Pharmaceutical chlorine dioxide antimicrobial liquid agent, preparation method therefor, and use thereof

Abstract

Disclosed in the present invention are a pharmaceutical chlorine dioxide antimicrobial liquid agent, a preparation method therefor, and use thereof. The pharmaceutical chlorine dioxide antimicrobial liquid agent comprises: a solvent and chlorine dioxide gas infused into the solvent, wherein the concentration of chlorine dioxide in the pharmaceutical chlorine dioxide antimicrobial liquid agent is 5000 mg / L-10000 mg / L. According to the pharmaceutical chlorine dioxide antimicrobial liquid agent, the preparation method therefor, and the use thereof provided by the present invention, the obtained pharmaceutical chlorine dioxide antimicrobial liquid agent has high concentration, good stability, and high purity, meeting the requirements for the use of the pharmaceutical chlorine dioxide antimicrobial liquid agent as a pharmaceutical product.

Description

A medicinal chlorine dioxide antimicrobial liquid agent and its preparation method and application TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine, in particular to a medicinal chlorine dioxide antimicrobial liquid agent and its preparation method and application. BACKGROUND

[0002] As the only A1 level disinfectant recognized by the World Health Organization and the Food and Agriculture Organization of the United Nations, chlorine dioxide is well known. Oxidized chlorine dioxide disinfectant is cheap, convenient and safe to use, and is currently the most commonly used high-efficiency disinfectant. However, the stability of oxidized chlorine dioxide disinfectant is poor or the impurity content is extremely high, which seriously affects the application of this type of disinfectant.

[0003] Chlorine dioxide disinfectant is generally directly filled with chlorine dioxide gas in water, although pure chlorine dioxide disinfectant products with higher purity can be obtained, but they are extremely unstable and can only be used on site in large equipment. The "stable chlorine dioxide solution" or "stable chlorine dioxide solid" prepared from chlorite or stable chlorite is actually a release precursor of chlorine dioxide or a release precursor of stable chlorine dioxide, which needs to release a small amount of chlorine dioxide gas in water after acid activation. But the purity of the application liquid after release is less than 10%, and the chlorine dioxide content is extremely low.

[0004] The present inventors have successfully developed a stable pure chlorine dioxide disinfectant (patent numbers: ZL202111439097.2 and ZL202111428769.X), with a chlorine dioxide percentage content of 99.93% and a chlorine dioxide mass fraction of more than 85%. However, there are still 15% impurities in the chlorine dioxide disinfectant, although the impurities are non-toxic and harmless carbon dioxide, but the application liquid has high acidity (pH = 2.5), and carbon dioxide has a certain mild corrosion effect on carbon steel. In special applications, it still cannot meet the higher demand of chlorine dioxide application, and is not conducive to the research and development of broad-spectrum anti-pathogenic microbial infection and as an exogenous oxidant (Reactive Oxygen Species, ROS) anticancer drug. SUMMARY

[0005] The purpose of the present application is to provide a medicinal chlorine dioxide antimicrobial liquid agent and its preparation method and application. The medicinal chlorine dioxide antimicrobial liquid agent and its preparation method and application provided by the present application have high concentration, good stability and high purity, and the stable use period can be more than one year, and long-term use does not produce drug resistance, which can meet the use demand of medicinal chlorine dioxide antimicrobial liquid agent as a medicine.

[0006] To solve the above technical problems, the present application provides a medicinal chlorine dioxide antimicrobial liquid agent, which at least comprises:

[0007] a solvent and chlorine dioxide gas, the chlorine dioxide gas being perfused into the solvent;

[0008] The concentration of the chlorine dioxide in the pharmaceutical chlorine dioxide antiseptic solution is 5000 mg / L to 10000 mg / L.

[0009] In an embodiment of the present application, the solvent is deionized water, and the purity of the chlorine dioxide gas is greater than or equal to 99.5%.

[0010] In an embodiment of the present application, the concentration of the chlorine dioxide in the pharmaceutical chlorine dioxide antiseptic solution decreases by less than 10% in a 54℃ oven for two weeks, and the pharmaceutical chlorine dioxide antiseptic solution is stored for one year in a normal temperature light-proof environment of 4℃ to 20℃.

[0011] In an embodiment of the present application, the concentration of the pharmaceutical chlorine dioxide antiseptic solution is 25 ppm, the action time is 5 min, and the killing logarithm of the Bacillus subtilis var. niger spores is greater than 5.0.

[0012] In an embodiment of the present application, the concentration of the pharmaceutical chlorine dioxide antiseptic solution is 200 ppm, the 90% human anticoagulant whole blood is used as the chlorine dioxide organic interference agent, the action time is 1 h to 5 h, and the killing rate of the Staphylococcus aureus is greater than 90%.

[0013] The present application further provides a preparation method of the pharmaceutical chlorine dioxide antiseptic solution.

[0014] The chlorine dioxide gas is perfused into the solvent, and the concentration of the chlorine dioxide in the pharmaceutical chlorine dioxide antiseptic solution is 5000 mg / L to 10000 mg / L, and the mass fraction of the chlorine dioxide is greater than 99%.

[0015] In an embodiment of the present application, the preparation method further comprises: perfusing the chlorine dioxide gas into the solvent at a first flow rate, and rotating the reaction kettle at a first rotating speed until the concentration of the chlorine dioxide reaches a first preset concentration; the first rotating speed is 10 rpm to 20 rpm, the first preset concentration is 2500 mg / L to 2900 mg / L, and the first flow rate is 40 mg / (min·L) to 100 mg / (min·L).

[0016] In an embodiment of the present application, the preparation method further comprises: after reaching the first preset concentration, the chlorine dioxide gas is perfused into the solvent at a second flow rate, the reaction kettle is slowly accelerated from the first rotation speed to a second rotation speed according to the change of the reaction liquid in the reaction kettle, and the rotation is continued until the perfusion is stopped when the concentration of the chlorine dioxide reaches a second preset concentration; wherein the second rotation speed is 60 rpm to 100 rpm, the second preset concentration is 5000 mg / L to 10000 mg / L, and the second flow rate is less than or equal to the first flow rate.

[0017] In an embodiment of the present application, under the second rotation speed, the chlorine dioxide gas and the solvent continue to form hydrated chlorine dioxide, and the hydrated chlorine dioxide comprises OClO(H2O) 6～10 and ClOO(H2O) 6～10 , the OClO(H2O) 6～10 forms ClOO(H2O) 6～10 in the isomerization under the slow increase of energy.

[0018] In an embodiment of the present application, the ClOO(H2O) 6～10 has good stability, is a stabilizer of the medicinal chlorine dioxide antimicrobial liquid agent, and can be gradually dissociated into water and chlorine dioxide with the addition of the solvent for dilution, when the chlorine dioxide concentration is less than 2900 mg / L after the addition of the solvent for dilution, the ClOO(H2O) 6～10 is completely dissociated into water and chlorine dioxide, and the medicinal chlorine dioxide antimicrobial liquid agent is converted from the storage state to the application state according to the requirement for dilution.

[0019] In an embodiment of the present application, the preparation method further comprises: after reaching the second preset concentration, the reaction kettle is stopped after continuing to rotate at the second rotation speed for a first preset time, and is placed for a second preset time.

[0020] In an embodiment of the present application, the first preset time is 8 min to 10 min, and the second preset time is 25 min to 35 min.

[0021] The present application also provides a medicinal chlorine dioxide antimicrobial liquid agent or a medicinal chlorine dioxide antimicrobial liquid agent obtained by the preparation method of the above-mentioned medicinal chlorine dioxide antimicrobial liquid agent for the use in medicines.

[0022] In an embodiment of the present application, the pharmaceutical chlorine dioxide antimicrobial liquid is diluted according to the requirements of use, and is used for inhalation, oral administration, and intravenous injection or drip treatment or adjuvant treatment of infections caused by pathogenic microorganisms, including but not limited to rhinitis, pharyngolaryngitis, pneumonia, pneumoconiosis, tuberculosis, halitosis, gastric diseases caused by Helicobacter pylori (including drug-resistant strains) and related gastric cancer, AIDS, viral hepatitis, Ebola, leukemia and cancer caused by viruses, and can also be used as an exogenous oxidant anticancer treatment drug.

[0023] In summary, the present application provides a pharmaceutical chlorine dioxide antimicrobial liquid and a preparation method and application thereof, which can obtain a pharmaceutical chlorine dioxide antimicrobial liquid containing only water and chlorine dioxide, and the concentration of the pharmaceutical chlorine dioxide antimicrobial liquid is high, which can reach 5000 mg / L to 10000 mg / L, and the mass fraction of chlorine dioxide is greater than 99%. The pharmaceutical chlorine dioxide antimicrobial liquid has good stability, high purity, and a stable use period of more than one year, and does not produce drug resistance after long-term use, and can meet the use requirements of the pharmaceutical chlorine dioxide antimicrobial liquid as a drug. In the synthesis process, no pollutants and organic chlorine compounds are generated, and no pollution to the environment is caused. Moreover, no complex manufacturing equipment is required, the preparation process is simple, the energy consumption is low, and the product is suitable for industrialization. The pharmaceutical chlorine dioxide antimicrobial liquid obtained by the present application has strong disinfection and sterilization ability, and can be applied to sterilization of the human body to treat or adjuvant treat diseases caused by pathogenic microorganism infections, and can also be used as an exogenous oxidant anticancer treatment.

[0024] Of course, it is not necessary for any product implementing the present application to achieve all the advantages mentioned above. BRIEF DESCRIPTION OF DRAWINGS

[0025] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for the description of the embodiments will be briefly introduced as follows. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0026] Fig. 1 is a schematic diagram of a pharmaceutical chlorine dioxide antimicrobial liquid and a synthesis device in an embodiment of the present application.

[0027] Fig. 2 is a schematic diagram of a pharmaceutical chlorine dioxide antimicrobial liquid and a synthesis device in another embodiment of the present application.

[0028] Fig. 3 is a schematic diagram of a preparation method of a pharmaceutical chlorine dioxide antimicrobial liquid in an embodiment of the present application.

[0029] Label explanation: 10, reaction kettle; 11, water source pipeline; 12, sampling pipeline; 13, liquid outlet pipeline; 14, third pressure reducing valve; 15, metering pump; 20, water jet; 30, chlorine dioxide gas source; 31, first pressure reducing valve; 32, raw material inlet; 33, chlorine dioxide gas outlet; 34, waste liquid outlet; 35, connecting piece; 40, waste liquid recovery device; 41, second pressure reducing valve; 50, neutralizing agent storage tank; 51, inductor; 52, normally closed electromagnetic valve. DETAILED DESCRIPTION

[0030] The advantages and effects of the present application can be easily understood by those skilled in the art from the above description. The present application can also be implemented or applied by other different specific embodiments, and the details in the description can be modified or changed based on different views and applications without departing from the spirit of the present application.

[0031] It should be noted that the following embodiments and features in the embodiments can be combined with each other without conflict. It should also be understood that the terms used in the embodiments of the present application are for the purpose of describing specific specific embodiments, and are not intended to limit the protection scope of the present application. The test methods in the following embodiments are not specified, and are usually carried out according to the conventional conditions or the conditions recommended by the manufacturers.

[0032] When the embodiments give numerical ranges, it should be understood that, unless otherwise stated by the present application, each numerical range of two endpoints and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used in the present application and the mastery of the prior art by those skilled in the art and the description of the present application can also use any method, equipment and material of the prior art similar or equivalent to the method, equipment, material described in the embodiments of the present application to realize the present application.

[0033] The present application provides a pharmaceutical chlorine dioxide antimicrobial solution, raw materials including a solvent and chlorine dioxide gas, the chlorine dioxide gas is dissolved in the solvent. Among them, the solvent includes deionized water, for example, the purity of chlorine dioxide gas is greater than or equal to 99.5%, the concentration of chlorine dioxide in the pharmaceutical chlorine dioxide antimicrobial solution is 5000mg / L-10000mg / L, or higher, because the purity of chlorine dioxide gas is greater than or equal to 99.5%, non-chlorine dioxide impurities are completely or almost completely zero, so the mass fraction of chlorine dioxide is greater than 99%. In other embodiments, the solvent is, for example, ultrapure water and other water meeting medical water standards. In this embodiment, only water and chlorine dioxide exist in the pharmaceutical chlorine dioxide antimicrobial solution, and the obtained pharmaceutical chlorine dioxide antimicrobial solution is a yellow liquid medicine, a single-component pure chlorine dioxide solution with a slight chlorine dioxide irritating odor, and the concentration of chlorine dioxide is high, the purity is high, and the pharmaceutical chlorine dioxide antimicrobial solution can meet the use requirements of different ways such as sterilization that can be applied to human body, treatment or auxiliary treatment of diseases caused by pathogenic microorganism infection, and exogenous oxidant anticancer treatment.

[0034] In an embodiment of the present application, the pharmaceutical chlorine dioxide antimicrobial solution is stored in a 54°C oven for two weeks, and the concentration of chlorine dioxide decreases by less than 10%, for example, at room temperature and in the dark for one year.

[0035] In an embodiment of the present application, to detect the sterilization ability of the pharmaceutical chlorine dioxide antimicrobial solution, the pharmaceutical chlorine dioxide antimicrobial solution is diluted with deionized water to a concentration of 25ppm, for example, and the killing logarithm of Bacillus subtilis var. niger spores is greater than 5.0 for a reaction time of 5min. In another embodiment of the present application, 90% human anticoagulant whole blood is used as a chlorine dioxide organic interference agent, the chlorine dioxide concentration is 200ppm, for example, and the killing rate of Staphylococcus aureus is greater than 90% for a reaction time of 1h-5h. The disinfection and sterilization ability of the pharmaceutical chlorine dioxide antimicrobial solution in the present application is strong, and it can act on intravenous injection or infusion, further indicating that the pharmaceutical chlorine dioxide antimicrobial solution can be used for injection, applied to human treatment or auxiliary treatment of diseases caused by pathogenic microorganism infection, and can be used as an exogenous oxidant anticancer treatment.

[0036] Referring to Fig. 1, in an embodiment of the present application, a synthesis device of the pharmaceutical chlorine dioxide antimicrobial liquid is also provided for synthesizing the pharmaceutical chlorine dioxide antimicrobial liquid. The synthesis device comprises a reaction kettle 10, a water jet 20, and a chlorine dioxide gas source 30, wherein the water jet 20 is arranged between the reaction kettle 10 and the chlorine dioxide gas source 30, and the components are connected by pipelines. In the embodiment, the chlorine dioxide gas source 30 is, for example, a chlorine dioxide gas generating device, and the synthesis device further comprises a waste liquid recovery device 40 and a neutralizing agent storage tank 50, wherein the waste liquid recovery device 40 is connected to the chlorine dioxide gas source 30, the neutralizing agent storage tank 50 is used for storing a neutralizing agent, and one end of the neutralizing agent storage tank 50 is connected to the chlorine dioxide gas source 30.

[0037] Referring to Fig. 1, in an embodiment of the present application, when the chlorine dioxide gas source 30 is a chlorine dioxide gas generating device, a first pressure reducing valve 31 and at least one raw material inlet 32 are arranged on the chlorine dioxide gas generating device. The first pressure reducing valve 31 is, for example, a one-way pressure reducing valve, and is arranged at the top of the chlorine dioxide gas generating device to prevent the pressure in the chlorine dioxide gas generating device from being too high. The raw material inlet 32 is, for example, arranged on the same side as the first pressure reducing valve 31, and is, for example, arranged at the bottom of the chlorine dioxide gas generating device to add reaction raw materials to the chlorine dioxide gas generating device. A valve is arranged on the raw material inlet 32 to adjust the addition of raw materials according to the reaction process. On the other side of the chlorine dioxide gas generating device, a plurality of outlets are arranged, such as a chlorine dioxide gas outlet 33 and a waste liquid outlet 34. The chlorine dioxide gas outlet 33 is, for example, arranged at the top of the chlorine dioxide gas generating device to facilitate the outflow of chlorine dioxide gas, and is connected to the water jet 20. The waste liquid outlet 34 is arranged in the middle of the chlorine dioxide gas generating device and is connected to the waste liquid recovery device 40. In the waste liquid recovery device 40, the waste liquid is treated again and chlorine dioxide gas is released. The released chlorine dioxide gas is connected to the water jet 20 through a pipeline to improve the utilization efficiency of the generated chlorine dioxide gas. A second pressure reducing valve 41 is arranged at the top of the waste liquid recovery device 40. The second pressure reducing valve 41 is, for example, a one-way pressure reducing valve to prevent the pressure in the waste liquid recovery device 40 from being too high and to improve the safety of the device.

[0038] Please refer to Fig. 1, in an embodiment of the present application, one end of the neutralizing agent storage tank 50 is connected with the chlorine dioxide gas generator, the neutralizing agent storage tank 50 is used for storing the neutralizing agent, and a normally closed electromagnetic valve 52 is arranged between the neutralizing agent storage tank 50 and the chlorine dioxide gas generator, a sensor 51 is arranged between the normally closed electromagnetic valve 52 and the neutralizing agent storage tank 50, and the sensor 51 is, for example, an emergency sensor. The sensor 51 and the normally closed electromagnetic valve 52 are arranged to improve the safety of the chlorine dioxide gas generator. In the present application, a connecting piece 35 and a valve are further arranged on the pipeline, the connecting piece 35 is used for connecting different pipelines, and the valve is used for controlling the connection or closing between different components, and the specific arrangement is according to the needs, and in the present application, the valves and the connecting piece 35 are not described one by one.

[0039] Please refer to Fig. 1, in an embodiment of the present application, the chlorine dioxide gas enters the reactor 10 for reaction through the water jet 20, a metering pump 15 is arranged on the pipeline between the water jet 20 and the reactor 10 to deliver the circulating reaction liquid of the reactor as raw material and adjust the flow. The dotted line in the reactor 10 is the water level scale. A third pressure reducing valve 14 is arranged at the top of the reactor 10, and the third pressure reducing valve 14 is, for example, a one-way pressure reducing valve to prevent the pressure in the reactor from being too large. A water source pipeline 11, a sampling pipeline 12 and a liquid outlet pipeline 13 are arranged at the bottom of the reactor 10, and valves are arranged on the water source pipeline 11, the sampling pipeline 12 and the liquid outlet pipeline 13. Among them, the water source pipeline 11 is arranged at the bottom of the side of the reactor 10 to deliver water source into the reactor 10, and the liquid outlet pipeline 13 is arranged at the bottom of the reactor 10 to take out the synthesized medicinal chlorine dioxide antimicrobial liquid agent, and the sampling pipeline 12 is a branch arranged on the liquid outlet pipeline 13, which is used for sampling and testing whether the medicinal chlorine dioxide antimicrobial liquid agent meets the synthesis standard during the synthesis process. In the present application, the specific type of the reactor is not limited, as long as the reactor 10 can operate at different speeds and react with chlorine dioxide gas. In the embodiment, any raw material for forming chlorine dioxide gas is added to the chlorine dioxide gas generator to react to obtain pure chlorine dioxide gas. In other embodiments, any applicable chlorine dioxide gas generator can be used for reaction, but the purity of the generated chlorine dioxide should be greater than or equal to 99.5%.

[0040] Referring to Fig. 1, in one embodiment of the present application, in standby state, each valve of the synthesizing device is in closed state. When starting, first open the valve on water source pipeline 11, then add water to the reaction kettle 10 until the scale, open the chlorine dioxide gas outlet and metering pump 15 of the waste liquid recovery device 40, open the multiple raw material inlets 32, and finally open the waste liquid outlet of the waste liquid recovery device 40. When shutting down, open the waste liquid outlet of the waste liquid recovery device 40, close the multiple raw material inlets 32, open the valve of the neutralizing agent storage tank 50, close the metering pump 15 when there is no chlorine dioxide discharge from the chlorine dioxide gas generating device, close the waste liquid recovery device 40, and finally replace the waste liquid recovery device 40.

[0041] Referring to Fig. 2, in another embodiment of the present application, the chlorine dioxide gas source 30 is, for example, a chlorine dioxide gas flow-through space device, with flowing chlorine dioxide gas for the synthesis of pharmaceutical chlorine dioxide antimicrobial liquid agent. The water jet 20 and the reaction kettle 10 are arranged the same as in the previous embodiment, and will not be described in detail here.

[0042] Referring to Fig. 3, the present application provides a method for preparing a pharmaceutical chlorine dioxide antimicrobial liquid agent, comprising steps S11-S13.

[0043] Step S11, chlorine dioxide gas is perfused into the solvent at a first flow rate, and the reaction kettle is rotated at a first rotational speed until the concentration of chlorine dioxide reaches a first preset concentration.

[0044] Step S12, chlorine dioxide gas is perfused into the solvent at a second flow rate, and the reaction kettle is accelerated from the first rotational speed to a second rotational speed and continues to rotate until the perfusion is stopped when the concentration of chlorine dioxide reaches a second preset concentration.

[0045] Step S13, the reaction kettle continues to rotate at the second rotational speed for a first preset time and then stops, and stands for a second preset time.

[0046] Referring to Fig. 3, in one embodiment of the present application, when synthesizing a pharmaceutical chlorine dioxide antimicrobial liquid agent, the production (or experimental) environment must be selected in a quiet section away from vehicle-congested traffic arteries, and the indoor temperature is less than or equal to 22°C. The production (or experimental) environment uses brown glass or brown transparent plastic paper filter for door and window glass, and uses brown light source to avoid the decomposition of chlorine dioxide.

[0047] Referring to FIG. 3, in an embodiment of the present application, in step S11, the first flow rate of chlorine dioxide gas injected into the solvent is, for example, 40 mg / (min·L) to 100 mg / (min·L), the solvent is, for example, deionized water, the first rotation speed of the reactor is, for example, 10 rpm to 20 rpm, and the first preset concentration is, for example, 2500 mg / L to 2900 mg / L. At a low rotation speed, a pure chlorine dioxide solution is obtained, wherein the first preset concentration is, for example, the upper limit of the concentration when chlorine dioxide is hydrolyzed.

[0048] Referring to FIG. 3, in an embodiment of the present application, in step S12, the second flow rate is, for example, equal to the first flow rate, and in other embodiments, the second flow rate is, for example, less than the first flow rate, so as to sufficiently hydrolyze and facilitate the free escape of chlorine dioxide molecules from water and the generation of hydrated chlorine dioxide in water. When chlorine dioxide gas continues to be injected, the reactor is slowly accelerated from the first rotation speed to the second rotation speed according to the changes in the reaction solution in the reactor, for example, by adjusting the color of the reaction solution. As the rotation speed increases, the solution continues to maintain the same yellow color, and if the color deepens or lightens, the speed should be stopped or slightly reduced. The second rotation speed is, for example, 60 rpm to 100 rpm, or greater. After the rotation speed of the reactor reaches the second rotation speed, the rotation continues until the concentration of chlorine dioxide reaches the second preset concentration, at which point the injection of chlorine dioxide gas is stopped, wherein the second preset concentration is, for example, 5000 mg / L to 10000 mg / L. In step S12, the changes in the color of the reaction solution and the surrounding environmental conditions are closely monitored, and the rotation speed is adjusted in real time. By increasing the rotation speed of the reactor, the molecular energy of chlorine dioxide gas is increased, thereby increasing the concentration of chlorine dioxide. That is, in the present application, low-speed injection is used when the concentration is less than the first preset concentration, and high-speed injection is used when the concentration is greater than the first preset concentration, thereby obtaining a high-concentration and stable pharmaceutical chlorine dioxide antimicrobial solution.

[0049] In another embodiment of the present application, when the production environment has high temperature and humidity or other unfavorable conditions, a trace amount of stabilizer can be added as appropriate, wherein the stabilizer is the technology in the inventor's previously granted Chinese patent 202111428769X, and the prepared 0.8% oxidizing agent stabilizing solution is added at 40% to 50% of the set concentration of chlorine dioxide. For example, when the set concentration of chlorine dioxide is 5000 mg / L, 2 ml to 3 ml of 0.8% oxidizing stabilizing solution is added per 1 L of water, or other trace amounts of non-toxic and harmless stabilizers can be used.

[0050] Referring to FIG. 3 , in one embodiment of the present invention, in step S13, when the chlorine dioxide concentration reaches a second predetermined concentration, the reactor continues to rotate at a second speed for a first predetermined time, then stops and rests for a second predetermined time. The first predetermined time may be, for example, 8 to 10 minutes, and the second predetermined time may be, for example, 25 to 35 minutes. Continued stirring and resting for the predetermined time after the chlorine dioxide gas injection stops allows the chlorine dioxide antimicrobial agent components to fully react and stabilizes the concentration of the medicinal chlorine dioxide antimicrobial solution.

[0051] Referring to Figures 1 and 3 , in one embodiment of the present invention, when synthesizing a medicinal chlorine dioxide antimicrobial liquid, two sets of synthesis apparatuses for the medicinal chlorine dioxide antimicrobial liquid can be linked together for continuous production. For example, the first set of apparatus operates to a second preset concentration, stops injecting chlorine dioxide gas, continues stirring for a first preset time, then stops, and allows the mixture to rest for a second preset time. The second set of apparatus then switches to a second set of apparatuses, which accelerates from the first speed to a second speed, operates to a second preset concentration, stops injecting chlorine dioxide gas, continues stirring for a first preset time, then stops, and allows the mixture to rest for a second preset time. While the second set of apparatuses is operating, the first set of apparatuses continues to operate, thereby improving production efficiency.

[0052] Referring to FIG. 3 , in one embodiment of the present invention, during the synthesis of a medicinal chlorine dioxide antimicrobial liquid, there are two stages: a low-concentration (≤2900 mg / L) pure chlorine dioxide solution and a high-concentration (≥2900 mg / L) stable chlorine dioxide solution. In the second stage, i.e., step S12, as the amount of chlorine dioxide gas injected increases, the concentration of the pure chlorine dioxide solution continues to increase. The escaping chlorine dioxide molecules and water generate a colorless and transparent new substance, hydrated chlorine dioxide, during the peroxidation process. Hydrated chlorine dioxide is neither water nor chlorine dioxide, but a new substance generated by chlorine dioxide and water. Hydrated chlorine dioxide includes OClO (H2O). 6～10 and ClOO(H2O) 6～10 Two types. Among them, OClO(H2O) 6～10 It has poor stability and is easily affected by factors such as power, light, and temperature, causing it to dissociate into non-hydrates. OClO(H2O) 6～10 As the energy slowly increases, the isomers dissociate to form ClOO(H2O) 6～10 , namely OClO(H2O) 6～10 At the moment of dissociation, OClO can be isomerized to ClOO and generate the more stable ClOO(H2O) with water. 6～10 , ClOO(H2O) 6～10 It has strong stability and is a stabilizer for medicinal chlorine dioxide antimicrobial liquid. It is also a precursor for the release of chlorine dioxide. The activation method is to dilute it with water, ClOO (H2O) 6～10When diluted with water, the solution dissociates into water and chlorine dioxide, and when the solution is diluted to a chlorine dioxide concentration of ≤2900 mg / L, CIOO(H2O) 6～ 10 All of the solution is dissociated into water and chlorine dioxide, and the solution becomes a pure chlorine dioxide solution with zero or almost zero non-chlorine dioxide impurities, and the pharmaceutical chlorine dioxide antimicrobial solution is converted from a stored stable state to an application state that can be diluted as needed. The pure chlorine dioxide solution can be further diluted to the concentration required for actual application, and can be used for clinical broad-spectrum anti-infection treatment or other uses, or can be used as a non-toxic oxide for cancer interventional therapy.

[0053] China applied chlorine dioxide disinfection technology in the 1980s of last century, in 1987, the health supervision department of Guangdong Province approved that it can be used for food disinfection, preservation and food equipment disinfection. In 1990, the health management department of Shanghai approved that it can be used for water treatment, food processing, aquaculture, deodorization, etc. The Ministry of Health of China also clearly proposed in 2000 that chlorine dioxide will gradually replace chlorine for disinfection of drinking water. Since 2003, chlorine dioxide has been listed as an important chlorine-containing disinfectant for preventing SARS. Among them, the chlorine dioxide antimicrobial solution is divided into medical grade and injection grade according to the requirements, the percentage of pure chlorine dioxide solution reaches more than 99.5%, and the mass fraction of chlorine dioxide is greater than 99%. Chlorine dioxide is listed as an AI grade disinfectant by the World Health Organization (WHO), and the WHO allows chlorine dioxide to be eaten directly. Based on the large amount of test data of chlorine dioxide used in animals and humans recognized by the WHO and the National Disease Control Center, the pharmaceutical chlorine dioxide antimicrobial solution provided in the application only includes water and chlorine dioxide, and the purity, concentration and stability of chlorine dioxide are high, and no drug resistance is generated after long-term use, which provides the possibility for use as a drug.

[0054] In an embodiment of the application, the pharmaceutical chlorine dioxide antimicrobial solution is a stable state including a mixture of a chlorine dioxide hydrate solution and a pure chlorine dioxide solution, and the pure chlorine dioxide solution after dilution and expansion with water is an application state of the pharmaceutical chlorine dioxide antimicrobial solution. The obtained pharmaceutical chlorine dioxide antimicrobial solution has the advantages of a broad-spectrum anti-pathogenic microbial infection, good effect and stable storage of the pharmaceutical chlorine dioxide antimicrobial solution.

[0055] In one embodiment of the present application, the pharmaceutical chlorine dioxide anti-microbial solution is allowed to be used after being tested, and can be used as a broad-spectrum anti-infection treatment drug, and can be inhaled, taken orally, and injected intravenously or dropped. When the pharmaceutical chlorine dioxide anti-microbial solution is inhaled, 25 mg / ampoule can be used, dissolved in 100 ml of water, placed in a nebulizer, inhaled for 15 minutes each time, inhaled every two hours, and the continuous use time of the prepared solution should not exceed 24 hours. The use dose should be based on the experimental data obtained from the subject animal or human body test, and within the allowable range of human body drug reaction. It can be used to treat or assist in the treatment of rhinitis, laryngopharyngitis, pneumonia, pneumoconiosis, and tuberculosis (including drug-resistant strains), and as a respiratory tract health care for residents in cities with serious air pollution.

[0056] In one embodiment of the present application, when the pharmaceutical chlorine dioxide anti-microbial solution is taken orally, 25 mg / ampoule can be used, and 2 ampoules are dissolved in 100 ml of water, taken 2 hours before a meal, and taken 1-2 times a day. The use dose should be based on the experimental data obtained from the subject animal or human body test, and within the allowable range of human body drug reaction. It can be used to treat or assist in the treatment of halitosis, gastric diseases caused by Helicobacter pylori (including drug-resistant strains), and related gastric cancer.

[0057] In one embodiment of the present application, when the pharmaceutical chlorine dioxide anti-microbial solution is used for intravenous injection, the intravenous pump is set at 3 ml / h (5 mg / ml), and 50 mg-100 mg is injected. The use dose should be based on the experimental data obtained from the subject animal or human body test, and within the allowable range of human body drug reaction. It can be used to treat or assist in the treatment of AIDS, viral hepatitis, Ebola, leukemia and cancer caused by viruses, etc. The pharmaceutical chlorine dioxide anti-microbial solution used as a broad-spectrum anti-pathogenic microbial infection treatment drug can comprehensively cover and replace the deficiencies and hazards caused by antibiotic treatment, and has no toxicity and exogenous oxidant, and can also be used for tumor treatment. For example, the anti-infection therapy is used to treat infectious tumors such as viral leukemia, liver cancer, cervical cancer, and gastric cancer caused by Helicobacter pylori (including drug-resistant strains). When the non-toxic chlorine dioxide intervention therapy is used to treat cancer, the pharmaceutical chlorine dioxide anti-microbial solution is directly injected into the cancer.

[0058] Hereinafter, the present application will be explained more specifically by referring to the examples, which should not be understood as limiting. Appropriate modifications can be made within the scope consistent with the gist of the present application, which all fall within the technical scope of the present application.

[0059] Example 1

[0060] Chlorine dioxide gas was injected into 10 L of water in the reaction kettle at a speed of 60 mg / (min·L) at room temperature 19.3℃, and the rotation speed of the reaction kettle was 20 rpm. When the chlorine dioxide concentration of the aqueous solution reached 2500 mg / L, the rotation speed was slowly increased from 20 rpm to 80 rpm. The color of the reaction solution and the surrounding environmental conditions were closely observed, and the rotation speed was adjusted in time. The process was continued until the preset concentration of 5000 mg / L was reached. The chlorine dioxide gas was stopped, and the rotation speed was continued for another 10 min. After 30 min of static state, the operation was ended.

[0061] Example 2

[0062] Chlorine dioxide gas was injected into 10 L of water in the reaction kettle at a speed of 60 mg / (min·L) at room temperature 19.3℃, and the rotation speed of the reaction kettle was 20 rpm. The process was continued until the chlorine dioxide concentration reached the preset 5000 mg / L. The rotation speed of the reaction kettle was continued until the chlorine dioxide gas was stopped, and then continued for another 10 min. After 30 min of static state, the operation was ended.

[0063] Example 3

[0064] Chlorine dioxide gas was injected into 10 L of water in the reaction kettle at a speed of 60 mg / (min·L) at room temperature 35.7℃, and the rotation speed of the reaction kettle was 20 rpm. When the chlorine dioxide concentration of the aqueous solution reached 2500 mg / L, the rotation speed was slowly increased from 20 rpm to 80 rpm. The color of the reaction solution and the surrounding environmental conditions were closely observed, and the rotation speed was adjusted in time. The process was continued until the preset concentration of 5000 mg / L was reached. The chlorine dioxide gas was stopped, and the rotation speed was continued for another 10 min. After 30 min of static state, the operation was ended.

[0065] Example 4

[0066] Chlorine dioxide gas was injected into 10 L of water in the reaction kettle at a speed of 60 mg / (min·L) at room temperature 35.7℃, and the rotation speed of the reaction kettle was 20 rpm. The process was continued until the chlorine dioxide concentration reached the preset 5000 mg / L. The rotation speed of the reaction kettle was continued until the chlorine dioxide gas was stopped, and then continued for another 10 min. After 30 min of static state, the operation was ended.

[0067] Performance test

[0068] The pharmaceutical chlorine dioxide antimicrobial liquid prepared in Examples 1-4 was subjected to stability performance test, and the test results are shown in Table 1. The detection method is as follows: the pharmaceutical chlorine dioxide antimicrobial liquid experimental sample is placed in an oven at 54℃ for two weeks, and the chlorine dioxide and the reduction rate in the sample are detected before and after 14 days of sample placement.

[0069] In an embodiment of the present application, the chlorine dioxide antiseptic solution obtained in Example 1 is diluted to 200 ppm with 90% human anticoagulant whole blood as an organic chlorine dioxide interference agent, and the killing rate of Staphylococcus aureus is tested for 1 hour and 5 hours, respectively. The test results are shown in Table 2, and the killing rate is greater than 90%.

[0070] Table 1, Stability test of pharmaceutical chlorine dioxide antiseptic solution

[0071] Table 2, 90% human anticoagulant whole blood organic interference sterilization test

[0072] Referring to Table 1, by controlling the lower room temperature during synthesis, the stability of the obtained pharmaceutical chlorine dioxide antiseptic solution can be improved in Comparative Examples 1-4. In addition, by stirring at different speeds at different concentrations during synthesis, stable chlorine dioxide hydrate can be generated. The pharmaceutical chlorine dioxide antiseptic solution acts as a stabilizer to improve the stability of the pharmaceutical chlorine dioxide antiseptic solution, so that the pharmaceutical chlorine dioxide antiseptic solution can be stably stored, and the pharmaceutical chlorine dioxide antiseptic solution can be used as a medicine. Referring to Table 2, by using 90% human anticoagulant whole blood as an organic interference agent, although there is a certain interference effect on chlorine dioxide, it does not affect the sterilization function of chlorine dioxide in the human body, which effectively proves that the pharmaceutical chlorine dioxide antiseptic solution can be used for systemic treatment of the human body through the intravenous route.

[0073] In summary, the present application provides a pharmaceutical chlorine dioxide antiseptic solution, a preparation method and application thereof. By controlling the synthesis process, a pharmaceutical chlorine dioxide antiseptic solution containing only water and chlorine dioxide can be obtained. The concentration of the pharmaceutical chlorine dioxide antiseptic solution is high, which can reach 5000 mg / L-10000 mg / L. The stability is good, the purity is high, which can reach more than 99%, the stable use period can be more than one year, and long-term use will not produce drug resistance. The pharmaceutical chlorine dioxide antiseptic solution can meet the demand of being used as a medicine. In the synthesis process, no pollutants and organic chlorine compounds are generated, which will not pollute the environment. In addition, no complex manufacturing equipment is required, the preparation process is simple, the energy consumption is low, and it is suitable for industrialization. The disinfection and sterilization ability of the pharmaceutical chlorine dioxide antiseptic solution obtained by the present application is strong, which can be applied to the sterilization of the human body to treat or assist in the treatment of infections caused by pathogenic microorganisms, and can also be used as an exogenous oxidant anticancer drug.

[0074] The above disclosed embodiments of the present application are only used to help explain the present application. The embodiments do not describe all of the details of the present application, and the present application is not limited to the specific embodiments described. Obviously, many modifications and changes can be made according to the content of the present specification. The present specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present application, so that those skilled in the art can well understand and utilize the present application. The present application is limited only by the claims and their full scope and equivalents.

Claims

1. A medicinal chlorine dioxide antimicrobial liquid, characterized in that: include: A solvent and chlorine dioxide gas, wherein the chlorine dioxide gas is injected into the solvent; Wherein, the concentration of chlorine dioxide in the medicinal chlorine dioxide antimicrobial liquid is 5000 mg / L to 10000 mg / L.

2. The medicinal chlorine dioxide antimicrobial liquid according to claim 1, characterized in that The solvent is deionized water, and the purity of the chlorine dioxide gas is greater than or equal to 99.5%.

3. The medicinal chlorine dioxide antimicrobial liquid according to claim 1, characterized in that After being stored in a 54° C. oven for two weeks, the concentration of chlorine dioxide in the medicinal chlorine dioxide antimicrobial liquid decreases by less than 10%, and can be stored in a light-proof environment at room temperature of 4° C. to 20° C. for one year.

4. The medicinal chlorine dioxide antimicrobial liquid according to claim 1, characterized in that The medicinal chlorine dioxide antimicrobial liquid has an action concentration of 25 ppm, an action time of 5 minutes, and a killing logarithm of Bacillus subtilis var. niger spores greater than 5.

0.

5. The medicinal chlorine dioxide antimicrobial liquid according to claim 1, characterized in that The medicinal chlorine dioxide antimicrobial liquid has an action concentration of 200 ppm, uses 90% human anticoagulated whole blood as a chlorine dioxide organic interfering agent, has an action time of 1 to 5 hours, and has a killing rate of more than 90% on Staphylococcus aureus.

6. A method for preparing a medicinal chlorine dioxide antimicrobial liquid, characterized in that: include: Chlorine dioxide gas is injected into a solvent; wherein the concentration of chlorine dioxide in the medicinal chlorine dioxide antimicrobial liquid is 5000mg / L to 10000mg / L, and the mass fraction of chlorine dioxide is greater than 99%.

7. The method for preparing the medicinal chlorine dioxide antimicrobial liquid according to claim 6, wherein: The preparation method further includes: injecting the chlorine dioxide gas into the solvent at a first flow rate, and rotating the reactor at a first speed until the concentration of the chlorine dioxide reaches a first preset concentration; wherein the first speed is 10 rpm to 20 rpm, the first preset concentration is 2500 mg / L to 2900 mg / L, and the first flow rate is 40 mg / (min·L) to 100 mg / (min·L).

8. The method for preparing the medicinal chlorine dioxide antimicrobial liquid according to claim 7, wherein: The preparation method further includes: after reaching the first preset concentration, the chlorine dioxide gas is perfused into the solvent at a second flow rate, the reactor is slowly accelerated from the first speed to a second speed depending on the change of the reaction liquid in the reactor, and the rotation is continued until the concentration of the chlorine dioxide reaches the second preset concentration, and the perfusion is stopped; wherein the second speed is 60 rpm to 100 rpm, the second preset concentration is 5000 mg / L to 10000 mg / L, and the second flow rate is less than or equal to the first flow rate.

9. The method for preparing the medicinal chlorine dioxide antimicrobial liquid according to claim 8, wherein: At the second speed, the continuously perfused chlorine dioxide gas and solvent form hydrated chlorine dioxide, and the hydrated chlorine dioxide includes OClO (H2O) 6～10 and ClOO(H2O) 6～10 , the OClO(H2O) 6～ 10 As the energy slowly increases, ClOO(H2O) is formed in the isomerization 6～10 .

10. The method for preparing the medicinal chlorine dioxide antimicrobial liquid according to claim 9, characterized in that: The ClOO(H2O) 6～10 It has good stability and is a stabilizer for the medicinal chlorine dioxide antimicrobial liquid. It can gradually dissociate into water and chlorine dioxide as the solvent is diluted. When the solvent is diluted to a chlorine dioxide concentration of less than 2900 mg / L, the ClOO (H2O) 6～10 After being completely dissociated into water and chlorine dioxide, the medicinal chlorine dioxide antimicrobial liquid is converted from a stable state for storage to an application state for dilution as required.

11. The method for preparing the medicinal chlorine dioxide antimicrobial liquid according to claim 8, wherein: The preparation method further includes: after reaching the second preset concentration, the reactor continues to rotate at the second speed for a first preset time, then stops and stands for a second preset time.

12. The method for preparing the medicinal chlorine dioxide antimicrobial liquid according to claim 11, characterized in that: The first preset time is 8 minutes to 10 minutes, and the second preset time is 25 minutes to 35 minutes.

13. Use of the medicinal chlorine dioxide antimicrobial liquid as claimed in any one of claims 1 to 5 or the medicinal chlorine dioxide antimicrobial liquid as claimed in any one of claims 6 to 12 in medicine.

14. The use according to claim 13, characterized in that The medicinal chlorine dioxide antimicrobial liquid is diluted according to the requirements of use and is used for inhalation, oral administration, intravenous injection or drip treatment or auxiliary treatment including but not limited to infections caused by pathogenic microorganisms, including rhinitis, pharyngitis, pneumonia, pneumoconiosis, tuberculosis, bad breath, Helicobacter pylori (including drug-resistant strains) gastric disease and related gastric cancer, AIDS, viral hepatitis, Ebola, virus-induced leukemia and cancer, and can also be used as an exogenous oxide anticancer drug for use.

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