Poultry phloretin solution and preparation method thereof

Abstract

The invention discloses a phloretin solution for poultry. The phloretin solution is prepared from the following components in parts by mass: 1 part of phloretin, 20 to 35 parts of ethanol serving as a solvent, 2.5 to 7.5 parts of polysorbate 80 serving as a cosolvent, 0.008 to 0.2 part of butylated hydroxytoluene serving as an antioxidant, 0.01 to 0.05 part of phosphoric acid serving as a synergist serving as an antioxidant and 5 to 20 parts of purified water. The preparation method comprises the following steps: dissolving phloretin and butylated hydroxytoluene in ethanol, adding polysorbate 80 and phosphoric acid, adding water to a constant volume, and filtering. The problem that phloretin is easy to separate out when being mixed with water to be administered is solved, the solution stability is high, accurate administration can be achieved, the composition is suitable for preventing necrotic enteritis caused by clostridium welchii in poultry intensive breeding, and the policy requirements of resisting limitation and resisting replacement are met.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of veterinary drugs, and particularly relates to a phloretin solution for poultry and a preparation method thereof. BACKGROUND

[0002] In the current intensive poultry farming, necrotic enteritis is a common intestinal disease caused by Clostridium welchii, which can cause poultry growth inhibition and mortality increase, causing great losses to the breeding industry. Phloretin, as a monomer active ingredient obtained by water extraction, enzymatic hydrolysis and purification from the leaves of Lithocarpus polystachyus Rehd, has a significant effect on preventing the disease, and is a new type of green, safe and residue-free antibacterial ingredient, which meets the national policy of limiting and replacing antibiotics and has a broad application prospect.

[0003] However, phloretin has solubility problems. It is insoluble in water and only soluble in organic solvents such as ethanol and methanol. If only ethanol and water are used as solvents to prepare it into a liquid preparation, the active ingredient phloretin will precipitate in large quantities when diluted with water for clinical application, which cannot achieve precise dosing and seriously affects the efficacy. Therefore, it is of great significance to develop a solution that can solve the problem of phloretin precipitation when diluted with water to meet the needs of the breeding industry. SUMMARY

[0004] The purpose of the present application is to provide a phloretin solution for poultry and a preparation method thereof to solve the problems of easy precipitation and poor stability of phloretin liquid preparation when diluted with water for administration.

[0005] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows: The prescription composition of the phloretin solution for poultry consists of phloretin, ethanol, polysorbate 80, dibutylhydroxytoluene, phosphoric acid and purified water, and the mass ratio of each component is as follows: phloretin 1 part, ethanol 20-35 parts, polysorbate 80 2.5-7.5 parts, dibutylhydroxytoluene 0.008-0.2 parts, phosphoric acid 0.01-0.05 parts, and purified water 5-20 parts.

[0006] Among them, phloretin is a monomer effective component obtained by water extraction, enzymatic hydrolysis and purification from the leaves of Lithocarpus polystachyus Rehd; ethanol is used as the main solvent for dissolving phloretin; polysorbate 80 is used as a cosolvent to enhance the solubility of phloretin when diluted with water for administration and prevent precipitation; dibutylhydroxytoluene is used as an antioxidant to delay the oxidation of phloretin; phosphoric acid is used as an antioxidant synergist to synergistically improve the antioxidant effect and solve the problem of easy oxidation and discoloration of the phloretin solution during storage; all the excipients are pharmaceutical-grade excipients included in the Chinese Pharmacopoeia.

[0007] Preparation method: Step (1) Take 1 part of phloretin and 0.008-0.2 part of dibutyl hydroxytoluene, add 20-35 parts of ethanol, stir until completely dissolved, to obtain mixed solution A; Step (2) Add 2.5-7.5 parts of polysorbate 80 and 0.01-0.05 parts of phosphoric acid to mixed solution A, and stir well to obtain mixed solution B; Step (3) Add 5-20 parts of purified water to mixed solution B, continue to stir until uniform, and then filter through a 0.45 μm filter membrane or filter cartridge to obtain the phloretin solution for poultry.

[0008] Compared with the prior art, the beneficial effects of the present application are that: (1) the problem of phloretin precipitation when diluted with water is solved: by adding a specific proportion of polysorbate 80 as a cosolvent, phloretin can remain in a dissolved state when diluted with water in clinical use (whether the dilution ratio is 1:50 or 1:100), forming a transparent solution and achieving precise dosing.

[0009] (2) Strong stability: the synergistic effect of dibutyl hydroxytoluene and phosphoric acid effectively inhibits the oxidation of phloretin. After 6 months of accelerated testing, the solution remains a light yellow clear solution, the active ingredient content is stable, and the quality is controllable.

[0010] (3) Comply with breeding needs: the solution dosage form is suitable for the dilution dosing method in intensive poultry breeding, is easy to use, and can improve breeding efficiency. The active ingredient is derived from traditional Chinese medicine extraction, is suitable for preventing necrotic enteritis caused by Clostridium perfringens in intensive poultry breeding, and meets the needs of the policy of limiting and replacing antibiotics. BRIEF DESCRIPTION OF DRAWINGS

[0011] Figure 1 Figure 1 is a 1:50 dilution state diagram of the examples and comparative examples of the present application.

[0012] Figure 2 Figure 2 is a 1:100 dilution state diagram of the examples and comparative examples of the present application.

[0013] Figure 3 Figure 3 is a 0-6 month solution stability comparison diagram of the examples and comparative examples of the present application. DETAILED DESCRIPTION

[0014] In order to make the purpose, technical scheme and advantages of the present application clearer, the present application will be further described in detail below with reference to the drawings and examples. It should be understood that the specific examples described herein are only used to explain the present application and do not limit the present application. Example 1

[0015] Phellopterin 1 kg and butylated hydroxytoluene 0.008 kg were weighed, 27.5 kg of ethanol was added, and stirred until completely dissolved; 2.5 kg of polysorbate 80 and 0.01 kg of phosphoric acid were added and stirred evenly; 20 kg of purified water was added, stirred evenly, and filtered through a 0.45 μm filter to obtain the phellopterin solution for poultry. Example 2

[0016] Phellopterin 1 kg and butylated hydroxytoluene 0.2 kg were weighed, 35 kg of ethanol was added, and stirred until completely dissolved; 7.5 kg of polysorbate 80 and 0.05 kg of phosphoric acid were added and stirred evenly; 7.5 kg of purified water was added, stirred evenly, and filtered through a 0.45 μm filter to obtain the phellopterin solution for poultry.

[0017] Comparative Example 1 Phellopterin 1 kg was weighed, 50 kg of ethanol was added, and stirred to dissolve, and filtered through a 0.45 μm filter to obtain the phellopterin solution.

[0018] Comparative Example 2 Phellopterin 1 kg was weighed, 30 kg of ethanol was added, and stirred to completely dissolve, and 20 kg of polyethylene glycol 400 was added, stirred evenly, and filtered through a 0.45 μm filter to obtain the phellopterin solution.

[0019] The samples prepared in Examples 1 and 2 and Comparative Examples 1 and 2 were subjected to the following tests: The water dilution test was simulated for clinical application, and the solubility of the samples in water was observed and compared; and the prepared samples were divided and subjected to an accelerated 6-month test in a pharmaceutical test chamber, and the properties and active ingredient content of the samples were observed and determined.

[0020] The content determination was performed by high performance liquid chromatography, and the chromatographic conditions were as follows: InfinityLab Poroshell 120 EC-C18 150*4.6mm 4μm column, detection wavelength 285 nm, mobile phase acetonitrile:water=30:70, column temperature 30℃, injection volume 10μl.

[0021] Table 1 Comparison of water dilution solubility

[0022] Table 2 Accelerated stability of liquid medicine properties

[0023] Table 3 Accelerated stability of liquid medicine content

[0024] Water dilution solubility test: simulate clinical application, dilute with water at a ratio of 1:50 and 1:100, respectively, and observe the solution state. The results are as follows Figure 1 andFigure 2 As shown, the samples of Examples 1 and 2 are both transparent solutions, while the sample of Comparative Example 1 appears white flocculent or granular precipitation, and the sample of Comparative Example 2 appears white granular precipitation.

[0025] The stability results are shown in Table 2 and Table 3. Figure 3 As shown in Table 2 and Table 3, the samples of Examples 1 and 2 are always light yellow clear solutions within 6 months, and the content is stable at about 20 mg / ml; the sample of Comparative Example 1 becomes orange yellow after 1 month, the sample of Comparative Example 2 becomes light orange yellow after 1 month, and becomes orange red after 2 months, although the content does not change much, but the stability of the property is poor.

[0026] The above test results fully prove that the phloridzin solution for poultry prepared by the present application has stable solution property and content, controllable quality; and the solution is easier to be uniformly dispersed without precipitation during clinical application, the administration is more accurate, and has significant advantages.

[0027] The above description is only the preferred specific implementation of the present application, but the protection scope of the present application is not limited to this, any skilled person in the art, according to the technical solution and the inventive concept of the present application, makes equivalent replacement or change within the disclosed technical scope, should be covered in the protection scope of the present application.

Claims

1. A poultry phlorizin solution, characterized in that, The composition by mass ratio includes the following components: 1 part phloretin, 20-35 parts solvent ethanol, 2.5-7.5 parts cosolvent polysorbate 80, 0.008-0.2 parts antioxidant dibutylhydroxytoluene, 0.01-0.05 parts antioxidant synergist phosphoric acid, and 5-20 parts purified water.

2. The poultry phloretin solution according to claim 1, characterized in that, The phloretin is a monomeric active ingredient obtained from the leaves of *Ligustrum lucidum* through water extraction, enzymatic hydrolysis, and purification.

3. The poultry phlorizin solution according to claim 1, characterized in that, The ethanol, polysorbate 80, butylated hydroxytoluene, and phosphoric acid are all pharmaceutical-grade excipients listed in the Chinese Pharmacopoeia.

4. The method for preparing poultry phlorizin solution according to any one of claims 1 to 3, characterized in that, Includes the following steps: Step (1): Weigh 1 part phloretin and 0.008-0.2 parts butylated hydroxytoluene, add 20-35 parts ethanol, and stir until completely dissolved; Step (2): Add 2.5-7.5 parts of polysorbate 80 and 0.01-0.05 parts of phosphoric acid to the solution obtained in step (1), and stir until homogeneous; Step (3): Add 5-20 parts of purified water to the mixture obtained in step (2), stir evenly, and then filter through a 0.45μm filter membrane or filter cartridge to obtain the final product.

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