JPH069409A - Therapeutic agent for mammitis - Google Patents

Abstract

PURPOSE:To obtain a therapeutic agent for mammitis containing a chitinous substance as an active ingredient. CONSTITUTION:The therapeutic agent contains a chitinous substance, e.g. chitin contained in crustacea such as prawn or crab, an insect such as grasshopper or beetle or cuttlebone, deacetylated chitin obtained by deacetylating chitin in an amount of 20-80%, chitosan obtained by deacetylating chitin in an amount of >=80% or sulfated chitin as an active ingredient. A method for using this therapeutic agent includes a method for using the agent in a state suspended or dissolved in Ringer's solution or physiological saline, etc., or a method for using the agent in a state of ointment dispersed or dissolved in a proper base and a method for administering the agent include a method for injecting the agent through catheter, probe, etc., into breast using an injection, etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a therapeutic agent effective for mastitis.

[0002]

2. Description of the Related Art Mastitis is a process in which microorganisms enter the breast
It causes inflammation of the ductal system and mammary gland tissue.

When infected with mastitis, abnormal milk (increase in the number of somatic cells such as white blood cells in milk) is secreted, and when the condition progresses, the function of synthesizing milk is impaired, resulting in a decrease in milk production and finally. Will stop lactation.

As a method of treating mastitis, a method of injecting a preparation containing an antibiotic as a main ingredient into the breast or an artery is usually adopted.

[0005]

However, the therapeutic method using antibiotics sometimes fails to reach the deep part of the lesion, resulting in insufficient killing of the infectious bacteria, resulting in the emergence of resistant bacteria and other chronic diseases. This leads to mastitis. Once mastitis develops, administration of antibiotics shows little improvement, and constitutional treatments such as vitamin therapy and Kampo therapy have been tried, but no definitive solution has been found.

[0006]

That is, the gist of the present invention is a therapeutic agent for mastitis containing chitin as an active ingredient.

Examples of the chitin used in the present invention include shrimp, crab and other shellfish, grasshopper, beetle and other insects, squid shell and other chitin, and deacetylated 20-80% of chitin. Examples include acetylated chitin, 80% or more deacetylated chitosan, and sulfated chitin, which are generally called chitin.

Examples of the chitin used in the therapeutic agent for mastitis of the present invention include water-insoluble, sparingly soluble or soluble chitin. As the chitin that is insoluble and hardly soluble in water, it is recommended to use fine particles that are finely dispersed to the extent that they are suspended in water during use. Examples of the method of forming fine particles include a method of dry-milling chitin using a mill such as a vibrating ball mill, a planetary ball mill, a centrifugal fluidizing mill. Further, in addition to the dry pulverization method, it is also recommended in use to employ a method in which the obtained finely divided chitin is wet pulverized with water, physiological saline or the like.
As a method for using the therapeutic agent for mastitis of the present invention, a method in which it is suspended or dissolved in water, Ringer's solution, physiological saline or the like, or a method in which it is dispersed or dissolved in an appropriate base and used as a so-called ointment state Can be mentioned.

As a method for administering the therapeutic agent for mastitis of the present invention, there can be mentioned a method of injecting the therapeutic agent into the breast via a catheter, a probe (deep needle) or the like using an injection cylinder or the like. .

No single-dose toxicity of the therapeutic agent of the present invention has been observed so far.
It is sufficient to administer a significant amount of 100 mg or less per 1 kg of body weight.

[0011]

The reason why the therapeutic agent for mastitis of the present invention exerts an effect on mastitis has not been clarified yet, but it is considered as follows. Represented by macrophages and polymorphonuclear leukocytes in the body, when a foreign body such as a microorganism enters the body, it recognizes the foreign body, moves to the foreign body, takes in the foreign body, and removes it by enzymatic treatment. There are cells that act, so-called phagocytes, but in the chitin,
It is thought to have chemotaxis that activates these phagocytes and further migrates toward the activator against the concentration gradient. By injecting chitin into the breast, It is thought that mastitis will be cured by migrating phagocytic cells and activating phagocytosis to eliminate microorganisms.

Reference Example 1 Chitosan produced from crab cuticle {Flownac
C, deacetylation degree 83% (calculated from elemental analysis value, Kyowa Technos Production Co., Ltd.) was dry-ground using a centrifugal fluidizing mill. As the crushing conditions, balls made of zirconia (10 mmφ, 10 kg used) were used, and the crushing was performed at a mill rotation speed of 420 rpm and a separator rotation speed of 3500 rpm. The obtained powder is SK Laser PR
As a result of measurement in ethanol by O-7000S (manufactured by Seishin Enterprise Co., Ltd.), the maximum particle size was 12 μm and the average particle size was 3.1 μm.

This powdered chitosan was dispersed in deionized water at a concentration of 5% (w / w) to prepare a treatment liquid of 5 liters. The particle size at this time was measured by a particle size analyzer (manufactured by Nikkiso Co., Ltd., Microtrac SPA type). As a result, the average particle size was 10.2 μm and the maximum particle size was 42.2 μm at a temperature of 11 ° C.

The obtained chitosan dispersion liquid was fed into a vessel (volume of 2 liters) of a sand grinder with stirring, and a zirconia pin blade and zirconia beads (0.
(5 mmφ, 1.7 liter) and the treatment liquid were strongly convected to pulverize. The treatment solution passes through the vessel 7 times, shows stable dispersibility without sedimentation even after storage for 6 months, and fine particle chitosan dispersion that smoothly passes through a hypodermic needle with a needle diameter of 0.4 mm and a needle length of 20 mm. A liquid was prepared.

Reference Example 2 100 g of chitin flakes purified from squid shell was added to 250 m of pyridine.
After immersing in l for 24 hours, a separately prepared sulfating reagent (600 ml of pyridine and 150 ml of chlorosulfonic acid was mixed) was added and reacted at a temperature of 90 ° C. for 2 hours and 30 minutes. The reaction solution was cooled to room temperature, added dropwise to 2000 ml of ethanol, and the formed precipitate was collected by centrifugation. Dissolve the collected precipitate in 500 ml of deionized water, adjust the pH to 7, remove the insoluble portion by filtration, and perform dialysis for 10 days (Dialysis Membrane 36, manufactured by Wako Pure Chemical Industries, Ltd.) to obtain a sulfated chitin aqueous solution. Obtained.

[0016]

EXAMPLES The present invention will be described in more detail with reference to the following examples.
The present invention is not limited to such embodiments.

Example 1 The fine particle chitosan dispersion prepared in Reference Example 1 was diluted to 100 μg / ml chitosan particles with Ringer's solution to prepare a therapeutic agent for mastitis containing chitosan as an active ingredient. After milking in the morning and evening, a 6-year-old dairy cow Holstein teat tube that did not heal even after half-year treatment with antibiotics injected into the breast,
A mastitis therapeutic agent containing chitosan produced as described above as an active ingredient for 10 consecutive days using a syringe equipped with a probe,
After milking in the morning and evening, 20 ml each was injected. A mastitis infection test with a PL tester for diagnosing mastitis (manufactured by Nippon Zenyaku Kogyo Co., Ltd.), the number of somatic cells in milk (measured by Fosomatic manufactured by Fujidaira Co., Ltd.), and the number of bacteria by the bleed method were measured over time.
The results are shown in Table 1.

Table 1

Example 2 A 4-year-old dairy cow Holstein breed with acute mastitis was prepared by using a syringe equipped with a probe for the therapeutic agent for mastitis containing chitosan as an active ingredient prepared in Example 1 for 2 consecutive days, morning and evening. After milking, 20 ml each was injected. A PL tester for diagnosing mastitis, a condition of breast induration, and lumps (coagulants of different sizes in milk observed during mastitis infection) were examined over time. The results are shown in Table 2.

Table 2

Example 3 This sulfated chitin aqueous solution prepared in Reference Example 2 was freeze-dried, dissolved in deionized water to a concentration of 5%, and the pH was adjusted.
After adjusting to 7, it was diluted 10-fold with Ringer's solution to produce a therapeutic agent for mastitis containing the sulfated chitin of the present invention as an active ingredient.
Inject 100 ml of a therapeutic agent for mastitis containing sulfated chitin as an active ingredient into the teat canal of a dairy cow (Holstein) whose treatment with antibiotics did not improve mastitis for 6 months.
After a day, a mastitis infection test using a PL tester was performed.

[0022]

EFFECTS OF THE INVENTION In Example 1 of chronic mastitis, the number of bacteria was remarkably reduced by the use of this drug, and as a result of the examination on the 22nd day, the mastitis was cured. In Example 2 of acute mastitis, an increase in the amount of spots was observed on the second day, but a rapid symptom (pain, heat sensation, induration) was observed to be relieved, and the patient was cured on the third day. Example 3, which had bloody milk, became normal milk after 7 days with the single use of this drug and was cured.

[Table 1]

[Table 2]

Claims (1)

[Claims] 1. A therapeutic agent for mastitis containing chitin as an active ingredient.