WO2021155795A1 - Pharmaceutical composition and use thereof - Google Patents

Pharmaceutical composition and use thereof Download PDF

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Publication number
WO2021155795A1
WO2021155795A1 PCT/CN2021/075001 CN2021075001W WO2021155795A1 WO 2021155795 A1 WO2021155795 A1 WO 2021155795A1 CN 2021075001 W CN2021075001 W CN 2021075001W WO 2021155795 A1 WO2021155795 A1 WO 2021155795A1
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pharmaceutical composition
bacteria
pathogen
virus
formate
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PCT/CN2021/075001
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French (fr)
Chinese (zh)
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秦才东
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秦才东
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Priority claimed from CN202011259180.7A external-priority patent/CN114432448A/en
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Publication of WO2021155795A1 publication Critical patent/WO2021155795A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics

Definitions

  • the present invention relates to the field of medicine. Specifically, the present invention relates to a pharmaceutical composition and its application.
  • the invention is a method and application for inhibiting and controlling the pathogenicity of viruses and bacteria and rapid proliferation of inflammatory cells as effectively as possible by inhibiting the gene synthesis process and increasing the alkalinity of body fluids at the same time.
  • each cell and virus contains a large amount of DNA, RNA and other substances.
  • Tumor cells, bacterial cells, and viruses and inflammatory cells involved in the present invention require a large amount of deoxygenation for rapid replication and proliferation.
  • Ribose, ribose, phosphoric acid, purine, and pyrimidine are essential raw materials for the synthesis of DNA and RNA. Among them, only pyrimidine cannot be obtained directly from food, and the production of a large number of pyrimidine nucleotides can only rely on the way of synthesis.
  • pyrimidine nucleotides In most organisms, there are two ways to synthesize pyrimidine nucleotides, one is de novo synthesis and the other is salvage. In quiescent or fully differentiated cells, the synthesis of pyrimidine nucleotides is mainly produced by the salvage pathway, that is, using free pyrimidine bases or pyrimidine nucleosides in the body as raw materials, passing through pyrimidine phosphoribosyltransferase or pyrimidine nucleoside kinase, etc. The process of catalyzing simple reactions to synthesize pyrimidines.
  • the required amount of pyrimidine nucleotides is much greater than that of normal cells, and its synthesis mainly depends on the de novo synthesis pathway in the cell.
  • the fourth step in the de novo synthesis pathway of pyrimidine nucleotides is catalyzed by dihydroorotate dehydrogenase (DHODH), and the dehydrogenation of dihydroorotate to orotate (pyrimidine derivative) is generated by coenzyme Q, etc.
  • DHODH dihydroorotate dehydrogenase
  • coenzyme Q etc.
  • Coenzymes provide oxidizing power.
  • DHODH is divided into two major families according to its amino acid sequence, coenzyme type, and location in the cell.
  • One type is located in the cytoplasm or the inner side of the cytoplasmic membrane and exists in prokaryotes and lower eukaryotes.
  • Its electron acceptor is fumaric acid (ester) or nicotinamide adenine dinucleotide (NAD).
  • NAD nicotinamide adenine dinucleotide
  • the other is located on the outer surface of the inner mitochondrial membrane of mammals and certain protozoa, and uses Coenzyme Q as an electron acceptor.
  • Human dihydroorotate dehydrogenase (hDHODH) belongs to the second category.
  • virus binding to cell receptors is mainly adsorbed on cell surface molecules through virus adsorption proteins (VAPs), and the receptor is the first cell molecule encountered by the virus. If the VAPs protein of the virus or the corresponding receptor on the cell can be shielded, the virus will not be able to recognize and attach to the surface of the host cell, and the infection will not actually occur.
  • VAPs virus adsorption proteins
  • VAPs and viral receptors you can clamp on both sides to block the binding of the virus to the receptor from two aspects. One is to block the binding site of the virus itself, and the other is to block the receptor. Cut off the binding of the virus to the receptor.
  • the purpose and effect of the present invention is to use a special reducing agent to inhibit the infection and proliferation of viruses, fungi, and bacterial cells, as well as the rapid proliferation of inflammatory cells.
  • An object of the present invention is to provide a pharmaceutical composition.
  • Another object of the present invention is to provide the application of the pharmaceutical composition.
  • the purpose and effect of the present invention is to consider and use the characteristic of adsorbing host cells as the first step in the process of all virus infections, to increase the pH value of body fluids, and to reduce the positive levels carried on the viral ligands or host cell receptors.
  • the number of charges reduces the electrostatic adsorption to host cells or viruses carrying opposite charges, and achieves the effect of inhibiting virus and bacterial infections.
  • the microenvironment of the virus is changed, and it actually provides a condition for dissolving blood clots and phlegm clots in the lungs (anticoagulation effect); on the other hand, considering the single use of increasing alkalinity , It may not be able to effectively prevent viral infections.
  • the existing injection of alkaline baking soda solution has not been found to be able to effectively solve the problem of viral infections. Therefore, the technical method that can be used at the same time is from the perspective of basic substances required for gene synthesis. , Complementing each other's inhibitory effectiveness, two-pronged approach to inhibit viral, fungal, and bacterial infections.
  • the present invention provides a pharmaceutical composition, wherein the pharmaceutical composition comprises formate and/or oxalate.
  • the pharmaceutical composition includes formate and oxalate
  • the mass ratio of formate and oxalate is (0.01:99.99) to (99.99:0.01).
  • the mass ratio of formate and oxalate is (10:90) to (90:10); preferably ( 20:80) to (80:20); more preferably (30:70) to (70:30); more preferably (40:60) to (60:40); still more preferably 50:50.
  • formate and/or oxalate are each independently selected from one or a combination of potassium salt, sodium salt, magnesium salt and calcium salt.
  • the pharmaceutical composition is a solid preparation or a solution preparation.
  • the present invention also provides the application of the pharmaceutical composition in the preparation of drugs for treating and inhibiting pathogens.
  • the pathogen is a pathogen that relies on surface charges to electrostatically attract and adhere to host cells.
  • the pathogen is selected from the group consisting of viruses, fungi, bacteria, chlamydia, mycoplasma, and protease toxoids.
  • the present invention also provides a method for inhibiting pathogens, wherein the method comprises administering the pharmaceutical composition of the present invention to animals or plants.
  • the pharmaceutical composition includes formate and/or oxalate.
  • formate and/or oxalate are each independently selected from one or a combination of potassium salt, sodium salt, magnesium salt and calcium salt.
  • the pharmaceutical composition is a solid preparation or a solution preparation.
  • the pathogen is a pathogen that relies on surface charges to electrostatically attract and adhere to host cells.
  • the pathogen is selected from the group consisting of viruses, fungi, bacteria, chlamydia, mycoplasma, and protease toxoids.
  • the bacteria are selected from anaerobic bacteria or aerobic bacteria.
  • the bacteria are charged bacteria.
  • the virus is an enveloped or non-enveloped virus.
  • the fungus is smut or yeast.
  • the method comprises administering the pharmaceutical composition of the present invention to a mammal by a combination of one or more selected from the following administration modes: oral administration, injection, smearing and spray.
  • low-toxic reducing agents can also be used as a choice for human body surface, plants, and animals when there is no other treatment method.
  • the animal is a mammal.
  • the animal is a human.
  • the pharmaceutical composition inhibits the utilization of dihydroorotic acid and/or the dehydrogenation reaction of dihydroorotic acid in the pyrimidine nucleotide synthesis reaction of the pathogen, and simultaneously increases
  • the pH value of body fluids achieves the inhibition of pathogens.
  • the present invention also provides a method for inhibiting the proliferation of viruses, fungi, bacteria, and inflammatory cells, the method comprising using formate, oxalate, or a mixture of both to inhibit viral, fungal or bacterial infections Or the rapid proliferation of inflammatory cells.
  • the use of dihydroorotic acid and/or dihydrolactic acid in the de novo synthesis of pyrimidine nucleotides necessary for DNA or RNA replication is inhibited by the use of formate and oxalate.
  • the dehydrogenation reaction of clear acid and the increase of the pH value of body fluids at the same time can effectively inhibit the proliferation of viruses, fungi and bacteria, infection and rapid proliferation of inflammatory cells.
  • inhibiting the utilization of dihydroorotic acid and/or the dehydrogenation reaction of dihydroorotic acid in the pyrimidine nucleotide synthesis reaction is by reducing intracellular oxidative coenzyme Q, NAD and The quantity or concentration of at least one of the fumaric acid is achieved.
  • the salt includes, but is not limited to, potassium salt, sodium salt, magnesium salt, and calcium salt.
  • the bacteria are aerobic bacteria or anaerobes.
  • the bacteria are charged bacteria.
  • the virus is an enveloped or non-enveloped virus.
  • the present invention also provides an application of a method for inhibiting the proliferation of viruses, fungi, bacteria, and inflammatory cells.
  • Formate and oxalate are used to inhibit viruses and fungi by oral or injection, smearing, spraying, or compound methods.
  • Bacterial infection and proliferation to achieve the effect of prevention and treatment of various viral, fungal or bacterial infections or rapid proliferation of inflammatory cells.
  • the salt includes, but is not limited to, potassium salt, sodium salt, magnesium salt, and calcium salt.
  • the present invention also provides a method for inhibiting the proliferation of viruses, fungi, bacteria, and inflammatory cells.
  • the method includes using a reducing agent to inhibit the de novo synthesis of pyrimidine nucleotides necessary for DNA or RNA replication.
  • the dihydroorotic acid dehydrogenation reaction is a reaction that is converted into orotic acid under the catalysis of dihydroorotic acid dehydrogenase and a coenzyme.
  • the reducing agent is formate, oxalate or a mixture of both.
  • the bacteria are aerobic bacteria or anaerobes.
  • the salt includes, but is not limited to, potassium salt and sodium salt.
  • the method includes the use of reducing substances by oral administration, injection, smearing, spraying, or compounding to inhibit the rapid proliferation of viruses, fungi, bacteria, and inflammatory cells to achieve protection against various viruses, The prevention and treatment of fungal or bacterial infections or rapid proliferation of inflammatory cells.
  • the mechanism is to inhibit or reduce the synthesis of new DNA or RNA by inhibiting the utilization of dihydroorotic acid and/or dehydrogenation of cells. At the same time increase the pH of body fluids.
  • the reducing substance is formate, oxalate or a mixture of the two, and is used as a solid medicament or a solution or a mixed solution.
  • the method includes using formate and other reducing agents as the prevention of viral, fungal, and bacterial infections in daily life, such as using a low concentration (such as mass/mass concentration 1%-30 %, the same below)
  • the solution is used as a daily mouthwash, a small amount added to daily beverages (such as content of 1%-10%), food (contents of 1% to 5%), a small amount added to personal daily cleaning and hygiene products middle.
  • the beverage can be bottled water, drinking water, fruit juice, alcoholic beverage; the food can be flour, rice noodles, pickled products, sauce products, etc.; the personal daily cleaning and hygiene products such as soap, cleaning liquid, skin care products, etc. .
  • the present invention also provides a method for inhibiting pathogens, wherein the method comprises administering the pharmaceutical composition according to any one of the preceding items of the present invention to a mammal as a prevention of pathogen infection.
  • the pharmaceutical composition is a low-concentration solution as a daily mouthwash; or a small amount is added to daily beverages, foods, and daily personal hygiene products.
  • the beverage can be bottled water, drinking water, fruit juice, alcoholic beverage;
  • the food can be flour, rice noodles, pickled products, sauce products, and the like.
  • the personal daily hygiene products such as soap, cleansing liquid, skin care products and the like.
  • the present invention also provides a method for adjusting the pH value of human body fluids, wherein the method comprises administering to the human body any of the aforementioned pharmaceutical compositions of the present invention.
  • the body fluid is blood and/or urine.
  • composition of the present invention inhibits pathogens as follows:
  • the inventor of the present application found that the isoelectric point of most viruses is between pH 4-5.5, and that of most bacteria is pH 3-4. Therefore, most viruses and bacteria carry negative charges under physiological conditions. Since the virus itself does not provide energy for metabolism, the attachment and binding of virus ligands to specific receptors on the cell membrane as the initial step of virus replication can only passively rely on the electrostatic attraction between the ligand and the receptor.
  • cell receptors when cell receptors are positively charged, they can only selectively accept viruses with negatively charged ligands. Similarly, when cell receptors are negatively charged, they can only selectively accept viruses with positively charged ligands. . It can be reasonably expected that if the nature and quantity of surface charges of viruses, fungi, bacteria or cell receptors can be actively adjusted, then whether the viruses, fungi, bacteria and cells can bind or the probability of binding can also be adjusted accordingly.
  • the charge of the surface proteins of viruses or cells comes from the hydrolysis reaction of amino and carboxyl groups on amino acid residues, where amino groups tend to carry positive charges and carboxyl groups tend to carry negative charges.
  • the reaction is affected by the pH value of the solution, so if the pH value of the solution (saliva, gastric juice or blood and other body fluids) can be actively adjusted, it can actively affect the charge state of viruses, bacteria, cell surfaces, and the electrostatic attraction between each other. size. Increase the pH of the solution. If there are undissociated carboxyl groups on the negatively charged amino acid residues, the negatively charged amino acid residues will continue to increase the number of negative charges until all the carboxyl groups on the amino acid residues are dissociated.
  • the present invention further uses reducing substances to inhibit the synthesis of pyrimidine derivatives by the dehydrogenation reaction of dihydroorotic acid in pyrimidine de novo synthesis.
  • the most important advantage of the present invention is that it has found reducing substances such as sodium formate, which can increase the alkalinity of body fluids through intermediate reactions, and can inhibit chemical reactions in the de novo synthesis of pyrimidines.
  • Sodium formate has the following tendency to react in an ionic manner in an aqueous solution (or body fluid):
  • reducing oxalate has a similar dehydrogenation reaction and can also form alkaline carbonate.
  • the salt can be sodium salt, potassium salt, magnesium salt, calcium salt and the like.
  • the above-mentioned reduced coenzyme Q is oxidized and restored to oxidized coenzyme Q in the cell.
  • the presence of sodium formate can at least reduce the amount or concentration of oxidative coenzyme Q, NAD, and fumaric acid, thus inhibiting dihydrogen
  • the effect of orotic acid is converted into orotic acid, thereby inhibiting the synthesis efficiency and quantity of pyrimidine nucleotides.
  • reducing sodium formate changes the chemical potential in the cell, thereby affecting the catalytic activity of the oxidizing coenzyme. According to the Nernst equation, this change is concentration-dependent.
  • the tricarboxylic acid cycle can provide a large amount of coenzyme NAD.
  • the effect of sodium formate on coenzyme NAD is weakened or ignored, so it does not affect the glycolytic part of normal cells. , Does not affect the tricarboxylic acid cycle.
  • reducing agents such as sodium formate do not affect the synthesis of pyrimidine nucleotides required for normal cell repair or division.
  • NADPH (Sodium formate + water) "dehydrogenation," the dehydrogenation is transferred to the oxidizing coenzyme NADP, which is converted into the reducing coenzyme NADPH.
  • NADPH is mainly derived from the intracellular pentose phosphate pathway and is not affected by sodium formate reducing agent.
  • Aerobic bacteria will continue to proliferate under suitable conditions.
  • the coenzymes NAD and NADPH in aerobic bacteria cells will not be affected by reducing agents, but the proliferation of aerobic bacteria or DNA replication depends on pyrimidine nucleosides.
  • the de novo synthesis reaction of acid provides reducing agents such as sodium formate with an opportunity and method to inhibit the growth of aerobic bacteria.
  • the reason is that the bacterial DHODH is located inside the cytoplasm or cytoplasmic membrane. Therefore, the NAD provided by the oxidation reaction in the mitochondria has no or only a small effect on the amount of the coenzyme NAD of DHODH.
  • the present invention breaks through the traditional technical habit of dealing with viruses only by focusing on the virus itself. Indirectly, the present invention controls the rapid replication of host cells' genes, which also controls the virus, and also breaks through the original inhibition of de novo synthesis of pyrimidine nucleotides in cells. The way of thinking cannot or did not think of the limitations of thinking that can be directly applied to non-cellular viruses.
  • Reducing agents such as sodium formate inhibit or reduce the quantity and concentration of oxidative coenzyme Q, NAD, and fumaric acid, and reduce the efficiency and quantity of pyrimidine nucleotide synthesis, and therefore, can indirectly inhibit the replication of viral DNA or RNA.
  • the number of virus replication, infectivity, and destructive power are limited, and the reaction preparation that inhibits the conversion of dihydroorotic acid into orotic acid becomes a broad-spectrum antidote to the virus.
  • the material and energy consumption of the host cell is expected to increase sharply, which may change the cell's respiratory metabolism to aerobic glycolysis.
  • lactic acid, a metabolite of respiratory reaction accumulates in the blood, and the acidic blood environment promotes the formation of embolism, which leads to various embolism problems.
  • the virus causing cell cancer may be related to the long-term change of the cell respiration pattern by the virus.
  • reducing agents such as sodium formate can not only inhibit the glycolytic respiratory reaction of cancer cells and anaerobic bacteria by inhibiting coenzyme NAD, but also inhibit the de novo synthesis of pyrimidine nucleotides by inhibiting oxidative coenzyme Q, NAD and fumaric acid.
  • the present invention also has the advantage of controlling the replication and synthesis of viral genes, cancer cells, bacterial cells, and inflammatory cells by controlling the synthesis reaction of gene replication, and solves the global drug resistance caused by gene mutation from the source. problem.
  • One of the advantages of the present invention is that because the pH value of body fluid can be increased, it helps to alleviate the problem of phlegm plug caused by pneumonia caused by virus or bacterial infection.
  • the synthesis of pyrimidine nucleotides is essential for virus replication by host cells, and for the proliferation and metabolism of cancer cells, bacterial cells, and inflammatory cells. Therefore, the method for inhibiting viruses, bacteria, and inflammatory cells of the present invention
  • the use of reducing agents such as formate, oxalate or a mixture of both not only increases the alkalinity of body fluids, hinders the electrostatic attraction contact between the virus and the host cell, but also inhibits the pyrimidine nucleus necessary for DNA or RNA replication
  • the utilization of dihydroorotic acid and/or the dehydrogenation reaction of dihydroorotic acid in the de novo synthesis reaction of uronic acid realizes the inhibition of viral and bacterial infection and proliferation, and the inhibition of the proliferation of inflammatory cells.
  • the method of the present invention for inhibiting viruses, bacteria, and inflammatory cells is to use the characteristic of adsorbing host cells as the first step in the infection process of all viruses, increase the pH value of body fluids, and reduce the viral ligands or host cell receptors carried The number of positive charges reduces the electrostatic adsorption to host cells or viruses carrying opposite charges. At the same time, it has the effect of inhibiting the de novo synthesis path of pyrimidine in virus or bacterial gene replication, and overcomes the effect of inhibiting the de novo synthesis path of pyrimidine alone to inhibit virus or bacterial infection.
  • Chlamydia and protease toxoids also use their outer surface membrane proteins to adhere to host cells as the first step to cause disease.
  • the proliferation and replication also involve gene synthesis. Therefore, the method of the present invention is also suitable for similar electrostatic attraction by surface charges.
  • Various pathogens that adhere to host cells Mycoplasma adheres to the surface of epithelial cells and red blood cells through its own adhesion protein. Therefore, in the present invention, mycoplasma can be used as a generalized bacteria or generalized virus that can carry charges. Because it can adhere to red blood cells, mycoplasma carries a positive charge and is therefore easily neutralized by an environment with increased pH.
  • Fig. 1 is a photograph of the surface of the water chestnut in Example 4.
  • the left picture shows the water chestnut surface immersed in the dihydroorotic acid solution alone, and the right picture is the water chestnut surface immersed in the dihydroorotic acid solution and added with sodium formate.
  • Figure 2 is a photograph of the surface of the dough surface of Example 5 added with dihydroorotic acid (the upper part of the figure) and both dihydroorotic acid and sodium formate (the lower part of the figure).
  • Oxalate also has a similar reaction as described above.
  • B is an oxidative substance (such as active free radicals) or an oxidative reaction process that can accept electrons in human body fluids or cells.
  • the above reaction not only inactivates free radicals or participates in redox reactions, such as inhibiting the de novo synthesis of pyrimidine, but also provides the human body with hydroxide anions that increase pH.
  • the individual specific dosage or the dosage required for direct injection because it is to adjust the pH value of body fluids, and everyone’s initial pH value is different, and the total amount of body fluids is also not the same. Therefore, it is necessary to achieve the same The pH level, the required dosage or injection volume are different. For the actual operation of all the embodiments, it can be increased or decreased according to the pH value of urine or blood. For example, when the pH value of urine is lower than 5.5, the dosage can be increased by 1 gram per day until the pH value of urine is not high. Is below 8 (the upper limit of the normal value), or the pH of the blood is not higher than 7.87.
  • Four hospital blood tests during the continuous use period The report showed that the blood pH value reached 7.57, 7.76, 7.87, and 7.77. During the period, the body felt good, indicating that the pH value of the blood of patients taking formate can be significantly increased, and can reach 7.87.
  • the above phenomenon shows that sodium formate itself inhibits the proliferation of smut fungus, and also inhibits the utilization and conversion of the added dihydroorotic acid of smut fungus. Because the smut is a fungus, it is an aerobic bacteria, so sodium formate will not affect its respiratory metabolism. What can affect should be the reaction of dihydroorotic acid dehydrogenation to orotic acid, thereby inhibiting the pyrimidine nucleus The synthesis of glycosides leads to the obstacles to the synthesis of DNA by smut fungus.
  • the coenzyme of the dihydroorotic acid dehydrogenation reaction in Zizania smut cells may be coenzyme NAD or coenzyme Q.
  • the above test can at least prove that reducing substances such as sodium formate can inhibit one of the coenzyme NAD or coenzyme Q of DHODH. After replacing the above sodium formate with sodium oxalate, similar experimental results were obtained.
  • the pH value of the dough added with sodium formate was about 3 according to the test paper, and the pH value of the dough added with dihydroorotic acid was about 4.
  • the dough (top of Figure 2) to which dihydroorotic acid was added alone was covered with a layer of turquoise mycelium about 5-10 mm thick, and dihydroorotic acid and dihydroorotic acid were added at the same time.
  • the surface of the sodium formate dough (bottom of Figure 2) is still the original milky white of the dough (the red part left on the surface of the dough is the color left by the wet pH test paper when the test is pressed, and the pH test shows that the pH is about 4). See there are hyphae. It shows that sodium formate has a long-lasting inhibitory effect on the proliferation of yeast bacteria (see Figure 2), because it inhibits the proliferation of bacteria by inhibiting the pyrimidine synthesis pathway in gene synthesis. Therefore, as long as the yeast has a long-lasting inhibitory effect, reducing agents such as A Acid salts have the same or similar inhibitory effect on the proliferation of other bacteria.
  • the acidic dihydroorotic acid (pKa 3.41) is converted to use synthetic pyrimidine nucleotides, as it is consumed, the pH value of the dough increases; while the dough added with sodium formate or sodium oxalate, the reducing agent inhibits the dihydrogen
  • the consumption reaction of orotic acid should be to inhibit and slow down the dehydrogenation conversion reaction of dihydroorotic acid in yeast cells, so the pH value of the dough basically remains unchanged or slowly increases.
  • the inhibition of fermentation by sodium formate and sodium oxalate should not be by inhibiting glycolysis, but by inhibiting the dehydrogenation reaction of dihydroorotic acid, that is, inhibiting the dehydrogenation reaction of dihydroorotic acid.
  • the coenzyme NAD or coenzyme Q The higher the concentration of reducing agent such as sodium formate, the stronger the inhibitory effect of coenzyme, therefore, the inhibitory effect is dose-dependent.
  • mitochondria can provide a large amount of coenzyme NAD products, according to the fact that the bacterial dihydroorotate dehydrogenase is located in the cytoplasm or inside the cytoplasmic membrane, it can be expected that the tricarboxylic acid cycle in the mitochondria will not be directly Influencing the catalytic reaction of DHODH here, in particular, does not directly affect the mutual conversion reaction between the coenzyme NAD-NADH of dihydroorotate dehydrogenase.
  • the aqueous solution of sodium formate reduces the oxidized coenzyme Q10, reduces the hydrophobic carbonyl group in the coenzyme to a hydrophilic hydroxyl group, increases the solubility of the coenzyme, and promotes the miscibility of the reducing coenzyme fine particles with the aqueous solution to form a colloid.
  • reducing agents such as sodium formate have the effect of inhibiting various viruses, in line with the theory of charge neutralization and the anticipation of the theory of inhibiting viral gene replication.
  • the neutralization of charge plus the inhibition of gene synthesis increases the effectiveness of a single action. It can be presumed that according to the same principle, it can also have the effect of inhibiting other viruses.
  • reducing agents such as formate can also be used to prevent viral and bacterial infections, such as using a low concentration (for example, 1%-30% by weight) solution as a daily routine
  • a low concentration (for example, 1%-30% by weight) solution as a daily routine
  • a small amount of mouthwash is added to daily beverages (for example, the content is 1%-10% by weight), food (the content is 1% to 5% by weight), and a small amount is added to personal daily cleaning and hygiene products.
  • the beverage can be bottled water, drinking water, fruit juice, alcoholic beverage; the food can be flour, rice noodles, pickled products, sauce products, etc.; the personal daily cleaning and hygiene products such as soap, cleaning liquid, skin care products, etc. .
  • Hepatitis B virus including its satellite virus, hepatitis D virus (HDV), like other enveloped viruses or non-enveloped viruses, must bind to cell surface receptor molecules to infect host cells.
  • the N-terminal of the hepatitis B virus ligand carries a positive charge, while the host cell receptor correspondingly carries a negative charge.
  • a hepatitis B virus carrier took 1 g of sodium formate a day. After half a year, the indicators were checked, and the somatosensory and indicators were all improved.
  • the reduction of the virus charge coupled with the inhibitory effect of the reducing agent on the de novo synthesis of pyrimidine in gene synthesis, has the effect of inhibiting the replication of hepatitis B virus.
  • hemagglutinin HA or a protein similar to hemagglutinin can be found on the surface of measles virus, mumps virus, parainfluenza virus, rubella, and many other bacteria and viruses as a ligand for the virus to invade host cells, thus increasing body fluids Alkalinity can also reduce the pathogenicity of these viruses by reductively inhibiting the de novo pyrimidine synthesis pathway in the process of gene replication.
  • influenza virus adheres and binds to host cells through hemagglutinin HA, and then enters the cell. It is known that the surface of red blood cells is negatively charged, and it is naturally speculated that hemagglutinin HA, as a viral ligand, carries a positive charge.
  • Increasing the alkalinity of body fluids will reduce the number of positive charges carried by hemagglutinin HA and reduce the pathogenicity of the virus.
  • the inhibitory effect of reducing agents on the de novo pyrimidine synthesis pathway will weaken the pathogenic effect and pathogenic symptoms of viral infections. .
  • the effect of taking potassium formate on a person with advanced AIDS is provided.
  • the patient took 3 grams of potassium formate (taken in 3 times) every day. After 3 days, the appetite was significantly increased, and the breathing, physical fitness, and body feeling gradually improved, which had the effect of relieving symptoms. .
  • CD4 molecule is a single-chain transmembrane protein mainly present on the surface of T cells.
  • the isoelectric point of chicken CD4 molecule is 10.1 (under physiological conditions, it is positively charged). It is speculated that it has great similarities with mammalian CD4 molecules.
  • the most noteworthy extracellular region of CD4 is its N-terminal (positively charged) two Ig-like regions, because they are binding regions with MHCII and are also HIV (human immunodeficiency virus) gp120 binding sites (for human CD4). In terms of).
  • the CD4 molecule is the primary receptor for the HIV virus to enter human cells.
  • MHC II should also be able to bind to CD4 only if it carries a negative charge. This inference is consistent with the previously speculated MHC II isoelectric point of 6.89.
  • a patient with cervical polyps is provided. Without other treatment, he simply took 15 ml of sodium formate saturated solution plus 15 ml of potassium formate saturated solution twice a day. After taking 30 days, the polyp was about 6 mm The size is so large that the endoscopy disappears.
  • the human papillomavirus HPV genome encodes E1, E2, E3, E4, E5, E6, E7, and L1, L2 capsid proteins, respectively.
  • the E1-E4 proteins are associated with host cell keratin through their N-terminal leucine-rich motifs. Therefore, the virus adsorption protein VAP is E1, and its N-terminus carries a positive charge, and the receptor keratin protein carries a negative charge.
  • a middle-aged man has a piece of local neurodermatitis on his neck (diagnosed by the hospital) with a size of 2 cm in diameter. He sweats in the summer and itching every day. The prescription drugs of hormones do not work for half a year. After 10 ml 3 times a day for 2 weeks, he basically recovered. It is estimated that the inhibition of pyrimidine synthesis inhibits the de novo pyrimidine synthesis step in gene synthesis required for rapid proliferation of inflammatory cells.
  • the hospital medical record diagnosis of an elderly man is erythema with unclear trunk and limb boundaries, papules, scratches, dry and cracked skin, and itching for about 1 year.
  • the symptoms of itching have not been controlled.

Abstract

Disclosed are a pharmaceutical composition comprising formate and/or oxalate, and the use of the pharmaceutical composition in inhibiting pathogen infections.

Description

一种药物组合物及其应用A pharmaceutical composition and its application 技术领域Technical field
本发明涉及医药领域，具体的说，本发明涉及一种药物组合物及其应用。本发明是通过抑制基因合成过程以及同时增加体液的碱性，达到尽可能有效抑制和控制病毒和细菌致病性、炎性细胞快速增殖的方法和应用。The present invention relates to the field of medicine. Specifically, the present invention relates to a pharmaceutical composition and its application. The invention is a method and application for inhibiting and controlling the pathogenicity of viruses and bacteria and rapid proliferation of inflammatory cells as effectively as possible by inhibiting the gene synthesis process and increasing the alkalinity of body fluids at the same time.
背景技术Background technique
从抑制基因复制的角度看，每个细胞以及病毒都含有大量的DNA、RNA等物质，肿瘤细胞、细菌细胞、还包括本发明涉及的病毒、炎性细胞快速复制增殖时，就需要大量的脱氧核糖、核糖、磷酸、嘌呤、嘧啶作为DNA、RNA合成的必须基础原材料。其中只有嘧啶无法从食物中直接获得，大量嘧啶核苷酸的生成只能依赖合成这一途径。From the perspective of inhibiting gene replication, each cell and virus contains a large amount of DNA, RNA and other substances. Tumor cells, bacterial cells, and viruses and inflammatory cells involved in the present invention require a large amount of deoxygenation for rapid replication and proliferation. Ribose, ribose, phosphoric acid, purine, and pyrimidine are essential raw materials for the synthesis of DNA and RNA. Among them, only pyrimidine cannot be obtained directly from food, and the production of a large number of pyrimidine nucleotides can only rely on the way of synthesis.
在大多数生物体内，嘧啶核苷酸的合成有两个途径，一种为从头合成途径，一种为补救途径。在处于静止期或者已经完全分化的细胞中，嘧啶核苷酸合成主要由补救途径产生，即利用体内游离的嘧啶碱基或嘧啶核苷为原料，经过嘧啶磷酸核糖转移酶或嘧啶核苷激酶等催化简单反应合成嘧啶的过程。而在肿瘤细胞、细菌细胞、炎性细胞快速增殖、以及本发明中涉及的病毒复制过程中，嘧啶核苷酸需要量远远大于正常细胞需要量，其合成主要依靠细胞内的从头合成途径。嘧啶核苷酸从头合成途径的步骤中的第4步是由二氢乳清酸脱氢酶(DHODH)催化，二氢乳清酸脱氢生成乳清酸(嘧啶衍生物)，由辅酶Q等辅酶提供氧化能力。In most organisms, there are two ways to synthesize pyrimidine nucleotides, one is de novo synthesis and the other is salvage. In quiescent or fully differentiated cells, the synthesis of pyrimidine nucleotides is mainly produced by the salvage pathway, that is, using free pyrimidine bases or pyrimidine nucleosides in the body as raw materials, passing through pyrimidine phosphoribosyltransferase or pyrimidine nucleoside kinase, etc. The process of catalyzing simple reactions to synthesize pyrimidines. In the rapid proliferation of tumor cells, bacterial cells, inflammatory cells, and virus replication involved in the present invention, the required amount of pyrimidine nucleotides is much greater than that of normal cells, and its synthesis mainly depends on the de novo synthesis pathway in the cell. The fourth step in the de novo synthesis pathway of pyrimidine nucleotides is catalyzed by dihydroorotate dehydrogenase (DHODH), and the dehydrogenation of dihydroorotate to orotate (pyrimidine derivative) is generated by coenzyme Q, etc. Coenzymes provide oxidizing power.
自然界中，DHODH根据其氨基酸顺序、辅酶种类、在细胞中的定位被分为两大家族。一类位于胞质或胞质膜内侧，存在于原核生物及低等真核生物体内，其电子受体为延胡索酸(酯)或烟酰胺腺嘌呤二核苷酸(NAD)。另一类位于哺乳动物和某些原生动物的线粒体内膜的外表面，以辅酶Q作为电子受体。人类二氢乳清酸脱氢酶(hDHODH)属于第二类。In nature, DHODH is divided into two major families according to its amino acid sequence, coenzyme type, and location in the cell. One type is located in the cytoplasm or the inner side of the cytoplasmic membrane and exists in prokaryotes and lower eukaryotes. Its electron acceptor is fumaric acid (ester) or nicotinamide adenine dinucleotide (NAD). The other is located on the outer surface of the inner mitochondrial membrane of mammals and certain protozoa, and uses Coenzyme Q as an electron acceptor. Human dihydroorotate dehydrogenase (hDHODH) belongs to the second category.
从病毒感染宿主细胞过程看，病毒结合细胞受体主要是通过病毒吸附蛋白(VAPs)吸附于细胞表面分子上，受体是病毒遇到的第一个细胞分子。若能对病毒的VAPs蛋白或细胞上病毒对应的受体进行屏蔽，病毒也就无法识别和附着宿主细胞表面，感染就不 会实际发生。From the process of virus infection of host cells, virus binding to cell receptors is mainly adsorbed on cell surface molecules through virus adsorption proteins (VAPs), and the receptor is the first cell molecule encountered by the virus. If the VAPs protein of the virus or the corresponding receptor on the cell can be shielded, the virus will not be able to recognize and attach to the surface of the host cell, and the infection will not actually occur.
如果找到病毒粘附蛋白VAPs以及病毒受体，就可以两面夹击，从两个方面阻断病毒与受体结合，一是封闭病毒自身的结合位点，另一方面可封闭受体，都可以阻断病毒与受体的结合。If you find the viral adhesion protein VAPs and viral receptors, you can clamp on both sides to block the binding of the virus to the receptor from two aspects. One is to block the binding site of the virus itself, and the other is to block the receptor. Cut off the binding of the virus to the receptor.
因此，无论是抑制了嘧啶的从头合成通路，还是抑制了病毒与宿主细胞之间的静电吸引力，都有可能实现对病毒感染的抑制。Therefore, whether it inhibits the de novo synthesis pathway of pyrimidine or inhibits the electrostatic attraction between the virus and the host cell, it is possible to achieve the inhibition of virus infection.
发明内容Summary of the invention
本发明的目的和效果是利用特别的还原剂对病毒、真菌、细菌细胞感染和增殖以及炎性细胞快速增殖起到抑制作用。The purpose and effect of the present invention is to use a special reducing agent to inhibit the infection and proliferation of viruses, fungi, and bacterial cells, as well as the rapid proliferation of inflammatory cells.
本发明的一个目的在于提供一种药物组合物。An object of the present invention is to provide a pharmaceutical composition.
本发明的另一目的在于提供所述的药物组合物的应用。Another object of the present invention is to provide the application of the pharmaceutical composition.
本发明的目的和效果一方面是考虑和利用吸附宿主细胞是所有病毒感染过程中第一步的特点，以增加体液的pH值为工具，降低病毒配体或宿主细胞受体上所携带的正电荷数量，减少对携带异性电荷的宿主细胞或病毒的静电吸附力，达到抑制病毒、细菌感染的效果。通过增加体液的pH值，改变了病毒的微环境，也事实上提供了一个溶解血液中血栓、肺部痰栓的条件(抗凝效果)；另一方面是考虑到单一利用增加碱性的方法，未必能有效的阻止病毒感染，比如现有的注射碱性的小苏打溶液并没有发现能够有效解决病毒感染的问题，因此想到可同时利用的技术方法是从基因合成所需的基础物质角度出发，互相补充抑制的效力，双管齐下，抑制病毒、真菌、细菌感染。On the one hand, the purpose and effect of the present invention is to consider and use the characteristic of adsorbing host cells as the first step in the process of all virus infections, to increase the pH value of body fluids, and to reduce the positive levels carried on the viral ligands or host cell receptors. The number of charges reduces the electrostatic adsorption to host cells or viruses carrying opposite charges, and achieves the effect of inhibiting virus and bacterial infections. By increasing the pH of body fluids, the microenvironment of the virus is changed, and it actually provides a condition for dissolving blood clots and phlegm clots in the lungs (anticoagulation effect); on the other hand, considering the single use of increasing alkalinity , It may not be able to effectively prevent viral infections. For example, the existing injection of alkaline baking soda solution has not been found to be able to effectively solve the problem of viral infections. Therefore, the technical method that can be used at the same time is from the perspective of basic substances required for gene synthesis. , Complementing each other's inhibitory effectiveness, two-pronged approach to inhibit viral, fungal, and bacterial infections.
虽然增加体液碱性以及同时抑制基因合成通路是本发明的指导思想或理论依据，但本发明的理论解释本身不是本申请的目的，也不是对本申请的目的和效果的限定，不排除还有其它可能的理论解释，但都不影响本发明的目的和效果及其事实上的实施。Although increasing body fluid alkalinity and simultaneously inhibiting gene synthesis pathways is the guiding ideology or theoretical basis of the present invention, the theoretical explanation of the present invention itself is not the purpose of this application, nor is it a limitation on the purpose and effects of this application, and others are not excluded. The possible theoretical explanations do not affect the purpose and effect of the present invention and its actual implementation.
为达上述目的，一方面，本发明提供了一种药物组合物，其中，所述药物组合物包括甲酸盐和/或草酸盐。To achieve the above objective, in one aspect, the present invention provides a pharmaceutical composition, wherein the pharmaceutical composition comprises formate and/or oxalate.
根据本发明一些具体实施方案，其中，所述药物组合物包括甲酸盐和草酸盐，甲酸盐和草酸盐的质量比为(0.01：99.99)至(99.99：0.01)。According to some specific embodiments of the present invention, wherein the pharmaceutical composition includes formate and oxalate, and the mass ratio of formate and oxalate is (0.01:99.99) to (99.99:0.01).
根据本发明一些具体实施方案，其中，所述药物组合物包括甲酸盐和草酸盐，甲酸盐和草酸盐的质量比为(10：90)至(90：10)；优选为(20：80)至(80：20)； 再优选为(30：70)至(70：30)；再优选为(40：60)至(60：40)；再优选为50：50。According to some specific embodiments of the present invention, wherein the pharmaceutical composition comprises formate and oxalate, the mass ratio of formate and oxalate is (10:90) to (90:10); preferably ( 20:80) to (80:20); more preferably (30:70) to (70:30); more preferably (40:60) to (60:40); still more preferably 50:50.
根据本发明一些具体实施方案，其中，所述甲酸盐和/或草酸盐各自独立的选自钾盐、钠盐、镁盐和钙盐中的一种或多种的组合。According to some specific embodiments of the present invention, wherein the formate and/or oxalate are each independently selected from one or a combination of potassium salt, sodium salt, magnesium salt and calcium salt.
根据本发明一些具体实施方案，其中，所述药物组合物为固体制剂或溶液制剂。According to some specific embodiments of the present invention, wherein the pharmaceutical composition is a solid preparation or a solution preparation.
另一方面，本发明还提供了所述的药物组合物在制备治疗抑制病原体的药物中的应用。On the other hand, the present invention also provides the application of the pharmaceutical composition in the preparation of drugs for treating and inhibiting pathogens.
根据本发明一些具体实施方案，其中，所述病原体为依靠表面电荷静电吸引与宿主细胞粘附的病原体。According to some specific embodiments of the present invention, the pathogen is a pathogen that relies on surface charges to electrostatically attract and adhere to host cells.
根据本发明一些具体实施方案，其中，所述病原体选自病毒、真菌、细菌、衣原体、支原体和蛋白酶类毒素。According to some specific embodiments of the present invention, wherein the pathogen is selected from the group consisting of viruses, fungi, bacteria, chlamydia, mycoplasma, and protease toxoids.
再一方面，本发明还提供了一种抑制病原体的方法，其中，所述方法包括向动物或植物给药本发明所述的药物组合物。In another aspect, the present invention also provides a method for inhibiting pathogens, wherein the method comprises administering the pharmaceutical composition of the present invention to animals or plants.
根据本发明一些具体实施方案，其中，所述药物组合物包括甲酸盐和/或草酸盐。According to some specific embodiments of the present invention, wherein the pharmaceutical composition includes formate and/or oxalate.
根据本发明一些具体实施方案，其中，所述甲酸盐和/或草酸盐各自独立的选自钾盐、钠盐、镁盐和钙盐中的一种或多种的组合。According to some specific embodiments of the present invention, wherein the formate and/or oxalate are each independently selected from one or a combination of potassium salt, sodium salt, magnesium salt and calcium salt.
根据本发明一些具体实施方案，其中，所述药物组合物为固体制剂或溶液制剂。According to some specific embodiments of the present invention, wherein the pharmaceutical composition is a solid preparation or a solution preparation.
根据本发明一些具体实施方案，其中，所述病原体为依靠表面电荷静电吸引与宿主细胞粘附的病原体。According to some specific embodiments of the present invention, the pathogen is a pathogen that relies on surface charges to electrostatically attract and adhere to host cells.
根据本发明一些具体实施方案，其中，所述病原体选自病毒、真菌、细菌、衣原体、支原体和蛋白酶类毒素。According to some specific embodiments of the present invention, wherein the pathogen is selected from the group consisting of viruses, fungi, bacteria, chlamydia, mycoplasma, and protease toxoids.
根据本发明一些具体实施方案，其中，所述细菌选自厌氧菌或好氧菌。According to some specific embodiments of the present invention, wherein the bacteria are selected from anaerobic bacteria or aerobic bacteria.
根据本发明一些具体实施方案，其中，所述细菌为携带电荷的细菌。According to some specific embodiments of the present invention, the bacteria are charged bacteria.
根据本发明一些具体实施方案，其中，所述病毒为有包膜或无包膜病毒。According to some specific embodiments of the present invention, wherein the virus is an enveloped or non-enveloped virus.
根据本发明一些具体实施方案，其中，所述真菌为黑粉菌或酵母菌。According to some specific embodiments of the present invention, wherein the fungus is smut or yeast.
根据本发明一些具体实施方案，其中，所述方法包括通过选自如下给药方式中的一种或多种的组合向哺乳动物给药本发明所述的药物组合物：口服、注射、涂抹和喷雾。According to some specific embodiments of the present invention, wherein the method comprises administering the pharmaceutical composition of the present invention to a mammal by a combination of one or more selected from the following administration modes: oral administration, injection, smearing and spray.
考虑到除了人体体内，还有人体体表、植物、动物病毒和细菌感染的防治需要， 低毒的还原剂也可以作为没有其它治疗方法时人体体表、植物、动物的一个选择。Considering that in addition to the human body, there is also the need for prevention and treatment of human body surface, plant, animal virus and bacterial infections, low-toxic reducing agents can also be used as a choice for human body surface, plants, and animals when there is no other treatment method.
根据本发明一些具体实施方案，其中，所述动物为哺乳动物。According to some specific embodiments of the present invention, the animal is a mammal.
根据本发明一些具体实施方案，其中，所述动物为人。According to some specific embodiments of the present invention, the animal is a human.
根据本发明一些具体实施方案，其中，所述药物组合物是通过抑制病原体的嘧啶核苷酸合成反应中的二氢乳清酸的利用和/或二氢乳清酸的脱氢反应、同时增加体液的pH值，实现对病原体的抑制。According to some specific embodiments of the present invention, wherein the pharmaceutical composition inhibits the utilization of dihydroorotic acid and/or the dehydrogenation reaction of dihydroorotic acid in the pyrimidine nucleotide synthesis reaction of the pathogen, and simultaneously increases The pH value of body fluids achieves the inhibition of pathogens.
再一方面，本发明还提供了一种抑制病毒、真菌、细菌、炎性细胞增殖的方法，所述方法包括利用甲酸盐、草酸盐或两者的混合物抑制病毒、真菌或细菌的感染或炎性细胞的快速增殖。In another aspect, the present invention also provides a method for inhibiting the proliferation of viruses, fungi, bacteria, and inflammatory cells, the method comprising using formate, oxalate, or a mixture of both to inhibit viral, fungal or bacterial infections Or the rapid proliferation of inflammatory cells.
根据本发明一些具体实施方案，其中，通过利用甲酸盐、草酸盐抑制DNA或RNA复制时所必须的嘧啶核苷酸从头合成反应中的二氢乳清酸的利用和/或二氢乳清酸的脱氢反应，以及同时增加体液的pH值，实现对病毒、真菌和细菌增殖、感染以及炎性细胞快速增殖的有效抑制。According to some specific embodiments of the present invention, the use of dihydroorotic acid and/or dihydrolactic acid in the de novo synthesis of pyrimidine nucleotides necessary for DNA or RNA replication is inhibited by the use of formate and oxalate. The dehydrogenation reaction of clear acid and the increase of the pH value of body fluids at the same time can effectively inhibit the proliferation of viruses, fungi and bacteria, infection and rapid proliferation of inflammatory cells.
根据本发明一些具体实施方案，其中，抑制嘧啶核苷酸合成反应中的二氢乳清酸的利用和/或二氢乳清酸的脱氢反应是通过减少细胞内氧化性辅酶Q、NAD和延胡索酸中的至少一种的数量或浓度来实现的。According to some specific embodiments of the present invention, wherein inhibiting the utilization of dihydroorotic acid and/or the dehydrogenation reaction of dihydroorotic acid in the pyrimidine nucleotide synthesis reaction is by reducing intracellular oxidative coenzyme Q, NAD and The quantity or concentration of at least one of the fumaric acid is achieved.
根据本发明一些具体实施方案，其中，所述的盐包括但不限于钾盐、钠盐、镁盐、钙盐。According to some specific embodiments of the present invention, wherein the salt includes, but is not limited to, potassium salt, sodium salt, magnesium salt, and calcium salt.
根据本发明一些具体实施方案，其中，所述细菌为好氧菌或厌氧菌。According to some specific embodiments of the present invention, wherein the bacteria are aerobic bacteria or anaerobes.
根据本发明一些具体实施方案，其中，所述细菌为携带电荷的细菌。According to some specific embodiments of the present invention, the bacteria are charged bacteria.
根据本发明一些具体实施方案，其中，所述病毒为有包膜或无包膜病毒。According to some specific embodiments of the present invention, wherein the virus is an enveloped or non-enveloped virus.
又一方面，本发明还提供了一种抑制病毒、真菌、细菌以及炎性细胞增殖的方法的应用，通过口服或注射或涂抹或喷雾或复合方式利用甲酸盐、草酸盐抑制病毒、真菌、细菌的感染和增殖，达到对各种病毒、真菌或细菌感染或炎性细胞快速增殖的预防和治疗的效果。In another aspect, the present invention also provides an application of a method for inhibiting the proliferation of viruses, fungi, bacteria, and inflammatory cells. Formate and oxalate are used to inhibit viruses and fungi by oral or injection, smearing, spraying, or compound methods. , Bacterial infection and proliferation, to achieve the effect of prevention and treatment of various viral, fungal or bacterial infections or rapid proliferation of inflammatory cells.
根据本发明一些具体实施方案，其中，所述的盐包括但不限于钾盐、钠盐、镁盐、钙盐。According to some specific embodiments of the present invention, wherein the salt includes, but is not limited to, potassium salt, sodium salt, magnesium salt, and calcium salt.
根据本发明一些具体实施方案，其中，所述甲酸盐、草酸盐或两者的混合物以固体药剂或溶液或混合溶液方式使用。According to some specific embodiments of the present invention, wherein the formate, oxalate or a mixture of the two are used as a solid medicament or a solution or a mixed solution.
又一方面，本发明还提供了一种抑制病毒、真菌、细菌、炎性细胞增殖的方法，所述方法包括利用还原剂抑制DNA或RNA复制时所必须的嘧啶核苷酸从头合成反应中的二氢乳清酸的利用和/或二氢乳清酸的脱氢反应，以及同时增加体液的pH值，实现对病毒、真菌和细菌、炎性细胞的快速增殖的抑制。In another aspect, the present invention also provides a method for inhibiting the proliferation of viruses, fungi, bacteria, and inflammatory cells. The method includes using a reducing agent to inhibit the de novo synthesis of pyrimidine nucleotides necessary for DNA or RNA replication. The utilization of dihydroorotic acid and/or the dehydrogenation reaction of dihydroorotic acid, as well as increasing the pH value of body fluids at the same time, realizes the inhibition of the rapid proliferation of viruses, fungi, bacteria, and inflammatory cells.
根据本发明一些具体实施方案，其中，所述二氢乳清酸脱氢反应是在二氢乳清酸脱氢酶以及辅酶的催化下转化为乳清酸的反应。According to some specific embodiments of the present invention, wherein the dihydroorotic acid dehydrogenation reaction is a reaction that is converted into orotic acid under the catalysis of dihydroorotic acid dehydrogenase and a coenzyme.
根据本发明一些具体实施方案，其中，所述还原剂为甲酸盐、草酸盐或两者的混合物。According to some specific embodiments of the present invention, wherein the reducing agent is formate, oxalate or a mixture of both.
根据本发明一些具体实施方案，其中，所述细菌为好氧菌或厌氧菌。According to some specific embodiments of the present invention, wherein the bacteria are aerobic bacteria or anaerobes.
根据本发明一些具体实施方案，其中，所述的盐包括但不限于钾盐、钠盐。According to some specific embodiments of the present invention, wherein the salt includes, but is not limited to, potassium salt and sodium salt.
根据本发明一些具体实施方案，其中，所述方法包括通过口服或注射或涂抹或喷雾或复合方式利用还原性物质，抑制病毒、真菌、细菌、炎性细胞的快速增殖，达到对各种病毒、真菌或细菌感染或炎性细胞快速增殖的预防和治疗的效果，其机理是通过抑制细胞对二氢乳清酸的利用和/或脱氢反应，抑制或减少了新增DNA或RNA的合成，同时增加体液的pH值。According to some specific embodiments of the present invention, the method includes the use of reducing substances by oral administration, injection, smearing, spraying, or compounding to inhibit the rapid proliferation of viruses, fungi, bacteria, and inflammatory cells to achieve protection against various viruses, The prevention and treatment of fungal or bacterial infections or rapid proliferation of inflammatory cells. The mechanism is to inhibit or reduce the synthesis of new DNA or RNA by inhibiting the utilization of dihydroorotic acid and/or dehydrogenation of cells. At the same time increase the pH of body fluids.
根据本发明一些具体实施方案，其中，所述还原性物质是甲酸盐、草酸盐或两者的混合物，并以固体药剂或溶液或混合溶液方式使用。According to some specific embodiments of the present invention, wherein the reducing substance is formate, oxalate or a mixture of the two, and is used as a solid medicament or a solution or a mixed solution.
根据本发明一些具体实施方案，其中，所述方法包括，在日常生活中将甲酸盐等还原剂作为病毒、真菌、细菌感染的预防，如以低浓度(比如质量/质量浓度1％-30％，下同)溶液作为日常的漱口水，少量添加于日用饮料中(如含量在1％-10％)，食品中(含量在1％-5％)，少量添加于个人日常清洁卫生用品中。所述饮料可以是瓶装水、饮用水、果汁、含酒精饮料；所述食品可以是面粉、米粉、腌制品、酱制品等；所述个人日常清洁卫生用品如肥皂、清洗液、护肤品等。According to some specific embodiments of the present invention, the method includes using formate and other reducing agents as the prevention of viral, fungal, and bacterial infections in daily life, such as using a low concentration (such as mass/mass concentration 1%-30 %, the same below) The solution is used as a daily mouthwash, a small amount added to daily beverages (such as content of 1%-10%), food (contents of 1% to 5%), a small amount added to personal daily cleaning and hygiene products middle. The beverage can be bottled water, drinking water, fruit juice, alcoholic beverage; the food can be flour, rice noodles, pickled products, sauce products, etc.; the personal daily cleaning and hygiene products such as soap, cleaning liquid, skin care products, etc. .
又一方面，本发明还提供了一种抑制病原体的方法，其中，所述方法包括向哺乳动物给药本发明前面任意一项所述的药物组合物，作为病原体感染的预防。In another aspect, the present invention also provides a method for inhibiting pathogens, wherein the method comprises administering the pharmaceutical composition according to any one of the preceding items of the present invention to a mammal as a prevention of pathogen infection.
根据本发明一些具体实施方案，其中，所述的药物组合物以低浓度溶液作为日常的漱口水；或少量添加于日用饮料中，食品中，日常个人卫生用品中。According to some specific embodiments of the present invention, wherein the pharmaceutical composition is a low-concentration solution as a daily mouthwash; or a small amount is added to daily beverages, foods, and daily personal hygiene products.
根据本发明一些具体实施方案，其中，所述饮料可以是瓶装水、饮用水、果汁、含酒精饮料；所述食品可以是面粉、米粉、腌制品、酱制品等。According to some specific embodiments of the present invention, wherein the beverage can be bottled water, drinking water, fruit juice, alcoholic beverage; the food can be flour, rice noodles, pickled products, sauce products, and the like.
根据本发明一些具体实施方案，其中，所述个人日常卫生用品如肥皂、清洗液、护肤品等。According to some specific embodiments of the present invention, the personal daily hygiene products such as soap, cleansing liquid, skin care products and the like.
又一方面，本发明还提供了一种调节人体体液pH值的方法，其中，所述方法包括向人体给药本发明前面任意所述的药物组合物。In another aspect, the present invention also provides a method for adjusting the pH value of human body fluids, wherein the method comprises administering to the human body any of the aforementioned pharmaceutical compositions of the present invention.
根据本发明一些具体实施方案，其中，所述体液为血液和/或尿液。According to some specific embodiments of the present invention, wherein the body fluid is blood and/or urine.
本申请发明人经过大量研究，认为本发明的组合物抑制病原体的原理如下：After a lot of research, the inventor of the present application believes that the composition of the present invention inhibits pathogens as follows:
改变体液pH值以及抑制基因基础物质的合成过程，这两者的共同作用使得能够同时增加体液的pH值以及抑制基因基础物质合成过程的还原剂如甲酸钠等物质具有对病毒、真菌、细菌以及炎性细胞、癌细胞***增殖有效的抑制效果。Changing the pH value of body fluids and inhibiting the synthesis process of gene basic substances, the combined effect of the two makes it possible to increase the pH value of body fluids and inhibit the synthesis process of gene basic substances at the same time. It has an effective inhibitory effect on the division and proliferation of sex cells and cancer cells.
关于抑制病毒与宿主细胞的结合，不管是病毒粘附蛋白VAPs直接与细胞受体相互吸附，还是通过调节分子的介导间接结合细胞受体，期间首先涉及到的都是静电吸引力。因此，减少配体或受体和/或调节分子的电荷数量，都会起到屏蔽病毒颗粒的作用。Regarding the inhibition of the binding of viruses to host cells, whether it is the direct adsorption of viral adhesion proteins VAPs to cell receptors or the indirect binding of cell receptors through the mediation of regulatory molecules, the first thing involved is electrostatic attraction. Therefore, reducing the charge number of ligands or receptors and/or regulatory molecules will play a role in shielding virus particles.
本申请发明人发现，大多数病毒的等电点在pH4-5.5之间，大多数细菌的等电点在pH3-4。因此生理条件下大多数病毒和细菌携带负电荷。由于病毒本身没有新陈代谢提供能量，病毒配体与细胞膜上特异性受体附着结合作为病毒复制的起始步骤只能被动的依靠配体-受体之间的静电吸引。The inventor of the present application found that the isoelectric point of most viruses is between pH 4-5.5, and that of most bacteria is pH 3-4. Therefore, most viruses and bacteria carry negative charges under physiological conditions. Since the virus itself does not provide energy for metabolism, the attachment and binding of virus ligands to specific receptors on the cell membrane as the initial step of virus replication can only passively rely on the electrostatic attraction between the ligand and the receptor.
因此，当细胞受体带正电荷时，只能选择性的接受配体带负电荷的病毒，同理，当细胞受体带负电荷时，只能选择性的接受配体带正电荷的病毒。可以合理预期的是，如果能够主动调节病毒、真菌、细菌或细胞受体表面电荷性质和数量，那么病毒、真菌、细菌和细胞之间是否可以结合或结合的几率也随之可以调节。Therefore, when cell receptors are positively charged, they can only selectively accept viruses with negatively charged ligands. Similarly, when cell receptors are negatively charged, they can only selectively accept viruses with positively charged ligands. . It can be reasonably expected that if the nature and quantity of surface charges of viruses, fungi, bacteria or cell receptors can be actively adjusted, then whether the viruses, fungi, bacteria and cells can bind or the probability of binding can also be adjusted accordingly.
病毒或细胞(包括细菌细胞)表面蛋白的电荷来源于氨基酸残基上氨基和羧基的水解反应，其中氨基易于携带正电荷，羧基易于携带负电荷。该反应受溶液的pH值影响，因此如果能够主动调节溶液(唾液、胃液或血液等体液)的pH值，就可以主动影响病毒、细菌、细胞表面电荷状态，以及相互之间的静电吸引力的大小。增加溶液的pH值，如果携带负电荷的氨基酸残基上还有未解离的羧基，则使携带负电荷的氨基酸残基继续增加负电荷数，直至氨基酸残基上所有的羧基全部解离，如果氨基酸残基上的羧基已经全部解离或只有一个羧基，则增加pH值，不能改变所携带负电荷的数量(饱和状态)。但增加pH值可以使携带正电荷的氨基酸残基上氨基所携带的正电荷逐步减少，即氨基上结合的氢离子H+逐步减少，直至携带电荷为0。The charge of the surface proteins of viruses or cells (including bacterial cells) comes from the hydrolysis reaction of amino and carboxyl groups on amino acid residues, where amino groups tend to carry positive charges and carboxyl groups tend to carry negative charges. The reaction is affected by the pH value of the solution, so if the pH value of the solution (saliva, gastric juice or blood and other body fluids) can be actively adjusted, it can actively affect the charge state of viruses, bacteria, cell surfaces, and the electrostatic attraction between each other. size. Increase the pH of the solution. If there are undissociated carboxyl groups on the negatively charged amino acid residues, the negatively charged amino acid residues will continue to increase the number of negative charges until all the carboxyl groups on the amino acid residues are dissociated. If all the carboxyl groups on the amino acid residues have been dissociated or there is only one carboxyl group, increase the pH value and cannot change the number of negative charges carried (saturation state). However, increasing the pH value can gradually reduce the positive charge carried by the amino group on the positively charged amino acid residue, that is, the hydrogen ion H+ bound to the amino group gradually decreases until the carrying charge is zero.
考虑大多数病毒、细菌携带负电荷，假设其羧基只有一个，或假设其最外侧的羧基(配体前端或被宿主蛋白酶切割后形成的前端)只有一个，或所有的羧基均已经饱和解离，则增加pH值，其最外侧配体携带的负电荷数不会再增加，即配体的负电荷数不受pH值增加的影响；但是，与病毒对应且携带正电荷的受体的正电荷数会随着pH值的增加而减少。其结果是，配体和受体之间的静电吸引减弱直至消失。Considering that most viruses and bacteria carry negative charges, assume that there is only one carboxyl group, or assume that the outermost carboxyl group (the front end of the ligand or the front end formed by the host protease) has only one, or all the carboxyl groups have been saturated and dissociated. If the pH value is increased, the number of negative charges carried by the outermost ligand will not increase, that is, the number of negative charges of the ligand will not be affected by the increase in pH; however, the positive charge of the receptor corresponding to the virus and carrying the positive charge The number will decrease as the pH value increases. As a result, the electrostatic attraction between the ligand and the receptor weakens until it disappears.
对于携带正电荷的病毒，增加pH值，病毒携带的正电荷数逐步减少；对应的携带负电荷的受体电荷数或不变或逐步增加，根据受体上羧基数量而定。其结果也是，配体和受体之间的静电吸引减弱直至消失。对配体或受体的实际屏蔽抑制效果依赖于pH值，依赖于剂量，即依赖于溶液的pH值的改变量。For viruses carrying positive charges, increasing the pH value will gradually reduce the number of positive charges carried by the virus; the corresponding number of negatively charged receptors will either remain unchanged or gradually increase, depending on the number of carboxyl groups on the receptor. As a result, the electrostatic attraction between the ligand and the receptor weakens until it disappears. The actual shielding inhibitory effect on the ligand or receptor depends on the pH value, on the dose, that is, on the amount of change in the pH value of the solution.
由于人体有自主调节和维持血液酸碱性在一定范围内的功能，加上局部电位涨落的可能性，病毒电荷、宿主细胞表面电荷未必能够被完全或稳定的中和，因此主动增加体液碱性的范围和有效性受到一定程度的限制，由此也即限制了通过单纯增加体液碱性的方法达到抑制病毒、细菌感染的目的和效果，从碱性的小苏打、醋酸钠难以有效的用于抑制病毒感染的实际现况，也证明了单一碱性的增加不能达到有效抑制病毒、细菌感染的效果和目的。Since the human body has the function of autonomously regulating and maintaining blood acidity and alkalinity within a certain range, coupled with the possibility of local potential fluctuations, virus charges and host cell surface charges may not be completely or stable neutralized, so actively increase body fluid alkalinity The range and effectiveness of sex are limited to a certain extent, which also limits the purpose and effect of inhibiting viral and bacterial infections by simply increasing the alkalinity of body fluids. It is difficult to effectively use alkaline baking soda and sodium acetate. The actual situation of inhibiting viral infections also proves that the increase of a single alkalinity can not achieve the effect and purpose of effectively inhibiting viral and bacterial infections.
为了解决单纯的增加体液碱性不能有效抑制病毒、细菌感染的问题，本发明进一步地利用还原性物质对嘧啶从头合成中二氢乳清酸脱氢反应合成嘧啶衍生物的抑制，双管齐下，从而达到抑制病毒、细菌、癌细胞、炎性细胞二代基因合成的目的和效果。In order to solve the problem that simply increasing the alkalinity of body fluids cannot effectively inhibit viral and bacterial infections, the present invention further uses reducing substances to inhibit the synthesis of pyrimidine derivatives by the dehydrogenation reaction of dihydroorotic acid in pyrimidine de novo synthesis. The purpose and effect of inhibiting the second-generation gene synthesis of viruses, bacteria, cancer cells, and inflammatory cells.
本发明的最重要的优点是，找到了甲酸钠等还原性物质，这些物质即可以通过中间反应，增加体液碱性，又能够抑制嘧啶的从头合成中的化学反应。The most important advantage of the present invention is that it has found reducing substances such as sodium formate, which can increase the alkalinity of body fluids through intermediate reactions, and can inhibit chemical reactions in the de novo synthesis of pyrimidines.
甲酸钠在水溶液(或体液)中以离子方式有如下倾向性反应：Sodium formate has the following tendency to react in an ionic manner in an aqueous solution (or body fluid):
HCOO -+Na ++H 2O＝＝＝Na ++HCO 3 -+[H]， HCOO - + Na + + H 2 O === Na + + HCO 3 - + [H],
上述反应类似脱氢反应。可见，甲酸钠或甲酸盐“脱氢”反应后，间接地形成水溶液中显碱性可增加溶液pH值的碳酸氢盐。The above reaction is similar to the dehydrogenation reaction. It can be seen that after the "dehydrogenation" reaction of sodium formate or formate, bicarbonate which is alkaline in the aqueous solution can be formed indirectly, which can increase the pH of the solution.
类似的，还原性草酸盐，也有类似的脱氢反应，也可以形成碱性的碳酸盐。Similarly, reducing oxalate has a similar dehydrogenation reaction and can also form alkaline carbonate.
其中所述的盐可为钠盐、钾盐、镁盐、钙盐等。The salt can be sodium salt, potassium salt, magnesium salt, calcium salt and the like.
当还原剂存在时，如甲酸钠存在时，存在如下竞争性反应:When a reducing agent is present, such as sodium formate, there are the following competitive reactions:
(1)二氢乳清酸脱氢，所脱氢转移至氧化性辅酶Q，后者转化为还原性辅酶Q；(1) Dihydroorotic acid dehydrogenation, the dehydrogenation is transferred to oxidizing coenzyme Q, which is converted into reducing coenzyme Q;
(2)(甲酸钠+水)“脱氢”，所脱氢转移至氧化性辅酶Q，后者转化为还原性辅酶Q。(2) (Sodium formate + water) "dehydrogenation", the dehydrogenation is transferred to oxidizing coenzyme Q, which is converted to reducing coenzyme Q.
上述还原性辅酶Q在细胞内被氧化恢复为氧化性辅酶Q。The above-mentioned reduced coenzyme Q is oxidized and restored to oxidized coenzyme Q in the cell.
或者or
(1)二氢乳清酸脱氢，所脱氢转移至氧化性的辅酶NAD，后者转化为还原性辅酶NADH；(1) Dihydroorotic acid dehydrogenation, the dehydrogenation is transferred to the oxidizing coenzyme NAD, which is converted into the reducing coenzyme NADH;
(2)(甲酸钠+水)“脱氢”，所脱氢转移至氧化性辅酶NAD，后者转化为还原性辅酶NADH。(2) (Sodium formate + water) "dehydrogenation", the dehydrogenation is transferred to the oxidizing coenzyme NAD, which is converted to the reducing coenzyme NADH.
或者or
(1)二氢乳清酸脱氢，所脱氢转移至氧化性的辅酶延胡索酸，后者转化为还原性的琥珀酸；(1) Dihydroorotic acid dehydrogenation, the dehydrogenation is transferred to the oxidizing coenzyme fumarate, which is converted to reducing succinic acid;
(2)(甲酸钠+水)“脱氢，”所脱氢转移至氧化性辅酶延胡索酸，后者转化为还原性的琥珀酸。(2) (Sodium formate + water) "dehydrogenation," the dehydrogenation is transferred to the oxidizing coenzyme fumaric acid, which is converted to reducing succinic acid.
当一个细胞内的辅酶Q、NAD、延胡索酸的数量给定时，同时氧的浓度保持不变时，甲酸钠的存在至少可以减少氧化性辅酶Q、NAD、延胡索酸的数量或浓度，因此起到了抑制二氢乳清酸转化为乳清酸的作用，从而抑制了嘧啶核苷酸的合成效率和数量。或者说，还原性的甲酸钠改变了细胞内的化学电位，从而影响了氧化性辅酶的催化活性。按能斯特方程所描述，这种改变是浓度依赖的。When the amount of coenzyme Q, NAD, and fumaric acid in a cell is given while the oxygen concentration remains the same, the presence of sodium formate can at least reduce the amount or concentration of oxidative coenzyme Q, NAD, and fumaric acid, thus inhibiting dihydrogen The effect of orotic acid is converted into orotic acid, thereby inhibiting the synthesis efficiency and quantity of pyrimidine nucleotides. In other words, reducing sodium formate changes the chemical potential in the cell, thereby affecting the catalytic activity of the oxidizing coenzyme. According to the Nernst equation, this change is concentration-dependent.
在人体正常细胞内，或好氧菌细胞内，氧分子浓度高，三羧酸循环可以提供大量的辅酶NAD，甲酸钠对辅酶NAD的效应减弱或不计，所以对正常细胞的糖酵解部分不影响，也不影响三羧酸循环。且由于正常细胞内DNA复制所需的嘧啶核苷酸依赖补救合成方式，所以，还原剂如甲酸钠不影响正常细胞修复或***时所需的嘧啶核苷酸的合成。In normal human cells, or in aerobic bacteria cells, where the concentration of oxygen molecules is high, the tricarboxylic acid cycle can provide a large amount of coenzyme NAD. The effect of sodium formate on coenzyme NAD is weakened or ignored, so it does not affect the glycolytic part of normal cells. , Does not affect the tricarboxylic acid cycle. And because the pyrimidine nucleotides required for DNA replication in normal cells depend on the salvage synthesis method, reducing agents such as sodium formate do not affect the synthesis of pyrimidine nucleotides required for normal cell repair or division.
在糖酵解反应过程中，涉及如下类似的竞争性反应：In the process of glycolysis, the following similar competitive reactions are involved:
(1)3-磷酸甘油醛脱氢，所脱氢转移至氧化性辅酶NAD，后者转化为还原性辅酶NADH；(1) Glyceraldehyde 3-phosphate dehydrogenation, the dehydrogenation is transferred to the oxidizing coenzyme NAD, which is converted into the reducing coenzyme NADH;
(2)(甲酸钠+水)“脱氢，”所脱氢转移至氧化性辅酶NAD，后者转化为还原性辅酶NADH。(2) (Sodium formate + water) "dehydrogenation," the dehydrogenation is transferred to the oxidizing coenzyme NAD, which is converted into the reducing coenzyme NADH.
在谷氨酸脱氢反应过程中，涉及如下类似的竞争性反应：In the process of glutamic acid dehydrogenation, the following similar competitive reactions are involved:
(1)谷氨酸脱氢，所脱氢转移至氧化性辅酶NADP，后者转化为还原性辅酶NADPH；(1) Dehydrogenation of glutamate, the dehydrogenation is transferred to the oxidizing coenzyme NADP, which is converted into the reducing coenzyme NADPH;
(2)(甲酸钠+水)“脱氢，”所脱氢转移至氧化性辅酶NADP，后者转化为还原性辅酶NADPH。NADPH主要来源于细胞内的戊糖磷酸途径，也不受甲酸钠还原剂的影响。(2) (Sodium formate + water) "dehydrogenation," the dehydrogenation is transferred to the oxidizing coenzyme NADP, which is converted into the reducing coenzyme NADPH. NADPH is mainly derived from the intracellular pentose phosphate pathway and is not affected by sodium formate reducing agent.
好氧菌在条件合适时将不停的增殖，然而如上所述，好氧菌细胞内的辅酶NAD以及NADPH不会受到还原剂的影响，但好氧菌的增殖或DNA的复制依赖嘧啶核苷酸的从头合成反应，由此给还原剂如甲酸钠等提供了抑制好氧菌增值的一个机会和方法。其原因是，细菌的DHODH位于胞质或胞质膜内侧，因此，线粒体中的氧化反应提供的NAD对DHODH的辅酶NAD数量没有影响或只有较小的影响。Aerobic bacteria will continue to proliferate under suitable conditions. However, as mentioned above, the coenzymes NAD and NADPH in aerobic bacteria cells will not be affected by reducing agents, but the proliferation of aerobic bacteria or DNA replication depends on pyrimidine nucleosides. The de novo synthesis reaction of acid provides reducing agents such as sodium formate with an opportunity and method to inhibit the growth of aerobic bacteria. The reason is that the bacterial DHODH is located inside the cytoplasm or cytoplasmic membrane. Therefore, the NAD provided by the oxidation reaction in the mitochondria has no or only a small effect on the amount of the coenzyme NAD of DHODH.
当病毒进入正常细胞内，病毒DNA、或RNA高速复制时，所需嘧啶核苷酸依赖宿主细胞的从头合成途径。本发明突破了对付病毒只从针对病毒本身的传统技术习惯，本发明间接地，控制了宿主细胞的基因快速复制，也就控制了病毒，也突破了原本是抑制细胞中嘧啶核苷酸从头合成途径的思路不能或没有想到可以直接用于非细胞性的病毒的思维局限性。还原剂如甲酸钠抑制或减少了氧化性辅酶Q、NAD、延胡索酸的数量和浓度，减少了嘧啶核苷酸合成的效率和数量，因此，能够间接抑制病毒DNA或RNA的复制。病毒复制的数量、感染力、破坏力受到限制，抑制二氢乳清酸转化为乳清酸的反应制剂即成为病毒的一种广谱解药。When the virus enters normal cells and the viral DNA or RNA replicates at a high speed, the required pyrimidine nucleotides depend on the de novo synthesis pathway of the host cell. The present invention breaks through the traditional technical habit of dealing with viruses only by focusing on the virus itself. Indirectly, the present invention controls the rapid replication of host cells' genes, which also controls the virus, and also breaks through the original inhibition of de novo synthesis of pyrimidine nucleotides in cells. The way of thinking cannot or did not think of the limitations of thinking that can be directly applied to non-cellular viruses. Reducing agents such as sodium formate inhibit or reduce the quantity and concentration of oxidative coenzyme Q, NAD, and fumaric acid, and reduce the efficiency and quantity of pyrimidine nucleotide synthesis, and therefore, can indirectly inhibit the replication of viral DNA or RNA. The number of virus replication, infectivity, and destructive power are limited, and the reaction preparation that inhibits the conversion of dihydroorotic acid into orotic acid becomes a broad-spectrum antidote to the virus.
当病毒进入宿主细胞并促使宿主细胞高速复制病毒基因和病毒时，宿主细胞的物质和能量消耗预期会骤增，有可能改变细胞的呼吸代谢方式为有氧糖酵解方式。在此模式下，呼吸反应的代谢产物乳酸在血液中堆积增加，而酸性的血液环境促进栓塞的形成，从而导致各种栓塞问题。另外，病毒导致细胞癌变或许与病毒长时间改变细胞呼吸模式有关。When the virus enters the host cell and prompts the host cell to replicate viral genes and viruses at a high speed, the material and energy consumption of the host cell is expected to increase sharply, which may change the cell's respiratory metabolism to aerobic glycolysis. In this mode, lactic acid, a metabolite of respiratory reaction, accumulates in the blood, and the acidic blood environment promotes the formation of embolism, which leads to various embolism problems. In addition, the virus causing cell cancer may be related to the long-term change of the cell respiration pattern by the virus.
利用糖酵解呼吸(葡萄糖至产物丙酮酸以及丙酮酸加氢的代谢路径)方式的癌细胞以及厌氧菌细胞内氧分子浓度低，嘧啶核苷酸从头合成时，氧化性辅酶NAD、氧化性辅酶Q、延胡索酸的再生速度慢。因此，还原剂如甲酸钠等对氧化性辅酶Q、NAD、延胡索酸的消耗，可发挥更加显着的作用。从而阻止嘧啶核苷酸的可持续合成。因此，还原剂如甲酸钠等不仅能够通过抑制辅酶NAD抑制癌细胞以及厌氧菌的糖酵解的呼吸反应，还可以通过抑制氧化性辅酶Q、NAD以及延胡索酸抑制嘧啶核苷酸的从头合成反应，阻碍癌细胞及厌氧菌包括好氧菌细胞的DNA复制，实现对厌氧菌和癌细胞能量合成、以及增殖复制的双重抑制，及对好氧菌细胞DNA复制的抑 制。Cancer cells and anaerobes that use glycolytic respiration (metabolic pathways from glucose to product pyruvate and pyruvate hydrogenation) have low intracellular oxygen molecule concentrations. When pyrimidine nucleotides are synthesized de novo, oxidative coenzymes NAD and oxidative The regeneration rate of coenzyme Q and fumaric acid is slow. Therefore, reducing agents such as sodium formate can play a more significant role in the consumption of oxidative coenzyme Q, NAD, and fumaric acid. Thus preventing the sustainable synthesis of pyrimidine nucleotides. Therefore, reducing agents such as sodium formate can not only inhibit the glycolytic respiratory reaction of cancer cells and anaerobic bacteria by inhibiting coenzyme NAD, but also inhibit the de novo synthesis of pyrimidine nucleotides by inhibiting oxidative coenzyme Q, NAD and fumaric acid. Inhibit the DNA replication of cancer cells and anaerobes, including aerobic cells, and achieve dual inhibition of energy synthesis, proliferation and replication of anaerobes and cancer cells, and inhibition of DNA replication of aerobic cells.
另外，本发明的优点还有，通过控制基因复制的合成反应控制病毒基因、癌细胞、细菌细胞、炎性细胞的复制合成，从源头就解决了基因变异所导致的耐药性这一世界性难题。本发明的优点之一还有，由于可以增加体液pH值，有助于缓解病毒或细菌感染引起的肺炎导致的痰栓问题。In addition, the present invention also has the advantage of controlling the replication and synthesis of viral genes, cancer cells, bacterial cells, and inflammatory cells by controlling the synthesis reaction of gene replication, and solves the global drug resistance caused by gene mutation from the source. problem. One of the advantages of the present invention is that because the pH value of body fluid can be increased, it helps to alleviate the problem of phlegm plug caused by pneumonia caused by virus or bacterial infection.
因此，嘧啶核苷酸的合成对病毒借助于宿主细胞的基因复制，癌细胞、细菌细胞、炎性细胞的增殖及新陈代谢都至关重要，所以本发明的抑制病毒、细菌、炎性细胞的方法，利用了还原剂如甲酸盐、草酸盐或两者的混合物，不仅增加了体液的碱性，阻碍病毒与宿主细胞的静电吸引接触，还同时抑制DNA或RNA复制时所必须的嘧啶核苷酸从头合成反应中的二氢乳清酸的利用和/或二氢乳清酸的脱氢反应，实现对病毒和细菌感染和增殖的抑制以及对炎性细胞增殖的抑制。Therefore, the synthesis of pyrimidine nucleotides is essential for virus replication by host cells, and for the proliferation and metabolism of cancer cells, bacterial cells, and inflammatory cells. Therefore, the method for inhibiting viruses, bacteria, and inflammatory cells of the present invention The use of reducing agents such as formate, oxalate or a mixture of both not only increases the alkalinity of body fluids, hinders the electrostatic attraction contact between the virus and the host cell, but also inhibits the pyrimidine nucleus necessary for DNA or RNA replication The utilization of dihydroorotic acid and/or the dehydrogenation reaction of dihydroorotic acid in the de novo synthesis reaction of uronic acid realizes the inhibition of viral and bacterial infection and proliferation, and the inhibition of the proliferation of inflammatory cells.
本发明抑制病毒、细菌、炎性细胞的方法是利用吸附宿主细胞是所有病毒感染过程中第一步的特点，增加体液的pH值为工具，降低病毒配体或宿主细胞受体上所携带的正电荷数量，减少对携带异性电荷的宿主细胞或病毒的静电吸附力，同时兼有抑制病毒或细菌基因复制中嘧啶的从头合成路径的效果，克服单独抑制嘧啶从头合成路径抑制病毒或细菌感染效力可能不足的问题，达到有效抑制病毒、细菌感染和炎性细胞快速增殖的效果，达到对相应疾病症状的缓解和治愈的目的。衣原体、蛋白酶类毒素也是借助于其外表面膜蛋白粘附宿主细胞作为致病的第一步，其中的增殖复制同样涉及基因的合成，因此，本发明的方法也适用于类似的依靠表面电荷静电吸引与宿主细胞粘附的各种病原体。支原体通过自身的粘附蛋白粘附于上皮细胞、红细胞表面，因此本发明中可将支原体作为一种可携带电荷的广义细菌或广义病毒。因其可与红细胞粘附，说明支原体携带正电荷，因此容易被pH值增加的环境所中和。The method of the present invention for inhibiting viruses, bacteria, and inflammatory cells is to use the characteristic of adsorbing host cells as the first step in the infection process of all viruses, increase the pH value of body fluids, and reduce the viral ligands or host cell receptors carried The number of positive charges reduces the electrostatic adsorption to host cells or viruses carrying opposite charges. At the same time, it has the effect of inhibiting the de novo synthesis path of pyrimidine in virus or bacterial gene replication, and overcomes the effect of inhibiting the de novo synthesis path of pyrimidine alone to inhibit virus or bacterial infection. The problem of possible insufficiency can achieve the effect of effectively inhibiting virus, bacterial infection and rapid proliferation of inflammatory cells, and achieve the purpose of alleviating and curing the symptoms of corresponding diseases. Chlamydia and protease toxoids also use their outer surface membrane proteins to adhere to host cells as the first step to cause disease. The proliferation and replication also involve gene synthesis. Therefore, the method of the present invention is also suitable for similar electrostatic attraction by surface charges. Various pathogens that adhere to host cells. Mycoplasma adheres to the surface of epithelial cells and red blood cells through its own adhesion protein. Therefore, in the present invention, mycoplasma can be used as a generalized bacteria or generalized virus that can carry charges. Because it can adhere to red blood cells, mycoplasma carries a positive charge and is therefore easily neutralized by an environment with increased pH.
附图说明Description of the drawings
图1为实施例4的茭白表面照片，左图为单独浸入了二氢乳清酸溶液的茭白表面，右图为浸入了二氢乳清酸溶液中添加了甲酸钠的茭白表面。Fig. 1 is a photograph of the surface of the water chestnut in Example 4. The left picture shows the water chestnut surface immersed in the dihydroorotic acid solution alone, and the right picture is the water chestnut surface immersed in the dihydroorotic acid solution and added with sodium formate.
图2为实施例5的添加了二氢乳清酸(图中上半部分)和同时添加了二氢乳清酸、甲酸钠(图中下半部分)的面团面表面照片。Figure 2 is a photograph of the surface of the dough surface of Example 5 added with dihydroorotic acid (the upper part of the figure) and both dihydroorotic acid and sodium formate (the lower part of the figure).
具体实施方式Detailed ways
以下结合实施例详细说明本发明的技术方案，但本发明的保护范围包括但是不限于此。The technical solutions of the present invention will be described in detail below with reference to the embodiments, but the protection scope of the present invention includes but is not limited thereto.
受时间的限制，实施例中也提供了仅供参考的案例，虽然个案或样本数量目前不足，但应该能够昭示符合本发明效果的必然性。历史上，诸多的重大药物或医疗方法的发现，都有从个案开始的偶然发现开始，最后推广并改变时代的经历，如青霉素、牛痘的发现；也还有很多有效的药物，往往都是先在临床上被医师发现有效，几十年，甚至上百年后，才发现它的真正原理，例如1929年发明的二甲双胍，例如砒霜制剂，例如甘草酸，人们明晰它们的机理，都花了半个世纪以上。Due to time constraints, the examples also provide cases for reference only. Although the number of cases or samples is currently insufficient, it should be able to show the inevitability of the effect of the present invention. In history, the discovery of many major drugs or medical methods started from accidental discoveries at the beginning of the case, and finally promoted and changed the experience of the times, such as the discovery of penicillin and vaccinia; there are also many effective drugs, often first. It was found to be effective by physicians in the clinic. It took decades or even hundreds of years to discover its true principle. For example, metformin was invented in 1929, such as arsenic preparations, such as glycyrrhizic acid. It took half a time for people to understand their mechanism. More than a century.
实施例1Example 1
成年人8位，***饱和甲酸钠溶液30毫升(该溶液的pH值为6-7)约30秒时间，然后吐出，都测得唾液pH从约5增加到约9，即唾液中氢氧根离子浓度增加了约1万倍，30秒后饮用凉白开水250毫升，15分钟后测唾液pH值仍然达到8，1小时后唾液恢复到正常状态的5。改用甲酸钾、草酸钠具有相同的增加唾液碱性的效果。碱性的增加是指，体液中氢氧根离子浓度的增加或相对而言氢离子浓度的降低。8 adults, mouth 30 ml of saturated sodium formate solution (the pH value of the solution is 6-7) for about 30 seconds, and then spit it out. It was measured that the saliva pH increased from about 5 to about 9, which is the hydroxyl radical in the saliva. The ion concentration increased by about 10,000 times. After 30 seconds, after drinking 250 ml of cool plain water, the pH value of saliva still reached 8 after 15 minutes, and the saliva returned to the normal state of 5 after 1 hour. Switching to potassium formate and sodium oxalate has the same effect of increasing saliva alkalinity. An increase in alkalinity refers to an increase in the concentration of hydroxide ions in body fluids or a relative decrease in the concentration of hydrogen ions.
甲酸钠在人体内或动物体内解离成为甲酸根离子以及钠离子，该两种离子独立发挥作用，在体液中的反应可以表示为：Sodium formate dissociates into formate ions and sodium ions in humans or animals. These two ions work independently. The reaction in body fluids can be expressed as:
HCOO -+Na ++H 2O+2B＝＝＝NaHCO 3+2HB HCOO - + Na + + H 2 O + 2B === NaHCO 3 + 2HB
以及as well as
NaHCO 3+H 2O＝＝＝Na++H 2CO 3+OH - NaHCO 3 + H 2 O === Na ++ H 2 CO 3 + OH -
草酸盐也具有上述类似反应。其中，B是人体体液中或细胞中可以接受电子的氧化性物质(如活性自由基)或氧化性反应过程。上述反应不仅灭活了自由基或参与了氧化还原性反应，如可以抑制嘧啶从头合成的通路，还为人体提供了增加pH值的氢氧根负离子。Oxalate also has a similar reaction as described above. Among them, B is an oxidative substance (such as active free radicals) or an oxidative reaction process that can accept electrons in human body fluids or cells. The above reaction not only inactivates free radicals or participates in redox reactions, such as inhibiting the de novo synthesis of pyrimidine, but also provides the human body with hydroxide anions that increase pH.
实施例2Example 2
十位成年人，晨起尿液pH值自测在4-5.5的范围，服用10g甲酸钠1小时后，测得尿液pH值达到6-7，氢氧根离子浓度增加了100-1000倍，2小时后仍然保持6-7左右，三小时后降低到5-6左右。1位成年女性，连续每天服用3g(分早中晚3次)甲酸钠一个月，测得尿液平均维持在7.5-8.5。因为尿液酸碱性反映了血液的酸碱性程度，因此可 知血液的碱性也增加了。有例证是，1位成年女性按每天1-2g连续服用2个月后，经医院测得血液pH值7.53。说明甲酸钠可以大幅增加血液的碱性。Ten adults, self-tested urine pH in the range of 4-5.5 in the morning. One hour after taking 10g of sodium formate, the urine pH was measured to reach 6-7, and the hydroxide ion concentration increased by 100-1000 times. After 2 hours, it still remains at about 6-7, and after three hours it drops to about 5-6. An adult female took 3g of sodium formate daily (3 times in the morning, midnight and evening) for one month, and her urine remained at an average of 7.5-8.5. Because urine acidity and alkalinity reflect the acidity and alkalinity of blood, it can be seen that the alkalinity of blood has also increased. An example is that after an adult woman took 1-2g a day for 2 months, the blood pH value of 7.53 was measured by the hospital. It shows that sodium formate can greatly increase the alkalinity of the blood.
关于个体具体的服用剂量或直接注射时所需的剂量，因为是调节体液的pH值，而每个人的初始pH值都不尽相同，体液的总量也不尽相同，因此，要达到同样的pH值水平，所需要的服用量或注射量是不同的。针对所有实施例的实际操作，可以根据尿液或血液的pH值进行增加或减少，比如当尿液的pH值低于5.5时，可以每天增加1克的用量，直到尿液的pH值不高于8(正常值的上限)，或血液的pH值不高于7.87。Regarding the individual specific dosage or the dosage required for direct injection, because it is to adjust the pH value of body fluids, and everyone’s initial pH value is different, and the total amount of body fluids is also not the same. Therefore, it is necessary to achieve the same The pH level, the required dosage or injection volume are different. For the actual operation of all the embodiments, it can be increased or decreased according to the pH value of urine or blood. For example, when the pH value of urine is lower than 5.5, the dosage can be increased by 1 gram per day until the pH value of urine is not high. Is below 8 (the upper limit of the normal value), or the pH of the blood is not higher than 7.87.
实施例3Example 3
一位小细胞肺癌病友在放化疗后复发无药可用的情况下，单独按每天3次每次服用甲酸钠3克连续一个月，再改成服用甲酸钾每天3次每次3克连续服用一个月，再改成服用甲酸钠每天3次每次20克连续服用约2个月，再改成服用甲酸钾每天3次每次20克连续服用约2个月，在持续服用期间的四次医院血液检查报告显示血液pH值分别达到7.57，7.76，7.87，7.77，期间体感良好，说明了通过服用甲酸盐病人血液的pH值可以显著增加，并可以达到7.87。A patient with small cell lung cancer who relapsed after radiotherapy and chemotherapy and no medicine was available, he alone took 3 grams of sodium formate 3 times a day for one month, and then changed to take potassium formate 3 times a day and 3 grams each time for one month. Change to taking sodium formate 3 times a day and 20 grams each time for about 2 months continuously, and then change to taking potassium formate 3 times a day and 20 grams each time for about 2 months continuously. Four hospital blood tests during the continuous use period The report showed that the blood pH value reached 7.57, 7.76, 7.87, and 7.77. During the period, the body felt good, indicating that the pH value of the blood of patients taking formate can be significantly increased, and can reach 7.87.
实施例4Example 4
采摘新鲜茭白直径约2.5厘米，用消毒后的刀片切割，所形成的基本对称的两个切面上可见茭白黑粉菌黑色的孢子堆。随即，其中一个切片浸入二氢乳清酸饱和溶液(由于二氢乳清酸溶解度低，将其粉末倒入清水中，室温下搅拌5分钟后，尚有未溶解颗粒，此时倒出溶液，假定为饱和溶液，测得其pH值5)中3秒，对称的另外一个切片浸入二氢乳清酸饱和溶液并另加入了甲酸钠粉末(甲酸钠在溶液中重量含量0.1％)，使得切片在该溶液中浸泡3秒。两片茭白片取出后置于同一烧杯内，对称的两个切面朝上，并用湿毛巾覆盖烧杯口。24小时后观察，单独涂抹了含二氢乳清酸溶液的茭白表面(如图1左图所示)的茭白黑粉菌黑色的孢子堆数量明显增加，孢子堆***，最长的长出表面约5毫米，而涂抹了二氢乳清酸和甲酸钠混合溶液的茭白表面(如图1右图所示)黑色的孢子堆只长出表面约2毫米，且新增加的褐色孢子堆数量明显少于单独涂抹了二氢乳清酸的茭白表面(见图1)。Pick fresh water bamboo with a diameter of about 2.5 cm, and cut it with a sterilized blade. The two basically symmetrical sections formed show black spore piles of Zizania smut fungus. Immediately, one of the slices was immersed in a saturated solution of dihydroorotic acid (due to the low solubility of dihydroorotic acid, pour its powder into clean water and stir at room temperature for 5 minutes, and there are still undissolved particles. Pour out the solution at this time. Assuming it is a saturated solution, the pH value is measured in 5) for 3 seconds, another symmetrical slice is immersed in a saturated solution of dihydroorotic acid and sodium formate powder (sodium formate in the solution is 0.1% by weight) is added to make the slice in this Soak in the solution for 3 seconds. After taking out the two pieces of water chestnut, put them in the same beaker, with the two symmetrical cut surfaces facing up, and cover the mouth of the beaker with a wet towel. Observed after 24 hours, the number of black spore piles of Zizania spore fungus on the surface of Zizania sibiricum containing dihydroorotic acid solution alone (as shown in the left picture in Figure 1) increased significantly, the piles of spores became thicker, and the longest spores grew. The surface is about 5 mm, while the surface of the water chestnut coated with a mixed solution of dihydroorotic acid and sodium formate (as shown in the right picture in Figure 1). The black spore piles only grow about 2 mm from the surface, and the number of newly added brown spore piles is obvious Less than the surface of water chestnuts with dihydroorotic acid alone (see Figure 1).
另外，将与上述类似切割开的两个茭白切面分别用清水和只含1％甲酸钠的溶液浸染3秒时间。同样时间间隔的对比可见，仅涂抹了清水的茭白表面的黑色的孢子堆高度和数量明显多于浸染了甲酸钠的茭白表面，但少于单独涂抹了二氢乳清酸的茭白 表面，多于同时涂抹了二氢乳清酸和甲酸钠混合溶液的茭白表面。In addition, two slices of water chestnut cut similarly to the above were soaked with water and a solution containing only 1% sodium formate for 3 seconds, respectively. Comparing the same time interval, it can be seen that the height and number of black spore piles on the surface of Zizania sibiricum only coated with water are significantly higher than those on the surface of Zizania spores impregnated with sodium formate, but less than the surface of Zizania spores coated with dihydroorotic acid alone, and more than at the same time. The surface of the water chestnut with a mixed solution of dihydroorotic acid and sodium formate.
上述现象说明，甲酸钠本身抑制了黑粉菌的增殖，也抑制了黑粉菌对外加的二氢乳清酸的利用转化。因为黑粉菌属真菌，为好氧菌，因此，甲酸钠不会影响其呼吸代谢反应，能够影响的应该是二氢乳清酸脱氢转化为乳清酸的反应，由此，抑制了嘧啶核苷酸的合成，导致黑粉菌合成DNA障碍。The above phenomenon shows that sodium formate itself inhibits the proliferation of smut fungus, and also inhibits the utilization and conversion of the added dihydroorotic acid of smut fungus. Because the smut is a fungus, it is an aerobic bacteria, so sodium formate will not affect its respiratory metabolism. What can affect should be the reaction of dihydroorotic acid dehydrogenation to orotic acid, thereby inhibiting the pyrimidine nucleus The synthesis of glycosides leads to the obstacles to the synthesis of DNA by smut fungus.
茭白黑粉菌细胞内二氢乳清酸脱氢反应的辅酶可能是辅酶NAD或辅酶Q，上述试验至少可以证明还原性的物质如甲酸钠可以抑制DHODH的辅酶NAD或辅酶Q其中之一。上述甲酸钠替换为草酸钠后，具有相似的实验结果。The coenzyme of the dihydroorotic acid dehydrogenation reaction in Zizania smut cells may be coenzyme NAD or coenzyme Q. The above test can at least prove that reducing substances such as sodium formate can inhibit one of the coenzyme NAD or coenzyme Q of DHODH. After replacing the above sodium formate with sodium oxalate, similar experimental results were obtained.
实施例5Example 5
10g面粉加5毫升水，水中溶解了约1毫克的市售面粉酵母粉。搅拌均匀后，用潮湿的pH试纸测面粉团表面的pH值约为6。Add 5 ml of water to 10 g of flour, and about 1 mg of commercially available flour yeast powder is dissolved in the water. After stirring evenly, measure the pH value of the dough surface to be about 6 with wet pH test paper.
取其中8克，加入二氢乳清酸粉末25毫克，并充分搅拌均匀，测得此时面粉团表面的pH值约为3-4。Take 8 grams of it, add 25 mg of dihydroorotic acid powder, and stir it evenly. It is measured that the pH value of the surface of the flour dough is about 3-4 at this time.
将上述面团一分为二等份，其中一份4克中加入4毫克甲酸钠，充分搅拌均匀。将此两份面团分别涂抹在250毫升的烧杯璧上，涂抹厚度约1毫米，以便保持面团发酵能在好氧状态下进行，湿毛巾覆盖杯口避免面团的自然干燥。Divide the dough into two equal portions, add 4 mg of sodium formate to 4 grams of one portion, and mix well. Spread the two pieces of dough on a 250 ml beaker, with a thickness of about 1 mm, in order to keep the dough fermented in an aerobic state, and cover the cup with a wet towel to avoid natural drying of the dough.
发酵6小时后，透过烧杯璧可见单独添加了二氢乳清酸的面团中出现大量微小气泡，面团含水量增加，体积增大，容易粘黏试纸，应该分别是有氧呼吸释放出的二氧化碳和水分所致，而同时添加了甲酸钠的面团没有出现可见的气泡，面团的大小没有可见的变化，也没有粘黏试纸的现象。因此可以说明，甲酸钠抑制了面团酵母菌的好氧发酵反应。After 6 hours of fermentation, it can be seen through the beaker that a large number of tiny bubbles appear in the dough added with dihydroorotic acid alone, the water content of the dough increases, the volume increases, and it is easy to stick to the test paper. It should be the carbon dioxide released by aerobic respiration. It is caused by moisture, and the dough with sodium formate added at the same time has no visible bubbles, the size of the dough has no visible change, and there is no sticky test paper. Therefore, it can be explained that sodium formate inhibits the aerobic fermentation reaction of dough yeast.
发酵12小时后，用pH试纸可测出，单独添加了二氢乳清酸的面团的pH值在缓慢增加，而同时又添加了甲酸钠的面团的pH值几乎不变。发酵24小时后，同时又添加了甲酸钠的面团的pH值也有所增加，但始终低于只添加了二氢乳清酸的面团的pH值。After 12 hours of fermentation, it can be measured with a pH test paper that the pH value of the dough added with dihydroorotic acid is slowly increasing, while the pH value of the dough added with sodium formate is almost unchanged. After 24 hours of fermentation, the pH value of the dough added with sodium formate also increased, but it was always lower than the pH value of the dough only added with dihydroorotic acid.
发酵48小时后，作为对比观察，同时添加了甲酸钠的面团的pH值根据试纸显示，约为3，单独添加二氢乳清酸的面团的pH值约为4。After 48 hours of fermentation, as a comparative observation, the pH value of the dough added with sodium formate was about 3 according to the test paper, and the pH value of the dough added with dihydroorotic acid was about 4.
7天后打开覆盖的毛巾观察，单独添加二氢乳清酸的面团(图2上方)面上覆盖了一层约5-10毫米厚的青绿色菌丝，而同时添加了二氢乳清酸和甲酸钠的面团(图2 下方)面上依旧是面团原来的乳白色(面团表面留下的红色部分是潮湿的pH试纸按压测试时留下的颜色，pH试纸按压测试显示pH值约4)，也未见有菌丝。说明了甲酸钠对酵母细菌增殖具有持久的抑制作用(见图2)，因为是通过抑制基因合成中嘧啶合成通路抑制了细菌的增殖，因此，如同对酵母菌具有持久抑制作用一样，还原剂如甲酸盐等对其它细菌的增殖具有相同或相似的抑制作用。After 7 days, the covered towel was opened and observed. The dough (top of Figure 2) to which dihydroorotic acid was added alone was covered with a layer of turquoise mycelium about 5-10 mm thick, and dihydroorotic acid and dihydroorotic acid were added at the same time. The surface of the sodium formate dough (bottom of Figure 2) is still the original milky white of the dough (the red part left on the surface of the dough is the color left by the wet pH test paper when the test is pressed, and the pH test shows that the pH is about 4). See there are hyphae. It shows that sodium formate has a long-lasting inhibitory effect on the proliferation of yeast bacteria (see Figure 2), because it inhibits the proliferation of bacteria by inhibiting the pyrimidine synthesis pathway in gene synthesis. Therefore, as long as the yeast has a long-lasting inhibitory effect, reducing agents such as A Acid salts have the same or similar inhibitory effect on the proliferation of other bacteria.
也正如预期，增加甲酸钠的浓度或量，上述pH值的差别更大，出现差别的时间更短。如将上述甲酸钠替换为草酸钠后，实验结果类似。As expected, increasing the concentration or amount of sodium formate will result in a greater difference in the above-mentioned pH value and a shorter time for the difference. If the above sodium formate is replaced with sodium oxalate, the experimental results are similar.
当酸性的二氢乳清酸(pKa 3.41)被转化利用合成嘧啶核苷酸后，随着其消耗，面团的pH值增加；而添加了甲酸钠或草酸钠的面团，由于还原剂抑制了二氢乳清酸的消耗反应，应该是抑制和减缓了酵母菌细胞中二氢乳清酸脱氢转化反应，因此面团的pH值基本不变或缓慢增加。When the acidic dihydroorotic acid (pKa 3.41) is converted to use synthetic pyrimidine nucleotides, as it is consumed, the pH value of the dough increases; while the dough added with sodium formate or sodium oxalate, the reducing agent inhibits the dihydrogen The consumption reaction of orotic acid should be to inhibit and slow down the dehydrogenation conversion reaction of dihydroorotic acid in yeast cells, so the pH value of the dough basically remains unchanged or slowly increases.
在好氧条件下，甲酸钠、草酸钠的这种对发酵的抑制应该不是通过抑制糖酵解反应，而是抑制了二氢乳清酸脱氢反应，即抑制了二氢乳清酸脱氢反应的辅酶NAD或辅酶Q。还原剂如甲酸钠的浓度越高，抑制辅酶的作用越强，因此，抑制效果是剂量依赖的。虽然好氧条件下，线粒体可以提供大量的辅酶NAD产物，但根据细菌的二氢乳清酸脱氢酶位于胞质或胞质膜内侧的事实，可以预期线粒体内的三羧酸循环不会直接影响此处DHODH的催化反应，尤其是，不会直接影响二氢乳清酸脱氢酶的辅酶NAD-NADH之间的相互转化反应。Under aerobic conditions, the inhibition of fermentation by sodium formate and sodium oxalate should not be by inhibiting glycolysis, but by inhibiting the dehydrogenation reaction of dihydroorotic acid, that is, inhibiting the dehydrogenation reaction of dihydroorotic acid. The coenzyme NAD or coenzyme Q. The higher the concentration of reducing agent such as sodium formate, the stronger the inhibitory effect of coenzyme, therefore, the inhibitory effect is dose-dependent. Although under aerobic conditions, mitochondria can provide a large amount of coenzyme NAD products, according to the fact that the bacterial dihydroorotate dehydrogenase is located in the cytoplasm or inside the cytoplasmic membrane, it can be expected that the tricarboxylic acid cycle in the mitochondria will not be directly Influencing the catalytic reaction of DHODH here, in particular, does not directly affect the mutual conversion reaction between the coenzyme NAD-NADH of dihydroorotate dehydrogenase.
实施例6Example 6
将市售CO Q-10(Q-SORB TM)一粒剪开，其中黄色带有红色的液状辅酶Q10滴到小烧杯底部。倒入蒸馏水后，无论如何摇晃或搅拌，底部的辅酶都与水呈分离状，清水仍然清澈透明。当加入少量甲酸钠后，含甲酸钠约为1％，再轻轻摇晃约15分钟，底部的辅酶缓慢溶解或分离，其中未溶解的辅酶颜色变黄(失去红艳色)，静置后溶液呈现淡淡的乳白色，光照呈现丁达尔现象，说明部分辅酶以胶体方式融入水溶液中，且检测到溶液pH值有增加。其原理应该是： Cut one pellet of commercially available CO Q-10 (Q-SORB TM ), and drop the yellow and red liquid coenzyme Q10 onto the bottom of the small beaker. After pouring in distilled water, no matter if it is shaken or stirred, the coenzyme at the bottom is separated from the water, and the water is still clear and transparent. After adding a small amount of sodium formate, the content of sodium formate is about 1%, and then gently shake for about 15 minutes, the coenzyme at the bottom slowly dissolves or separates, and the color of the undissolved coenzyme turns yellow (lost the red color), and the solution appears light after standing. The color is milky white, and the light shows Tyndall phenomenon, indicating that some of the coenzymes are colloidally incorporated into the aqueous solution, and the pH of the solution has been detected to increase. The principle should be:
泛醌(氧化态辅酶Q10)+HCOO -+Na ++H 2O＝＝＝泛酚(还原态辅酶Q10)+NaHCO 3(显碱性) Ubiquinone (coenzyme in oxidation state Q10) + HCOO - + Na + + H 2 O === pan phenol (of reduced coenzyme Q10) + NaHCO 3 (basic significant)
即甲酸钠的水溶液还原了氧化态辅酶Q10，使辅酶中疏水的羰基还原为亲水的羟基，增加了辅酶的溶解度，促进了还原性的辅酶微细颗粒与水溶液混溶形成胶体。That is, the aqueous solution of sodium formate reduces the oxidized coenzyme Q10, reduces the hydrophobic carbonyl group in the coenzyme to a hydrophilic hydroxyl group, increases the solubility of the coenzyme, and promotes the miscibility of the reducing coenzyme fine particles with the aqueous solution to form a colloid.
本实施例证明了甲酸钠的水溶液具有还原辅酶Q10的化学能力。说明在含水的人体细胞内，还原性物质如甲酸钠同样可以抑制和减少二氢乳清酸脱氢反应所需要的氧化性的辅酶Q的含量，从而抑制二氢乳清酸的脱氢反应。This example proves that the aqueous solution of sodium formate has the chemical ability to reduce coenzyme Q10. It shows that in water-containing human cells, reducing substances such as sodium formate can also inhibit and reduce the content of oxidative coenzyme Q required for the dehydrogenation reaction of dihydroorotic acid, thereby inhibiting the dehydrogenation reaction of dihydroorotic acid.
上述甲酸钠置换为草酸钠具有类似的形成还原性辅酶Q10微细颗粒胶体现象。The replacement of the above sodium formate with sodium oxalate has a similar phenomenon of forming colloidal particles of reducing coenzyme Q10.
实施例7Example 7
本实施例中，有疑似新冠病毒(2019-Covid)感染者3人服用甲酸钠或甲酸钾每天2克3天后食欲开始增加、咳嗽症状减轻好转，3个月后完全康复。另有30位感冒患者，其共同的症状为喉咙疼痛，患者***甲酸钠或甲酸钾每天3-6次，每次约0.5克吞服，服用后疼痛缓解，喉咙疼痛症状第二天基本消失，起到了缓解症状或治愈疾病的效果。综合而言，说明了还原剂如甲酸钠具有抑制各种病毒的效果，符合电荷中和理论也符合抑制病毒基因复制理论的预期，电荷中和加上基因合成的抑制，增加了单个作用的有效性，可以推定按相同的原理，同样可具有抑制其它病毒的效果。In this example, 3 people suspected of being infected with the new coronavirus (2019-Covid) took 2 grams of sodium formate or potassium formate daily for 3 days. After 3 days, their appetite began to increase, their cough symptoms alleviated and improved, and they recovered completely after 3 months. Another 30 cold patients have a common symptom of sore throat. The patient's mouth contains sodium formate or potassium formate 3-6 times a day, and swallows about 0.5 grams each time. After taking it, the pain is relieved, and the symptoms of throat pain basically disappeared the next day. It has the effect of relieving symptoms or curing diseases. In summary, it shows that reducing agents such as sodium formate have the effect of inhibiting various viruses, in line with the theory of charge neutralization and the anticipation of the theory of inhibiting viral gene replication. The neutralization of charge plus the inhibition of gene synthesis increases the effectiveness of a single action. It can be presumed that according to the same principle, it can also have the effect of inhibiting other viruses.
本实施例以及下述实施例进一步地说明，日常生活中还可以将甲酸盐等还原剂作为病毒、细菌感染的预防，如以低浓度(比如1％-30％重量比)溶液作为日常的漱口水，少量添加于日用饮料中(如含量在1％-10％重量比)，食品中(含量在1％-5％重量比)，少量添加于个人日常清洁卫生用品中。所述饮料可以是瓶装水、饮用水、果汁、含酒精饮料；所述食品可以是面粉、米粉、腌制品、酱制品等；所述个人日常清洁卫生用品如肥皂、清洗液、护肤品等。This example and the following examples further illustrate that in daily life, reducing agents such as formate can also be used to prevent viral and bacterial infections, such as using a low concentration (for example, 1%-30% by weight) solution as a daily routine A small amount of mouthwash is added to daily beverages (for example, the content is 1%-10% by weight), food (the content is 1% to 5% by weight), and a small amount is added to personal daily cleaning and hygiene products. The beverage can be bottled water, drinking water, fruit juice, alcoholic beverage; the food can be flour, rice noodles, pickled products, sauce products, etc.; the personal daily cleaning and hygiene products such as soap, cleaning liquid, skin care products, etc. .
实施例8Example 8
乙型肝炎病毒(HBV)包括其卫星病毒丁型肝炎病毒(HDV)与其它包膜病毒或非包膜病毒一样，都必须通过结合细胞表面受体分子，才能实现对宿主细胞的感染。乙肝病毒配体的N端携带正电荷，而宿主细胞受体对应携带负电荷。本实施例中，一位乙肝病毒携带者，服用甲酸钠每天1g，半年后检查指标，体感和指标均好转。作为一种可能，病毒电荷的减少，加上还原剂对基因合成中嘧啶从头合成的抑制效果，起到了抑制乙肝病毒复制的效果。Hepatitis B virus (HBV), including its satellite virus, hepatitis D virus (HDV), like other enveloped viruses or non-enveloped viruses, must bind to cell surface receptor molecules to infect host cells. The N-terminal of the hepatitis B virus ligand carries a positive charge, while the host cell receptor correspondingly carries a negative charge. In this example, a hepatitis B virus carrier took 1 g of sodium formate a day. After half a year, the indicators were checked, and the somatosensory and indicators were all improved. As a possibility, the reduction of the virus charge, coupled with the inhibitory effect of the reducing agent on the de novo synthesis of pyrimidine in gene synthesis, has the effect of inhibiting the replication of hepatitis B virus.
实施例9Example 9
本实施例中，12位从2018年3月至2020年1月持续每天服用约1g甲酸钠的人士的报告(其中清扫马路的清洁工1位，机关工作人员5位，农业从业人员6位)，在没 有服用甲酸钠之前的过往，每年都会感冒4-5数次，但在服用甲酸钠的2年未发现有感冒现象。说明甲酸盐等具有预防病毒感染的效果。In this example, the reports of 12 people who continued to take about 1g of sodium formate daily from March 2018 to January 2020 (including 1 street cleaner, 5 office workers, and 6 agricultural workers), In the past before taking sodium formate, I would have colds 4-5 times a year, but no colds were found during the 2 years of taking sodium formate. It shows that formate etc. have the effect of preventing virus infection.
公知在麻疹病毒、腮腺炎病毒、副流感病毒、风疹以及许多其它细菌和病毒表面均能找到血凝素HA或类似血凝素作用的蛋白作为病毒侵袭宿主细胞的配体，因此，增加体液的碱性，同时通过还原性抑制基因复制过程中的嘧啶从头合成通路，同样可以减少这些病毒的致病性。It is well known that hemagglutinin HA or a protein similar to hemagglutinin can be found on the surface of measles virus, mumps virus, parainfluenza virus, rubella, and many other bacteria and viruses as a ligand for the virus to invade host cells, thus increasing body fluids Alkalinity can also reduce the pathogenicity of these viruses by reductively inhibiting the de novo pyrimidine synthesis pathway in the process of gene replication.
进一步研究推测，流感病毒通过血凝素HA与宿主细胞附着和结合，再进入细胞。公知红细胞表面带负电荷，自然推测血凝素HA作为病毒配体携带的是正电荷。Further research speculates that influenza virus adheres and binds to host cells through hemagglutinin HA, and then enters the cell. It is known that the surface of red blood cells is negatively charged, and it is naturally speculated that hemagglutinin HA, as a viral ligand, carries a positive charge.
增加体液的碱性，将减少血凝素HA携带的正电荷数，降低病毒的致病性，加上还原剂对嘧啶从头合成通路的抑制效果，削弱了病毒感染的致病作用和致病症状。Increasing the alkalinity of body fluids will reduce the number of positive charges carried by hemagglutinin HA and reduce the pathogenicity of the virus. In addition, the inhibitory effect of reducing agents on the de novo pyrimidine synthesis pathway will weaken the pathogenic effect and pathogenic symptoms of viral infections. .
实施例10Example 10
本实施例中，提供了晚期艾滋病1人服用甲酸钾效果。病人在已经发生肺部感染和癌变的情况下，每天服用3克甲酸钾(分3次服用)，3天后食欲明显增加，呼吸顺畅方面、体能、体感逐步有所好转，起到了缓解症状的效果。In this example, the effect of taking potassium formate on a person with advanced AIDS is provided. In the case of pulmonary infection and cancer, the patient took 3 grams of potassium formate (taken in 3 times) every day. After 3 days, the appetite was significantly increased, and the breathing, physical fitness, and body feeling gradually improved, which had the effect of relieving symptoms. .
进一步研究推测，公知，CD4分子是主要存在于T细胞表面的一种单链跨膜蛋白。鸡CD4分子等电点为10.1(生理条件下，带正电)。推测与哺乳动物CD4分子具有很大的相似性。CD4胞外区最值得人们注意的是其N端(正电荷)的2个Ig样区，因为它们是与MHCII结合区域，并且也是HIV(人类免疫缺陷病毒)gp120结合位点(对人的CD4而言)。显见，CD4分子是HIV病毒进入人体细胞的首要受体。也显见的是，生理条件下HIV携带负电荷时，才有可能与带正电荷的CD4受体粘附结合。MHC II也应该是携带了负电荷才可能与CD4结合，此推论与之前推测的MHC II等电点6.89相符。Further research speculated that it is well known that CD4 molecule is a single-chain transmembrane protein mainly present on the surface of T cells. The isoelectric point of chicken CD4 molecule is 10.1 (under physiological conditions, it is positively charged). It is speculated that it has great similarities with mammalian CD4 molecules. The most noteworthy extracellular region of CD4 is its N-terminal (positively charged) two Ig-like regions, because they are binding regions with MHCII and are also HIV (human immunodeficiency virus) gp120 binding sites (for human CD4). In terms of). Obviously, the CD4 molecule is the primary receptor for the HIV virus to enter human cells. It is also obvious that only when HIV carries a negative charge under physiological conditions, it is possible to adhere to the positively charged CD4 receptor. MHC II should also be able to bind to CD4 only if it carries a negative charge. This inference is consistent with the previously speculated MHC II isoelectric point of 6.89.
预期服用甲酸钠、甲酸钾等甲酸盐或草酸盐，间接增加血液的碱性，将会减少CD4分子携带正电荷的数量，血液中高浓度的负电荷氢氧根负离子也会屏蔽HIV病毒，在HIV携带负电荷已经饱和情况下，携带负电荷数不再增加，同时通过还原性抑制病毒基因复制所需的嘧啶从头合成通路，双管齐下，从而达到有效减少或避免HIV外源性或内生(HIV复制)造成的感染。其效果依赖于pH值增加的强度，以及还原性的强度，因此与服用量或注射量成正相关。It is expected that taking formate or oxalate such as sodium formate and potassium formate will indirectly increase the alkalinity of the blood and will reduce the number of positive charges carried by CD4 molecules. The high concentration of negatively charged hydroxide anions in the blood will also shield the HIV virus. When HIV carries negative charges and is saturated, the number of negative charges will no longer increase. At the same time, the de novo synthesis of pyrimidine pathway required for viral gene replication is suppressed through a two-pronged approach, so as to effectively reduce or avoid HIV exogenous or endogenous (HIV) Replication) infection. The effect depends on the strength of the pH increase and the strength of the reduction, so it is positively correlated with the dosage or the amount of injection.
实施例11Example 11
本实施例中，提供了一位***患者，未经其它治疗的情况下，单纯服用甲酸钠 饱和溶液15毫升加上15毫升甲酸钾饱和溶液，每天2次，服用30天后，息肉从约6毫米大小至内窥镜检查消失。In this example, a patient with cervical polyps is provided. Without other treatment, he simply took 15 ml of sodium formate saturated solution plus 15 ml of potassium formate saturated solution twice a day. After taking 30 days, the polyp was about 6 mm The size is so large that the endoscopy disappears.
进一步研究推测，人***瘤病毒HPV基因组分别编码E1、E2、E3、E4、E5、E6、E7以及L1、L2衣壳蛋白。E1～E4蛋白通过其N端富含亮氨酸的基序与宿主细胞角蛋白相关联。因此，病毒吸附蛋白VAP是E1，其N端携带正电荷，受体角蛋白携带负电荷。如前述实施例可以预期，增加体液的碱性，将减少病毒携带正电荷数量，减低或可避免病毒和细胞之间的静电吸引，同时通过还原性抑制病毒基因复制所需的嘧啶从头合成通路，双管齐下，达到有效缓解病情和治疗的效果。Further research speculated that the human papillomavirus HPV genome encodes E1, E2, E3, E4, E5, E6, E7, and L1, L2 capsid proteins, respectively. The E1-E4 proteins are associated with host cell keratin through their N-terminal leucine-rich motifs. Therefore, the virus adsorption protein VAP is E1, and its N-terminus carries a positive charge, and the receptor keratin protein carries a negative charge. As can be expected in the foregoing embodiment, increasing the alkalinity of body fluids will reduce the number of positive charges carried by the virus, reduce or avoid the electrostatic attraction between the virus and the cell, and at the same time reduce the de novo synthesis pathway of pyrimidine required for viral gene replication by reductively inhibiting it. The two-pronged approach can effectively alleviate the condition and achieve the effect of treatment.
实施例12Example 12
本实施例中，一位中年女性，鼻腔长期肿胀，不通气，经医院检查确诊为霉菌性鼻炎，使用消炎药后，有点作用，但只能缓解，炎症却一直在，且稍不注意炎症就加重。每天将饱和的甲酸钠溶液兑水一倍冲洗4-5次鼻腔1天后，肿胀感即缓解也比较通气了，且在业已冲洗的约1个月时间内，通气的舒适感能保持，没有炎症明显出现或加重的现象。说明了还原剂如甲酸钠通过具有或超过消炎药的抑制细菌的效果，理论上，应该是还原剂抑制了细菌细胞增殖时基因复制所需的嘧啶合成通路。In this example, a middle-aged woman with long-term swelling of the nasal cavity and no ventilation, was diagnosed as fungal rhinitis after a hospital examination. After using anti-inflammatory drugs, it has some effect, but it can only relieve the inflammation, but the inflammation is always there, and she does not pay attention to the inflammation. Just aggravate. After doubling the saturated sodium formate solution with water to rinse the nasal cavity 4-5 times a day for 1 day, the swelling is relieved and it is more ventilated, and the comfort of ventilation can be maintained for about 1 month after rinsing, and there is no obvious inflammation Appearing or aggravating phenomenon. It shows that reducing agents such as sodium formate have or exceed the anti-inflammatory effects of anti-inflammatory drugs. In theory, it should be that reducing agents inhibit the pyrimidine synthesis pathway required for gene replication during bacterial cell proliferation.
实施例13Example 13
本实施例中，一位中年女性病人，牙龈脓肿，且剧烈疼痛，在服用甲硝唑、***氯己定漱口水无法缓解的情况下，***甲酸钠，每天3次，每次0.5克，第二天疼痛即缓解消失。应该是甲酸钠通过抑制基因合成中的嘧啶合成通路抑制了细菌微生物增殖复制的效果。In this example, a middle-aged female patient with gingival abscess and severe pain cannot be relieved by taking metronidazole and mouthwash with chlorhexidine in her mouth, with sodium formate in her mouth, 3 times a day, 0.5 g each time , The pain was relieved and disappeared the next day. It should be that sodium formate inhibits the proliferation and replication of bacteria and microorganisms by inhibiting the pyrimidine synthesis pathway in gene synthesis.
实施例14Example 14
本实施例中，一位中年女性，牙周炎多年，最近1年每次刷牙都会出血。***甲酸钠，每天3次，每次0.5克，服用两天后，早晨刷牙时第一次没有出血，此后再没报告有刷牙出血现象。说明甲酸钠通过抑制基因合成中的嘧啶合成通路抑制了牙周内细菌增殖复制引起的感染。In this example, a middle-aged woman had periodontitis for many years, and she bleeds every time she brushed her teeth in the past year. I took sodium formate in my mouth, 3 times a day, 0.5 g each time. After taking it for two days, I did not bleed for the first time when I brushed my teeth in the morning, and there has been no report of bleeding after brushing my teeth. It shows that sodium formate inhibits the infection caused by bacterial proliferation and replication in the periodontal by inhibiting the pyrimidine synthesis pathway in gene synthesis.
实施例15Example 15
本实施例中，中年男性，脖子上有一块局部性神经性皮炎(经医院诊断)，大小直径2厘米，夏天出汗每天奇痒，激素类处方药物涂抹半年未见效，涂抹甲酸钠饱和 溶液每次10毫升每天3次2周后，基本痊愈。估计是嘧啶合成的抑制，抑制了炎性细胞快速增殖所需要的基因合成中嘧啶从头合成步骤。In this example, a middle-aged man has a piece of local neurodermatitis on his neck (diagnosed by the hospital) with a size of 2 cm in diameter. He sweats in the summer and itching every day. The prescription drugs of hormones do not work for half a year. After 10 ml 3 times a day for 2 weeks, he basically recovered. It is estimated that the inhibition of pyrimidine synthesis inhibits the de novo pyrimidine synthesis step in gene synthesis required for rapid proliferation of inflammatory cells.
实施例16Example 16
本实施例中，老年男性，医院病历诊断是躯干四肢边界不清的红斑，丘疹抓痕，皮肤干裂，骚痒约1年时间，医生诊断为疑似荨麻疹。其间经各种方法治疗一直无法控制瘙痒症状，睡前涂抹甲酸钠饱和溶液100毫升一次后(涂抹覆盖全部瘙痒的皮肤表面)的当天晚上瘙痒好转，没有再影响睡眠。估计是嘧啶合成的抑制，抑制了炎性细胞的快速增殖或病因若是病毒感染则是抑制了病毒复制所需要的基因合成中嘧啶从头合成步骤。In this embodiment, the hospital medical record diagnosis of an elderly man is erythema with unclear trunk and limb boundaries, papules, scratches, dry and cracked skin, and itching for about 1 year. The doctor diagnosed as suspected urticaria. In the meantime, after various treatments, the symptoms of itching have not been controlled. After applying 100 ml of saturated sodium formate solution before going to bed (applied to cover all the itchy skin surface), the itching improved in the same night and no longer affected sleep. It is estimated that it is the inhibition of pyrimidine synthesis, which inhibits the rapid proliferation of inflammatory cells, or if the cause is viral infection, it inhibits the de novo pyrimidine synthesis step in gene synthesis required for virus replication.

Claims (17)

  1. 一种药物组合物，其中，所述药物组合物包括甲酸盐和/或草酸盐。A pharmaceutical composition, wherein the pharmaceutical composition comprises formate and/or oxalate.
  2. 根据权利要求1的药物组合物，其中，所述甲酸盐和/或草酸盐各自独立的选自钾盐、钠盐、镁盐和钙盐中的一种或多种的组合。The pharmaceutical composition according to claim 1, wherein the formate and/or oxalate are each independently selected from one or a combination of potassium salt, sodium salt, magnesium salt and calcium salt.
  3. 根据权利要求1或2所述的药物组合物，其中，所述药物组合物为固体制剂或溶液制剂。The pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition is a solid preparation or a solution preparation.
  4. 权利要求1～3任意一项所述的药物组合物在制备治疗抑制病原体的药物中的应用。Use of the pharmaceutical composition according to any one of claims 1 to 3 in the preparation of a medicine for treating and inhibiting pathogens.
  5. 根据权利要求4所述的应用，其中，所述病原体为依靠表面电荷静电吸引与宿主细胞粘附的病原体。The application according to claim 4, wherein the pathogen is a pathogen that relies on surface charges to electrostatically attract and adhere to host cells.
  6. 根据权利要求5所述的应用，其中，所述病原体选自病毒、真菌、细菌、衣原体、支原体和蛋白酶类毒素。The use according to claim 5, wherein the pathogen is selected from the group consisting of viruses, fungi, bacteria, chlamydia, mycoplasma, and protease toxoids.
  7. 一种抑制病原体的方法，其中，所述方法包括向哺乳动物给药权利要求1～3任意一项所述的药物组合物。A method for inhibiting pathogens, wherein the method comprises administering the pharmaceutical composition according to any one of claims 1 to 3 to a mammal.
  8. 根据权利要求7所述的方法，其中，所述病原体为依靠表面电荷静电吸引与宿主细胞粘附的病原体。8. The method according to claim 7, wherein the pathogen is a pathogen that relies on surface charges to electrostatically attract and adhere to host cells.
  9. 根据权利要求8所述的应用，其中，所述病原体选自病毒、真菌、细菌、衣原体、支原体和蛋白酶类毒素。The use according to claim 8, wherein the pathogen is selected from the group consisting of viruses, fungi, bacteria, chlamydia, mycoplasma, and protease toxoids.
  10. 根据权利要求8所述的应用，其中，所述细菌选自厌氧菌或好氧菌。The use according to claim 8, wherein the bacteria are selected from anaerobic bacteria or aerobic bacteria.
  11. 根据权利要求7～10任意一项所述的方法，其中，所述方法包括通过选自如下给药方式中的一种或多种的组合向动物或植物给药权利要求1～3任意一项所述的药物组合物：口服、注射、涂抹和喷雾。The method according to any one of claims 7 to 10, wherein the method comprises administering any one of claims 1 to 3 to animals or plants by a combination of one or more selected from the following administration modes The pharmaceutical composition: oral, injection, smear and spray.
  12. 根据权利要求7～11任意一项所述的方法，其中，所述药物组合物是通过抑制病原体的嘧啶核苷酸合成反应中的二氢乳清酸的利用和/或二氢乳清酸的脱氢反应、同时增加体液的pH值，实现对病原体的抑制。The method according to any one of claims 7 to 11, wherein the pharmaceutical composition is obtained by inhibiting the utilization of dihydroorotic acid and/or dihydroorotic acid in the pyrimidine nucleotide synthesis reaction of the pathogen. Dehydrogenation reaction, while increasing the pH value of body fluids, to achieve the inhibition of pathogens.
  13. 根据权利要求7～12任意一项所述的方法，其中，所述动物为哺乳动物；优选为人。The method according to any one of claims 7-12, wherein the animal is a mammal; preferably a human.
  14. 一种抑制病原体的方法，其中，所述方法包括向哺乳动物给药权利要求1～3任意一项所述的药物组合物，作为病原体感染的预防。A method for inhibiting pathogens, wherein the method comprises administering the pharmaceutical composition according to any one of claims 1 to 3 to a mammal as a prevention of pathogen infection.
  15. 根据权利要求14所述的应用，其中，所述的药物组合物以低浓度溶液作为日常的漱口水；或少量添加于日用饮料中，食品中，日常个人卫生用品中。The application according to claim 14, wherein the pharmaceutical composition uses a low-concentration solution as a daily mouthwash; or a small amount is added to daily beverages, foods, and daily personal hygiene products.
  16. 根据权利要求15所述的应用，其中，所述饮料包括瓶装水、饮用水、果汁或含酒精饮料；所述食品包括面粉、米粉、腌制品或酱制品。The application according to claim 15, wherein the beverage includes bottled water, drinking water, fruit juice or alcoholic beverage; the food includes flour, rice noodles, pickled products or sauce products.
  17. 根据权利要求15所述的应用，其中，所述个人日常卫生用品包括肥皂、清洗液或护肤品。The application according to claim 15, wherein the personal daily hygiene products include soap, cleansing liquid or skin care products.
PCT/CN2021/075001 2020-02-03 2021-02-03 Pharmaceutical composition and use thereof WO2021155795A1 (en)

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Citations (2)

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CN109549952A (en) * 2017-09-27 2019-04-02 秦才东 A kind of method and application inhibiting cell glycolytic cycle
CN110559284A (en) * 2018-06-06 2019-12-13 秦才东 Method for increasing blood alkalinity and dissolving sediment containing ester and fat and application

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109549952A (en) * 2017-09-27 2019-04-02 秦才东 A kind of method and application inhibiting cell glycolytic cycle
CN110559284A (en) * 2018-06-06 2019-12-13 秦才东 Method for increasing blood alkalinity and dissolving sediment containing ester and fat and application

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