JP2015093861A - Preventive or therapeutic agent for parvovirosis - Google Patents

Abstract

For parvovirosis, there is currently no specific medicine, a high mortality rate, and there is a strong demand for an immediate treatment of a reliable treatment method including an effective, reliable and effective prevention method. A preventive or therapeutic agent for parvovirosis characterized by containing lipopolysaccharide derived from a microorganism belonging to the genus Pantoea as an active ingredient. [Selection] Figure 1

Description

  The present invention relates to a preventive or therapeutic agent for parvovirosis.

  Canine parvovirus infection (CPVD) is a linear single-stranded DNA virus belonging to the family Parvoviridae, which forms an icosahedral structure with a diameter of 20 nm and has no envelope. It spread all over the world in the late 1970s, and it became very popular in Japan. Once it develops, it is still a serious problem at breeding grounds and pet shops because of its high mortality rate and infectivity. Initially unknown cause of illness was caused by a series of cases where puppies flapped and died, and they were feared as “Pokkuri's disease” or “Colori's disease”. Vaccine development has also been carried out, and the number of cases of canine parvovirus infection has decreased with the spread of vaccination. However, puppies and old dogs that have not been vaccinated and have weak physical strength and immunity often die from infection with a dog parvovirus.

  Parvovirosis usually develops after an incubation period of 2 to 12 days in dogs after 4 to 6 weeks of age, such as loss of appetite, depressed mood, and vomiting. Viruses that have spread throughout the body through the bloodstream are replicated in cardiomyocytes in the neonatal period, and intestinal crypt cells and bone marrow cells in the subsequent neonatal period. For this reason, very young people may suddenly die after taking a heart-shaped course and may not be aware of a canine parvovirus infection. In the enteritis type, normal intestinal mucosa cannot be formed due to destruction of intestinal crypt cells, and diarrhea and characteristic watery mucous stool (tomato juice-like) are exhibited. Moreover, sepsis is caused by opportunistic infection caused by a decrease in the number of leukocytes due to destruction of bone marrow cells, disseminated intravascular coagulation syndrome is caused, and death occurs due to multiple organ failure.

International Publication No. 2005/0300938

Nishizawa T. et al, "Homeostasisas Regulated by Activated Macrophage. I. Lipopolysaccharide (LPS) from WheatFlour: Isolation, Purification and Some Biological Activities", Chem. Pharm. Bull., 40 (2), p.479-483 (1992 ).

  The only treatment for canine parvovirus infection is supportive care and symptomatic treatment to relieve dehydration and shock. If the infected individual has physical strength, recovery may be seen with this, but young dogs up to about 2 to 3 months old often die. Cat interferon preparations are often administered in the hope of helping to maintain the dog's own immunity, but no established results have been obtained. In addition, infusion therapy that replenishes the body's water and electrolytes lost due to vomiting and diarrhea, and administration of antibiotics to suppress secondary infection caused by enteric bacteria. However, there is currently no specific medicine, a high mortality rate, and there is a strong demand for an immediate treatment of a reliable treatment method including an effective, reliable and effective prevention method.

  The preventive or therapeutic agent of the present invention is for parvovirosis characterized by containing lipopolysaccharide derived from a microorganism belonging to the genus Pantoea as an active ingredient.

  According to the present invention, a prophylactic or therapeutic agent for parvovirosis can be provided.

It is a figure which shows the experimental result as a therapeutic agent of Example 1. FIG. It is a figure which shows the experimental result as a preventive agent of Example 2. FIG.

  DESCRIPTION OF EMBODIMENTS Hereinafter, embodiments for carrying out the present invention will be described in detail with reference to the accompanying drawings.

  Canine parvovirosis is diagnosed by the presence of extremely characteristic clinical symptoms (existence of vitality / activity, diarrhea, vomiting, appetite) and canine parvovirus antigen detection kit (Checkman ELISA-kit; Adtech), or polymerase chain It was confirmed by parvovirus genetic diagnosis by reaction. A part of the cases was collected and subjected to blood biochemistry (Spotchem EZ SP4430; Arkley, Inc.) and hemocytometer (pocH-100iV; Sysmex Corporation).

  Depending on the condition of the case, coping therapy may include infusion (Sordem 1), liver function improver (Strong Minophagen C), nutrient (Vitamin B group, Neurobitan), analgesic (Neurotropin), antibiotics (ampicillin, Normal doses of tribrissene, baitril, clindamycin, and convenia), antiemetics (selenia), and antidiarrheals (berinol) were given.

  As treatment, Tamiflu (Tamiflu; Chugai Pharmaceutical) 2.2 mg / kg body weight is administered orally, feline interferon (Intercat; Toray) 2,000,000 units / kg body weight is injected intravenously, Pantoea lipopolysaccharide (LPS) 10 μg / kg body weight Given orally.

  Pantoea lipopolysaccharide (LPS) was obtained by culturing pantoea agglomerans, a gram-negative bacterium symbiotic with wheat, in wheat flour, extracting LPS from the cells with hot water, and removing solids (Patent Document 1, Non-patent document 1).

  In dog parvovirus cases, dogs ingesting spontaneous diets were divided into 3 groups, and the above treatment was given, and each group was given feline interferon, Tamiflu, or Pantoea lipopolysaccharide as a therapeutic agent. After 7 weeks, the group of feline interferon was 73.7% (19 animals, 14 surviving, 5 deaths, mean age of 9.0 weeks), and Tamiflu group was 40.0% (5 out of 2 animals, 2 surviving, 3 dead) (Average onset 8.6 weeks), Pantoea lipopolysaccharide group was 88.9% (9 out of 8, 8 surviving, 1 dead, average onset 9.6 weeks), and surviving significantly when given Pantoea lipopolysaccharide The effect was shown (refer FIG. 1).

  Since parvovirus is highly malignant and usually has about half the survival rate, it can be said that the survival rate by administration of Pantoea lipopolysaccharide is extremely high.

  The group that received Pantoea lipopolysaccharide in advance (7 animals, mean 8.6 weeks old) and the group that did not give it to dogs (9 animals, mean 10.0 weeks old until onset) subsequently developed parvovirosis. Since it developed, Pantoea lipopolysaccharide was given to all of them after the onset. The survival rate 10 days after the onset of the disease was examined. The group that received Pantoea lipopolysaccharide before the onset of the disease reached a survival rate of 85.7% (7 out of 6, 6 lived, 1 dead). On the other hand, the group given Pantoea lipopolysaccharide only after onset had a survival rate of 55.6% (9 out of 9, 5 surviving, 4 dead), and surviving when Pantoea lipopolysaccharide was given before onset The effect was shown (refer FIG. 2).

  In addition, this invention is not limited to the said Example.

Lipopolysaccharide (LPS) consists of lipid A, core polysaccharide, and O-antigen polysaccharide. It is known that the structure of lipid A and core polysaccharide is highly conserved within the same family. The effect of LPS acts by binding to an LPS receptor group of cells related to immunity such as macrophages, B cells, dendritic cells, epithelial cells, particularly TLR-4. Although the O antigen polysaccharide also affects the biological activity, it is known that lipid A of LPS and a part of the sugar chain of the core polysaccharide are mainly involved in this binding. Therefore, it can be said that the fact that Pantoea agglomerans LPS has this effect also has the same effect on LPS of other bacteria belonging to Pantoea.

Claims (3)

  A preventive or therapeutic agent for parvovirosis characterized by containing lipopolysaccharide derived from a microorganism belonging to the genus Pantoea as an active ingredient.   The preventive or therapeutic agent according to claim 1, wherein the microorganism belonging to the genus Pantoea is Pantoea agglomerans. A formulation comprising the preventive or therapeutic agent according to claim 1 or 2, wherein the formulation is a food, a pharmaceutical product, a quasi-drug, an animal drug, or an animal quasi-drug. .

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