A kind of povidone iodine effervescent tablet and its preparation method and application

Abstract

The present invention relates to the technical field of disinfectants, and more particularly to a povidone-iodine effervescent tablet and its preparation method and application. The povidone-iodine effervescent tablet comprises the following components by mass: 10-20 parts of povidone-iodine, 30-60 parts of acidifier, 20-30 parts of desiccant, 5-15 parts of effervescent agent, 1-8 parts of release agent, 5-15 parts of lubricant, 0.1-5 parts of transdermal agent, and 3-8 parts of stabilizer. The povidone-iodine effervescent tablet provided by the present invention is added with a stabilizer so that after the povidone-iodine effervescent tablet is dissolved, the effective iodine concentration within 24 hours is greater than 88%, the stability is good, and it is conducive to maintaining efficient sterilization and disinfection functions; by adding a transdermal agent, the killing effect of povidone-iodine effervescent tablet on grass carp reovirus and Edwardsiella is improved; it can be used for the prevention and treatment of grass carp reovirus and Edwardsiella in aquaculture water, reducing the death of aquatic products such as fish due to viral or bacterial infection, and reducing the economic losses of farmers.

Description

Technical Field

[0001] The invention relates to the technical field of disinfectants, and in particular to a povidone-iodine effervescent tablet and a preparation method and application thereof. Background Art

[0002] Iodine preparation disinfectants can be divided into two categories: iodine disinfectants (such as iodine tincture, iodine water, etc.) and iodine disinfectants (such as povidone iodine). Among them, povidone iodine (PVP-I) is a complex formed by iodine with a surface active polyvinyl pyrrolidone as a carrier. Its bactericidal activity is provided by the surfactant PVP. The affinity for the bacterial membrane combines the iodine it carries with the cell membrane and cytoplasm, oxidizing sulfhydryl compounds, peptides, proteins, enzymes, lipids, etc., thereby achieving the purpose of sterilization. Compared with iodine, povidone iodine has the advantages of low volatility, good water solubility, mild and long-lasting action, and safe use. It is a new type of external disinfectant with high efficiency, broad spectrum and low toxicity.

[0003] Grass carp reovirus is a highly pathogenic virus to grass carp and other perch-shaped fish. After infection, multiple symptoms such as skin ulcers, bleeding, protruding eyes, inflammation of internal organs, etc. will appear, which can lead to a high mortality rate in fish populations, especially in high-density farming environments. Even if the fish do not die, fish infected with grass carp reovirus may also show symptoms such as slow growth and decreased appetite, which will affect farming efficiency and cause serious economic losses to farmers. Regular disinfection of fish ponds is an effective measure to prevent grass carp reovirus.

[0004] At present, there are 20 kinds of dosage forms of disinfectants with povidone iodine as the main ingredient, including solutions, ointments, suppositories, gels, sprays, etc., but in China, the dosage forms of povidone iodine have not been fully developed. In the field of veterinary medicine, povidone iodine used for sterilization and disinfection of animal skin surfaces and mucous membranes is mostly solution. Povidone iodine solution has different degrees of bactericidal effect on most bacteria, fungi and viruses, and can be used for disinfection of livestock and poultry farms, sheds and aquatic animal surfaces, but the solution has the defect of being extremely inconvenient in transportation and storage.

[0005] When povidone iodine is used in aquaculture, because the aquaculture water contains a large amount of organic matter, povidone iodine is affected by organic matter and water hardness in the aquaculture water, and its solubility and bactericidal effect are greatly reduced, so it cannot be used in large quantities in the aquaculture water. Therefore, developing a povidone iodine disinfectant with good solubility and stability in aquaculture water and good disinfection and bactericidal effect on aquaculture water is of great significance for ensuring the survival rate of aquatic products and reducing the economic losses of farmers. Summary of the invention

[0006] The present invention aims to solve at least one of the above-mentioned technical problems existing in the prior art. To this end, one of the purposes of the present invention is to provide a povidone-iodine effervescent tablet; the second purpose of the present invention is to provide a preparation method of the povidone-iodine effervescent tablet; the third purpose of the present invention is to provide the application of the povidone-iodine effervescent tablet.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is:

[0008] The first aspect of the present invention provides a povidone-iodine effervescent tablet, which comprises the following components, by weight: 10-20 parts of povidone-iodine, 30-60 parts of an acidifier, 20-30 parts of a desiccant, 5-15 parts of an effervescent agent, 1-8 parts of a release agent, 5-15 parts of a lubricant, 0.1-5 parts of a transdermal agent, and 3-8 parts of a stabilizer.

[0009] In some embodiments of the present invention, the povidone-iodine effervescent tablet comprises the following components, measured by mass: 13-18 parts of povidone-iodine, 35-45 parts of acidifier, 20-25 parts of desiccant, 5-10 parts of effervescent agent, 1-5 parts of release agent, 5-10 parts of lubricant, 1-5 parts of transdermal agent, and 3-5 parts of stabilizer.

[0010] In some embodiments of the present invention, the acidulant is selected from at least one of sodium bisulfate, oxalic acid, citric acid, tartaric acid and malic acid.

[0011] In some specific embodiments of the present invention, the acidulant is selected from at least one of citric acid and malic acid.

[0012] In the present invention, organic acids are preferably used as acidulants. Compared with inorganic acids, organic acids have milder effervescent effects and less irritation.

[0013] In some embodiments of the present invention, the effervescent agent comprises alkali metal carbonates or alkali metal bicarbonates.

[0014] In some embodiments of the present invention, the effervescent agent is selected from at least one of sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.

[0015] In some specific embodiments of the present invention, the effervescent agent is selected from at least one of sodium carbonate and sodium bicarbonate.

[0016] In the present invention, sodium carbonate and sodium bicarbonate with relatively low cost are preferably used as effervescent agents. In practical applications, since sodium carbonate and acid undergo a two-step reaction, while sodium bicarbonate and acid undergo a one-step reaction, the acid consumption is relatively small and has little effect on the pH value of the main reaction system solution, sodium bicarbonate is more preferably used as the effervescent agent.

[0017] In some embodiments of the invention, the desiccant comprises an alkali metal salt.

[0018] In some specific embodiments of the present invention, the desiccant is selected from at least one of anhydrous calcium chloride, anhydrous magnesium sulfate, anhydrous sodium sulfate, and anhydrous ferric sulfate.

[0019] In the present invention, a desiccant is added to ensure the stability of the effervescent tablet. The stability of the medicament refers to whether the quality of the drug preparation will change during the preparation and storage of the drug. In this formula system, only when there is no medium water, will no reaction occur, so that the effervescent tablet remains stable for a long time. Therefore, an alkali metal salt is added to the system as a diluting desiccant to quickly absorb moisture and improve the stability of the product; wherein, anhydrous magnesium sulfate is preferably used, because if the tablet absorbs moisture during production, transportation, and storage, the moisture will be preferentially absorbed by anhydrous magnesium sulfate to form crystal water that is difficult to separate, which is more conducive to eliminating the influence of free water on the system and improving product stability.

[0020] In some embodiments of the present invention, the transdermal agent is selected from at least one of fatty alcohol polyoxyethylene ether, laurocapram, and α-olefin sulfonate.

[0021] In some specific embodiments of the present invention, the transdermal agent is fatty alcohol polyoxyethylene ether, laurocapram and α-olefin sulfonate in a mass ratio of 1:(0.8-1.2):(0.8-1.2).

[0022] Transdermal agents are drugs that can increase the absorption and penetration rate of the surface of biological bodies and promote drug absorption. The main technology used is penetration enhancement technology, which is divided into physical penetration enhancement technology, chemical penetration enhancement technology and biological penetration enhancement technology. In order to improve the drug absorption effect of povidone-iodine effervescent tablets on the surface of biological bodies, transdermal agents (chemical penetration enhancers) are introduced to enter the stratum corneum, affect the liquefaction of the stratum corneum, and interact with its components to destroy the lipid bilayer of the stratum corneum or increase fluidity, temporarily reduce the barrier function of the stratum corneum, and will not cause significant damage to cells, thereby enhancing skin permeability.

[0023] The present invention preferably uses at least one of fatty alcohol polyoxyethylene ether, laurocapram, and alpha-olefin sulfonate as a transdermal agent, which has the characteristics of specificity, non-toxicity, non-irritation, non-allergy, rapid onset, ability to restore the barrier function of the stratum corneum after removal, no damage to endogenous substances, compatibility with drugs and formula excipients, and no effect on the efficacy and quality of effervescent tablets.

[0024] In some embodiments of the present invention, the lubricant comprises a water-soluble lubricant.

[0025] In some embodiments of the present invention, the lubricant is selected from polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 10000, polyethylene glycol 20000, mannitol, and sorbitol.

[0026] In some specific embodiments of the present invention, the lubricant is polyethylene glycol 4000 (PEG4000).

[0027] In the present invention, lubricant is added in the prescription to improve the lubricity of particles, reduce the friction between tableting particles, improve particle fluidity, make prescription materials easier to enter into the membrane hole, and greatly improve tableting efficiency. For tablet dissolution without residue, water-soluble lubricant is selected, wherein, polyethylene glycol 4000 is a white or off-white powder, has good solubility and biocompatibility, and has strong polarity and hydrophilicity because a large amount of oxygen atoms are contained in its molecular structure. This also makes it possible to form hydrogen bonds or van der Waals forces with many organic substances, so as to improve solubility, as a kind of solubilizing agent, povidone iodine is the complex of organic povidone and elemental iodine, and PEG4000 can promote dissolution. The present invention preferably uses polyethylene glycol 4000 as lubricant, not only can lubricate tableting particles, but also can be used as a solubilizing agent, improve solubility, and accelerate effervescence time.

[0028] In some embodiments of the present invention, the particle size of the release agent is 1-10 μm.

[0029] In some embodiments of the present invention, the release agent is selected from at least one of sodium chloride, boric acid, and magnesium stearate.

[0030] In some specific embodiments of the present invention, the release agent is sodium chloride with a particle size of 1-10 μm.

[0031] In the present invention, sodium chloride with a particle size of 1-10 μm is preferably used as a release agent. The weight difference of the finished tablets of sodium chloride directly compressed is small, and the hardness, brittleness, disintegration, dissolution rate and moisture resistance are good. Controlling its particle size to 1-10 μm can effectively improve the mixing uniformity of the prescription and improve the quality of the effervescent tablets.

[0032] In some embodiments of the present invention, the stabilizer is selected from at least one of potassium iodide, potassium iodate, and ethylenediaminetetraacetic acid.

[0033] In some embodiments of the present invention, the stabilizer is potassium iodide, potassium iodate and ethylenediaminetetraacetic acid in a mass ratio of 1:(0.5-1):(0.6-1).

[0034] In some specific embodiments of the present invention, the stabilizer is potassium iodide, potassium iodate and ethylenediaminetetraacetic acid in a mass ratio of 1:(0.3-0.7):(0.4-0.8).

[0035] In the present invention, stabilizer is added to improve the stability of the solution after the dissolution of povidone-iodine effervescent tablets, so that the effective ingredient can maintain the effective iodine concentration for a long time in a liquid state, and then achieve the effect of long-term disinfection. It is found that when potassium iodide, potassium iodate and ethylenediaminetetraacetic acid are used in combination, the stability of the solution after the dissolution of povidone-iodine effervescent tablets can be effectively improved, and the mass ratio of the three is 1: (0.5-1): (0.6-1), the effective iodine content is significantly improved compared to when no stabilizer is added, and based on cost considerations, the mass ratio of potassium iodide, potassium iodate and ethylenediaminetetraacetic acid is 1: (0.3-0.7): (0.4-0.8) when the best.

[0036] In some embodiments of the present invention, the mass of the povidone-iodine effervescent tablet is 0.4-0.6 g / tablet.

[0037] In some embodiments of the present invention, the hardness of the povidone-iodine effervescent tablet is 5-7 kg / cm 2 .

[0038] The second aspect of the present invention provides a method for preparing the povidone-iodine effervescent tablets according to the first aspect of the present invention, comprising the following steps:

[0039] Firstly, povidone iodine, an acidifier and a desiccant are mixed, then an effervescent agent, a release agent and a lubricant are added and mixed continuously, then a transdermal agent and a stabilizer are added and mixed, and tableting is performed to obtain the povidone iodine effervescent tablet.

[0040] In some embodiments of the present invention, the mixing time of the povidone-iodine, the acidifier and the desiccant is 10-15 min.

[0041] In some embodiments of the present invention, the mixing time after adding the effervescent agent, the release agent and the lubricant is 10-15 minutes.

[0042] In some embodiments of the present invention, the mixing time after adding the transdermal agent and the stabilizer is 10-15 minutes.

[0043] In some embodiments of the present invention, after the tableting, a packaging step is also included.

[0044] The third aspect of the present invention provides use of the povidone-iodine effervescent tablets described in the first aspect of the present invention in aquaculture.

[0045] In some embodiments of the present invention, the application includes the prevention and treatment of grass carp reovirus and / or Edwardsiella infection in aquaculture water.

[0046] In some embodiments of the present invention, the amount of the povidone-iodine effervescent tablets used in the prevention and treatment of grass carp reovirus in aquaculture water is greater than or equal to 5 mg / L.

[0047] In some specific embodiments of the present invention, the dosage of the povidone-iodine effervescent tablets in the prevention and treatment of grass carp reovirus in aquaculture water is 5-50 mg / L.

[0048] In some embodiments of the present invention, the amount of the povidone-iodine effervescent tablets used in the prevention and treatment of Edwardsiella in aquaculture water is greater than or equal to 40 μg / L.

[0049] In some embodiments of the present invention, when the application is the prevention of Edwardsiella infection in aquaculture water, the povidone-iodine effervescent tablets are applied in the aquaculture water at a frequency of 6-7 days / time.

[0050] In some embodiments of the present invention, when the application is the treatment of Edwardsiella infection in aquaculture water, the povidone-iodine effervescent tablets are applied in the aquaculture water at a frequency of 2-3 days / time.

[0051] Compared with the prior art, the present invention has the following beneficial effects:

[0052] 1) The povidone-iodine effervescent tablet provided by the present invention has a stabilizer added thereto so that after the povidone-iodine effervescent tablet is dissolved, the effective iodine concentration within 24 hours is greater than 88%, the stability is good, and it is conducive to maintaining efficient sterilization and disinfection functions; by adding a transdermal agent, the killing effect of the povidone-iodine effervescent tablet on grass carp reovirus and Edwardsiella is improved;

[0053] 2) The present invention utilizes the characteristic that povidone iodine is easy to become sticky when dissolved in water to prepare an effervescent tablet. When the effervescent preparation is dissolved, it can be gradually dissolved from the outside to the inside, gradually releasing povidone iodine. Under the action of carbon dioxide released by the effervescence of the tablet, the povidone iodine is quickly diffused into the water, forming a stirring effect around the tablet, promoting the dissolution of povidone iodine, and making the povidone iodine better play the disinfection and sterilization function;

[0054] 3) The preparation process of the povidone-iodine effervescent tablets provided by the present invention is simple, and the tablets can be transported and stored easily;

[0055] 4) The povidone-iodine effervescent tablets provided by the present invention can be used for the prevention and treatment of grass carp reovirus and Edwardsiella in aquaculture water, reducing the death of fish and other aquatic products caused by virus or bacterial infection and reducing the economic losses of farmers. DETAILED DESCRIPTION

[0056] The present invention is further described in detail below by specific examples. Unless otherwise specified, the raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial sources or can be obtained by prior art methods. Unless otherwise specified, the experiments or test methods are conventional methods in the art.

[0057] Example 1

[0058] This embodiment prepares a povidone-iodine effervescent tablet, the formula of which is shown in Table 1:

[0059] Table 1 The formula of povidone iodine effervescent tablets in Example 1

[0060]

[0061]

[0062] The preparation method is:

[0063] First, mix povidone iodine, acidifier and desiccant for 10 minutes, add effervescent agent, release agent and lubricant and continue mixing for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0064] Example 2

[0065] This embodiment prepares a povidone-iodine effervescent tablet, and the formula is shown in Table 2:

[0066] Table 2 Formulation of povidone iodine effervescent tablets in Example 2

[0067]

[0068] The preparation method is:

[0069] First, mix povidone iodine, acidifier and desiccant for 10 minutes, add effervescent agent, release agent and lubricant and continue mixing for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0070] Example 3

[0071] This embodiment prepares a povidone-iodine effervescent tablet, and the formula is shown in Table 3:

[0072] Table 3 Formulation of povidone iodine effervescent tablets in Example 3

[0073]

[0074] The preparation method is:

[0075] First, mix povidone iodine, acidifier and desiccant for 10 minutes, add effervescent agent, release agent and lubricant and continue mixing for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0076] Comparative Example 1

[0077] This comparative example prepares a povidone-iodine effervescent tablet, the formula of which is shown in Table 4:

[0078] Table 4 Formula of Povidone-iodine Effervescent Tablets in Comparative Example 1

[0079]

[0080] The preparation method is:

[0081] First, mix povidone iodine, acidifier and desiccant for 10 minutes, add effervescent agent, release agent and lubricant and continue mixing for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0082] Comparative Example 2

[0083] This comparative example prepares a povidone-iodine effervescent tablet, the formula of which is shown in Table 5:

[0084] Table 5: Formula of Povidone-iodine Effervescent Tablets in Comparative Example 2

[0085]

[0086] The preparation method is:

[0087] First, mix povidone iodine, acidifier and desiccant for 10 minutes, add effervescent agent, release agent and lubricant and continue mixing for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0088] Comparative Example 3

[0089] This comparative example prepares a povidone-iodine effervescent tablet, the formula of which is shown in Table 6:

[0090] Table 6 Formula of Povidone-iodine Effervescent Tablets in Comparative Example 3

[0091]

[0092]

[0093] The preparation method is:

[0094] First, mix povidone iodine, acidifier and desiccant for 10 minutes, add effervescent agent, release agent and lubricant and continue mixing for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0095] Comparative Example 4

[0096] This comparative example prepares a povidone-iodine effervescent tablet, the formula of which is shown in Table 7:

[0097] Table 7 Formula of Povidone-iodine Effervescent Tablets in Comparative Example 4

[0098]

[0099] The preparation method is:

[0100] First, mix povidone iodine, acidifier and desiccant for 10 minutes, add effervescent agent, release agent and lubricant and continue mixing for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0101] Comparative Example 5

[0102] This comparative example prepares a povidone-iodine effervescent tablet, the formula of which is shown in Table 8:

[0103] Table 8: Formula of Povidone-iodine Effervescent Tablets in Comparative Example 5

[0104]

[0105]

[0106] The preparation method is:

[0107] First, mix povidone iodine, acidifier, desiccant and release agent for 10 minutes, add effervescent agent and lubricant and continue to mix for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0108] Comparative Example 6

[0109] This comparative example prepares a povidone-iodine effervescent tablet, the formula of which is shown in Table 9:

[0110] Table 9 Formula of Povidone-iodine Effervescent Tablets in Comparative Example 6

[0111]

[0112] The preparation method is:

[0113] First, mix povidone iodine, acidifier, desiccant and release agent for 10 minutes, add effervescent agent and lubricant and continue to mix for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0114] Comparative Example 7

[0115] This comparative example prepares a povidone-iodine effervescent tablet, the formula of which is shown in Table 10:

[0116] Table 10: Formula of Povidone-Iodine Effervescent Tablets in Comparative Example 7

[0117]

[0118] The preparation method is:

[0119] First, mix povidone iodine, acidifier, desiccant and release agent sodium sulfate for 10 minutes, add effervescent agent and lubricant and continue mixing for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes, and finally the mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0120] Comparative Example 8

[0121] This comparative example prepares a povidone-iodine effervescent tablet, the formula of which is shown in Table 11:

[0122] Table 11 Formula of Povidone-Iodine Effervescent Tablets in Comparative Example 8

[0123]

[0124] The preparation method is:

[0125] First, mix povidone iodine, acidifier, desiccant and release agent for 10 minutes, add effervescent agent and lubricant and continue to mix for 10 minutes, then add transdermal agent and stabilizer and mix for 10 minutes. The final mixture is compressed on a rotary tablet press. The weight of each tablet is controlled to be 0.5g and the hardness is 5-7kg / cm 2 , povidone iodine effervescent tablets are obtained, and the finished tablets are packaged in aluminum foil bags.

[0126] Stability test

[0127] Stability test of the solution after dissolution of the povidone iodine effervescent tablets in Examples 1-3 and Comparative Examples 1-8:

[0128] The povidone-iodine effervescent tablets and commercially available povidone-iodine disinfectant (500 g / bag, effective iodine content 2 wt%) in Examples 1-3 and Comparative Examples 1-8 were dissolved in water to prepare a solution with an initial effective iodine theoretical concentration of 500 mg / L. The effective iodine concentration in the solution was detected at 0 h, 1 h, 6 h, 12 h and 24 h after the preparation was completed to investigate the stability of the solution after the povidone-iodine effervescent tablets were dissolved.

[0129] Method for testing effective iodine concentration: accurately transfer 10mL of povidone-iodine solution into a 50mL iodine volumetric bottle, shake well, and titrate with sodium thiosulfate titrant (0.01mol / L). When the solution is close to the end point, add 2mL of starch indicator solution and continue titrating until the blue color disappears. The formula for calculating effective iodine concentration is: effective iodine concentration = V×C×0.1269,

[0130] Where: V—titration volume of sodium thiosulfate, mL

[0131] C—concentration of sodium thiosulfate, mol / L.

[0132] Table 12 Stability test results of the solution after dissolution of povidone iodine effervescent tablets in Examples 1-3 and Comparative Examples 1-8

[0133]

[0134] Table 12 shows the stability test results of the solution after the povidone iodine effervescent tablets in Examples 1-3 and Comparative Examples 1-8 are dissolved. It can be seen from Table 12 that after the povidone iodine effervescent tablets prepared in Examples 1-3 are dissolved, the effective iodine concentration within 24 hours is greater than 88%, which is significantly higher than the commercially available povidone iodine disinfectant, indicating that the solution after the povidone iodine effervescent tablets provided by the present invention are dissolved has good stability, and when the addition amount of potassium iodide, potassium iodate and ethylenediaminetetraacetic acid composite stabilizer in the formula is greater than 4wt%, the stability is optimal.

[0135] Test Example 1

[0136] Experiment on the quantitative killing effect of grass carp reovirus:

[0137] Grass carp reovirus was diluted to a concentration of 5×10 5 / mL, inoculated into a 96-well plate, 100 μL per well, and cultured overnight; the povidone-iodine effervescent tablets in Examples 1-3 and Comparative Examples 1-8, and the commercially available povidone-iodine disinfectant were respectively prepared into solutions with effective iodine concentrations of 5 mg / L, 50 mg / L and 500 mg / L; 4.5 mL of each concentration solution was mixed with 0.5 mL of grass carp reovirus working solution, and the mixed solution was placed in a 20°C water bath for 10 min, and 1 mL of each treatment group solution was taken, 9 mL of neutralizer was added, mixed, and treated in a water bath for 10 min, the cell culture medium was discarded, and the phosphate buffer was washed once to obtain a 10-fold diluted virus neutralization solution, 100 μL was taken and inoculated on the cells, each sample was repeated in 8 replicate wells, incubated for 1 hour, the neutralization solution was discarded, and 200 μL of culture medium was added to each well; the cell pathological condition was observed and observed for 10 days.

[0138] The virus titer was calculated using the Reed-Muench method, and the virus inactivation rate was calculated based on the formula:

[0139] Virus inactivation rate (%) = (virus titer before disinfection - virus titer after disinfection) / virus titer before disinfection * 100%.

[0140] Among them, the positive drug control group was selected as povidone-iodine solution, the negative control used a sample without povidone-iodine and the same experimental operation as the positive drug control group, and the blank control was without any drug.

[0141] Table 13 Quantitative killing results of grass carp reovirus

[0142]

[0143]

[0144] Table 13 is the quantitative killing experiment result of grass carp reovirus. It can be seen from Table 13 that when the effective iodine concentration of the povidone-iodine effervescent tablets prepared in Examples 1-3 reaches 5 mg / L after dissolution, the inactivation rate of grass carp reovirus can be greater than that of the commercially available povidone-iodine effervescent tablets. When the content of the composite transdermal agent composed of fatty alcohol polyoxyethylene ether, laurocapram and alpha olefin sulfonate in the povidone-iodine effervescent tablets is greater than 2wt%, when the effective iodine concentration reaches 5 mg / L after dissolution, the inactivation rate of grass carp reovirus can reach 100%. It shows that the povidone-iodine effervescent tablets provided by the present invention have a good killing effect on grass carp reovirus, and can be applied to the elimination of grass carp reovirus in the breeding water of other perch fish such as California perch, to prevent perch fish from having symptoms such as skin ulcers due to infection with grass carp reovirus, and to reduce the economic losses of farmers.

[0145] Test Example 2

[0146] Experiment on the control effect of Edwardsiella:

[0147] Several California bass of the same specifications were purchased, and 1 control group, 1 infection group, and 9 infection prevention groups and infection cure groups were set up, each group including 30 California bass. Among them, the control group was not artificially infected with Edwardsiella; the infection group was artificially infected with Edwardsiella and no medication was given; the infection prevention group was given medication when some fish showed rotten meat symptoms on the body surface 24 hours after artificial infection with Edwardsiella, and the infection cure group was given medication after artificial infection with Edwardsiella and rotten meat symptoms appeared on the body surface. The infection prevention group and the infection cure group were respectively administered with the povidone-iodine effervescent tablets in Examples 1-3 and Comparative Examples 1-8, and the commercially available povidone-iodine disinfectant.

[0148] Among them, the single dosage of the infection prevention group was 40 mg of povidone iodine effervescent tablets per cubic meter of water, once every 7 days. After 14 days of breeding, the survival number of California bass in the control group, infection group and infection prevention group was investigated and recorded, and the prevention rate was calculated. The calculation formula was: Prevention rate (%) = (number of live fish in the infection prevention group - number of live fish in the infection group) / number of live fish in the control group * 100%.

[0149] The single dosage for the infection cured group was 40 mg of povidone iodine effervescent tablets per cubic meter of water, once every other day. After 7 days of breeding, the number of surviving California bass was investigated and recorded, and the cure rate was calculated. The calculation formula was: cure rate (%) = (number of live fish in the infection cured group - number of live fish in the infection group) / number of live fish in the control group * 100%.

[0150] Table 14 Edwardsiella control effect experimental results

[0151]

[0152]

[0153] Table 14 is the experimental results of the control effect of Edwardsiella. It can be seen from Table 14 that the povidone-iodine effervescent tablets prepared in Examples 1-3 have a good control effect on Edwardsiella, and the prevention rate and cure rate are both higher than 90%, which is significantly better than the commercially available povidone-iodine disinfectant. When the content of the composite transdermal agent composed of fatty alcohol polyoxyethylene ether, laurocaprolactone and alpha olefin sulfonate in the povidone-iodine effervescent tablet is greater than 2wt%, the control effect on Edwardsiella is the best. The experimental results show that the povidone-iodine effervescent tablets provided by the present invention can be used for the control of Edwardsiella in aquaculture water during the aquaculture of California bass, etc., and reduce the death of aquatic products caused by Edwardsiella infection.

Claims

1. A povidone-iodine effervescent tablet, characterized in that: The composition comprises the following components by weight: 10-20 parts of povidone iodine, 30-60 parts of acidifier, 20-30 parts of desiccant, 5-15 parts of effervescent agent, 1-8 parts of release agent, 5-15 parts of lubricant, 0.1-5 parts of transdermal agent and 3-8 parts of stabilizer.

2. Povidone-iodine effervescent tablet according to claim 1, characterized in that, The acidulant is selected from at least one of sodium bisulfate, oxalic acid, citric acid, tartaric acid and malic acid; And / or, the effervescent agent comprises alkali metal carbonate or alkali metal bicarbonate; and / or, the desiccant comprises an alkali metal salt; And / or, the transdermal agent is selected from at least one of fatty alcohol polyoxyethylene ether, laurocapram, and α-olefin sulfonate.

3. Povidone-iodine effervescent tablet according to claim 1, characterized in that, The lubricant includes a water-soluble lubricant; preferably, the lubricant is selected from at least one of polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 10000, polyethylene glycol 20000, mannitol, and sorbitol.

4. The povidone-iodine effervescent tablet according to claim 1, characterized in that The particle size of the release agent is 1-10 μm; Preferably, the release agent is selected from at least one of sodium chloride, boric acid and magnesium stearate.

5. The povidone-iodine effervescent tablet according to claim 1, characterized in that The stabilizer is selected from at least one of potassium iodide, potassium iodate and ethylenediaminetetraacetic acid.

6. The povidone-iodine effervescent tablet according to claim 5, characterized in that The stabilizer is in a mass ratio of 1:(0.5-1): (0.6-1) of potassium iodide, potassium iodate and ethylenediaminetetraacetic acid.

7. The povidone-iodine effervescent tablet according to any one of claims 1 to 6, characterized in that The mass of the povidone iodine effervescent tablet is 0.4-0.6 g / tablet; And / or, the hardness of the povidone iodine effervescent tablet is 5-7kg / cm 2 .

8. The method for preparing the povidone-iodine effervescent tablet according to any one of claims 1 to 7, characterized in that: The following steps are involved: Firstly, povidone iodine, an acidifier and a desiccant are mixed, then an effervescent agent, a release agent and a lubricant are added and mixed continuously, then a transdermal agent and a stabilizer are added and mixed, and tableting is performed to obtain the povidone iodine effervescent tablet.

9. Use of the povidone-iodine effervescent tablet according to any one of claims 1 to 7 in aquaculture.

10. The use according to claim 9, characterized in that: The application includes the prevention and treatment of grass carp reovirus and / or Edwardsiella infection in aquaculture water; And / or, the dosage of the povidone-iodine effervescent tablets in the prevention and treatment of grass carp reovirus in aquaculture water is greater than or equal to 5 mg / L; And / or, the dosage of the povidone-iodine effervescent tablets in the prevention and treatment of Edwardsiella in aquaculture water is greater than or equal to 40 μg / L.

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