Sodium dichloroisocyanurate powder disinfectant for livestock and preparation method of sodium dichloroisocyanurate powder disinfectant

Abstract

The invention discloses a sodium dichloroisocyanurate powder disinfectant for veterinary use and a preparation method thereof, and belongs to the technical field of veterinary drug preparations, and the sodium dichloroisocyanurate powder disinfectant comprises the following components in percentage by mass: 50-70% of sodium dichloroisocyanurate, 5-15% of a stabilizer, 3-8% of a synergist, and the balance of anhydrous sodium sulfate, totaling 100%. A pH buffer system-physical barrier-crystal form protection triple stable synergistic mechanism is adopted, a stability strengthening system is formed, the available chlorine retention rate is increased, and metal corrosivity is reduced; tartaric acid and sodium dodecyl sulfate have a dual synergistic effect, so that the drug efficiency is improved, and meanwhile, the interference of organic matters can be effectively resisted. The disinfectant disclosed by the invention has the effects of long-term stability and rapid sterilization, and the sterilization rate is greater than 99.999%.

Description

Technical Field

[0001] The invention belongs to the field of veterinary drug preparations, and particularly relates to a sodium dichloroisocyanurate powder veterinary disinfectant and a preparation method thereof. Background Art

[0002] Sodium dichloroisocyanurate is a highly effective, broad-spectrum disinfectant, but its powder formulation is susceptible to factors such as ambient humidity and temperature, leading to a decrease in available chlorine content and poor stability. Existing formulations also suffer from unstable dissolution rates and insufficient chlorine release during use, compromising sterilization effectiveness. Current technologies often mitigate decomposition by adding stabilizers (such as silicates) or improving packaging, but these efforts struggle to balance long-term stability with rapid sterilization. Summary of the Invention

[0003] The invention aims to provide a sodium dichloroisocyanurate powder disinfectant for animals.

[0004] Another object of the present invention is to provide a method for preparing the above-mentioned preparation.

[0005] Based on the above objectives, the present invention has the following technical effects:

[0006] The invention discloses a sodium dichloroisocyanurate powder disinfectant for animals. The main components and their proportions thereof are as follows, calculated by mass percentage: 50-70% of sodium dichloroisocyanurate, 5-15% of a stabilizer, 3-8% of a synergist, and anhydrous sodium sulfate added to 100%.

[0007] Furthermore, the stabilizer is one or a mixture of two or more of anhydrous sodium carbonate, trisodium citrate and micropowder silica gel in any proportion.

[0008] Preferably, the stabilizer is a mixture of anhydrous sodium carbonate, trisodium citrate and micropowder silica gel in any proportion.

[0009] More preferably, the stabilizer is a mixture of anhydrous sodium carbonate, trisodium citrate and micropowder silica gel in a mass ratio of ((1.8-2.3):(0.9-1.2):(0.7-1.3). Specifically, in the stabilizer, the mass ratio of anhydrous sodium carbonate, trisodium citrate and micropowder silica gel is 2:1:1.

[0010] Furthermore, the synergist is one of tartaric acid and sodium lauryl sulfate or a mixture of the two in any proportion.

[0011] Preferably, the synergist is a mixture of tartaric acid and sodium lauryl sulfate in any proportion.

[0012] More preferably, the synergist is a mixture of tartaric acid and sodium lauryl sulfate in a mass ratio of (2.5-3.5):1.

[0013] Specifically, in the synergist, the mass ratio of tartaric acid to sodium lauryl sulfate is 3:1.

[0014] The preparation method of the above-mentioned sodium dichloroisocyanurate powder veterinary disinfectant is as follows:

[0015] (1) drying the sodium dichloroisocyanurate raw material to a moisture content of ≤0.5%;

[0016] (2) adding anhydrous sodium sulfate, a stabilizer, and a synergist to the sodium dichloroisocyanurate dried in step (1) in order and mixing them uniformly;

[0017] (3) using dry granulation technology to prepare granules of 80-120 mesh in diameter from the material of step (2) at a pressure of 10-15 MPa;

[0018] (4) spraying a hydrophobic film solution on the outer surface of the particles in step (3), drying, and increasing the weight of the particles by 0.45% to 0.50% after drying;

[0019] (5) Repack and you are done.

[0020] Furthermore, in step (1), the drying temperature is 40-50°C.

[0021] Furthermore, in step (2), the ambient humidity during the mixing process is ≤30%; and the ambient temperature is 25±2°C.

[0022] Furthermore, in step (3), the pressure is increased in steps of (10-11) MPa, (12-13) MPa, and (14-15) MPa, and the pressure is maintained for 2-8 seconds at each pressure.

[0023] Furthermore, in step (4), the hydrophobic membrane component is one or a mixture of any proportion of calcium stearate and hydroxypropyl methylcellulose (HPMC), the solvent in the hydrophobic membrane solution is at least one of acetone, ethanol and water, and the concentration of the hydrophobic membrane solution is (0.5 to 1) wt%.

[0024] Preferably, in step (4), the hydrophobic membrane component is a mixture of calcium stearate and hydroxypropyl methylcellulose (HPMC) in any proportion; and the solvent in the hydrophobic membrane solution is a mixture of acetone and ethanol.

[0025] More preferably, in step (4), the hydrophobic membrane component is a mixture of calcium stearate and hydroxypropyl methylcellulose (HPMC) in a mass ratio of (1-3):1, and the solvent in the hydrophobic membrane solution is a mixed solvent of acetone and ethanol in a volume ratio of (2-4):1. Specifically, the hydrophobic membrane component is a mixture of calcium stearate and hydroxypropyl methylcellulose (HPMC) in a mass ratio of 2:1; and the solvent is a mixed solvent of acetone and ethanol in a volume ratio of 3:1.

[0026] Furthermore, in step (4), the drying temperature is 28-35°C.

[0027] Furthermore, in step (5), the packaged product is vacuum-packed using an aluminum-plastic composite film with a built-in desiccant.

[0028] The present invention has the following advantages and beneficial effects:

[0029] (1) A triple stabilization synergistic mechanism of pH buffer system, physical barrier and crystal protection is adopted to form a stability enhancement system, improve the effective chlorine retention rate and reduce metal corrosion;

[0030] (2) The dual synergistic effect of tartaric acid and sodium lauryl sulfate is used to increase the efficacy of the drug while effectively resisting the interference of organic matter;

[0031] (3) A composite coating system is used to achieve a good moisture-proof effect; the product of the present invention adopts aluminum-plastic composite film packaging + silica gel composite adsorbent, which can effectively control the increase in the moisture content of the product. DETAILED DESCRIPTION

[0032] The present invention is further described below with reference to examples, but the protection scope of the present invention is not limited thereto.

[0033] Example 1 A sodium dichloroisocyanurate powder veterinary disinfectant (available chlorine content 30%) and its preparation method

[0034] In this embodiment, the main components and proportions of the sodium dichloroisocyanurate powder veterinary disinfectant are as follows: 50% sodium dichloroisocyanurate, 5% stabilizer, 4% synergist, and 41% anhydrous sodium sulfate, calculated by mass ratio.

[0035] The stabilizer is a complex composed of anhydrous sodium carbonate, trisodium citrate and micropowder silica gel in a mass ratio of 2:1:1.

[0036] The synergist is a mixture of tartaric acid and sodium lauryl sulfate in a mass ratio of 3:1.

[0037] The preparation method of the above-mentioned sodium dichloroisocyanurate powder veterinary disinfectant is as follows:

[0038] (1) Raw material pretreatment: vacuum drying the sodium dichloroisocyanurate raw material at 40-50°C to a moisture content of ≤0.5%;

[0039] (2) Mixing: adding anhydrous sodium sulfate, a stabilizer, and a synergist to the raw materials of step (1) in proportion, and mixing them three-dimensionally for 20 minutes under the conditions of an ambient humidity of ≤30% and a temperature of 25±2°C;

[0040] (3) Granulation: Using dry granulation technology, the raw material of step (2) was made into granules with a particle size of 80-120 mesh by holding the pressure at 10 MPa for 2 seconds, 12 MPa for 3 seconds, and 15 MPa for 8 seconds;

[0041] (4) Coating: Spraying (0.5-1) wt% hydrophobic membrane solution to reduce hygroscopicity; the hydrophobic membrane component is a mixture of calcium stearate and hydroxypropyl methylcellulose (HPMC) in a mass ratio of 2:1, and the solvent in the hydrophobic membrane solution is an acetone-ethanol mixture system (volume ratio of 3:1); after spraying, drying is carried out in a fluidized bed with a fluidized bed inlet temperature of 35°C, a fluidized bed outlet temperature of 28°C, a wind speed of 1.5 m / s, and a drying time of 30 min. The particle weight gain rate after spraying the hydrophobic membrane is 0.49±0.03%;

[0042] (5) Packaging: Use aluminum-plastic composite film vacuum packaging with a built-in independent desiccant unit to obtain the product of the present invention.

[0043] Example 2 A sodium dichloroisocyanurate powder veterinary disinfectant (available chlorine content 36%) and its preparation method

[0044] In this embodiment, the main components and proportions of the sodium dichloroisocyanurate powder veterinary disinfectant are as follows: 60% sodium dichloroisocyanurate, 10% stabilizer, 5% synergist, and 25% anhydrous sodium sulfate, calculated by mass ratio.

[0045] The stabilizer is a complex composed of anhydrous sodium carbonate, trisodium citrate and micropowder silica gel in a mass ratio of 2:1:1.

[0046] The synergist is a mixture of tartaric acid and sodium lauryl sulfate in a mass ratio of 3:1.

[0047] The preparation method of the above-mentioned sodium dichloroisocyanurate powder veterinary disinfectant is as follows:

[0048] (1) Raw material pretreatment: vacuum drying the sodium dichloroisocyanurate raw material at 40-50°C to a moisture content of ≤0.5%;

[0049] (2) Mixing: adding anhydrous sodium sulfate, a stabilizer, and a synergist to the raw materials of step (1) in proportion, and mixing them three-dimensionally for 20 minutes under the conditions of an ambient humidity of ≤30% and a temperature of 25±2°C;

[0050] (3) Granulation: Using dry granulation technology, the raw material of step (2) was made into granules with a particle size of 80-120 mesh by holding the pressure at 10 MPa for 2 seconds, 12 MPa for 3 seconds, and 15 MPa for 8 seconds;

[0051] (4) Coating: Spraying (0.5-1) wt% hydrophobic membrane solution to reduce hygroscopicity; the hydrophobic membrane component is a mixture of calcium stearate and hydroxypropyl methylcellulose (HPMC) in a mass ratio of 2:1, and the solvent in the hydrophobic membrane solution is an acetone-ethanol mixture system (volume ratio of 3:1); after spraying, drying is carried out in a fluidized bed with a fluidized bed inlet temperature of 35°C, a fluidized bed outlet temperature of 28°C, a wind speed of 1.5 m / s, and a drying time of 30 min. The particle weight gain rate after spraying the hydrophobic membrane is 0.49±0.03%;

[0052] (5) Packaging: Use aluminum-plastic composite film vacuum packaging with a built-in independent desiccant unit to obtain the product of the present invention.

[0053] Example 3 A sodium dichloroisocyanurate powder veterinary disinfectant (available chlorine content 42%) and its preparation method

[0054] In this embodiment, the main components and proportions of the sodium dichloroisocyanurate powder veterinary disinfectant are as follows: 70% sodium dichloroisocyanurate, 12% stabilizer, 8% synergist, and 10% anhydrous sodium sulfate, calculated by mass ratio.

[0055] The stabilizer is a complex composed of anhydrous sodium carbonate, trisodium citrate and micropowder silica gel in a mass ratio of 2:1:1.

[0056] The synergist is a mixture of tartaric acid and sodium lauryl sulfate in a mass ratio of 3:1.

[0057] Preparation method:

[0058] (1) Raw material pretreatment: vacuum drying the sodium dichloroisocyanurate raw material at 40-50°C to a moisture content of ≤0.5%;

[0059] (2) Mixing: adding anhydrous sodium sulfate, a stabilizer, and a synergist to the raw materials of step (1) in proportion, and mixing them three-dimensionally for 20 minutes under the conditions of an ambient humidity of ≤30% and a temperature of 25±2°C;

[0060] (3) Granulation: Using dry granulation technology, the raw material of step (2) was made into granules with a particle size of 80-120 mesh by holding the pressure at 10 MPa for 2 seconds, 12 MPa for 3 seconds, and 15 MPa for 8 seconds;

[0061] (4) Coating: Spraying (0.5-1) wt% hydrophobic membrane solution to reduce hygroscopicity; the hydrophobic membrane component is a mixture of calcium stearate and hydroxypropyl methylcellulose (HPMC) in a mass ratio of 2:1, and the solvent in the hydrophobic membrane solution is an acetone-ethanol mixture system (volume ratio of 3:1); after spraying, drying is carried out in a fluidized bed with a fluidized bed inlet temperature of 35°C, a fluidized bed outlet temperature of 28°C, a wind speed of 1.5 m / s, and a drying time of 30 min. The particle weight gain rate after spraying the hydrophobic membrane is 0.49±0.03%;

[0062] (5) Packaging: Use aluminum-plastic composite film vacuum packaging with a built-in independent desiccant unit to obtain the product of the present invention.

[0063] Comparative Example 1: Stabilizer Ratio Change

[0064] Formula adjustment: the stabilizer ratio was changed from anhydrous sodium carbonate: trisodium citrate: micropowder silica gel = 2:1:1 to a mass ratio of 1:2:1 (reducing the proportion of sodium carbonate and increasing the proportion of trisodium citrate). Other ingredients were the same as in Example 1.

[0065] The products obtained in Example 1 and Comparative Example 1 were tested with reference to the 2020 edition of the Chinese Pharmacopoeia of Veterinary Medicine. The results are detailed in the table below.

[0066]

[0067] As can be seen from the above table, the effective chlorine retention rate of the sodium dichloroisocyanate powder disinfectant prepared in the present application for 6 months is significantly higher than that of Comparative Example 1, and the particle moisture absorption rate and solution pH stability (5.0 g of powder is added to 100 mL of deionized water) are also significantly better than those of Comparative Example 1.

[0068] Comparative Example 2: Adjustment of dry granulation process parameters

[0069] Process adjustment: the dry granulation pressure was changed from 10 MPa-12 MPa-15 MPa gradient pressurization to a constant 8 MPa, and the pressure gradient control was cancelled. Other procedures were the same as in Example 2.

[0070] The compressive strength, dissolution time and uniformity of effective chlorine release of the particles were tested. The compressive strength of the particles was tested according to the GB / T4750-2024 method, and the other two were tested according to the 2020 edition of the "Chinese Veterinary Pharmacopoeia". The results are detailed in the table below.

[0071]

[0072] As can be seen from the above table, the sodium dichloroisocyanate powder disinfectant granules prepared in the present application have high compressive strength, short dissolution time and more uniform release of effective chlorine.

[0073] Conclusion: The formulation and process parameters of the present invention have been strictly optimized: the mass ratio of anhydrous sodium carbonate, trisodium citrate and micro-powdered silica gel in the stabilizer is 2:1:1, which balances the three indispensable functions of pH buffering, physical barrier and chelation protection; gradient compression granulation: bubbles are expelled and the particles are compacted by stepwise pressure (10→15MPa), ensuring structural density and coating integrity.

[0074] Any single factor change will lead to: accelerated decomposition of available chlorine (>10% / month); deterioration of particle physical properties (powdering / moisture absorption).

[0075] Test Example 1: Product Stability Test Comparison

[0076] 1. Test materials

[0077] Commercially available brand of sodium dichloroisocyanurate powder (40% based on available chlorine), sodium dichloroisocyanurate powder veterinary disinfectant (prepared in Example 1)

[0078] 2. Test methods

[0079] Take an appropriate amount of this product (approximately equivalent to 0.1g of available chlorine), accurately weigh it, and place it in a 250mL iodine bottle. Add 100mL of water to dissolve it. Add 3g of potassium iodide and shake to dissolve it. Add 20mL of sulfuric acid solution (prepared by mixing 1 volume of concentrated sulfuric acid with 5 volumes of water). Seal the bottle tightly, shake well, and let it stand in the dark for 5 minutes. Wash the stopper and the inner wall of the bottle with 5mL of water. Titrate with sodium thiosulfate solution (0.1mol / L) to the end point. Add 2mL of starch indicator solution. Continue titrating until the blue color disappears. Correct the titration result with a blank test. Each 1mL of sodium thiosulfate solution (0.1mol / L) is equivalent to 3.545mg of Cl.

[0080] 3. Test results

[0081]

[0082] It can be seen that the preparation method of the present application can effectively improve the stability of the product and reduce the decomposition of available chlorine.

[0083] Test Example 2 Comparison of 5% Solution Onset Time

[0084] 1. Test materials

[0085] A certain brand of sodium dichloroisocyanurate powder (30% based on available chlorine) on the market

[0086] Sodium dichloroisocyanurate powder veterinary disinfectant (prepared from Example 2 and Example 3)

[0087] Standard strains: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538, Salmonella ATCC14028

[0088] Resistant strains: ESBL-producing Escherichia coli (clinical isolates)

[0089] Fungus: Candida albicans ATCC 10231

[0090] Virus surrogate: bacteriophage PhiX174 (non-enveloped virus model)

[0091] 2. Test methods

[0092] 2.1 Test condition control

[0093] Temperature: 20±1℃ (simulating normal use environment)

[0094] Organic matter interference: add 3% bovine serum albumin (BSA)

[0095] Water quality impact: Use hard water (Ca 2+ 400ppm)

[0096] 2.2 Experimental process

[0097] 2.2.1 Dynamic sterilization test

[0098] Prepare 5% (available chlorine) disinfectant (available chlorine is standardized by DPD method), prepare 1×10 8 CFU / mL standard bacterial suspension (Escherichia coli, Staphylococcus aureus, Candida albicans). Add 0.1mL of bacterial suspension to 0.9mL of disinfectant and incubate at 20°C in a gradient (0, 30s, 1, 2, 5min). Immediately add a neutralizer (containing 0.5% sodium thiosulfate, 1% lecithin, and 0.3% Tween 80) to terminate the reaction. Prepare 0.5mL of the neutralized suspension, perform a 10-fold gradient dilution, and pour onto TSA plates (bacteria) or SDA plates (fungi). Incubate at 37°C for 48 hours and count colonies. A commercially available similar product was used as a control group.

[0099] 2.2.2 Simulated instrument disinfection test

[0100] The biofilm (1×10 6 CFU / cm 2 ) stainless steel sheets were immersed in 5% disinfectant, and samples were taken at regular intervals (0, 1 min, and 3 min) to detect the amount of residual bacteria, and the biofilm thickness was measured using a confocal laser scanning microscope (CLSM).

[0101] 2.3 Calculation formula

[0102] 2.3.1 Calculation of the killing logarithm: KL = lgN0 - lgN t

[0103] (N0: initial bacterial count, N t : Bacterial amount after action)

[0104] Onset time determination criteria:

[0105] Bacteria: KL ≥ 5 (killing rate ≥ 99.999%)

[0106] Fungi: KL ≥ 4 (killing rate ≥ 99.99%)

[0107] Virus: log removal rate ≥ 4

[0108] 2.3.2 Calculation of biofilm killing rate

[0109] Killing rate = (N0-N t ) / N0×100%

[0110] (N0: bacterial count before disinfection, N t : Bacterial count after disinfection)

[0111] 2.4 Data and Results

[0112] 2.4.1 Dynamic sterilization test data

[0113]

[0114]

[0115] As shown in the table above, a 5% solution kills common pathogens such as Escherichia coli and Staphylococcus aureus with a logarithmic kill rate of KL ≥ 5 within 30 seconds (kill rate > 99.999%), 2-3 times faster than commercially available products (which require over 92 seconds) and covers a wide range of microorganisms. In the presence of 3% serum, the killing efficiency remains > 85% (commercially available products drop to 60%), and the product is highly tolerant to organic interference.

[0116] 2.4.2 Bacterial counts before and after simulated instrument disinfection

[0117]

[0118] As can be seen from the table above, the product of this application achieved a killing rate of 99.97% in 1 minute, which is close to complete inactivation. After 3 minutes, the bacterial count was below the detection limit (<10 CFU / cm 2 ), the killing rate is >99.99%, which meets the disinfection standards for medical devices.

[0119] The commercial product still had 0.44% surviving bacteria (5.7×10 3 CFU / cm 2 ), may not meet the requirements of high-risk scenarios.

[0120] 2.4.3 Changes in biofilm thickness

[0121]

[0122] As can be seen from the table above, the biofilm thickness of the product in this application is reduced from 25.8 μm to 1.2 μm after 3 minutes of disinfection.

[0123] Commercially available products: only reduced to 12.5μm at the same time.

[0124] Changes in biofilm thickness reflect the penetration and destructive capabilities of disinfectants. This product thins biofilms, demonstrating its effectiveness in breaking down the extracellular polysaccharide matrix. This accelerates the penetration of disinfectants into the core bacterial flora, reduces the probability of microbial reattachment, and significantly improves the speed and thoroughness of sterilization. This product is particularly suitable for disinfecting instrument crevices and complex surfaces.

Claims

1. A sodium dichloroisocyanurate powder veterinary disinfectant, characterized in that: Calculated by mass percentage, its main components and their proportions are: 50-70% sodium dichloroisocyanurate, 5-15% stabilizer, 3-8% synergist, and anhydrous sodium sulfate added to 100%.

2. The sodium dichloroisocyanurate powder veterinary disinfectant according to claim 1, characterized in that: The stabilizer is one or a mixture of two or more of anhydrous sodium carbonate, trisodium citrate and micropowder silica gel in any proportion.

3. The sodium dichloroisocyanurate powder veterinary disinfectant according to claim 1, characterized in that: The synergist is one of tartaric acid and sodium lauryl sulfate or a mixture of the two in any proportion.

4. The sodium dichloroisocyanurate powder veterinary disinfectant according to claim 2, characterized in that: The stabilizer is a mixture of anhydrous sodium carbonate, trisodium citrate and micro-powder silica gel; and the mass ratio of anhydrous sodium carbonate, trisodium citrate and micro-powder silica gel is (1.8~2.3): (0.9~1.2): (0.7~1.3).

5. The sodium dichloroisocyanurate powder veterinary disinfectant according to claim 3, characterized in that: The synergist is a mixture of tartaric acid and sodium lauryl sulfate; and the mass ratio of tartaric acid to sodium lauryl sulfate is (2.5~3.5):

1.

6. The method for preparing the sodium dichloroisocyanurate powder veterinary disinfectant according to any one of claims 1 to 5, characterized in that: The specific process is as follows: (1) Drying the sodium dichloroisocyanurate raw material to a moisture content of ≤0.5%; (2) adding anhydrous sodium sulfate, a stabilizer, and a synergist to the sodium dichloroisocyanurate dried in step (1) in order according to proportion, and mixing them evenly; (3) using dry granulation technology to prepare the material of step (2) into granules with a particle size of 80-120 mesh at a pressure of 10-15 MPa; (4) spraying a hydrophobic film solution on the outer surface of the particles in step (3) and drying the particles, wherein the particles gain weight by 0.45% to 0.50% after drying; (5) Repack and you are done.

7. The preparation method according to claim 6, characterized in that In step (4), the hydrophobic membrane component in the hydrophobic membrane solution is one of calcium stearate and hydroxypropyl methylcellulose or a mixture of the two in any proportion, the solvent is at least one of acetone, ethanol and water, and the concentration of the hydrophobic membrane solution is (0.5~1) wt%.

8. The preparation method according to claim 7, characterized in that The hydrophobic membrane component in the hydrophobic membrane solution is a mixture of calcium stearate and hydroxypropyl methylcellulose, and the mass ratio of calcium stearate to hydroxypropyl methylcellulose is (1-3):

1. The solvent is a mixed solvent composed of acetone and ethanol in a volume ratio of (2-4):

1.

9. The preparation method according to claim 6, characterized in that In step (2), the ambient humidity during the mixing process is ≤30%, and the ambient temperature is 25±2°C; in step (3), stepwise pressurization is performed in sequence using (10~11) MPa, (12~13) MPa, and (14~15) MPa, and the pressure is maintained for 2~8 seconds at each pressure.

10. The preparation method according to claim 6, characterized in that In step (5), the subpackaged product is vacuum-packed using an aluminum-plastic composite film with a built-in desiccant.

Images