Povidone-iodine oral liquid and preparation method thereof

Abstract

The invention relates to the technical field of veterinary drugs, in particular to povidone-iodine oral liquid and a preparation method thereof. The oral liquid comprises the following components: povidone, a water-soluble anionic polysaccharide derivative, iodine, a metal ion chelating agent, a nonionic surfactant, a water-soluble organic solvent, a pH regulator, a flavoring agent and water. Compared with traditional prevention and treatment preparations with the problems of low bioavailability, poor stability, poor taste and the like, the povidone-iodine oral liquid can effectively prevent and treat the diseases, by optimizing the formula of povidone-iodine and the composite auxiliary materials, adding a proper taste regulator, improving the production process and simplifying the process, the cost is greatly reduced, and the oral liquid is suitable for large-scale popularization and application. The bioavailability is improved, the stability is enhanced, the palatability is improved, the production operation is simpler and more convenient, industrial production can be better adapted, and a practical solution is provided for the breeding industry.

Description

Technical Field

[0001] This invention relates to the field of veterinary drug technology, and in particular to a povidone-iodine oral solution and its preparation method. Background Technology

[0002] Povidone-iodine (PVP-I) is a highly effective and low-toxicity disinfectant composed of polyvinylpyrrolidone (PVP) and iodine. Due to its broad-spectrum antimicrobial activity (including bacteria, viruses, fungi and protozoa), it has been widely used in the field of veterinary medicine, especially for disinfection of the skin and mucous membranes of livestock and poultry, as well as for oral prevention and treatment of gastrointestinal infectious diseases.

[0003] Although povidone-iodine preparations have been used for many years, current technology, especially for oral liquid formulations, still faces several significant technical bottlenecks and shortcomings, restricting their large-scale application and economic viability. These are mainly reflected in the following aspects: First, the raw material costs are high, making it uneconomical. In traditional povidone-iodine oral solution formulations, povidone, as the iodine carrier, typically accounts for 20% to 25% of the total composition. Simultaneously, to ensure effective iodine concentration, the amount of elemental iodine added must be maintained at a high level of 4.5% to 5.6% (see, for example, Chinese patent CN110624012A). Furthermore, to improve solubility and stability, an additional 1.3% to 2.5% of solubilizers such as glycerol and ethanol are often added. This results in the main raw material cost accounting for over 60% of the total formulation cost, placing an excessive economic burden on livestock and poultry farming industries that require large-scale application.

[0004] Secondly, its stability is inherently flawed, making it difficult to guarantee shelf-life quality. Povidone-iodine is prone to decomposition under light and high temperatures, leading to a rapid decrease in effective iodine content. Ordinary povidone-iodine solutions, after 72 hours of exposure to light, show an effective iodine decay rate of 15% to 30%, severely impacting the product's efficacy within its shelf life. Although patented technologies (such as CN108670948A) attempt to improve stability using complex processes like nano-microencapsulation, these methods require the introduction of additional polymers and emulsifiers, complicating the production process, increasing costs, and failing to fundamentally solve the problem of photodecomposition.

[0005] Furthermore, iodine preparations suffer from poor palatability and low animal compliance. The inherently strong, pungent odor of iodine preparations easily causes piglets, poultry, and other animals to refuse to eat, making administration difficult and failing to achieve the desired preventative and therapeutic effects. While existing technologies include adding natural flavoring agents such as hawthorn extract (2.1%-3.1%) to improve palatability, the water extraction process for these natural products is cumbersome, increasing production steps and costs, and their masking effect is limited, failing to fundamentally solve the problem.

[0006] Finally, the choice of stabilizer may bring potential side effects. Some existing technologies use potassium iodide as an iodine source stabilizer; however, the introduction of excessive potassium ions may disrupt the electrolyte balance in livestock and poultry, potentially having adverse effects on their health.

[0007] Therefore, there is an urgent need in this field to develop a novel technology for preparing povidone-iodine oral solution that can significantly reduce production costs and simplify the preparation process while ensuring or even improving the product's bioavailability, stability, and palatability, thereby meeting the urgent needs of modern livestock and poultry farming for efficient, economical, and safe veterinary drugs. Summary of the Invention

[0008] To address the shortcomings of the prior art, this invention provides a povidone-iodine oral solution and its preparation method.

[0009] To address the aforementioned technical problems, one of the technical solutions provided by this invention is as follows: A povidone-iodine oral solution comprises the following components: povidone, a water-soluble anionic polysaccharide derivative, iodine, a metal ion chelating agent, a nonionic surfactant, a water-soluble organic solvent, a pH adjuster, a flavoring agent, and water.

[0010] In one embodiment of the present invention, the product comprises the following components in weight percentage: 14%-18% povidone; 7%-9% water-soluble anionic polysaccharide derivative; 3%-4% iodine; 0.1%-0.3% metal ion chelating agent; 8%-15% nonionic surfactant; 12%-15% water-soluble organic solvent; 0.5% pH adjuster; 3%-10% flavoring agent; and the balance being water.

[0011] In one embodiment of the present invention, the water-soluble anionic polysaccharide derivative is sodium carboxymethyl starch or sodium carboxymethyl cellulose.

[0012] In one embodiment of the present invention, the mass ratio of the povidone to the water-soluble anionic polysaccharide derivative is (1.5-2.5):1.

[0013] In one embodiment of the present invention, the metal ion chelating agent is ethylenediaminetetraacetic acid or its salt.

[0014] In one embodiment of the present invention, the nonionic surfactant is a fatty alcohol polyoxyethylene ether surfactant.

[0015] In one embodiment of the present invention, the pH adjuster is a citrate-disodium hydrogen phosphate buffer pair, used to maintain the pH value of the composition between 4.0 and 5.0.

[0016] The second technical solution provided by this invention is as follows: A method for preparing the povidone-iodine oral solution as described above includes the following steps: A first complexing solution is obtained by dissolving povidone and a water-soluble anionic polysaccharide derivative in a first solvent; the first solvent comprises a water-soluble organic solvent and water. Iodine, a nonionic surfactant, and a metal ion chelating agent are dissolved in a second solvent to obtain an iodine-containing mixture; The iodine-containing mixture is mixed with the first complexing solution and stirred at a set temperature to form a second complexing solution; A pH adjuster and a flavoring agent were added sequentially to the second complexing solution, and the mixture was stirred to obtain povidone-iodine oral solution.

[0017] In one embodiment of the present invention, the mass percentage of water-soluble organic solvent in the first complexing solution is 35%-45%.

[0018] In one embodiment of the present invention, the second solvent is water, and the temperature of the second solvent is 45-55°C; and / or The set temperature is the same as the temperature of the second solvent.

[0019] The povidone-iodine oral solution provided by this invention can effectively solve the problem of bacterial and viral digestive tract diseases that often plague piglets and broilers in livestock and poultry farming, which reduces survival rate and increases farming costs. Furthermore, compared to traditional preventative agents which suffer from low bioavailability, poor stability, and unpleasant taste, the povidone-iodine oral solution of this invention can effectively prevent and treat these diseases. By optimizing the formulation of povidone-iodine and compound excipients, adding suitable taste modifiers, and improving the production process and simplifying the procedures, it not only significantly reduces costs but also improves bioavailability, enhances stability, and enhances palatability. Moreover, the production operation is simpler, making it better suited for industrial production and providing a practical solution for the aquaculture industry.

[0020] Other features and beneficial effects of the invention will be set forth in the following description, and will be apparent in part from the description, or may be learned by practicing the invention. The objects of the invention and other beneficial effects may be realized and obtained by means of the structures particularly pointed out in the description and claims. Detailed Implementation

[0021] 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 clearly and completely described below. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments. The technical features designed in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] In the description of this invention, it should be noted that all terms used in this invention (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains, and should not be construed as limiting the invention; it should be further understood that the terms used in this invention should be understood to have the same meaning as those in the context of this specification and in the relevant field, and should not be understood in an idealized or overly formal sense, except as expressly defined in this invention.

[0023] This invention provides a povidone-iodine oral solution, comprising the following components: povidone, a water-soluble anionic polysaccharide derivative, iodine, a metal ion chelating agent, a nonionic surfactant, a water-soluble organic solvent, a pH adjuster, a flavoring agent, and water.

[0024] First, this invention uses sodium carboxymethyl starch and povidone to construct a composite iodine carrier. Sodium carboxymethyl starch is obtained from natural starch (corn, potato, cassava, etc.) through chemical modification. While retaining the biocompatibility of starch, the introduction of hydrophilic anionic groups significantly improves solubility, stability, and functional diversity. Due to its wide availability, low cost, and good complexing ability, sodium carboxymethyl starch is used in this invention as an iodine carrier after being mixed with povidone in a certain proportion. The carboxymethyl groups form a hydrogen bond network with the povidone molecules, encapsulating the iodine complex, inhibiting iodine sublimation, and replacing part of the expensive povidone, thereby reducing production costs, improving efficiency, and facilitating industrial production.

[0025] Iodine is the active ingredient in this formula, which plays a role in killing microorganisms and viruses.

[0026] Secondly, this invention improves product stability through the synergistic effect of disodium ethylenediaminetetraacetate (EDTA-2Na) and the citrate-disodium hydrogen phosphate buffer pair. EDTA-2Na chelates metal ions (such as Fe) in the solution. 2+ Cu 2+ The buffer pair blocks the catalytic oxidation pathway of iodine, while the buffer pair stabilizes the pH of the system within the optimal range of 4.0-5.0, reducing the generation of free iodine.

[0027] In addition, the fatty alcohol polyoxyethylene ether (AEO-7) in the formulation, as a nonionic surfactant, enhances the drug's permeability to the gastrointestinal mucosa, reducing the minimum inhibitory concentration (MIC) by 50%. The propylene glycol-water composite solvent system (propylene glycol accounting for 12%-15%) maintains the fluidity of the system at low temperatures, effectively preventing the precipitation of sodium carboxymethyl starch gel.

[0028] In a preferred embodiment of the present invention, the povidone-iodine oral solution comprises the following components by weight percentage: 14%-18% povidone; 7%-9% water-soluble anionic polysaccharide derivative; 3%-4% iodine; 0.1%-0.3% metal ion chelating agent; 8%-15% nonionic surfactant; 12%-15% water-soluble organic solvent; 0.5% pH adjuster; 3%-10% flavoring agent; and the balance being water. By defining the precise ratio range of each component, an optimal balance of the functions of each component is achieved. This specific ratio ensures that povidone and anionic polysaccharide derivative can form a stable composite carrier structure; the iodine content is sufficient to ensure an effective bactericidal concentration; the surfactant content effectively improves permeability without causing irritation; and the organic solvent ratio better prevents low-temperature gelation, thereby achieving optimal product performance in terms of cost, stability, efficacy, and palatability.

[0029] More preferably, in a more preferred embodiment of the present invention, the povidone-iodine oral solution is composed of the following components in weight percentage: 16% povidone; 8% water-soluble anionic polysaccharide derivative; 3.5% iodine; 0.25% metal ion chelating agent; 12% nonionic surfactant; 13% water-soluble organic solvent; 0.5% pH adjuster; 5% flavoring agent; and the balance being water.

[0030] In a preferred embodiment of the present invention, the water-soluble anionic polysaccharide derivative is sodium carboxymethyl starch or sodium carboxymethyl cellulose. Sodium carboxymethyl starch or sodium carboxymethyl cellulose is preferred because these two anionic polysaccharide derivatives are widely available, inexpensive, and highly safe. Furthermore, the large number of carboxyl groups in their molecular structure can form a dense hydrogen bond network with povidone molecules, synergistically encapsulating iodine molecules and significantly inhibiting iodine sublimation. This is key to achieving the dual goals of reducing costs and improving stability.

[0031] In a preferred embodiment of the present invention, the mass ratio of the povidone to the water-soluble anionic polysaccharide derivative is (1.5-2.5):1, for example, 1.5:1, 1.8:1, 2.0:1, 2.2:1, 2.5:1, etc., but is not limited to the listed values; other unlisted values ​​within this range are also applicable. This specific mass ratio is key to forming a stable "hydrogen bond network-cage structure." At this ratio, the two carrier molecules can bind in the most efficient way, achieving maximum encapsulation and fixation of iodine molecules. A ratio that is too high or too low will affect the stability of the complex, leading to an increased iodine loss rate. This ratio is crucial for achieving efficient complexation (complexity > 95%) and significantly reducing iodine sublimation (reduced by 67%).

[0032] In a preferred embodiment of the present invention, the metal ion chelating agent is ethylenediaminetetraacetic acid (EDTA) or its salt. EDTA and its salts are highly efficient and broad-spectrum metal ion chelating agents, capable of strongly complexing Fe in solution. 2+ Cu 2 + The presence of catalytic metal ions completely blocks the iodine oxidation and decomposition pathway catalyzed by these ions, thereby significantly improving the chemical stability of the oral liquid during storage and extending the product's shelf life.

[0033] In a preferred embodiment of the present invention, the nonionic surfactant is a fatty alcohol polyoxyethylene ether surfactant. Fatty alcohol polyoxyethylene ether surfactants (such as AEO-7) have high safety and low irritation, and can effectively reduce the interfacial tension between the drug solution and the gastrointestinal mucosa, significantly enhancing the permeability and adsorption of the active pharmaceutical ingredient to the mucosa, thereby reducing the minimum inhibitory concentration (MIC) of the drug by up to 50%, greatly improving bioavailability and therapeutic effect.

[0034] In a preferred embodiment of the present invention, the pH adjuster is a citrate-disodium hydrogen phosphate buffer pair, used to maintain the pH value of the composition between 4.0 and 5.0. Citrate-disodium hydrogen phosphate constitutes a mild and stable weakly acidic buffer system. Precisely maintaining the pH within this range minimizes the formation of free iodine, thereby reducing product irritation, improving palatability, and further enhancing the chemical stability of the iodine complex, which is an important condition for ensuring the overall performance of the product.

[0035] This invention provides a method for preparing the povidone-iodine oral solution as described above, comprising the following steps: A first complexing solution is obtained by dissolving povidone and a water-soluble anionic polysaccharide derivative in a first solvent; the first solvent comprises a water-soluble organic solvent and water. Iodine, a nonionic surfactant, and a metal ion chelating agent are dissolved in a second solvent to obtain an iodine-containing mixture; The iodine-containing mixture is mixed with the first complexing solution and stirred at a set temperature to form a second complexing solution; A pH adjuster and a flavoring agent were added sequentially to the second complexing solution, and the mixture was stirred to obtain povidone-iodine oral solution.

[0036] This invention employs a two-step complexation preparation process. First, povidone and sodium carboxymethyl starch form a primary carrier network, then iodine is introduced for primary complexation. This process results in an iodine complexation degree of up to 95.2% in the final product, far exceeding that of traditional processes (≤85%), significantly reducing the free iodine content and thus substantially improving the palatability of the oral liquid.

[0037] In a preferred embodiment of the present invention, the mass percentage of the water-soluble organic solvent in the first complexing solution is 35%-45%, such as 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, etc., but not limited to the listed values; other unlisted values ​​within this range are also applicable. Controlling the concentration of the water-soluble organic solvent in the first complexing solution within this range ensures that povidone and sodium carboxymethyl starch are fully dissolved and spread, creating optimal conditions for the subsequent formation of a uniform and dense hydrogen bond network. Too low a concentration may lead to insufficient dissolution of the carrier; too high a concentration increases costs and may affect subsequent complexation.

[0038] In a preferred embodiment of the present invention, the second solvent is water, and the temperature of the second solvent is 45-55°C, such as 45°C, 48°C, 50°C, 52°C, 55°C, etc., but not limited to the listed values; other unlisted values ​​within this range are also applicable. In some other preferred embodiments of the present invention, the set temperature is the same as the temperature of the second solvent. Using warm water at 45-55°C as the second solvent and carrying out the main complexation reaction at this temperature can significantly improve the dissolution rate and reactivity of iodine, which is beneficial for the rapid and sufficient diffusion of iodine molecules into the formed carrier network, thereby achieving high-efficiency and high-degree complexation, shortening the production cycle, and ensuring a high degree of complexation in the product.

[0039] The experimental results demonstrating the technical advantages of the present invention will be described below using examples and comparative examples.

[0040] Example 1 A povidone-iodine oral solution comprises the following components by mass fraction: 16% povidone; 8% sodium carboxymethyl starch; 3.5% iodine; 0.25% disodium ethylenediaminetetraacetate (EDTA-2Na); 12% fatty alcohol polyoxyethylene ether (AEO-7); 13% propylene glycol; 0.2% citric acid; 0.3% disodium hydrogen phosphate; 5% sorbitol; the balance being purified water. According to the above formula, weigh each component and prepare the sample solution according to the following process: 1) First complexing solution: First solvent is obtained by mixing propylene glycol and a portion of water, then polyvinyl ketone and sodium carboxymethyl starch are added to the first solvent in sequence and stirred to dissolve; the first complexing solution accounts for 1 / 3 of the total volume; 2) Slowly add fatty alcohol polyoxyethylene ether (AEO-7), disodium ethylenediaminetetraacetate (EDTA-2Na), and iodine to the remaining water (50°C) to obtain an iodine-containing mixture; mix the iodine-containing mixture with the first complexing solution and shear and stir at 50°C for 3 hours to obtain a second complexing solution; 3) Add citric acid and disodium hydrogen phosphate to the second complexing solution to adjust the pH to 4.5, add sorbitol, stir for 8 hours to obtain a uniform povidone-iodine oral solution; 4) The iodine content of povidone-iodine oral solution was determined to be 0.51% (based on available iodine), and the pH value was 4.52.

[0041] Example 2 A povidone-iodine oral solution comprises the following components by mass fraction: 14% povidone; 7% sodium carboxymethyl starch; 3% iodine; 0.1% disodium ethylenediaminetetraacetate (EDTA-2Na); 8% fatty alcohol polyoxyethylene ether (AEO-7); 12% propylene glycol; 0.2% citric acid; 0.3% disodium hydrogen phosphate; 5% sorbitol; the balance being purified water. According to the above formula, weigh each component and prepare the sample solution according to the following process: 1) First complexing solution: First solvent is obtained by mixing propylene glycol and a portion of water, then polyvinyl ketone and sodium carboxymethyl starch are added to the first solvent in sequence and stirred to dissolve; the first complexing solution accounts for 1 / 3 of the total volume; 2) Slowly add fatty alcohol polyoxyethylene ether (AEO-7), disodium ethylenediaminetetraacetate (EDTA-2Na), and iodine to the remaining water (50°C) to obtain an iodine-containing mixture; mix the iodine-containing mixture with the first complexing solution and shear and stir at 50°C for 3 hours to obtain a second complexing solution; 3) Add citric acid and disodium hydrogen phosphate to the second complexing solution to adjust the pH to 4.5, add sorbitol, stir for 8 hours to obtain a uniform povidone-iodine oral solution; 4) The iodine content of povidone-iodine oral solution was determined to be 0.50% (based on available iodine), and the pH value was 4.48.

[0042] Example 3 A povidone-iodine oral solution comprises the following components by mass fraction: 18% povidone; 9% sodium carboxymethyl starch; 4% iodine; 0.3% disodium ethylenediaminetetraacetate (EDTA-2Na); 15% fatty alcohol polyoxyethylene ether (AEO-7); 15% propylene glycol; 0.2% citric acid; 0.3% disodium hydrogen phosphate; 5% sorbitol; the balance being purified water. According to the above formula, weigh each component and prepare the sample solution according to the following process: 1) First complexing solution: First solvent is obtained by mixing propylene glycol and a portion of water, then polyvinyl ketone and sodium carboxymethyl starch are added to the first solvent in sequence and stirred to dissolve; the first complexing solution accounts for 1 / 3 of the total volume; 2) Slowly add fatty alcohol polyoxyethylene ether (AEO-7), disodium ethylenediaminetetraacetate (EDTA-2Na), and iodine to the remaining water (50°C) to obtain an iodine-containing mixture; mix the iodine-containing mixture with the first complexing solution and shear and stir at 50°C for 3 hours to obtain a second complexing solution; 3) Add citric acid and disodium hydrogen phosphate to the second complexing solution to adjust the pH to 4.5, add sorbitol, stir for 8 hours to obtain a uniform povidone-iodine oral solution; 4) The iodine content of povidone-iodine oral solution was determined to be 0.50% (based on available iodine), and the pH value was 4.56.

[0043] Comparative Example 1 A povidone-iodine oral solution is composed of the following components by mass fraction: 16% povidone; 8% sodium carboxymethyl starch; 3.5% iodine; 12% fatty alcohol polyoxyethylene ether (AEO-7); 13% propylene glycol; 0.2% citric acid; 0.3% disodium hydrogen phosphate; 5% sorbitol; the balance being purified water. According to the above formula, weigh each component and prepare the sample solution according to the following process: 1) First complexing solution: First solvent is obtained by mixing propylene glycol and a portion of water, then polyvinyl ketone and sodium carboxymethyl starch are added to the first solvent in sequence and stirred to dissolve; the first complexing solution accounts for 1 / 3 of the total volume; 2) Slowly add fatty alcohol polyoxyethylene ether (AEO-7) and iodine to the remaining water (50°C) to obtain an iodine-containing mixture; mix the iodine-containing mixture with the first complexing solution and shear and stir at 50°C for 3 hours to obtain a second complexing solution; 3) Add citric acid and disodium hydrogen phosphate to the second complexing solution to adjust the pH to 4.5, add sorbitol, stir for 8 hours to obtain a uniform povidone-iodine oral solution; 4) The iodine content of povidone-iodine oral solution was determined to be 0.51% (based on available iodine), and the pH value was 4.53.

[0044] Comparative Example 2 A povidone-iodine oral solution comprises the following components by mass fraction: 16% povidone; 8% sodium carboxymethyl starch; 3.5% iodine; 12% fatty alcohol polyoxyethylene ether (AEO-7); 0.25% disodium ethylenediaminetetraacetate (EDTA-2Na); 0.2% citric acid; 0.3% disodium hydrogen phosphate; 5% sorbitol; the balance being purified water. According to the above formula, weigh each component and prepare the sample solution according to the following process: 1) First complexing solution: Dissolve povidone and sodium carboxymethyl starch in water by stirring; the first complexing solution accounts for 1 / 3 of the total volume; 2) Slowly add fatty alcohol polyoxyethylene ether (AEO-7), disodium ethylenediaminetetraacetate (EDTA-2Na), and iodine to the remaining water (50°C) to obtain an iodine-containing mixture; mix the iodine-containing mixture with the first complexing solution and shear and stir at 50°C for 3 hours to obtain a second complexing solution; 3) Add citric acid and disodium hydrogen phosphate to the second complexing solution to adjust the pH to 4.5, add sorbitol, stir for 8 hours to obtain a uniform povidone-iodine oral solution; 4) The iodine content of povidone-iodine oral solution was determined to be 0.50% (based on available iodine), and the pH value was 4.49.

[0045] The following tests were conducted on the povidone-iodine oral solution of the present invention.

[0046] Test case Experiment 1: Light Illumination Experiment Refer to Appendix 246 of the 2010 edition of the *Veterinary Pharmacopoeia of the People's Republic of China* - "Guidelines for Veterinary Drug Stability Testing" The povidone-iodine solution prepared in Example 1 was subjected to an influencing factor test. The specific procedure was as follows: the solution was placed under an illuminance of 4500 Lx ± 500 Lx, and the effective iodine content (the ratio of the actual effective iodine content of the povidone oral solution in Example 1 to the qualified effective iodine content in the 2010 edition of the Chinese Veterinary Pharmacopoeia, Part 1), pH value, and appearance were measured at 5 and 10 days. The results were compared with those at 0 days to examine the stability of the test sample under the influence of these factors. The test results are shown in Table 1. Table 1. Results of the illumination test in the embodiments.

[0047] The experimental results show that the test sample remained stable after 10 days of light exposure under illumination.

[0048] Experiment 2: High Temperature Test Influence factor tests were conducted on the povidone-iodine solutions prepared in Example 1 and the comparative example. The specific procedure was as follows: a high-temperature factor test was conducted at 60°C. The effective iodine content (the ratio of the actual effective iodine content of the povidone oral solution in the examples to the qualified effective iodine content according to the Chinese Veterinary Pharmacopoeia 2010 edition, Part 1), pH value, and appearance were measured at 5 and 10 days respectively. The results were compared with those at 0 days to examine the stability of the test samples under the influence factors. The test results are shown in Table 2. Table 2. High-temperature test results of the examples and comparative examples.

[0049] The experimental results showed that when povidone-iodine oral solution was placed under high temperature conditions for 5 days, both the effective iodine content and pH value decreased significantly; after 10 days, the measured content was close to the lower limit of the labeled amount specified in the draft quality standard. This indicates that the test sample is unstable at 60℃, with the changes in various indicators of the test sample of Comparative Example 1 being particularly significant. It is evident that disodium ethylenediaminetetraacetate plays a key role in maintaining the stability of the solution.

[0050] Experiment 3: Low Temperature Test Referring to the actual effective iodine content of povidone oral solution in the *Chinese Veterinary Pharmacopoeia* and the low-temperature test in the *Chinese Veterinary Pharmacopoeia*, the specific operation method was as follows: the solution was placed at -15℃. Samples were taken on days 5 and 10 of the test period to detect the effective iodine content (the ratio of the actual effective iodine content of povidone oral solution in Example 1 to the qualified effective iodine content in Part 1 of the 2010 edition of the *Chinese Veterinary Pharmacopoeia*), pH value, and appearance. The results were compared with those from day 0 to examine the accelerated stability of the povidone-iodine solution. The test results are shown in Table 3.

[0051] Table 3. Low-temperature test results of the examples and comparative examples.

[0052] Test results: The test sample was stable under low temperature conditions, but the test sample in Comparative Example 2 showed a small amount of flocculent material in its appearance and its flowability was not as good as that in Example 1. It can be seen that propylene glycol maintains good flowability of the system at low temperatures, while avoiding the precipitation of sodium carboxymethyl starch gel.

[0053] Experiment 4: Accelerated Test Accelerated stability tests were conducted on the povidone-iodine solutions prepared in Examples 1-3, according to Appendix 246 of the 2010 edition of the *Veterinary Pharmacopoeia of the People's Republic of China*, entitled "Guiding Principles for Veterinary Drug Stability Testing." The specific procedure was as follows: the solutions were placed at 40℃±2℃ and 75%±5% relative humidity for 3 months. Samples were taken at the end of month 0, month 3, and month 6 of the test period to detect the effective iodine content (the ratio of the actual effective iodine content of the povidone oral solution in Examples 1-4 to the qualified effective iodine content in Part 1 of the 2010 edition of the *Veterinary Pharmacopoeia of the People's Republic of China*), pH value, and appearance. The results were compared with those from day 0 to assess the accelerated stability of the povidone-iodine solution. The test results are shown in Table 4.

[0054] Table 4. Accelerated test results of the examples and comparative examples.

[0055] The test results showed that after the test sample was placed at 40℃ and 75% relative humidity for 6 months, the content and pH value both decreased, indicating that the test sample was unstable under these conditions. The variation range of various indicators of the comparative sample under these conditions was much greater than that of Examples 1-3.

[0056] Experiment 5: Stability Test The povidone-iodine oral solution from Example 1 was diluted 20 times with distilled water according to the usage instructions and left at room temperature. Samples were taken for analysis at 0, 1, 3, 5, and 7 days to examine the stability of the diluted sample. The actual content of available iodine, pH value, and appearance were used as evaluation indicators. The results are shown in Table 5.

[0057] Table 5 Stability test data of the embodiments

[0058] Analysis of the data in the table shows that after the test sample was diluted 20 times and left for one week, its properties, actual effective iodine content, and pH value showed no significant changes compared to day 0. This indicates that the product is stable under these conditions.

[0059] In summary, the povidone-iodine oral solution provided by this invention can effectively solve the problem of bacterial and viral digestive tract diseases that often plague piglets and broilers in livestock and poultry farming, which reduces survival rate and increases farming costs. Furthermore, compared to traditional preventative agents which suffer from low bioavailability, poor stability, and unpleasant taste, the povidone-iodine oral solution of this invention can effectively prevent and treat these diseases. By optimizing the formulation of povidone-iodine and compound excipients, adding suitable taste modifiers, and improving the production process and simplifying the procedures, it not only significantly reduces costs but also improves bioavailability, enhances stability, and enhances palatability. Moreover, the production operation is simpler, making it better suited for industrial production and providing a practical solution for the aquaculture industry.

[0060] Furthermore, those skilled in the art should understand that although many problems exist in the prior art, each embodiment or technical solution of the present invention can be improved in only one or a few aspects, without necessarily solving all the technical problems listed in the prior art or the background art simultaneously. Those skilled in the art should understand that any content not mentioned in a claim should not be construed as a limitation on that claim.

[0061] Although this document frequently uses terms such as povidone, water-soluble anionic polysaccharide derivative, iodine, metal ion chelating agent, nonionic surfactant, water-soluble organic solvent, pH adjuster, flavoring agent, and water, the possibility of using other terms is not excluded. These terms are used merely for the convenience of describing and explaining the essence of the invention; interpreting them as any additional limitation would contradict the spirit of the invention. The terms "first," "second," etc. (if present) in the description and claims of the embodiments of the invention are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence.

[0062] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A povidone-iodine oral solution, characterized in that, It includes the following components: povidone, water-soluble anionic polysaccharide derivative, iodine, metal ion chelating agent, nonionic surfactant, water-soluble organic solvent, pH adjuster, flavoring agent, and water.

2. The povidone-iodine oral solution according to claim 1, characterized in that, It consists of the following components by weight percentage: 14%-18% povidone; 7%-9% water-soluble anionic polysaccharide derivatives; 3%-4% iodine; 0.1%-0.3% metal ion chelating agents; 8%-15% nonionic surfactants; 12%-15% water-soluble organic solvents; 0.5% pH adjusters; 3%-10% flavoring agents; and the balance being water.

3. The povidone-iodine oral solution according to claim 1, characterized in that, The water-soluble anionic polysaccharide derivative is sodium carboxymethyl starch or sodium carboxymethyl cellulose.

4. The povidone-iodine oral solution according to claim 1, characterized in that, The mass ratio of the povidone to the water-soluble anionic polysaccharide derivative is (1.5-2.5):

1.

5. The povidone-iodine oral solution according to claim 1, characterized in that, The metal ion chelating agent is ethylenediaminetetraacetic acid or its salt.

6. The povidone-iodine oral solution according to claim 1, characterized in that, The nonionic surfactant is a fatty alcohol polyoxyethylene ether surfactant.

7. The povidone-iodine oral solution according to claim 1, characterized in that, The pH adjuster is a citrate-disodium hydrogen phosphate buffer pair, used to maintain the pH of the composition between 4.0 and 5.

0.

8. A method for preparing povidone-iodine oral solution as described in any one of claims 1-7, characterized in that, Includes the following steps: A first complexing solution is obtained by dissolving povidone and a water-soluble anionic polysaccharide derivative in a first solvent; the first solvent comprises a water-soluble organic solvent and water. Iodine, a nonionic surfactant, and a metal ion chelating agent are dissolved in a second solvent to obtain an iodine-containing mixture; The iodine-containing mixture is mixed with the first complexing solution and stirred at a set temperature to form a second complexing solution; A pH adjuster and a flavoring agent were added sequentially to the second complexing solution, and the mixture was stirred to obtain povidone-iodine oral solution.

9. The method according to claim 8, characterized in that, The mass percentage of water-soluble organic solvent in the first complexing solution is 35%-45%.

10. The method according to claim 8, characterized in that, The second solvent is water, and the temperature of the second solvent is 45-55℃; and / or The set temperature is the same as the temperature of the second solvent.

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