JPS63196523A - Preventive and remedy for protozoological disease - Google Patents

Abstract

PURPOSE:To obtain the titled preventive and remedy containing a resin glycoside. CONSTITUTION:A preventive and remedy for protozoological disease containing one or more of the whole plant containing a resin glycoside [e.g. pharbitin, jarapin, orizabin, compound shown by formula I (R1 is H, etc.; R2 is mba, etc.; R3 is mba, etc.), compound shown by formula II (R1 is iba, etc.; R2 is H, etc., with the proviso that mba is alpha-methylbutyric acid and iba is iso-butyric acid), etc.] found in a plant of the family Convolvulaceae, raw or secondarily processed parts (e.g. blossom part, seed, root or stem part). Powder, dust, granule, tablet, solution, premix, injection, etc., may be used as the dosage form. The agent is directly added to feed, drink etc., or dispersed into a carrier and added. The amount of the agent is 1-20wt.%, preferably 2-10wt.% based on feed when the agent is added to feed. The agent is effective chicken coccidiosis, toxoplasmosis, malaria, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a prophylactic and therapeutic agent for protozoal diseases containing a resin glycoside.

PRIOR ART Diseases caused by protozoa include, for example, chicken coccinodiosis, chicken leukocytozoonosis, porcine and bovine coccinodiasis, toxoplasmosis, malariasis, piroplasmosis, human malariasis, tropical fever, chickens.

Various protozoal diseases such as trypanosomiasis and leishmaniasis that occur in pigs and cattle are known, and conventional preventive and therapeutic agents for these protozoal diseases include sulfa drugs, quinoline derivatives, nucleic acid derivatives, quinazoline derivatives, and guaninone derivatives. Acid antagonists, polyether antibiotics, etc. are used.

On the other hand, the resin glycosides contained in the Convolvulus plant have several sugars bonded to fatty acids, and the sugar water ili! It is a substance with a structure in which lower fatty acids are ester bonded to two groups, and its biological activity against protozoa has not been reported at all.

Problems to be Solved by the Invention Chicken coccidiosis, an example of a protozoal disease, is caused by the orally ingested protozoan Eimeria tenella.
tenella), Eimeria necatolic (Ei
meria necatrix), Eimeria acervulina
The disease is caused by the proliferation of sporulating oats in the gastrointestinal tract of chickens, and affected chickens excrete diarrhea, mucus, mucus, bloody stool, etc., and lose their appetite. This results in delayed growth, decreased body weight, decreased egg production rate, and even death. Chicken Leucocytozoonosis is caused by the protozoan Leucocytozoon callaraeri (L.

caulleryi),
Affected chickens exhibit symptoms such as anemia and green stools, which results in delayed growth, weight loss, reduced egg production, and even death.

Furthermore, swine coccidiosis is a disease in which young pigs are generally susceptible to infection after weaning, and the symptoms include clear diarrhea, mainly catarrhal enteritis, and in cases of heavy infection, the wings may be affected. In such cases, anemia, weakness and loss of appetite are seen, leading to subsequent growth retardation.

As mentioned above, diseases caused by protozoa, especially sporophytes, cause great damage to livestock industries such as poultry and pig farming.

Sulfa drugs, quinoline derivatives, nucleic acid derivatives, quinazoline derivatives, which are conventionally used for such protozoal diseases;
Guanidine derivative 1m acid antagonists, polyether antibiotics, and the like are expensive and have a very narrow safety margin, so there are many problems when mixing them with feed etc. and using them in large quantities.

Means for Solving the Problems In view of the above-mentioned circumstances, the present inventors have made intensive studies to provide an excellent prophylactic and therapeutic agent for protozoal diseases. However, it was unexpectedly discovered that it exhibits biological activity against protozoa, and as a result of further research based on this finding, the present invention was completed.

That is, the present invention is a prophylactic and therapeutic agent for protozoal diseases, which contains a resin glycoside.

Examples of resin glycosides in the present invention include farvidin, Jarapin, and
pin), Orzabin, and Mb-1 (↓), Mb-2 (, j) represented by the following formula (1)
, Mb-3 (, J), Mb-4 (4), Mb-5 (Dan)
[27th Natural Organic Compounds Conference Lecture Abstracts 427~
434 (1985)], and further 0 represented by the following formula (II)
c-1 (view), Oc-2 (1), Oc-3 (garden),
Examples include 0c-4 (5L) [same as above]. -M
b −1(,L):Rt= )I , Rt=mba, R
s=mbaMb-2(,g,):Rt=H,Rt=mb
a, Rs=ibaMb-3(,J):R+=mba,R
t=H, R3=mbaMb −4(i): Rt=Ill
ba, Rt=H, Rs=ibaMb-5(5):R,=
a+ba, 1'tt=H, Rs=HOc -1 (6):
R,=tba, Rt=HOC-2(:L):rL=H,
Rt=mbaOc-3(,11):rt,=H,Rt=
ibaOc-4(jj):IN,=1-1. rtt=
nla [where mba is α-methyl butyric acid.

iba is iso-butyric acid.

nla indicates nilic acid. ] The resin glycoside may be a purified resin glycoside, and a resin glycoside-containing material, for example, a whole plant containing the resin glycoside or a part containing the resin glycoside (e.g. Flower parts (seeds, roots, stems, etc.) may be used as they are, or secondary products obtained by processing such as drying, crushing, powdering, etc. (e.g.
Beef roe, orizaba fat.

yarappa fat, cow roe fat, orizaba root, yarappa root, etc.)
It is better to use

Examples of plants containing resin glycosides used in the present invention include morning glory (Pharbitis n1lCh).
oisy), Pharbitis
hederacea Choisy), Rukosou (Qua
mocrit pennata Bojer).

Ipomoea Batatas L
aw), Ibomea oryzaba (lpomea 0rtZ
abenSiS Ledanois), Ibomea purga (lpomea purga), and P. abenSiS Ledanois (
Ipomea muricata (L) JaCQ
), among which preferred are morning glory, morning glory, Ipomea pulga, and Ibomea pulga, and more preferred are morning glory and morning glory.

When administering the above-mentioned plants and their secondary processed products as prophylactic and therapeutic agents for protozoal diseases, whole or raw parts containing resin glycosides (e.g. flower part 1 seeds, roots, stem parts, etc.) Alternatively, one type or a mixture of two or more secondary processed products (preferably secondary processed products) may be administered.

The purified resin glycoside used in the present invention can be produced, for example, by the following method.

The whole or resin glycoside-containing parts of the above-mentioned plants (e.g., flowers, seeds, roots, stems, etc.) are prepared in a raw form or a secondary processed product (preferably a secondary processed product) is mixed with alcohol. (e.g., anhydrous methanol, anhydrous ethanol, water-containing methanol, water-containing ethanol, etc.), ketone ff1 (e.g., acetone, methyl ethyl ketone, etc.), chloroform, etc. alone or a mixed solvent thereof, using about 5 to 10 m of the solvent, is used at room temperature to reflux. Extract under heating conditions for 2 hours to 2 weeks. Concentrate the extract and add polystyrene resin or dextran resin (e.g., Diaion HP-20, Diaion XA).
D-2, MCI gel CHP-20, Yafadex H
Resin glycosides can be obtained by performing column chromatography using a column chromatogram (e.g. -20) and concentrating the eluted fractions of alcohol, acetone, hydrous alcohol, or hydrous acetone. It can also be obtained by concentrating the extract, layering an ether such as diethyl ether on the concentrate, and filtering off the precipitated resin glycosides.

The dosage of the resin glycoside-containing plant and its secondary products in the preventive and therapeutic agent for protozoal diseases of the present invention is determined by the administration method,
Although it varies depending on the administration purpose, subject, target disease, disease symptoms, etc., when mixed with feed, the amount is preferably about 1 to 20% by weight of the normal feed, and more preferably about 2 to IO
This is the amount in weight%. In the case of purified resin glycosides, the amount is preferably about 250 to 2500 ppm, more preferably about 500 to 1500 ppII.

The purified resin glycosides used in the present invention, the plants containing the resin glycosides, and their secondary processing have extremely low toxicity; for example, when administered orally to 9-day-old white leghorns, m
Observation for 8 days after administration) was 1.0 g/k of purified resin glycoside.
g/day or more, and 50 g/kg/day or more for plants containing resin glycosides and their secondary processed products (e.g. morning glory seeds, morning glory seeds, snails, etc.).
The prophylactic and therapeutic agent for protozoal diseases of the present invention can be safely administered.

The preventive and therapeutic agent for protozoal diseases of the present invention comprises purified resin glycosides,
The above-mentioned plants or their secondary processed products are diluted with a solid or liquid carrier, or not diluted, or stabilized by coating, etc., such as powders, powders, granules, Ii agents, liquid agents,
It is produced in the form of emulsions, pastes, capsules, premixes, injections, etc., or by adding it directly or dispersed in a carrier to feeds, drinks, etc. Any carrier may be used as long as it is physiologically harmless in itself, and it is more desirable that it can be used as feed or a component of feed. Solid carriers include, for example, lactose, sucrose, starch, wheat flour, corn flour.

Bran, large, soybean oil lees, defatted rice bran, rapeseed oil lees, tofu lees, cellulose yeast cells, fish meal, groundnut lees, shell powder.

Examples of the liquid carrier include water, physiological saline, and physiologically harmless organic solvents. Other appropriate adjuvants such as emulsifiers, dispersants, suspending agents, wetting agents, aggregation agents, gelling agents, and solubilizing agents may be added in appropriate amounts. Furthermore, preservatives, bactericidal agents, colorants, fragrances, antibacterial agents, antibiotics, enzyme preparations, lactic acid bacteria preparations, antipyretics, analgesics, anti-inflammatory agents, etc. may be added, and conventionally used protozoal disease It can also be used in combination with preventive and therapeutic agents. Additionally, various vitamins, minerals, amino acids, etc. may be added.

Target diseases of the preventive and therapeutic agent for protozoal diseases of the present invention include:
For example, chicken coccidiosis, 80 icocytozoonosis, pigs,
Bovine coccidiosis, toxoplasmosis, malariasis,
Piroplasmosis 0. human malaria, tropical fever, chickens,
Examples include trypanosomiasis and leishmaniasis that occur in pigs and cattle, but among them, chicken coccidiosis, pigs,
Bovine coccidiosis is preferred.

EXAMPLES The present invention will be specifically explained with reference to Examples below, but the present invention is not limited thereto.

Example 1 An efficacy test against coccidia was conducted using chickens. Namely, each group of 9-day-old white Leghorn male chicks was made up of 3 birds, and 24 hours after the start of the test, 5XlO' sporulating oocysts of Eimeria tenella per bird were orally administered to the chickens in all groups except the non-infected control group. was inoculated.

The drug is dried and ground into standard feed (SDL No.
, l: Nippon Compound Feed Co., Ltd.) was added in a predetermined amount and administered continuously by ad libitum feeding method for 9 days from 24 hours before infection to 80 days after infection.The weight of each chick was measured every day during the rearing period. At the same time, the appearance of bloody stool was observed, and the lesion status of the caecum, which was autopsied on the 8th day after oocyst inoculation, was examined to determine the anti-coccidial effect of the administered test drug. The results are shown in Table 1.

As is clear from the test results in Table 1, the weight gain ratio increased in the non-invention plots compared to the infected plots, and excellent anti-coccidial effects were observed.

As controls, persimmon leaves, whole mugwort plants, and valerian roots, which do not contain resin glycosides, were used.

2) Blood stool index: The amount of bloody stool excreted from the intestines of the chicks is expressed by the number of blood stains found on the bedding (number of blood stains: 7 birds).

3) Cecal lesion knee: normal, +: mild, 廿: moderate, *:
Severe 9 volumes: Extremely severe lesions. The numbers indicate the number of birds.

Example 2 Farbitin was produced by the method shown below, and the anti-coccidial effect was determined in the same manner as in Example 1.

Grind the dried beef roe (500g), degrease it with hexane (212), and dissolve the residue in chloroform-methanol (1:1) 2Q.
The chloroform-soluble part was extracted twice under reflux for 2 hours, and the obtained concentrate (47.7 g) was extracted with Sephadex LH.
-20 (312) column, and 30 g of farbitin was obtained from the fraction eluted with methanol.

Recrystallization was performed from methanol-ethyl ether (1:1) to obtain a colorless powder. Melting point: 144-148°C, optical rotation: [α]25-47.7° (c=2, O, Me
OH), IR spectrum: Characteristic absorption bands were observed at the following frequencies (cm-'): 3600-32
When 00.1730°11000 pp was added, no hematochezia index was observed, cecal lesions were improved, and the weight gain ratio was also good.

Example 3 Corn, North Sea meal, soybean oil cake, powdered refined beef tallow,
Flour, alfalfa meal, and vitamins.

Shibari feed for broiler fattening using minerals as raw material 5
The protozoal disease prophylactic and therapeutic agent of the present invention can be produced by mixing and blending 10 kg of DB-No. 1 (manufactured by Nippon Compound Feed Co., Ltd.) with 1 Og of farvidin.

Example 4 A premix of the preventive and therapeutic agent for protozoal diseases of the present invention can be produced by mixing farbitin long with 1 kg of soybean oil cake. This premix preparation can be diluted 100 times, mixed into feed, and administered as the preventive and therapeutic agent of the present invention.

Effects of the Invention The prophylactic and therapeutic agent for protozoal diseases of the present invention exhibits safe and economically excellent effects against protozoan diseases, and is particularly advantageous in livestock farming.

Claims (1)

[Claims] A prophylactic and therapeutic agent for protozoal diseases containing resin glycosides.