Application of ectoine in medicine for preventing and treating organic solvent poisoning

Abstract

The invention relates to an application of ectoine in a medicine for preventing and treating poisoning caused by an organic solvent. The organic solvent is one or a mixed solvent of more of ethanol, n-propanol, isopropanol, n-butanol and dimethyl sulfoxide. The ectoine disclosed by the invention has many applications in the aspects of resisting oxidation, resisting inflammation, promoting cell growth and protecting biomacromolecules, and has the effects of improving the tolerance of an organism to an organic solvent, reducing the cell inhibition rate and reducing the damage of poisoning of the organic solvent to cells.

Description

Technical Field

[0001] The invention relates to the technical field of pharmacy, and in particular to the application of ectoine in medicine for preventing and treating organic solvent poisoning. Background Art

[0002] Organic solvents are widely used in production and life due to their unique physical and chemical properties. These volatile and fat-soluble compounds can easily enter the human body through the skin, mucous membranes, respiratory tract and other pathways, and have serious toxicity to cells due to their chemical structure, physical properties, metabolic pathways and products. Ethanol, n-propanol, dimethyl sulfoxide, isopropanol and n-butanol are organic solvents that are widely used and indispensable in the food industry, chemical industry, biomedicine and other fields. Their fat solubility, low boiling point and volatility make a large amount of vapor generated during use, which enters the human body through the respiratory tract and skin, thereby causing toxicity to human cells.

[0003] Studies have shown that organic solvents can damage human cells by dissolving cell membranes, destroying cell membrane permeability, and causing membrane protein denaturation, leading to cell death. In addition, they produce free radicals and toxic metabolites during intracellular metabolism, damaging biological macromolecules in cells and interfering with the normal functioning of organelles. Therefore, taking measures to protect against the toxicity of organic solvents can effectively improve people's physical health, improve the quality of life, and increase production and living efficiency.

[0004] The metabolism of organic solvents depends on the normal functioning of various detoxification enzymes in cells, among which catalase is widely distributed in the human body and is most abundant in detoxification organs such as the liver and kidneys. They are indispensable key enzymes in the process of cellular detoxification and are mediating enzymes for cells to oxidize organic solvents, increase their water solubility and excrete them from the body. However, the organic solvents themselves and their metabolites will have a serious inhibitory effect on the enzymes, limiting the metabolic rate of organic solvents, causing organic solvents to stay in cells for a longer time, causing cell damage or even death. Increasing the activity of detoxification enzymes and accelerating the metabolic rate of organic solvents can effectively enhance the detoxification capacity of organs such as the liver and kidneys and reduce the toxicity of organic solvents.

[0005] In order to reduce the toxic effects of organic solvents on the human body, a variety of protective measures have been proposed and applied. For example, the use of personal protective equipment such as gas masks, protective gloves and protective clothing, as well as improving the ventilation conditions of the working environment, can reduce the exposure concentration of organic solvents. However, these measures cannot completely eliminate the potential hazards of organic solvents to the human body, especially in the case of long-term or high-concentration exposure. Therefore, it is particularly important to develop new methods for the prevention and treatment of organic solvent poisoning. As a compound with potential medicinal value, the application research of tetrahydropyrimidine in the prevention and treatment of organic solvent poisoning provides a new idea for solving this problem. Summary of the invention

[0006] The problem to be solved by the present invention is to provide an application of ectoine in the prevention and treatment of organic solvent poisoning in view of the above-mentioned deficiencies in the prior art. The ectoine has many applications in anti-oxidation, anti-inflammation, promoting cell growth, and protecting biomacromolecules, and has the effects of improving the body's tolerance to organic solvents, reducing cell inhibition rate, and reducing damage to cells caused by organic solvent poisoning.

[0007] The above-mentioned object of the present invention is achieved through the following technical solutions: The invention discloses an application of tetrahydropyrimidine in a medicine for preventing and treating organic solvent poisoning.

[0008] Specifically, in the “application” of the present invention, according to the International Classification of Diseases (ICD-11) accepted by the World Health Organization, “organic solvent poisoning” considered in the present invention refers to categories such as PB31, PD01, PE91, PH51, NE6, etc.; (1) Tetrahydropyrimidine, alias: (S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid, C6H 10 N2O2, CAS No. 96702-03-3, molecular weight 142.16; (2) Poisoning is a pathological state caused by an abnormality in the chemical homeostasis resulting from the interaction of different biochemical structures of an organism with toxic substances of exogenous or endogenous origin; the term "poisoning" denotes the complete poisoning process, which develops from its very primitive symptoms until the full-blown clinical pattern of the disease, the content of which depends on the physiological function of the toxicity of the main receptors, i.e. certain biochemical structures that selectively interact with organic solvents; exogenous poisoning, which is usually called poisoning, is associated with the accumulation of toxic substances in an organism according to its own metabolism (autointoxication), in contrast to endogenous poisoning; From the perspective of pathogenesis principles, the poisoning discussed in this invention: Classified as accidental and / or intentional, depending on the cause of development; According to origin, as a principle, it is classified as industrial, and more rarely as domestic; The route of entry of organic solvents into the organism is classified as inhalation through the respiratory tract, rarely as transdermal delivery, and even more rarely as oral administration; Poisoning is classified as exogenous based on the origin of the organic solvent; (3) Typical organic solvents (poisoning caused by them will be discussed in the present invention), for example, but not limited to: 1. Monohydric alcohols (alkanols): methyl alcohol (methanol, protoalcohol, wood alcohol) CH3OH, ethyl alcohol (ethanol, alcohol) C2H5OH, propyl alcohol (n-propanol, isopropanol) C3H7OH, butyl alcohol (n-butanol) C4H9OH, amyl alcohol (n-pentanol) C5H 12 OH, etc.; these monohydric alcohol compounds are widely used as solvents, cleaning agents and fuels in industry; however, their misuse or excessive exposure can lead to poisoning, manifested as central nervous system depression, visual impairment, and even organ damage; tetrahydropyrimidines, as drugs, can reduce cell damage after poisoning by these monohydric alcohol compounds through their antioxidant and anti-inflammatory properties, thus playing an important role in prevention and treatment; 2. Diols (diols, alkanediols): ethylene glycol (ethanediol) HOCH2CH2OH, propylene glycol (propanediol) CH3CHOHCH2OH, butanediol (butanediol) CH3CH(OH)CH2CH2OH, etc.; these diol compounds are used as solvents, coolants and wetting agents in industry; their misuse or overexposure may also lead to poisoning, and its symptoms include metabolic disorders, kidney damage and central nervous system depression; tetrahydropyrimidine as a drug, its antioxidant and anti-inflammatory effects are also applicable to reduce cell damage after diol compound poisoning, providing a new way for prevention and treatment; 3. Polyols: Tetrahydrofurfuryl alcohol (tetrahydrofuran alcohol, tetrahydrofuranyl alcohol) CHCHCHC (OH) CH2O, furfural (furan aldehyde), glycerol, sorbitol, mannitol, etc.; these polyol compounds are widely present in the food, cosmetics and pharmaceutical industries; they have good moisturizing properties and stability, and therefore play an important role in these fields; however, misuse or excessive intake of polyol compounds may also cause poisoning, and its symptoms include hypoglycemia, metabolic acidosis and nervous system dysfunction; tetrahydropyrimidine also shows its potential therapeutic value in this field. Through its unique biological activity, it can effectively alleviate the cell damage caused by polyol compound poisoning, providing new ideas and methods for the prevention and treatment of related poisoning; 4. Sulfoxides: dimethyl sulfoxide (DMSO), dimethylformamide (DMF), dimethylacetamide (DMAC), etc. These sulfoxide compounds are used as solvents, extractants and reaction media in industry; their misuse or excessive exposure may cause skin irritation, eye damage and central nervous system depression; as a drug, tetrahydropyrimidine has anti-inflammatory and cell-protective effects that are also applicable to reducing cell damage after sulfoxide poisoning, providing a new approach for prevention and treatment; Furthermore, the organic solvent is one or a mixed solvent of ethanol, n-propanol, isopropanol, n-butanol and dimethyl sulfoxide.

[0009] Still further, the drug is administered by enteral and / or portal vein infusion or transumbilical infusion.

[0010] Still further, the drug is used as a specific antidote when treating poisoning caused by the organic solvent.

[0011] Furthermore, the drug is administered enterally and / or intra-portally or via umbilical infusion.

[0012] Furthermore, the enteral administration is achieved by using an oral dosage form.

[0013] Alternatively, the enteral administration is achieved via a probe.

[0014] Furthermore, the dosage is 0.5-1.5 mg / mL.

[0015] Furthermore, the application can obtain at least one effect related to the kinetic correction of organic solvent poisoning, and the effect is selected from: reducing the inhibitory effect of organic solvent metabolites on the cellular enzyme system; restoring the detoxification function of the cellular enzyme system to organic solvents.

[0016] And / or, the use can obtain at least one effect related to the correction of toxicokinetics of organic solvent poisoning, the effect being selected from the group consisting of accelerating the excretion of organic solvents and / or their toxic metabolites from organisms; and improving the excretion of organic solvents.

[0017] And / or, the application can obtain at least one effect related to the risk of organic solvent poisoning, the effect being selected from: enhancing the detoxification function of the liver and kidney during the damage process before the onset of organic solvent poisoning; reducing the inhibitory effect of organic solvent metabolites on the liver and kidney detoxification enzyme system.

[0018] In summary, the beneficial technical effects of the present invention are as follows: the tetrahydropyrimidine of the present invention has many applications in anti-oxidation, anti-inflammation, promoting cell growth, and protecting biological macromolecules, and has the effects of improving the body's tolerance to organic solvents, reducing cell inhibition rate, and reducing damage to cells caused by organic solvent poisoning. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a test chart of cell inhibition rate of the experimental group and the negative group in Example 1 of the present invention.

[0020] Figure 2 It is a test chart of cell inhibition rate of the experimental group and the positive group in Example 1 of the present invention.

[0021] Figure 3 It is a test chart of cell inhibition rate of the experimental group and the negative group in Example 2 of the present invention.

[0022] Figure 4This is a test chart of cell inhibition rate of the experimental group and the positive group in Example 2 of the present invention.

[0023] Figure 5 This is a test chart of cell inhibition rate of the experimental group and the negative group in Example 3 of the present invention.

[0024] Figure 6 It is a test chart of cell inhibition rate of the experimental group and the positive group in Example 3 of the present invention.

[0025] Figure 7 It is a test chart of cell inhibition rate of the experimental group and the negative group in Example 4 of the present invention.

[0026] Figure 8 This is a test chart of cell inhibition rate of the experimental group and the negative group in Example 5 of the present invention.

[0027] Fig. 9 This is a graph showing the catalase activity test of the experimental group and the negative group in Example 6 of the present invention. Fig.10 This is a graph showing the catalase activity test of the experimental group and the negative group in Example 7 of the present invention. DETAILED DESCRIPTION

[0028] In order to make the technical means, creative features, objectives and functions achieved by the present invention clearer and easier to understand, the present invention is further explained below in conjunction with the accompanying drawings and specific implementation methods.

[0029] Example 1: Application of an ectoine disclosed in the present invention in a drug for preventing and treating organic solvent poisoning.

[0030] 1. Materials 1.1 Drugs and reagents Ethanol, Sinopharm Chemical Reagent Co., Ltd.; n-Propanol, Sinopharm Chemical Reagent Co., Ltd.; n-Butanol, Sinopharm Chemical Reagent Co., Ltd.; Dimethyl sulfoxide, Sinopharm Chemical Reagent Co., Ltd.; Isopropyl alcohol, Sinopharm Chemical Reagent Co., Ltd.; High-glucose DMEM medium, Sigma-Aldrich; FBS, Cellmax Corporation; Bispecific antibodies, Cellmax Company; Ectoin, Shanghai Abyss Biomedical Engineering Co., Ltd. Ascorbic acid, aladdin MTT reagent, Bio-Tech Company Culture medium: (1) Serum-free DMEM medium: Add 5 mL of dual antibody to 500 mL of high-glucose DMEM medium and set aside.

[0031] (2) Complete DMEM medium: Add 5 mL of dual antibody and 50 mL of FBS to 500 mL of high-glucose DMEM medium and set aside.

[0032] 1.2 Instruments 1300 Series Class II Type A2 Biological Safety Cabinet (Thermo Fisher Suzhou Instrument Co., Ltd.); Nikon MODEL ECLIPSE Ta2-FL inverted microscope; Multifunctional microplate reader SpectraMax-iD3; Cell culture incubator STERI-Cycle (Thermo Fisher Suzhou Instrument Co., Ltd.); This example provides a general and / or specific description of the materials and test methods used in the test. In the following examples, unless otherwise specified, % represents vol%, i.e., volume percentage. The reagents or instruments used without indicating the manufacturer are all conventional reagent products that can be purchased commercially.

[0033] 1.3 Experimental cells Experimental cells: Mouse mononuclear macrophage leukemia cells RAW264.7; Cell culture: Mouse mononuclear macrophage leukemia cells (RAW264.7) stored at -80°C were thawed in a 37°C water bath, 7 mL of complete DMEM medium was added, centrifuged at 1000 rpm for 5 min, the supernatant was discarded, and 7 mL of complete DMEM medium was added to resuspend the cells and then all were transferred to a 25 cm 2 The cells were cultured in a permeable cell culture flask at 37°C and 5% carbon dioxide for 72 hours, and all the culture medium was removed every 24 hours and then 7 mL of new complete DMEM culture medium was added. After the culture was completed, the cells were observed to be spherical under an inverted microscope and occupied more than 80% of the area in the field of view. The culture medium was removed and 6 mL of 4°C PBS was added. The attached cells were gently blown off and centrifuged again to discard the supernatant. The cells were resuspended in 6 mL of complete DMEM culture medium to obtain a cell suspension. The cell number was determined using a cell counting plate under an inverted microscope, and the cell suspension was diluted to 1.5 × 10 5 Pieces / mL.

[0034] 2. Experiment and content 2.1. Toxicity protection evaluation of organic solvents Preparation of 96-well plate for organic solvent toxicity protection activity test: Add the diluted cell suspension to columns 2 to 9 and rows B to G of the 96-well plate, 100 μL per well, and the 10th column is a blank column, adding only 100 μL complete DMEM culture medium without cells. In subsequent operations, columns 9 and 10 are used as negative columns and blank columns, and the culture medium and MTT reagent that are exactly the same as those in the remaining columns are added, but no organic solvents and drugs are added. 200 μL PBS is added to all other remaining wells in the plate and cultured in a cell culture incubator at 37°C and 5% carbon dioxide for 24 hours.

[0035] Before administration, all liquid in the plate was aspirated, and PBS was added to wash once before administration. All drug solutions were dissolved and diluted with complete DMEM culture medium. After administration, culture was continued for 24 hours, the drug solution was aspirated, and the plate was washed 3 times with PBS. 100 μL of 0.5 mg / mL MTT reagent diluted with serum-free DMEM culture medium was added to each well in the dark, and culture was continued for 4.5 hours in the dark. The MTT reagent was aspirated, 150 μL of DMSO was added to each well, and the plate was shaken at 2000 rpm for 10 min in the dark, then placed in an enzyme reader to measure the absorbance at a wavelength of 570 nm.

[0036] 2.2 Evaluation methods and result determination 2.2.1 Cell inhibition rate The OD value of each well was measured at 570 nm using an enzyme marker. The cell inhibition rate of each well was expressed as: ; The cell inhibition rate of each well in the plate was calculated according to the above formula. Six replicate wells were set for each dosing well, control well and blank control well. During statistical analysis, one well with the highest absorbance and one well with the lowest absorbance were removed, and four replicate wells were retained.

[0037] 2.2.2 Statistical analysis The concentration wells of the experimental group were compared with the same concentration wells of the positive group and the negative group, respectively, and the t-test was used for statistical analysis. ns means p>0.05 is considered to have no statistical difference, * means p<0.05 is considered to have a statistical difference, ** means p<0.01 is considered to have a significant statistical difference, and *** means p<0.001 is considered to have a very significant statistical difference.

[0038] Finally, the dosage of organic solvents and drugs in the experimental group, positive group and negative group are shown in Table 1, and the results of cell inhibition rate test are shown in Figure 1 and Figure 2 shown.

[0039] Table 1 Experimental Group Positive group Negative group 16% ethanol + 1mg / mL ectoine 16% ethanol + 0.1mg / mL ascorbic acid 16% ethanol 8% ethanol + 1mg / mL ectoine 8% ethanol + 0.1 mg / mL ascorbic acid 8% ethanol 4% ethanol + 1mg / mL ectoine 4% ethanol + 0.1 mg / mL ascorbic acid 4% ethanol 2% ethanol + 1mg / mL ectoine 2% ethanol + 0.1 mg / mL ascorbic acid 2% ethanol 1% ethanol + 1mg / mL ectoine 1% ethanol + 0.1 mg / mL ascorbic acid 1% ethanol 0.5% ethanol + 1mg / mL ectoine 0.5% ethanol + 0.1 mg / mL ascorbic acid 0.5% ethanol 0.25% ethanol + 1mg / mL ectoine 0.25% ethanol + 0.1 mg / mL ascorbic acid 0.25% ethanol from Figure 1 and Figure 2It can be seen that ectoine effectively protected the toxicity of ethanol to RAW264.7 cells at 1% and 2% volume concentration of ethanol, and the protective effect was significantly better than that of the positive control drug ascorbic acid.

[0040] Example 2: The use of a drug disclosed in the present invention, ectoine, in the prevention and treatment of organic solvent poisoning, is different from Example 1 in that the dosage of organic solvents and drugs in the experimental group, positive group and negative group are shown in Table 2, and the cell inhibition rate test results are shown in Table 2. Figure 3 and Figure 4 shown.

[0041] Table 2 Experimental Group Positive group Negative group 8% n-propanol + 1mg / mL tetrahydropyrimidine 8% n-propanol + 0.1mg / mL ascorbic acid 8% n-propanol 4% n-propanol + 1mg / mL ectoine 4% n-propanol + 0.1mg / mL ascorbic acid 4% n-propanol 2% n-propanol + 1mg / mL tetrahydropyrimidine 2% n-propanol + 0.1mg / mL ascorbic acid 2% n-propanol 1% n-propanol + 1mg / mL ectoine 1% n-propanol + 0.1mg / mL ascorbic acid 1% n-propanol 0.5% n-propanol + 1mg / mL ectoine 0.5% n-propanol + 0.1mg / mL ascorbic acid 0.5% n-propanol 0.25% n-propanol + 1mg / mL tetrahydropyrimidine 0.25% n-propanol + 0.1mg / mL ascorbic acid 0.25% n-propanol 0.125% n-propanol + 1mg / mL tetrahydropyrimidine 0.125% n-propanol + 0.1mg / mL ascorbic acid 0.125% n-propanol from Figure 3 and Figure 4 It can be seen that tetrahydropyrimidine can significantly reduce the cell inhibition rate in n-propanol with a volume concentration of 8% and below, effectively protecting the toxicity of n-propanol, and when the volume concentration of n-propanol is lower than 2%, the cell inhibition rate is significantly lower than that of the positive control drug ascorbic acid.

[0042] Example 3: The use of a drug disclosed in the present invention, ectoine, in the prevention and treatment of organic solvent poisoning, is different from Example 1 in that the dosage of organic solvents and drugs in the experimental group, positive group and negative group are shown in Table 3, and the cell inhibition rate test results are shown in Table 3. Figure 5 and Figure 6 shown.

[0043] Table 3 Experimental Group Positive group Negative group 8% n-butanol + 1mg / mL tetrahydropyrimidine 8% n-butanol + 0.1 mg / mL ascorbic acid 8% n-Butanol 4% n-butanol + 1mg / mL ectoine 4% n-butanol + 0.1mg / mL ascorbic acid 4% n-Butanol 2% n-butanol + 1mg / mL ectoine 2% n-butanol + 0.1 mg / mL ascorbic acid 2% n-Butanol 1% n-butanol + 1mg / mL ectoine 1% n-butanol + 0.1 mg / mL ascorbic acid 1% n-Butanol 0.5% n-butanol + 1mg / mL tetrahydropyrimidine 0.5% n-butanol + 0.1mg / mL ascorbic acid 0.5% n-butanol 0.25% n-butanol + 1mg / mL tetrahydropyrimidine 0.25% n-butanol + 0.1mg / mL ascorbic acid 0.25% n-butanol 0.125% n-butanol + 1mg / mL tetrahydropyrimidine 0.125% n-butanol + 0.1mg / mL ascorbic acid 0.125% n-Butanol from Figure 5 and Figure 6 It can be seen that tetrahydropyrimidine can significantly reduce the cell inhibition rate in n-butanol with a volume concentration of 4% and below, effectively protecting the toxicity of n-butanol, and when the volume concentration of n-butanol is lower than 2%, the cell inhibition rate is significantly lower than that of the positive control drug ascorbic acid.

[0044] Example 4: The use of a drug disclosed in the present invention, ectoine, in the prevention and treatment of organic solvent poisoning. The difference from Example 1 is that the dosage of organic solvent and drug in the experimental group and the negative group is shown in Table 4, and the cell inhibition rate test results are shown in Table 4. Figure 7 shown.

[0045] Table 4 Experimental Group Negative group 16% dimethyl sulfoxide + 1mg / mL ectoine 16% dimethyl sulfoxide 8% dimethyl sulfoxide + 1mg / mL ectoine 8% dimethyl sulfoxide 4% dimethyl sulfoxide + 1mg / mL ectoine 4% dimethyl sulfoxide 2% dimethyl sulfoxide + 1mg / mL ectoine 2% dimethyl sulfoxide 1% dimethyl sulfoxide + 1mg / mL ectoine 1% dimethyl sulfoxide 0.5% dimethyl sulfoxide + 1mg / mL ectoine 0.5% dimethyl sulfoxide 0.25% dimethyl sulfoxide + 1mg / mL ectoine 0.25% dimethyl sulfoxide from Figure 7 It can be seen that ectoine can significantly reduce the cell inhibition rate in dimethyl sulfoxide at a volume concentration of 2% or less, effectively protecting against the toxicity of dimethyl sulfoxide, while there is no report on ascorbic acid protecting against the toxicity of dimethyl sulfoxide.

[0046] Example 5: The use of a drug disclosed in the present invention, ectoine, in the prevention and treatment of organic solvent poisoning. The difference from Example 1 is that the dosage of organic solvent and drug in the experimental group and the negative group is shown in Table 5, and the cell inhibition rate test results are shown in Table 5. Figure 8 shown.

[0047] Table 5 Experimental Group Negative group 8% isopropanol + 1mg / mL ectoine 8% Isopropyl Alcohol 4% isopropanol + 1mg / mL ectoine 4% Isopropyl Alcohol 2% isopropanol + 1mg / mL ectoine 2% Isopropyl Alcohol 1% isopropanol + 1mg / mL ectoine 1% Isopropyl Alcohol 0.5% isopropanol + 1mg / mL ectoine 0.5% isopropyl alcohol 0.25% isopropanol + 1mg / mL ectoine 0.25% isopropyl alcohol 0.125% isopropanol + 1mg / mL ectoine 0.125% Isopropyl Alcohol from Figure 8 It can be seen that tetrahydropyrimidine can significantly reduce the cell inhibition rate in isopropanol with a volume concentration of 4% or less, effectively protecting the toxicity of isopropanol.

[0048] Example 6: The mechanism of a drug disclosed in the present invention for preventing and treating organic solvent poisoning using tetrahydropyrimidine 1 Materials 1.1 Materials and reagents Catalase from bovine liver, Damas-Beta Catalase activity kit (ammonium molybdate colorimetric method), Baishengyue Company Acetic acid, Anaiji Chemical 1.2 Instruments HH-S4 Digital Constant Temperature Water Bath UV-5200 UV Spectrophotometer This example provides a general and / or specific description of the materials and test methods used in the test. In the following examples, unless otherwise specified, % represents vol%, i.e., volume percentage. The reagents or instruments used without indicating the manufacturer are all conventional reagent products that can be purchased commercially.

[0049] 2 Experimental content Accurately weigh 0.0755 g of catalase and dissolve it in 7.55 mL of deionized water to prepare a 10 mg / mL catalase mother solution. Take 50 μL of the mother solution and dissolve it in 4950 μL of deionized water to obtain a 0.1 mg / mL catalase solution sample.

[0050] The prepared samples were loaded, reacted and tested according to the requirements of the kit instructions, and the catalase activity was calculated according to the sample protein concentration calculation method provided in the kit instructions.

[0051] Finally, the dosage of organic solvents and agents in the experimental group, positive group and negative group are shown in Table 6, and the results of enzyme activity test are shown in Fig. 9 shown.

[0052] Table 6 Experimental Group Negative group 0.1mg / mL catalase + 1mg / mL ectoine 0.1mg / mL catalase Depend on Fig. 9 It can be seen that ectoine significantly increased the activity of catalase and effectively improved the detoxification ability of catalase.

[0053] Example 7: The mechanism of the drug of ectoine in the prevention and treatment of organic solvent poisoning disclosed in the present invention is different from Example 6 in that the dosage of organic solvent and drug in the experimental group and the negative group is shown in Table 7, and the catalase activity is shown in Table 7. Fig.10 shown.

[0054] Table 7 Experimental Group Negative group 0.1mg / mL catalase + 1mg / mL ectoine + 0.1% acetic acid 0.1mg / mL catalase + 0.1% acetic acid Depend on Fig.10 It can be seen that tetrahydropyrimidine can effectively protect the inhibitory effect of acetic acid, a metabolite of organic solvent ethanol, on catalase, and restore the enzymatic activity of catalase inhibited by acetic acid.

[0055] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution of the present invention, which should be included in the scope of the claims of the present invention.

Claims

1. An application of tetrahydropyrimidine in a drug for preventing and treating organic solvent poisoning.

2. The use of an ectoine according to claim 1 in a drug for preventing and treating organic solvent poisoning, characterized in that: The organic solvent is one or a mixed solvent of ethanol, n-propanol, isopropanol, n-butanol and dimethyl sulfoxide.

3. The use of an ectoine according to claim 2 in a drug for preventing and treating organic solvent poisoning, characterized in that: The drug is used as a specific antidote when treating poisoning caused by the organic solvent.

4. The use of an ectoine according to any one of claims 1 to 3 in a drug for preventing and treating organic solvent poisoning, characterized in that: The drug is administered enterally and / or intraportally or via umbilical infusion.

5. The use of an ectoine according to claim 4 in a drug for preventing and treating organic solvent poisoning, characterized in that: The enteral administration is achieved by using an oral dosage form.

6. The use of an ectoine according to claim 4 in a drug for preventing and treating organic solvent poisoning, characterized in that: The enteral administration is achieved via a probe.

7. The use of an ectoine according to claim 4 in a drug for preventing and treating organic solvent poisoning, characterized in that: The dosage is 0.5-1.5 mg / mL.

8. The use of an ectoine in a drug for preventing and treating organic solvent poisoning according to claim 2, characterized in that: The application can obtain at least one effect related to the kinetic correction of organic solvent poisoning, and the effect is selected from: reducing the inhibitory effect of organic solvent metabolites on the cell enzyme system; enhancing the detoxification function of the cell enzyme system on organic solvents.

9. The use of an ectoine in a drug for preventing and treating organic solvent poisoning according to claim 2, characterized in that: The use can obtain at least one effect related to the correction of toxicokinetics of organic solvent poisoning, which is selected from the group consisting of accelerating the excretion of organic solvents and / or their toxic metabolites from organisms; and improving the excretion of organic solvents.

10. The use of an ectoine in a drug for preventing and treating organic solvent poisoning according to claim 2, characterized in that: The application can obtain at least one effect related to the risk of organic solvent poisoning, wherein the effect is selected from: enhancing the detoxification function of the liver and kidney during the damage process before the onset of organic solvent poisoning; reducing the inhibitory effect of organic solvent metabolites on the liver and kidney detoxification enzyme system.

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