Slow-release solid hydrogen peroxide as well as preparation method and application thereof

Abstract

The invention provides sustained-release solid hydrogen peroxide as well as a preparation method and application thereof, and belongs to the technical field of hydrogen peroxide preparation, the sustained-release solid hydrogen peroxide comprises a hydrogen peroxide solution, a stabilizer, an excipient and a sustained-release agent, wherein the slow release agent is a compound of ethyl cellulose and chitosan, and the weight ratio of ethyl cellulose to chitosan is (1-2): 1; the addition amount of the slow-release agent is 0.5%-10% of the total mass of the slow-release solid hydrogen peroxide; according to the invention, ethyl cellulose (hydrophobic barrier) and chitosan (pH response degradation) are combined for use in the sustained-release agent, so that overhigh local concentration caused by concentrated release of hydrogen peroxide is avoided, and the explosion risk is reduced; the preparation method provided by the invention is a crystallization-drying integrated process, the production period can be shortened to 4 hours, while the traditional process needs more than 8 hours, and the energy consumption is reduced by 40%.

Description

Technical Field

[0001] The present invention relates to the technical field of hydrogen peroxide preparation, and in particular to a slow-release solid hydrogen peroxide and a preparation method and application thereof. Background Art

[0002] Hydrogen peroxide, commonly known as hydrogen peroxide, is a strong oxidant. High-concentration hydrogen peroxide solutions are highly effective disinfectants. Due to its strong oxidizing properties, it can powerfully oxidize and degrade organic matter. However, liquid hydrogen peroxide is unstable and slowly decomposes into oxygen and water at room temperature, rendering it ineffective. This property can be effectively utilized to increase the solubility of hydrogen peroxide in water. Furthermore, hydrogen peroxide is an explosive oxidant, reacting with combustibles to release significant heat and cause explosions. Storage conditions require shielding from light, keeping it airtight, and storing it in a cool, dark place. These demanding conditions make it unsuitable for clinical application.

[0003] With the intensive development of animal husbandry, the requirements for disease prevention and control are increasing. Currently, disinfection is the core prevention and control method in livestock and poultry farming. However, traditional disinfectants have problems such as poor stability and degradation of active ingredients during storage and transportation, making it difficult to ensure disinfection effectiveness. At the same time, the accumulation of leftover bait and feces in aquaculture leads to eutrophication and sediment corruption, and insufficient dissolved oxygen poses a serious threat to the health of farmed animals. Hydrogen peroxide has the functions of disinfection, water purification, and oxygenation, which can simultaneously solve these problems. However, its liquid form has the disadvantages of high storage risks, rapid decomposition, and short duration of action. The development of efficient and stable hydrogen peroxide dosage forms that achieve safe storage, controlled release, and long-lasting action has become an urgent need for the sustainable development of the livestock and aquaculture industries.

[0004] To improve the applicability of hydrogen peroxide, existing technologies have employed a variety of methods to prepare fixed-form hydrogen peroxide. Chinese patents such as CN101559929 and CN1040008A rely on single crystallization aids or complex coating processes, resulting in limited inhibition of hydrogen peroxide decomposition, and some adjuvants pose biosafety risks. Chinese patents such as CN107128880 only offer powder formulations, and CN1040008A requires a complex fluidized bed spraying process, resulting in high equipment costs and energy consumption. Conventional liquid or powdered hydrogen peroxide release rates are uncontrollable, with short action times (<6 hours). Frequent dosing can easily lead to pH fluctuations in the water (above ±1.0), impacting the survival of aquatic animals. Chinese patent CN111771905A mentions a sustained-release period of up to 48 hours for solid-state hydrogen peroxide. Summary of the Invention

[0005] Purpose of the invention: The purpose of the present invention is to address the deficiencies of the existing technology and provide a sustained-release solid hydrogen peroxide and its preparation method and application. The present invention can convert liquid hydrogen peroxide into a stable and safe solid dosage form, and innovatively introduces sustained-release technology to solve the problems of traditional liquid hydrogen peroxide such as poor stability, high storage risk, and short action time, while achieving multifunctional synergy of disinfection, oxygenation and sediment improvement.

[0006] Technical solution: The sustained-release hydrogen peroxide powder of the present invention comprises a hydrogen peroxide solution, a stabilizer, an excipient and a sustained-release agent;

[0007] The hydrogen peroxide solution is a hydrogen peroxide solution with a mass fraction of 28% or 50%;

[0008] The stabilizer is carbomer;

[0009] The excipient is a mixture of sodium sulfate and sodium chloride;

[0010] The sustained-release agent is a complex of ethyl cellulose and chitosan.

[0011] Furthermore, the amount of carbomer used in each liter of hydrogen peroxide solution is 2.5 g.

[0012] Furthermore, in the excipient, the weight ratio of the sodium sulfate to the sodium chloride is (7-10):1; the weight ratio of the excipient to the hydrogen peroxide solution is (1.3-1.5):1.

[0013] Furthermore, in the sustained-release agent, the weight ratio of the ethyl cellulose to the chitosan is (1-2):1; and the added amount of the sustained-release agent is 0.5% to 10% of the total mass of the sustained-release solid hydrogen peroxide.

[0014] A method for preparing sustained-release hydrogen peroxide powder comprises the following steps:

[0015] Step 1: adding sodium sulfate, a stabilizer, and a sustained-release agent in a good ratio to a hydrogen peroxide solution and stirring to dissolve the mixture to obtain a solution A;

[0016] Step 2: Add sodium chloride in a suitable proportion to solution A, stir and dissolve, and obtain solution B;

[0017] Step 3: Cool Solution B with ice-salt water at a temperature of 0-5°C and stir slowly at 5-15 rpm for 1-2 hours to induce crystallization; go to step 4.

[0018] Step 4: centrifuging or filtering the crystals obtained in step 3 to obtain wet material C;

[0019] Step 5: Dry the wet material C by microwave drying or vacuum drying at a temperature ≥ 90° C. to obtain a sustained-release hydrogen peroxide powder.

[0020] A sustained-release solid hydrogen peroxide preparation comprises the sustained-release hydrogen peroxide powder described above, and further comprises a diluent, a binder, and a lubricant; the weight percentage of the sustained-release solid hydrogen peroxide in the solid hydrogen peroxide preparation ranges from 0.5% to 10%; the weight percentage of the diluent in the solid hydrogen peroxide preparation ranges from 0 to 85%; the weight percentage of the binder in the solid hydrogen peroxide preparation ranges from 0 to 10%; and the weight percentage of the lubricant in the solid hydrogen peroxide preparation ranges from 0 to 10%; in the sustained-release solid hydrogen peroxide, the total weight percentage of the diluent, binder, and lubricant is 100%.

[0021] Furthermore, the diluent is one or more of calcium chloride, sodium sulfate or potassium bicarbonate; the binder is one or more of hydroxypropyl methylcellulose, povidone or polyethylene glycol; and the lubricant is micropowder silica gel or polyethylene glycol 6000.

[0022] A method for preparing the above-mentioned sustained-release solid preparation of hydrogen peroxide comprises the following steps:

[0023] Step A, adding a binder to the undried wet material C in the preparation process of the slow-release hydrogen peroxide powder, granulating and then drying to obtain slow-release granules;

[0024] Step B: mixing the sustained-release granules obtained in step A with the diluent and lubricant, and then tableting to obtain sustained-release tablets.

[0025] The invention relates to the use of a sustained-release hydrogen peroxide powder or solid formulation in the preparation of a long-lasting aquaculture water disinfectant, sediment improver, or continuous oxygenator. The sustained-release agent controls the hydrogen peroxide release rate, achieving a cumulative release rate of 50% to 70% over 48 hours and a release rate of ≥90% over 60 hours, while also ensuring a water pH fluctuation range of ≤±0.3.

[0026] Beneficial effects: Compared with the prior art, the advantages of the present invention are:

[0027] (1) The sustained-release agent of the present invention uses ethyl cellulose (hydrophobic barrier) in combination with chitosan (pH-responsive degradation) to avoid excessive local concentrations caused by concentrated release of hydrogen peroxide, thereby reducing the risk of explosion.

[0028] (2) The preparation method of the present invention is an integrated crystallization-drying process, which can shorten the production cycle to 4 hours, while the traditional process requires more than 8 hours. The energy consumption of the present invention is reduced by 40%;

[0029] (3) Hydrophobic barrier + pH response: Ethyl cellulose forms a hydrophobic network to delay the dissolution of H2O2, and chitosan degrades in the weakly acidic environment of the sediment, achieving a 60-hour gradient release (50% to 70% release in 48 hours and ≥90% release in 60 hours). DETAILED DESCRIPTION

[0030] The technical solution of the present invention is described in detail below, but the protection scope of the present invention is not limited to the embodiments.

[0031] The hydrogen peroxide solution used in the examples was purchased from Anhui Huaertai Chemical Co., Ltd., Carbomer U20 and Carbomer 941 were purchased from Shandong Tianqi Pharmaceutical Co., Ltd., sodium sulfate was purchased from Shandong Haihua Group Co., Ltd., sodium chloride was purchased from Henan Pingmei Shenma Tiantai Salt Co., Ltd., ethyl cellulose was purchased from Taian Ruitai Cellulose Co., Ltd. with a viscosity of 45-55 MPa.s, and chitosan was purchased from Qingdao Honghai Biotechnology Co., Ltd. with a viscosity of 44 MPa.s.

[0032] Example 1 Slow-release hydrogen peroxide powder

[0033] Components and proportions: 28% hydrogen peroxide solution: 10 L; Carbomer U20: 0.025 kg; Sodium sulfate: 12.8 kg; Sodium chloride: 1.6 kg; Sustained-release agent (ethyl cellulose: chitosan = 1.5:1): 0.5 kg.

[0034] Preparation method:

[0035] 1. Add sodium sulfate, carbomer U20 and sustained-release agent to hydrogen peroxide solution and stir to dissolve to obtain solution A;

[0036] 2. Add sodium chloride and stir for 1 hour to obtain solution B;

[0037] 3. Cool the mixture with ice-salt water and crystallize by stirring at 10 rpm for 6 hours;

[0038] 4. Centrifuge the wet material C and dry it at 105℃ to obtain powder.

[0039] The hydrogen peroxide content of the obtained solid hydrogen peroxide powder was 9.6% to 9.7% (three batches) by content determination of three batches of samples. The content is high and stable with little difference between batches.

[0040] Example 2 Slow-release hydrogen peroxide powder

[0041] Components and proportions: 50% hydrogen peroxide solution: 10 L; Carbomer 941: 0.025 kg; Sodium sulfate: 11.5 kg; Sodium chloride: 1.5 kg; Sustained-release agent (ethyl cellulose: chitosan = 1.5:1): 1.2 kg.

[0042] Preparation method:

[0043] 1. Add sodium sulfate, carbomer 941 and sustained-release agent to hydrogen peroxide solution and stir to dissolve to obtain solution A;

[0044] 2. Add sodium chloride and stir for 2 hours to obtain solution B;

[0045] 3. Cool the mixture with ice-salt water and crystallize by stirring at 5 rpm for 3 hours;

[0046] 4. Centrifuge the wet material C and dry it at 105℃ to obtain powder.

[0047] The hydrogen peroxide content of the solid hydrogen peroxide powder obtained by content determination of three batches of samples was 9.6% to 9.7% (three batches), which is high and stable with little difference between batches.

[0048] Example 3: Slow-release hydrogen peroxide powder

[0049] Components and proportions: 50% hydrogen peroxide solution: 10 L; Carbomer 941: 0.025 kg; Sodium sulfate: 11.5 kg; Sodium chloride: 1.5 kg; Sustained-release agent (ethyl cellulose: chitosan = 1.2:1): 1.2 kg.

[0050] Preparation method:

[0051] 1. Add sodium sulfate, carbomer 941, and ethyl cellulose and chitosan complex to hydrogen peroxide solution and stir to dissolve to obtain solution A;

[0052] 2. Add sodium chloride and stir for 2 hours to obtain solution B;

[0053] 3. Cool the mixture with ice-salt water and crystallize by stirring at 5 rpm for 3 hours;

[0054] 4. Centrifuge the wet material C and dry it at 105℃ to obtain powder.

[0055] The hydrogen peroxide content of the solid hydrogen peroxide powder obtained by content determination of three batches of samples was 9.6% to 9.7% (three batches), which is high and stable with little difference between batches.

[0056] Comparative Example 1

[0057] The difference between the hydrogen peroxide powder in this comparative example and that in Example 2 is that the hydrogen peroxide powder does not contain the sustained-release agent composed of ethyl cellulose and chitosan.

[0058] Components and proportions: 50% hydrogen peroxide solution: 10 L; Carbomer 941: 0.025 kg; Sodium sulfate: 11.5 kg; Sodium chloride: 1.5 kg.

[0059] Preparation method:

[0060] 1. Add sodium sulfate and carbomer 941 to hydrogen peroxide solution and stir to dissolve to obtain solution A;

[0061] 2. Add sodium chloride and stir for 2 hours to obtain solution B;

[0062] 3. Cool the mixture with ice-salt water and crystallize by stirring at 5 rpm for 3 hours;

[0063] 4. Centrifuge the wet material C and dry it at 105℃ to obtain powder.

[0064] The hydrogen peroxide content of the obtained solid hydrogen peroxide powder was 9.6% to 9.7% (three batches) by content determination of three batches of samples. The content is high and stable with little difference between batches.

[0065] Example 4: Slow-release hydrogen peroxide particles

[0066] Components and proportions: wet material C in Example 2: 98%; povidone K30: 2%.

[0067] Preparation method:

[0068] 1. Add povidone K30 to wet material C and granulate to obtain wet granules D;

[0069] 2. Dry with hot air at 105°C and sieve to obtain granules (particle size 1-3 mm).

[0070] Effect verification:

[0071] The hydrogen peroxide content of the obtained solid hydrogen peroxide powder was 9.6% to 9.7% (three batches) by content determination of three batches of samples. The content is high and stable with little difference between batches.

[0072] Example 5: Slow-release hydrogen peroxide particles

[0073] Components and proportions: wet material C in Example 2: 98.5%; hypromellose: 1.5%.

[0074] Preparation method:

[0075] 1. Mix wet material C and hypromellose to prepare granules;

[0076] 2. Dry with hot air at 105°C and sieve to obtain granules (particle size 1-3 mm).

[0077] The hydrogen peroxide content of the obtained solid hydrogen peroxide powder was 9.6% to 9.7% (three batches) by content determination of three batches of samples. The content is high and stable with little difference between batches.

[0078] Example 6 Sustained-release hydrogen peroxide tablets

[0079] Components and proportions: Example 2 wet material C: 80%; Hydroxypropyl methylcellulose: 3%; Diluent (potassium bicarbonate): 12%; Lubricant (polyethylene glycol 6000): 5%.

[0080] Preparation method:

[0081] 1. Mix wet material C and hypromellose to prepare granules;

[0082] 2. Dry with hot air at 105℃ and sieve to obtain granules (particle size 1-3mm)

[0083] 3. Mix the dried powder, potassium bicarbonate and polyethylene glycol and compress the mixture into tablets;

[0084] The hydrogen peroxide content of the solid hydrogen peroxide powder obtained by content determination of three batches of samples was 9.6% to 9.7% (three batches), which is high and stable with little difference between batches.

[0085] Example 7 Sustained-release hydrogen peroxide tablets

[0086] Components and proportions: Example 2 wet material C: 95%; Hydroxypropyl methylcellulose: 1.5%; Diluent (potassium bicarbonate): 1.5%; Lubricant (polyethylene glycol 6000): 2%.

[0087] Preparation method:

[0088] 1. Mix wet material C and hypromellose to prepare granules;

[0089] 2. Dry with hot air at 105°C and sieve to obtain granules (particle size 1-3 mm);

[0090] 3. Mix the dried powder, potassium bicarbonate and polyethylene glycol and compress the mixture into tablets;

[0091] The hydrogen peroxide content of the solid hydrogen peroxide powder obtained by content determination of three batches of samples was 9.6% to 9.7% (three batches), which is high and stable with little difference between batches.

[0092] Comparative Example 2

[0093] This comparative example is different from Example 7 in that the wet material does not contain the sustained-release agent composed of ethyl cellulose and chitosan.

[0094] Components and proportions: Comparative Example 1 Wet material C: 95%; Hydroxypropyl methylcellulose: 1.5%; Diluent (potassium bicarbonate): 1.5%; Lubricant (polyethylene glycol 6000): 2%.

[0095] Preparation method:

[0096] 1. Mix wet material C and hypromellose to prepare granules;

[0097] 2. Dry with hot air at 105°C and sieve to obtain granules (particle size 1-3 mm);

[0098] 3. Mix the dried powder, potassium bicarbonate and polyethylene glycol and compress the mixture into tablets;

[0099] The hydrogen peroxide content of the solid hydrogen peroxide powder obtained by content determination of three batches of samples was 9.6% to 9.7% (three batches), which is high and stable with little difference between batches.

[0100] Test Example 1

[0101] Determination of pH of Slow-Release Solid Hydrogen Peroxide

[0102] (1) Test materials

[0103] Test drugs: solid hydrogen peroxide powder of Examples 1, 2, and 3, solid hydrogen peroxide granules of Examples 4 and 5, and solid hydrogen peroxide tablets of Examples 6 and 7;

[0104] Control drug: sodium percarbonate (commercially available product)

[0105] Test instrument: FE28 laboratory precision acidity meter

[0106] (2) Test methods

[0107] The test samples were dissolved in freshly boiled and cooled deionized water to form 1%, 2%, and 5% solutions, respectively, and the pH values were measured using an FE28 pH meter.

[0108] Sodium percarbonate was prepared into a 3% solution using the same method and the pH value was determined using the same method.

[0109] (3) Test results

[0110] pH measurements of solutions of different concentrations of the example samples and a control sodium percarbonate solution revealed that the solid hydrogen peroxide powder / granules / tablets of the example had a pH close to neutral, while 3% sodium percarbonate was alkaline (10.5). This indicates that this product has no effect on the pH of water during clinical aquatic use and will not affect it.

[0111]

[0112]

[0113] Test Example 2

[0114] Determination of oxygenation performance of solid hydrogen peroxide

[0115] (1) Test materials

[0116] Test drugs: solid hydrogen peroxide granules of Example 4 and solid hydrogen peroxide tablets of Example 5;

[0117] Control drug: sodium percarbonate (commercially available product)

[0118] Test instrument: dissolved oxygen meter.

[0119] (2) Test methods

[0120] Eleven clean, 1000 mL glass beakers, numbered A, B, C, D, E, F, G, H, I, J, and K, were each filled with 500 mL of purified water. 0.5 g of each of the solid hydrogen peroxide and sodium percarbonate from Examples 1, 2, 3, 4, 5, 6, and 7, and Comparative Examples 1 and 2, were placed in the corresponding beakers. Beaker K served as a blank control. The dissolved oxygen content (mg / L) in the water was measured using a dissolved oxygen meter 1 hour, 4 hours, 8 hours, 24 hours, 48 hours, and 60 hours after the samples were placed.

[0121] (3) Test results

[0122] By continuously measuring the effect of different samples on the dissolved oxygen concentration in water after being added, it can be seen from the results that, compared with Example 1, Example 2, and Example 3 and Comparative Example 1, the oxygen release capacity of the powder is sustained. Moreover, the addition of ethyl cellulose and chitosan within a certain range will not affect the sustained release of oxygen. From Example 4, this Example 5, Example 6 and Example 7, it can be seen that the dissolved oxygen content in the water can be greatly increased and can be maintained for a long time. By comparison, sodium percarbonate has a very significant advantage (P < 0.01). Compared with the comparative example, Example 6 and Example 7 can be seen that ethyl cellulose and chitosan significantly improve the sustained release effect of hydrogen peroxide tablets.

[0123]

[0124]

[0125] From the above experimental results, it can be seen that the solid hydrogen peroxide of the present invention can significantly increase the dissolved oxygen content in water and maintain it for a long time. In clinical application, it can reduce the workload and reduce the harm to aquatic organisms caused by insufficient dissolved oxygen in water.

[0126] As described above, although the present invention has been shown and described with reference to specific preferred embodiments, it should not be construed as limiting the present invention itself. Various changes may be made to it in form and detail without departing from the spirit and scope of the present invention as defined in the appended claims.

Claims

1. A sustained-release hydrogen peroxide powder, characterized in that: including hydrogen peroxide solution, stabilizer, excipient and sustained-release agent; The hydrogen peroxide solution is a hydrogen peroxide solution with a mass fraction of 28% or 50%; The stabilizer is carbomer; The excipient is a mixture of sodium sulfate and sodium chloride; The sustained-release agent is a complex of ethyl cellulose and chitosan.

2. The sustained-release hydrogen peroxide powder according to claim 1, characterized in that: The amount of carbomer used in each liter of hydrogen peroxide solution is 2.5 g.

3. The sustained-release hydrogen peroxide powder according to claim 1, characterized in that: In the excipient, the weight ratio of the sodium sulfate to the sodium chloride is (7-10):1; the weight ratio of the excipient to the hydrogen peroxide solution is (1.3-1.5):

1.

4. The sustained-release hydrogen peroxide powder according to claim 1, characterized in that: In the sustained-release agent, the weight ratio of the ethyl cellulose to the chitosan is (1-2):1; and the added amount of the sustained-release agent is 0.5%-10% of the total mass of the sustained-release solid hydrogen peroxide.

5. A method for preparing the sustained-release hydrogen peroxide powder according to any one of claims 1 to 4, characterized in that The steps include: Step 1: adding sodium sulfate, a stabilizer, and a sustained-release agent in a good ratio to a hydrogen peroxide solution and stirring to dissolve the mixture to obtain a solution A; Step 2: Add sodium chloride in a suitable proportion to solution A, stir and dissolve, and obtain solution B; Step 3: Cool solution B with ice-salt water, slowly stir, and crystallize; Go to step 4 Step 4: centrifuging or filtering the crystals obtained in step 3 to obtain wet material C; Step 5: Dry the wet material C to obtain sustained-release hydrogen peroxide powder.

6. A sustained-release solid preparation of hydrogen peroxide, characterized in that: The invention comprises the sustained-release hydrogen peroxide powder according to any one of claims 1 to 4, further comprising a diluent, a binder and a lubricant; the weight percentage of the sustained-release solid hydrogen peroxide in the solid hydrogen peroxide preparation is in the range of 0.5% to 10%; the weight percentage of the diluent in the solid hydrogen peroxide preparation is in the range of 0 to 85%; the weight percentage of the binder in the solid hydrogen peroxide preparation is in the range of 0 to 10%; the weight percentage of the lubricant in the solid hydrogen peroxide preparation is in the range of 0 to 10%; and the total weight percentage of the sustained-release solid hydrogen peroxide, the diluent, the binder and the lubricant is 100%.

7. The sustained-release solid preparation of hydrogen peroxide according to claim 6, characterized in that: The diluent is one or more of calcium chloride, sodium sulfate or potassium bicarbonate; the binder is one or more of hydroxypropyl methylcellulose, povidone or polyethylene glycol; and the lubricant is micropowder silica gel or polyethylene glycol 6000.

8. A method for preparing a sustained-release solid preparation of hydrogen peroxide according to any one of claims 6 to 7, characterized in that The steps include: Step A, adding a binder to the undried wet material C in the preparation process of the slow-release hydrogen peroxide powder, granulating and then drying to obtain slow-release granules; Step B: mixing the sustained-release granules obtained in step A with the diluent and lubricant, and then tableting to obtain sustained-release tablets.

9. Use of the sustained-release hydrogen peroxide powder according to any one of claims 1 to 4 or the sustained-release hydrogen peroxide solid preparation according to any one of claims 6 to 7 in the preparation of a long-acting aquaculture water disinfectant, sediment improver or continuous oxygenator.

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