NZ312211A

NZ312211A - Antipiroplasmotic agent containing a sulphated polysaccharide

Info

Publication number: NZ312211A
Application number: NZ312211A
Authority: NZ
Inventors: Ivan Havlik; Yutaro Kaneko; G E Swan; J H Taylor; Tohru Mimura
Original assignee: Ajinomoto Kk
Priority date: 1995-07-13
Filing date: 1996-07-12
Publication date: 1999-09-29
Also published as: AU704517B2; AU6369996A; WO1997003095A1; ZA965962B; BR9609606A

Description

New Zealand No 312211 International No. PCT/JP96/01 959 TO BE ENTERED AFTER ACCEPTANCE AND PUBLICATION Priority dates 13 07 1995, Complete Specification Filed 12 07 1996 Classification (6) C08B37/00 Publication date 29 September 1999 Journal No 1444 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION Title of Invention Anti-piroplasmotic agent Name, address and nationality of applicant(s) as in international application form AJINOMOTO CO , LTD , 15-1, Kyobashi 1-chome, Chuo-ku, Tokyo 104, Japan SPECIFICATION Anti-piroplasmotic Agent Detailed Description of the Invention Field of the Invention This invention relates to an anti-piroplasmotic agent for use m human or mammals other than human, which contains a sulfated polysaccharide as its active ingredient.

Prior Art Piroplasmosis is an infectious disease caused by Piroplasmida parasites carried by ticks, which is one of the important diseases m the field of veterinary science, because it broadly spreads m cattle, horses, dogs, cats, sheep, pigs, camels, water buffaloes, reindeer and the like domestic and wild animals. Cases of this disease have recently been reported even in hvuuan caused by Piroplasmida parasites through rodents and cattle.

The infected Piroplasmida parasites live upon erythrocytes or lymphocytes and cause strong hemolytic anemia in the host. Mortality rate of this disease is 30 to 80%.

Though trypan blue, diminazene, aminoquinoline and the like are known as its therapeutic drugs, their doses are limited due to strong side effects such as nervous disorder and the like, so that it is difficult to exterminate Piroplasmida parasites.

On the other hand, it is known that the sulfated polysaccharide 1 31 y ■' * , iL-t to be used m the present invention has an anti-blood coagulation activity, antiviral activity (Japanese Patent Application KokaiNo. 62-215529) and antimalarial activity (WO 95/08334).

Problems to be resolved by the Invention The object of the present invention is to provide a novel anti-piroplasmotic agent having low side effects and high therapeutic effects, or to at least provide a useful alternative Means for resolving the Problems With the aim of resolving such problems, the inventors of the present invention have conducted intensive studies and found as the result that a sulfated polysaccharide has an anti-piroplasmotic activity and hardly shows side effects, hence resulting m the accomplishment of the present invention- Accordingly, the present invention relates to the use of a sulfated polysaccharide or a pharmaceutically acceptable salt thereof m the preparation of a medicament for the treatment of piroplasmosis caused by Piroplasmida parasites Mode of carrying out the Invention Examples of the sulfated polysaccharide to be used in the present invention include synthetic or natural sulfated polysaccharides such as sulfated curdlan, dextran sulfate, chondroitin sulfate A, B, C, D, E, H and K, heparin, keratan sulfate, keratan polysulfate, heparan sulfate, carrageenan and the like, of which curdlan sulfate is particularly preferred in view of the anti-piroplasmotic effect. Also included in the sulfated polysaccharide of the present invention are chemically modified sulfated polysaccharides obtained by subjecting a sulfated intellectual property office 2 of- in z - 6 JUL 1999 RECEIVED polysaccharide to partial oxidation to effect ring-opening and then to reduction in order to increase water solubility of the sulfated polysaccharide or by subjecting a sulfated polysaccharide to carboxymethylation for the purpose of increasing its blood retentivity. A preferred sulfated polysaccharide to be used may have a sulfur content of from 5 to 25% by weight, preferably from 10 to 20% by weight, most preferably from 12 to 17% by weight, and a weight average molecular weight, when calculated by a gel filtration method (GPC), of from 5,000 to 500,000, preferably from 20,000 to 200,000, most preferably from 50,000 to 120,000. The sulfated polysaccharide can be produced from a known polysaccharide m accordance with a known method described for example in Japanese Patent Application Kokai No. 61-130301, 61-130302 or 2-145601.

Examples of the pharmaceutically acceptable salt of sulfated polysaccharide include inorganic salts such as sodium salt, potassium salt, calcium salt, magnesium salt and the like.

Dosage form of the anti-piroplasmotic agent of the present invention is not particularly limited, and the agent can be made into optional dosage forms such as injections, drippings, suppositories, nasal sprays and the like.

Formulation of the agent also has no particular limitation, and, in the case of injections or drippings, the sulfated polysaccharide is used together with lactose, glucose, mannitol, maltose, amino acids, gelatin, distilled water, ethanol, Ringer solution, isotonic sodium chloride solution and the like. In the case of suppositories, the sulfated polysaccharide can be formulated 3 by mixing it with non-irritant fillers which are solid at ordinary-temperature but dissolve and release the drug at the body temperature, such as cocoa butter, glycende ester, polyethylene glycol and the like.

Dose of the anti-piroplasmotic agent of the present invention varies depending on the species, age, body weight, symptoms, pnysical condition, sex and feed of each animal to be administered, combination with other drugs, its administration method and the like, and is generally from 0.1 to 1,000 mg/kg body weight/day, preferably from 1 to 500 mg/kg/day, in terms of the active ingredient.

The anti-piroplasmotic agent of the present invention exerts its anti-piroplasmotic effect when it is administered before or after Piroplasmida infection.

In addition, the anti-piroplasmotic agent of the present invention can be used m combination with trypan blue, dimmazene, aminoquinoline and the like conventional therapeutic drugs, and, in that case, the combined use exerts excellent therapeutic effect in comparison with their single use.

Examples Examples of the present invention are given below by way of illustration and not by way of limitation.

Test Example 1 (Effect of sulfated curdlan on babeslasis in dog) Two beagle dogs (18 to 24 months of age) which have been confirmed for the absence of anti-babes la antibody titer m advance were inoculated and infected with a Piroplasmida species, Babesia cams. After the infection, the number of babes la-infected erythrocytes m peripheral blood was counted, and, when the ratio reached 8%, sulfated curdlan sodium salts (CRDS; 7 9,500 in molecular weight and 12 to 13% m sulfation degree) was administered CRDS was dissolved in physiological saline and administered by drip infusion in a dose of 5 mg/kg spending 30 minutes The administration was carried out every 6 hours for 2 days m a total of 8 times. Fig. 1 shows changes m the ratio of babesia-infected erythrocytes in peripheral blood until 11 days after inoculation of Babesia cams. Also, conditions of the dogs were observed to obtain crisis scores based on the following criteria (Fig. 2).

(Crisis score) 0: death 1: coma 2: faint 3: serious fever, anemia 4: slight fever, anemia l : healthy As the results, sulfated curdlan excluded Babesia cams effectively and showed no side effects.

Formulation Example 1 (Dripping preparation) A 100 mg portion of sulfated curdlan sodium salts, 50 mg of manmtol and sodium hydrogenphosphate 12H20 were dissolved in 2 ml of distilled water for injection use, and the solution was adjusted to pH 6.5 with phosphoric acid and then freeze-dried to /Ms 9 obtain a dripping preparation.

Effect of the Invention Since the anti-babesia agent of the present invention has excellent therapeutic effect and shows low side effects, it is markedly useful as a preventive or therapeutic agent for mammals. Brief Description of the Drawings Fig. 1 is a graph showing changes m the ratio of babesia-mfected erythrocytes m peripheral blood carried out in Test Example 1.

Fig. 2 is a graph showing changes in the crisis scores carried out m Test Example 1. 6 51 L! p 11 1 „ J

Claims

CLAIM

1 Use of a sulfated polysaccharide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of piroplasmosis caused by Piroplasmida parasites
2 Use according to claim 1, wherein the sulfated polysaccharide is sulfated curdlan
3 Use according to claim 1, substantially as herein described with reference to Formulation Example 1

END OF CLAIMS

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ABSTRACT

[Object] To provide a novel anti-piroplasmotic agent having low side effects and high therapeutic effects.

[Resolving Means] To contain a sulfated polysaccharide or a pharmaceutically acceptable salt thereof as an active ingredient. Sulfated curdlan sulfate is particularly desirable.

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