WO2008035795A1 - Method for preventing and treating disease with hypochlorous acid - Google Patents

Abstract

It is intended to provide a method for preventing or treating a disease of a mammal or a bird caused by a microorganism such as a virus, a bacterium, a fungus or a protozoan as an inexpensive and simple method without fear of losing its preventive or therapeutic effect due to a viral mutation or a resistant bacterium. In the method, an aqueous solution of hypochlorous acid, which is widely used as a disinfectant in the field of prevention and treatment of diseases, approved as a food additive in the food field, and known to be secreted by neutrophils in the blood with myeloperoxidase enzyme in the medical field is used as an injection.

Description

 Prevention and treatment of diseases caused by hypochlorous acid

 The present invention is an aqueous solution of hypochlorous acid, a mixed aqueous solution of hypochlorous acid and hypochlorite, or an aqueous solution of hypochlorite, which can be produced inexpensively and easily in large quantities, mammals or humans other than humans. The present invention relates to a technique for preventing or treating diseases caused by microorganisms such as viruses, bacteria and the like by administering them into the body by injection, drip infusion or the like. Background art

 Conventionally, in the medical and veterinary medicine fields, vacciniacin, antibiotics, synthetic antibacterial agents and the like have been used for the treatment and prevention of diseases caused by microorganisms such as viruses and bacteria.

 However, these vaccine fields, antibiotics and synthetic antibacterial agents are expensive for research and development and production. In addition, regarding vaccines, as is widely known for human influenza vaccines, there is a problem that when the virus is mutated, the effects of the vaccine may be lost. Furthermore, with regard to antibiotics and synthetic antibacterial agents, there is a problem of resistant bacteria as widely known.

 Therefore, it can be produced inexpensively and easily in large quantities, and can be used continuously even if the virus is mutated, and the problem with few resistant bacteria occurring is caused by microorganisms such as viruses and bacteria. There is a demand for the development of techniques to prevent or treat various diseases.

 In the context of the present invention, JP-A-2005 / 075375 discloses hypochlorous acid compositions containing hypochlorous acid and sodium hypochlorite as septic arthritis. A method is disclosed for treating septic arthritis by injecting it into the joint.

 However, this method is an injection into a joint without blood vessels, and is not a method for treating or preventing a disease by administering a drug solution to a wide area of the body, spreading, penetrating, or blood circulation.

 Further, in Japanese Patent Publication No. 2 346, a mixture of sodium chlorite solution, sodium hypochlorite solution, chloryl sulfate, sodium perborate or sodium percarbonate, and sodium peroxide are mixed and reacted. An injectable drug component for treating an infectious disease, which is obtainable, is disclosed.

However, the medicinal solution for injection described in this patent specification is an invention utilizing the pharmacological effect of chlorite ion (C 1 0 ₂ ), and does not utilize the pharmacological effect of hypochlorous acid. Disclosure of the invention

 (1) Problems to be solved by the invention

 The present invention relates to diseases caused by microorganisms such as viruses, bacteria and the like by administering a substance (aqueous solution) which can be produced inexpensively and easily in large quantities into a mammalian or avian body by injection, infusion or other methods. The task is to provide technology to prevent or treat

(2) Means to solve the problem

In the present invention, first, an aqueous solution of hypochlorous acid or hypochlorous acid having a pH of 4.0 or more and 100 or less, and a free chlorine concentration of 1 mg or more Z kg or more and 1000 mg / kg or less Provides injections and drops that are a mixed aqueous solution of chloric acid and hypochlorite or an aqueous solution of hypochlorite Do.

 Second, the present invention excludes a person who is easy to spread, permeate, or circulate blood of the injected drug or drip of the present invention to the site of the body necessary for the injected drug or dripping drug S administered, prophylactic or therapeutic. Provided is a method for treating or preventing a disease caused by microorganisms such as viruses and bacteria, fungi, protozoa etc. by administration to any part of mammals or birds by injection, infusion or other methods. . Effect of the invention

 According to the present invention, a substance which can be produced inexpensively and easily in large quantities (an aqueous solution of hypochlorous acid, or a mixed aqueous solution of hypochlorous acid and hypochlorite, or an aqueous solution of hypochlorite) Injections or drops) are provided.

 Further, according to the present invention, a disease caused by microorganisms such as viruses, bacteria and the like by administering the injection or drip of the present invention to a predetermined site of a mammal or a bird by injection, infusion or the like. Techniques for the prevention or treatment of BEST MODE FOR CARRYING OUT THE INVENTION

 Hereinafter, the present invention will be described in detail.

 (1) The first aspect of the present invention is: pH 4.0 or more and 10.0 or less, free chlorine concentration is lmg

It is an aqueous solution of hypochlorous acid or mixed aqueous solution of hypochlorous acid and hypochlorite, or an aqueous solution of hypochlorite, or an aqueous solution of hypochlorous acid or an aqueous solution of hypochlorite. .

 After World War I, research on bioactive substances has been widely carried out for the prevention and treatment of infectious diseases, but in the process, hypochlorous acid composition is produced by neutrophils in blood. It was discovered as an oxidant to be produced. The progress of research on medical use and manufacturing methods of hypochlorous acid thereafter is described in Japanese Patent Application Publication No. 2005-2005.

 Neutrophils are blood cells that account for less than 60% of blood cells excluding red blood cells in the case of human beings, but activated neutrophils are much more potent from hydrogen peroxide to sodium hypochlorite by the Mye mouth peroxidase enzyme. Active production of hypochlorous acid having high bactericidal activity has been clarified, and it is widely known as a known fact.

 If the pH of the injectable drug and the drip agent is pH 4.0 or less, chlorine gas is likely to be generated, and if the pH is 10.0 or more, the tissue at the injection site is easily inflamed. , 4.0 or more 10. 0 or less is desirable.

 With regard to the effective chlorine concentration of injectable and instillable drugs, when the effective chlorine concentration is 1 mgZkg or less, the volume of the injectable solution or instilled drug becomes extremely large, and the physiological burden on the animal receiving injection or drip increases excessively. The task of injection or instillation becomes difficult, and if it is 10, 000 mg z kg or more, the site of injection or instillation becomes prone to inflammation, so lmg z kg or more and 10,000 mg Z kg or less preferable.

 The preparation of an aqueous solution of hypochlorous acid, a mixed aqueous solution of hypochlorous acid and hypochlorite, or an aqueous solution of hypochlorous acid salt is extremely simple, and the aqueous solution of hypochlorous acid is a saline solution or dilute hydrochloric acid. Can be easily manufactured in large quantities inexpensively by the electrolysis method of

 Among the hypochlorites, sodium hypochlorite, which is most widely used, is industrially easily produced in large quantities by absorbing the chlorine gas generated by the electrolysis of sodium chloride into an aqueous solution of sodium hydroxide. It is manufactured.

 The aqueous solution of hypochlorous acid can be easily produced by adding the acid of a food additive as a pH adjusting agent to an aqueous solution of sodium hypochlorite.

The mixed aqueous solution of hypochlorous acid and hypochlorite can be easily produced by mixing an aqueous solution of hypochlorous acid and an aqueous solution of hypochlorite. In addition, an aqueous solution of sodium hypochlorite is a safe substance, has long been approved as a food additive, and is widely used for sterilization in the food industry worldwide. It has been revealed that an aqueous solution of hypochlorous acid is a safe substance with much higher bactericidal power than sodium hypochlorite aqueous solution, and it has been approved as a food additive in Japan in 2002 and widely used. It is done.

 Hypochlorous acid is a substance that exhibits a bactericidal effect as a stronger oxidant than hydrogen peroxide in the body, and is considered to be the most important component in the preventive and therapeutic effects of the present invention. Hypochlorous acid and hypochlorous acid In the case of a mixed aqueous salt solution, hypochlorous acid (HCIO) dissociates in the alkaline region to form hypochlorite ion (CIO-) and hydrogen ion (H +), and hypochlorous acid and hypochlorite ion The ratio between and greatly depends on the pH of the solution.

 For example, in the case of a mixed aqueous solution of hypochlorous acid and sodium hypochlorite at room temperature, pH 4.0 power, such as at least 99% in 5.5, pH95, such as pH 7.0. 9 to 80%, about 60% of pH 7.4 in human blood is hypochlorous acid, and the rest is dissociated into hypochlorite ion and hydrogen ion. On the contrary, about 70% is dissociated into hypochlorite ion and hydrogen ion in the alkaline region of pH 800, and it is about 95% in pH 9.5 and almost 10 0 in pH 9.5 or more. It is dissociated into 0% hypochlorite ion and hydrogen ion.

 As a method of analyzing the concentration of hypochlorous acid and a method of analyzing the concentration of hypochlorite ion, UV-visible absorption methods of wavelengths of 235 nm and 292 nm are known, respectively. The total concentration of hypochlorous acid and hypochlorite ion can be measured by measuring the concentration of free available chlorine, from the correlation between the value measured by the above and the available chlorine concentration.

The available chlorine generally hypochlorite, the hypochlorite ion, dissolved chlorine (C 1 ₂₎ of the total (free available chlorine) chlorambucil and reacts with及Pi ammonium compounds in water Min (binding effective chlorine The total amount of). However, if the aqueous solution of hypochlorous acid has a pH value of less than 4.0, chlorine gas is likely to be generated. However, hypochlorous acid containing no ammonia compound, such as pH 4.0 to 10. 0. In an aqueous solution of chlorate ion or a mixture of both, the total concentration of hypochlorous acid and hypochlorite ion can be approximately known by measuring the effective chlorine concentration. Therefore, the product specifications for the aqueous solution of hypochlorous acid and the mixed aqueous solution of hypochlorous acid and hypochlorite are generally indicated or defined in Japan as mg Z kg of effective chlorine concentration.

 Because the method of measuring effective chlorine concentration is simple, effective chlorine measurement method called DPD method is widely used in Japan for measuring hypochlorous acid and hypochlorite ion concentration. Generally, blood of animals to be injected is used. The amount of injection solution injected as compared to the amount is very small as shown in the later examples, and the animal has a physiological function to keep the pH of blood at a constant value. Therefore, even if the pH of the injection solution is higher than the pH of blood, and hypochlorous acid is mostly dissociated into hypochlorous acid ions and hydrogen ions, in the stage where the injection solution permeates and diffuses into the blood, Hypochlorous acid, hypochlorite ion, and hydrogen ion in the injection solution decrease the degree of dissociation to the corresponding state of pH, temperature, and dissolved substances in blood, and the hypochlorous acid It is believed that it will exert a great sterilizing power. However, the pH range of the injection solution is preferably 4.0 to 100.0, preferably 6.0 to 9.0, and most preferably 6.5 to 7.5.

 (2) In the second aspect of the present invention, the injection or infusion drug of the present invention is administered to a mammal or a bird by injection, infusion or other means to a site which is easily diffused, penetrated, or circulated in the body. It is a method for preventing or treating diseases caused by viruses such as mammalian viruses, bacteria, fungi, protozoa and the like (hereinafter referred to as "the methods of the present invention for preventing or treating").

Mammals or birds targeted by the methods of prevention or treatment of the present invention include, but not particularly limited to, domestic animals such as pigs, cows, horses, sheep, goats and chickens, and poultry. The preventive or therapeutic method of the present invention is mammalian or avian virus, bacteria, mold

There are no particular restrictions on the disease caused by microorganisms such as protozoa. In the following, taking piglets in a pig farm as an example, techniques for preventing and treating diseases caused by microorganisms such as virus and bacteria are explained below.

 Diseases caused by viruses in swine: E-Squier disease (AD), Breeding pig 'Respiratory disorder (Poor Reproductive and Respiratory Syndrome) (abbreviated as h PRR S), Japanese encephalitis, porcine parvovirus disease, swine Enterovirus disease, swine fluenza, postweaning multisystemic growth syndrome (PMWS), swine infectious gastroenteritis (TGE), swine epidemic diarrhea (PED), swine fever, swine fever, foot disease, etc. There are 5 types of illness.

 In addition, as diseases caused by bacteria of swine, erysipelas, rickets virus, salmonella disease, streptococcal disease, coliform disease, necrotizing enteritis, grazer disease, mycoplasmal disease, atrophic rhinitis (AR), soot disease, swine pleura pneumonia, pasilella There are about 18 kinds of diseases such as sickness, swine dysentery, anthrax and tetanus.

 Among swine diseases, it is the disease with the highest frequency of occurrence of P RR S and the measures for which are regarded as important. In the early 1990s, PRRS virus was first confirmed in Japan, and various measures have been taken, but the measures are extremely difficult.

 If a pig is infected with PRRS virus alone, it does not become a serious symptom, but PRRS is a complex infectious disease, and complex infections such as mycoplasma, circovirus, streptococcus, and pastrella. Symptoms become severe due to

 The preventive or therapeutic method of the present invention is to administer a prescribed amount of hypochlorous acid injection solution to mammals or birds other than humans by injection, infusion or other methods at a site where it is easy to diffuse, penetrate, or circulate in the body. It is

 As other administration methods other than injection and infusion, there is a method of permeating the drug solution from the skin by pressure using a "needleless syringe", and there are places adopted by the livestock industry.

 The effective chlorine concentration of the injection solution is lmg / kg to 10, OO Omgzkg, preferably 5mg / kg force, etc. 200mg / kg, most preferably 50mg / kg to 1 000mg / kg It is kg. Example

Hereinafter, the present invention will be described with respect to the most frequently occurring PRR S disease among swine diseases, in which examples are carried out on delivery piglets and weaned piglets. However, the present invention is in no way limited to the following examples.

 The most disease-prone time of the pig's lifetime is the so-called weanling piglets from weaning to 70 days of age, when the transfer antibody from sows decreases and it becomes easy to be infected with pathogens in the field. . Especially for diseases affecting the weaning period, PRRS is the most frequent, and it is not uncommon for piglet mortality to exceed 30%.

Table 1 shows hypochlorous acid injection (P H 6.9), which was prepared by electrolysis of a saline solution, to baby weaned piglets (average body weight at weaning 6 kg) which had moved to the weaning house 25 days after parturition. Test chlorine dose of 60 mg / kg (effective chlorine concentration) 2 times no (effective chlorine amount 0.1 2 mg) Based on the test mouth injected with 5 injections once a week into the neck of a piglet and no injection Table 1 shows comparative piglet mortality data for the target ports. The same injection was carried out every third day after delivery and every 10th day after delivery, even in the A pig farm only, and in the distribution stable. Distribution house

 p \ (翁

 Pig farm

 Delivery 2 5th Dec. 4 5th Dec. 1st Dec. 10th Dec. End * Category · Mortality rate 7 0 Decrease Mortality

 Piglet number Piglet number Piglet number Piglet number

 Piglet number Mortality rate 1 2 1 2 3 4 4/2 4 1 No injection 231 211 12% 188 166 160 24% 31%

A

 Injection 238 228 4% 220 210 203 11% 15% Not injected 29 28 4 4 24 19 18 36% 38%

B

 Injection 30 29 4% 27 26 26 10% 13% Not injected 34 33 3 3% 29 28 27 18% 21%

C

 Injected 33 33 0% 31 31 30 9% 9% Not injected 38 33 3 3 33 31 31 6% 18%

D

 Injection 37 37 0% 35 34 34 8% 8% Not injected 46 44 5% 33 31 31 30% 33%

E

 Injections 47 46 2% 44 42 42 9% 11% From Table 1, mortality after weaning of weaned piglets decreased on average from 23% to 9% and overall mortality on average 28% It is clearly reduced to 11%, and it is clear that there is a big effect. Industrial Applicability The present invention has the following three effects, and has high industrial application value.

(1) It has a great effect on prevention and treatment of diseases caused by microorganisms such as viruses and bacteria that infect mammals or birds, and reduction of mortality.

 2 Unlike vaccines and antibiotics, there are no problems caused by virus mutations or resistant bacteria.

 The manufacturing cost of hypochlorous acid injection is much cheaper than vaccines and antibiotics.

Claims

The scope of the claims 1 · Η 以上 4.0 or more and 10. 0 or less, effective chlorine concentration, for use in injection or infusion in any area that is easy to spread, penetrate, or circulate in the body necessary for the prevention or treatment of a disease Injections and drops consisting of an aqueous solution of hypochlorous acid, a mixed aqueous solution of hypochlorous acid and hypochlorite, or an aqueous solution of hypochlorite, of lmgZk g to 100, OO Omgzk g or less .  2. Any part of mammals or birds other than humans that are easy to spread, penetrate, and circulate blood in the area of the body required for the prevention or treatment of a disease in which the injection or drip of claim 1 was administered. A method for treating or preventing a disease caused by microorganisms such as viruses and bacteria, molds and protozoa by administering them by injection, infusion or the like. 3. A method according to claim 2 which targets pig disease. : 4. A method according to claim 2, which is directed to Porcine Reproductive and Respiratory Syndrome.