prepared into paper sheets with the diameter of 2cm by a puncher and is sterilized at 120 ℃ for 2 h) into the disinfectant obtained after diluting the products of the examples and the comparative examples by 10 times (the paper sheets are completely soaked by the disinfectant), respectively obtaining the paper sheets, pasting the paper sheets on the plate, culturing for 35 hours at 37 ℃, observing the result, and recording the size of a bacteriostatic circle.

Table 7.

	Diameter of zone of inhibition, mm
		Example 1	11.36
Example 2	10.93
		Example 3	11.17
Example 4	10.55
		Example 5	11.13
Comparative example 1	9.26
		Comparative example 2	9.18
Comparative example 3	8.33
		Comparative example 4	9.14
Comparative example 5	8.65
		Comparative example 6	10.59
Comparative example 7	10.78

The embodiment shows that the product realizes good antibacterial performance, wherein the effect of the embodiment 1 is optimal, the comparative examples 1-3 lack certain components and cannot exert synergistic action, so that the antibacterial effect on two kinds of bacteria is reduced, and the comparative examples 5-6 show that the optimized ratio of povidone iodine, povidone, cationic polymerized polypeptide and malic acid can obtain better synergistic antibacterial action. Comparative example 7 shows that the change of the addition sequence in the preparation process has an influence on the final bacteriostatic effect.

4. Clinical application

Respectively using the povidone-iodine solution of the embodiments 1-5 and the comparative examples 1-7 of the invention and commercially available povidone iodine for snakehead culture, counting the survival rate of snakeheads after using two months, adding the povidone-iodine solution into a snakehead culture water body, using the amount of the povidone-iodine solution being 750 mL/mu, using the povidone-iodine solution once every 10 days, using the povidone-iodine solution for 3 days every time, and sharing for 6 times; and another group of solutions without povidone iodine is used as blank control, and after 2 months, the results of calculating the snakehead survival rate are as follows:

raw fish variety: snakehead fish

The number of raw fish is as follows: 2 thousands of plants per mu

The use method comprises the following steps: it is administered every 10 days for 3 days for 6 times

And counting the death number in the process, and calculating the survival rate after 2 months.

Table 8.

It can be seen that the product of the application can greatly improve the snakehead culture survival rate.

5. Bacterial drug resistance detection

After sampling of examples 3.1 and 3.2, example 1, comparative example 2, comparative example 3, comparative example 5 were used continuously in fixed pigsty sections, using the following method: the barn was sterilized once a month with povidone iodine and sprayed at a dilution of 1:200 each time, and after 12 months of continuous use, in vitro bacteriostatic tests were performed according to examples 3.1 and 3.2.

The results are shown in tables 9 and 10, respectively:

TABLE 9 bacteriostatic results for E.coli

Diameter of zone of inhibition, mm	Initial	After 12 months
			Example 1	12.76	11.87
Comparative example 2	8.58	5.21
			Comparative example 3	7.88	4.43
Comparative example 5	9.95	7.75

TABLE 10 Staphylococcus aureus bacteriostasis results

Diameter of zone of inhibition, mm	Initial	After 12 months
			Example 1	11.36	10.33
Comparative example 2	9.18	6.89
			Comparative example 3	8.33	4.07
Comparative example 5	8.65	6.38

After the product of the embodiment of the application is used for 12 months, the drug resistance of escherichia coli and staphylococcus aureus is weak, and the drug resistance is proved to be difficult to generate.

6. Hog cholera virus killing experiment

The effect test for killing the hog cholera virus: diluting the povidone-iodine solution obtained in example 1 by deionized water in a non-diluted mode, a diluted mode of 1:4, a diluted mode of 1:5, a diluted mode of 1:6 and a diluted mode of 1:7, respectively mixing the solution with hog cholera virus diluted by 0.04mol/L phosphate buffer solution (pH7.6) in an equivalent mode of 1:500, acting for 30min at room temperature, and injecting 0.2ml of virus-povidone-iodine solution mixed solution into the back of a 4-day-old suckling mouse subcutaneously; meanwhile, a virus control group is arranged, and 0.2ml of virus solution diluted by 1:1000 times is injected into the back of each suckling mouse subcutaneously; a blank group was prepared and each suckling mouse was injected subcutaneously into the back with 0.2ml of deionized water. The observation was continued for 7 days after injection and each test was repeated 5 times. The experimental group of suckling mice have no death or abnormality in the observation period and are regarded as effective; the test group had a suckling mouse dead or abnormal and detected classical swine fever virus and was considered ineffective.

Table 11.

Dilution ratio	Number of inoculation	Number of deaths	Determination of results
				Undiluted	20	0	Is effective
1:4	20	0	Is effective
				1:5	20	0	Is effective
1:6	20	0	Is effective
				1:7	20	18	Invalidation
Viral control	20	20	-
				Blank space	20	0	-

It can be seen that the product of example 1 of the present application has a good killing effect on classical swine fever viruses.

The present invention is not limited to the above-described preferred embodiments, but rather, the present invention is to be construed broadly and cover all modifications, equivalents, and improvements falling within the spirit and scope of the present invention.