JPH0352815A - Remedy for intravascular blood coagulation syndrome - Google Patents

Abstract

PURPOSE:To obtain a remedy for intravascular blood coagulation syndrome containing sulfonoglycolipid or a salt thereof as an active ingredient. CONSTITUTION:A remedy containing a compound expressed by the formula or pharmacologically acceptable salt thereof as an active ingredient. The dose of the aforementioned compound for an adult per day is within the range of 1-100mg, especially 5-15mg in one or more divided portions for oral administration, 0.01-1mg/kg, preferably 0.03-0.1mg/kg for an injection or 1-20mg/kg/hr, preferably 1-5mg/kg/hr for an intravenous drip.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a medicament containing sulfonoglycolipid or a pharmacologically acceptable salt thereof as an active ingredient. More specifically, the present invention relates to a therapeutic agent for intravascular blood coagulation syndrome, which uses sulfonoglycolipid or a pharmacologically acceptable salt thereof as an effective ingredient.

[Background of the Invention, Prior Art 2 Heparin is currently mainly used to treat intravascular blood coagulation syndrome, which is an extremely serious disease. However, heparin has the disadvantage that it tends to promote bleeding, making it difficult to control the disease state. Therefore, the development of better therapeutic agents is desired.

In view of these circumstances, the present inventors have conducted intensive research over many years to develop a therapeutic agent for intravascular blood coagulation syndrome. It was found that it is effective as a drug.

[Structure and effect of the invention]

The effective component of the present invention is a sulfonoglycolipid represented by the following chemical structural formula (I) or a pharmacologically acceptable salt thereof.

Sulfonoglycolibide is a compound having the above chemical structural formula, and is described, for example, in the following literature. That is, regarding the extraction method from plants, A.A. Benson
et al., Proc., N.A.S. Vol.4
5. 1582~15g? (1959),
Regarding the extraction method from sponges, see H. Kikuchi e.
tal, Chem. Pharm. Bull,,
Vol, 30. 3544-3547 (1982);
tal,, J, C, S, Perkin I, 2
490-249.3 (1980).

The above-mentioned sulfonoglycolipid has stereoisomers with respect to the glycerin side chain as is clear from the above chemical structural formula, but in the present invention, RS produced by a synthesis method is used.
It may be a body, or it may be an S body or an R body.

In addition, in the above chemical structural formula, the wavy line (~) is an expression that includes any of the above-mentioned RS form, S form, and R form.

The RS bodies are combined, for example, according to the above-mentioned literature, but to obtain the R bodies and the S bodies, the RS bodies are divided by a conventional method.

The above compounds can be obtained in free or salt form. Preferred salt forms include, for example, potassium, calcium, triethylamine, tris(hydroxymethyl)
Aminomethane, more preferably pharmacologically acceptable salts such as sodium, are mentioned.

Next, pharmacological experimental examples will be shown to explain in detail the effects of the compounds of the present invention.

For the test, 230 to 260 g of F3<</DLl[:r
J-series male rats were used in groups of 5 rats.

0. 3mg/kg/hr ribopolysaccharide (L
By continuously injecting PS) from the right jugular vein for 4 hours,
This caused intravascular blood coagulation syndrome. The compound of the present invention (R
Continuous infusion of S form) was started 10 minutes before the start of LPS infusion, and the infusion was stopped at the same time as LPS. In contrast, there are 5 Q.
M! ．． 1 of phosphate buffered saline (pH 7.4) was administered. Immediately after the continuous infusion, blood was collected from the abdominal aorta, and the platelet count and plasma fibrinogen concentration were measured. The platelet count was measured using Sysmex-3000 (manufactured by Toa Medical Denki Co., Ltd.). Plasma fibrinogen concentration was analyzed by statistical processing using a t-test using a fibrinogen measurement reagent. The results obtained are shown in Table 1.

As is clear from Table 1, the compound of the present invention was administered at 10 mg/k
Continuous infusion at 1 g/hr significantly suppressed the decrease in platelets and fibrinogen induced by LPS.

The above pharmacological experiment examples show that the compound of the present invention, sulfonoglycolipid, is effective in treating and preventing intravascular blood coagulation syndrome.

When the compound of the present invention was intravenously administered at 200 mg/kg to Fischer male rats (body weight 90-110 g), no deaths were observed. Therefore, the compound of the present invention is highly safe.

When the compound of the present invention is used as a therapeutic agent for intravascular blood coagulation syndrome, it is administered orally or parenterally (intramuscularly, subcutaneously, intravenously, intravenously, etc.). The dosage varies depending on the difference in the disease, the severity of the symptoms, the patient's age, health condition, weight, the type of concurrent treatment (if any), the degree of treatment, the nature of the desired effect, etc., but is not particularly limited. Orally about 1 mg to 100 mg, preferably about 5 mg to 50 mg, more preferably about 5 mg per day
Approximately 15 mg is administered once a day or more frequently. In the case of injections, approximately 0.01mg/kg
~lmg/kg, preferably about 0. 03mg/k
g～O. lmg/kg. In the case of intravenous drip,
■~20mg/kg/hr, preferably l~5mg/hr
kg/hr.

Examples of dosage forms include powders, fine granules, granules, tablets, capsules, suppositories, and injections. When preparing a formulation, it is produced by a conventional method using a conventional pharmaceutical carrier.

That is, when preparing a solid preparation for oral use, excipients are added to the crude drug, and if necessary, binders, disintegrants, lubricants, colorants,
After adding flavoring agents and the like, it is made into tablets, coated tablets, granules, powders, capsules, etc. by conventional methods.

Examples of excipients include lactose, corn starch, sucrose,
Dextrose, sorbitol, microcrystalline cellulose, silicon dioxide, etc. are used as binders, for example, polyvinylalconovinyl ether, ethyl cellulose, methyl cellulose, gum arabic, tragacanth, gelatin, Sierrac, hydroxypyl cellulose, hydroxypyl starch, polyvinyl vinyl Examples of disintegrants include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium bicarbonate, calcium citrate, dextrin, and pectin. Examples of lubricants include magnesium stearate and talc. , polyethylene glycol, silica, hydrogenated TTL oil, etc. are permitted to be added to pharmaceuticals as coloring agents, and as flavoring agents, cocoa powder, peppermint, aromatic acids,
Peppermint oil, dragon brain, cinnamon powder, etc. are used. Of course, these tablets and granules may be coated with sugar coating, gelatin coating, or other coatings as appropriate.

When preparing an injection, a pH adjuster, a buffer, a stabilizer, a solubilizer, etc. are added to the herbal medicine as necessary, and an intravenous injection is prepared by a conventional method.

Claims (1)

[Scope of Claims] 1. A sulfonoglycolipid represented by the following chemical structural formula (numerical formula, chemical formula, table, etc.) or a pharmacologically acceptable salt thereof as an active ingredient for treating intravascular blood coagulation syndrome. therapeutic agent.