WO1995020968A1

WO1995020968A1 - Prophylatic for domestic animal mastitis

Info

Publication number: WO1995020968A1
Application number: PCT/JP1994/000160
Authority: WO
Inventors: Shigeru Saito; Megumi Tomita
Original assignee: Nippon Soda Co., Ltd.
Priority date: 1992-08-07
Filing date: 1994-02-03
Publication date: 1995-08-10
Also published as: JPH0656675A

Abstract

A prophylactic for mastitis comprising a combination of chitosan or a derivative thereof with a quaternary ammonium salt bactericide. It has a potent bactericidal activity and can form a good chitosan film, and hence can prevent mastitis effectively. Since it does not irritate the skin so much, it is less liable to cause heretofore problematic cracking of the nipple due to the use of a medicine.

Description

Specification

Veterinary mastitis prevention agent

【Technical field】

The present invention relates to an agent for preventing mastitis used for preventing mastitis in livestock. More specifically, it is characterized by forming a film containing a quaternary ammonium salt fungicide having antibacterial and bactericidal properties and chitosan and / or a chitosan derivative on livestock such as dairy cows. ₃ related to mastitis prevention agent

[Background Art]

Dairy cows · Mastitis in any domestic animal is a disease in which Staphylococcus aureus, Streptococcus aga lactiae, Escherichia coli and other pathogens invade the udder through the nipple and cause inflammation.

For dairy farmers in particular, the disease has a high incidence, reduced milk yield, reduced milk quality, reduced service life, and public health problems and somatic cells due to bacterial contamination of milk. It is a serious illness that causes large losses, such as poor yields when processing dairy products due to an increase in dairy products.

As described above, mastitis is a serious disease of livestock.However, in the past, appropriate measures for raising livestock to increase resistance to pathogens and clean milking have been used, as well as for measures such as povidone land, hordehole, and glucoside. Preventive methods such as disinfecting (dipping) the nipple with a teat dip containing a bactericide such as chlorhexidine acid chloride and benzalkonium chloride are known.

Other types of nipple pacifiers that form a film that blocks the nipple from pathogens in the external environment are also used, but are not themselves bactericidal and cannot prevent the transmission of pathogens during milking. :

DISCLOSURE OF THE INVENTION

(Problems of conventional technology)

The use of teat dips is effective in reducing the incidence of mastitis, but the effect is It depends on the disinfecting power, disinfecting speed, disinfecting bacteria type, and persistence of the disinfecting agent. In addition to the sterilizing effect, it is important not to cause damage to the skin and mucous membranes of dairy cows and workers.

Nipple immersion containing a fungicide such as poppy donde is widely used, but it has high irritation to the skin and mucous membranes. cause. Cucorhexidine dalconate fungicides have problems of low sterilization rate and mucosal irritation. Benzalkonim dichloride fungicide has the advantage of being less irritating to the skin, but some bactericidal bacteria have insufficient bactericidal activity. Further, these disinfectants do not have a film property and are easily washed away by water, so that there is a problem that the disinfecting power is not maintained for a long time. Therefore, there has been a demand for the development of a type of mastitis preventive agent which has a strong bactericidal activity, does not irritate the skin, and forms a stable film which prevents the infection of pathogenic bacteria for a long time.

(Problems to be solved by the present invention)

The present invention provides a new agent for preventing mastitis that forms a coating on the nipples of livestock animals such as dairy cows, suppresses the growth of pathogenic bacteria in the nipples, prevents the invasion of pathogenic bacteria into the udder, and has little skin irritation The task is to

(Detailed description of the present invention)

The present inventors have conducted intensive studies to solve the above problems, and as a result, a mastitis preventive agent comprising a combination of chitosan or a chitosan derivative and a quaternary ammonium salt fungicide has a strong bactericidal activity. The present inventors have found that the invasion of the pathogenic bacteria into the breast can be prevented by forming a good film with little irritation to the skin and completing the present invention.

Hereinafter, the present invention will be described in detail.

The agent for preventing mastitis according to the present invention is characterized by comprising a quaternary ammonium salt-based bactericide and chitosan and Z or a chitosan derivative as active ingredients.

Hitherto, chitosan or chitosan derivatives have various functions such as antibacterial property, bactericidal property, wound healing action, immunostimulatory action, etc., and form a highly biocompatible film. It is known for use in the fields of industry, agriculture and food.

The present inventors have first focused on the excellent characteristics of the above-described chitosan or chitosan derivative, and have proposed an aqueous solution of chitosan or chitosan derivative for preventing mastitis in livestock such as dairy cows.

-- Found that spraying or dipping an acidic aqueous solution was extremely effective (Japanese Patent Application No. 2-290082), but as a fungicide that can be used in combination and has a synergistic effect. We found benzalkonium chloride and reached the present invention (Japanese Patent Application No. 4-233032, filed on August 7, 1992)

The chitosan used in the present invention is obtained by deacetylating chitin (a polysaccharide of X-acetyl-D-glucosamine), which is a constituent of shells of crustaceans such as Rikido and insects such as beetles. It is a basic poly-macromolecular substance having a free amino group, and the molecular weight is not particularly limited. The chitosan derivative used in the present invention also includes chitin, which is a raw material that has not been deacetylated, and a substance containing a mildly decomposed product generated by a chemical treatment. All or part of the free amino group or hydroxyl group is an alkyl group, an alkoxyalkyl group, an alkylthioalkyl group, an aryl group, an aralkyl group, an acyl group, a sulfonyl group, an alkoxycarbonyl group or a phosphoric acid residue And the like, which have been chemically modified.

These chitosan derivatives can be obtained, for example, by a common synthetic chemical modification such as the method described in the following literature.

(1) Published Patent Gazette 1979-180 602

(2) Published Patent Gazette Showa 59-106 106

The mastitis preventive agent comprising the quaternary ammonium salt fungicide of the present invention and chitosan and Z or a chitosan derivative is quaternary ammonium based on 100 parts by weight of chitosan and Z or chitosan derivative. It contains the salt-based fungicide in an amount of 0.2 to 100 parts by weight, preferably 2 to 50 parts by weight.

The agent for preventing mastitis according to the present invention comprises an aqueous solution or an organic acid or a quaternary ammonium salt-based fungicide, preferably containing chitosan and a Z or chitosan derivative, preferably in an amount of 0.05 to 10% by weight. Used in dilute aqueous solutions of inorganic acids.

Examples of the acid used in the present invention include inorganic acids such as hydrochloric acid and nitric acid, and organic acids such as acetic acid, kunnic acid, succinic acid, lactic acid, and lingic acid.

The amount of the mastitis preventive agent used is not limited because it varies depending on the treatment method and the concentration used, but it is appropriately selected and used within a range where the effect can be exhibited. And quaternary Anmoniumu salt fungicides for use in the present invention, chloride Benzarukoni ©厶, ¾ of benzene Bok Niu厶_{_{(C 2: H, 2 C}} 1 X 0 2), cetyl Application Benefits main Chiruanmo Niumuku b And didecyldimethylammonium chloride. The benzalkonium chloride is represented by the general formula: C _δ Η = C Η 2 X (C Η 3) 2 R]-C 1 (R is a straight-chain or branched alkyl group having 8 to 18 carbon atoms. : Quaternary ammonium salt indicated by)

Representative compounds of the present invention include octyldimethylbenzylammonium chloride, decyldimethylbenzylammonium chloride, dodecyldimethylbenzylbenzylammonium chloride, tetradecyldimethylmethylbenzylammonium chloride, Hexadecyl dimethyl benzyl ammonium chloride, octadecyl dimethyl benzyl ammonium chloride, cocoalkyl dimethyl benzyl ammonium chloride and the like are exemplified.

The prepared quaternary ammonium salt fungicide and the mastitis preventive agent containing chitosan and / or a chitosan derivative can be applied to a film having strong bactericidal activity on the nipple by a method such as spraying or dipping. Mastitis can be prevented by forming pathogens, killing pathogens in the nipple, and preventing the pathogens from entering the udder.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will be described in more detail by way of examples. However, the scope of the present invention is not limited by the following embodiments.

[Test Example 1]

(Antibacterial evaluation test)

The following MIC tests were performed on the disinfectants shown in Table 1.

It was measured by the drug dilution agar plate method according to the MIC measurement method of the Japanese Society of Chemotherapy. The concentration of bacteria was adjusted to 1 0 ⁶ CF Ji / ml, and 2 4 hours at 3 7 hand, to determine the dead dark bacteria. Table 1 shows the results.

Test bacteria: Staphylococcus aureus (St hyi occus aureus I FO 12732;

Milk-free streptococci (Strep tococcus agal ac ti ae ATC C 13813) Escherichia coli (Escherichia aco li ATCC 2 166) H SS CPse domonas aenuginosa I FO 12689)

Test drug:

Benzalconium chloride BAC, Nissan cation M ₂ -100 Nippon Oil & Fat) Benzetonium chloride (BEC, Hyamin Sankyo)

Alkyl glycine :: AG, Nissan Anon LG Nippon Oil Co., Ltd.

Colhexyl dalconate (CHG, videndalconate solution

—I-Pharma Corporation

Hall (3% effective iodine, Sanyo Chemical)

Kitosan (LLWP Kimitsu Chemical)

The values of MIC in Table 1 indicate the concentration of the fungicide excluding chitosan. The composition weight ratio of chitosan to fungicide is chitosan Z fungicide = 10/1.

Also, chitosan and groundhole were excluded from the test due to their incompatibility. Cloth 1 (ug / m £ Fungicide name Staphylococcus aureus Lactococcus aureus Pseudomonas aeruginosa

B A C τ chitosan 1-6 1.6 12.5 200

B E C Pakitosan 1.6 1.6 6.2 200

C H G + Kitsan 1.6 3.1 400 400

A G + chitosan 200 6.2 200 800

B A C 6.2 3.1 12.5 400

B E C 6.2 6.2 12.5 400

C H G 1.6 • 1.6 6.2 200

A G 50 50 200 400 Host 100 100 200 200 Chitosan 3100 6200 3100〉 10000

Test example 2:

The test drugs of Examples 1 and 2 and Comparative Examples 1 to 4 having the components shown in Table 1 were prepared.

― D The following tests were performed.

(Mastitis prevention test)

Nipple spraying after milking was performed for 6 months using the test agents of Examples 1-2 and Comparatives 1-4. The results are shown in Table 3:

(Skin irritation test)

For the test drugs of Examples 1 and 2 and Comparative Examples 1 to 4, patch tests using a lint cloth were performed on the skin of 20 adult men. Pasting time is 6 hours. Twenty-four hours after the end of application, the condition of the skin was observed.

Table 3 summarizes the results of observation of the condition of nipple skin roughness during the mastitis prevention test.

Table 2 — 丄 Example 1 Example 2 Example 2 Ratio K Example 1 Component weight (g) Component weight (g) 'Component weight (g) Purified water 100 Purified water 100; Purified water 100 Glacial acetic acid 0.5? Citric acid 1.5, glacial acetic acid 0.5 Chitosan 1.0 Γ "7" no 1.0: Chitosan 1.0

(CTA-4) (L) '' (CTA-4)

^ ィ Dark benzalkoni ή 1 0.1

Nifunoru 5.0 5.0

Table 2 Comparative Example 4 Example 2 Comparative Example 3 1 Comparative Example 4

Component weight (g) Component weight (g)! Component Weight (g) Purified water 100 Purified water 100! Purified water 100 Glacial acetic acid 0.5

Popi Don 2.0

Lord

Penzalconi chloride U 0.1

i

Ethanor 5.0

note)

① C T A—4: Kitsan made by Katakura Chiryo Lin Co., Ltd.

② L: Kimitsusan made by Kimitsu Kitosan

③ as a base chloride Nzarukoniu厶, two Tsu support Nkachio down M ₂ - 1 0 0 use (NOF Co., Ltd.).

ハイ Hyamine (Sankyo Co., Ltd.) is used as the benzennium chloride.

⑤Popian don't:: ¹ ) Ruby M don't '(Fujita Pharmaceutical Co., Ltd.) : Head number i clinical mastitis: percentage; skin irritation ¹ of the cows of the nipple:

-Shape,

夹 t gun fc 丄 '1' 0 0 .-)-O 0 ''

0 0 D. "Θ

Tenshi 2 39 No 0 1 0

^. 1 υ ο Ushitorayoshimi

Comparative Example 1 35 '4 1 1.4 °

'Comparative Example 2 35; 0: 8.6%: good

i Comparative example 3 35 '5.1% Cracking: Comparative example 4 30; 10 33.3¾; Good: Table

Skin Irritation indication No response

Three

Erythema

Edema, papules

(The invention's effect)

As shown in Test Example 1, when a quaternary ammonium salt-based bactericide is used in combination with chitosan and Z or a chitosan derivative, the bactericidal activity is not impaired, and a synergistic effect on the bactericidal activity is exhibited. There is also. The combination of another fungicide with chitosan did not give favorable results because the antibacterial activity was impaired, and the formic fungicide and chitosan were not compatible and were unsuitable for mixed use.

Also, as shown in Test Example 2, in a mastitis prevention test using dairy cows, the mastitis prevention agent of the present invention showed an excellent effect as compared with other comparative test drugs. The flame preventive agent caused cracks in the nipple due to skin irritation.

As described above, the mastitis preventive agent of the present invention exhibits excellent bactericidal activity by combining a specific bactericide with chitosan and Z or a chitosan derivative, and has a problem of cracking the nipple, which has been a problem in the past. It is characterized by having no skin irritation such as causing a cause and preventing the invasion of pathogenic bacteria into the breast by good film formation of chitosan and / or a chitosan derivative.

This is due to the synergistic effect of chitosan's film-forming properties and bactericidal properties and the bactericidal properties of quaternary ammonium salt fungicides. It is considered that the ability was effectively exhibited.

[Industrial applicability]

As described above, the present invention provides a novel anti-mastitis agent that forms a film on the nipple of livestock animals such as dairy cows, suppresses the growth of pathogenic bacteria in the nipple, and prevents the invasion of pathogenic bacteria into the udder. To provide farmers with an effective means of preventing livestock mastitis.

Claims

The scope of the claims

1. Veterinary mastitis preventive agent characterized by containing a quaternary ammonium fungicide and chitosan and Ζ or chitosan derivative:

2. A preventive agent for veterinary mastitis, wherein the quaternary ammonium salt fungicide according to claim 1 is benzalkonium chloride or benzetonium chloride.

3. The method according to claim 1, wherein the quaternary ammonium salt bactericide is contained in a proportion of 2 to 50 parts by weight based on 100 parts by weight of chitosan and / or chitosan SI conductor. The veterinary mastitis preventive agent according to the above.

4. A claim characterized by being a quaternary ammonium salt fungicide and an aqueous solution containing 0.05 to 10% by weight of chitosan and Ζ or chitosan derivative, or an aqueous solution of an organic acid or an inorganic acid. Item 4. The livestock S mastitis preventive agent according to Item 1.