JPH04368331A - Anti-rs virus agent - Google Patents

Abstract

PURPOSE:To obtain an anti-RS virus agent having high safety by using rutin or its derivative as an active component. CONSTITUTION:The objective agent contains rutin or its derivative as an active component. Rutin is a compound separated from various plants such as buckwheat, effective for reinforcing capillary vessel and known as a vasodilator for preventing cerebral apoplexy, hypertension, pulmonary hemorrhage, peliosis, retinal apoplexy, etc. The rutin derivative is e.g. a compound produced by methoxylating a part or total of the hydroxyl group of the aglycon part of rutin and a compound produced by the sugar-transfer of a glycoside part of rutin. The rutin-containing plant is e.g. phagopilam, aesculentum, Nicotiana tabacum and viola.

Description

[Detailed description of the invention]

0001

FIELD OF THE INVENTION The present invention relates to antiviral agents.

0002

[Prior Art] Rutin is isolated from many plants such as buckwheat, and is known as a vasodilator that strengthens capillaries and is used to prevent cerebral hemorrhage, hypertension, pulmonary hemorrhage, purpura, retinal hemorrhage, etc. It is being

[0003] Furthermore, rutin has been found to be effective in suppressing influenza viruses and the like. [Arzneim
ittwelforschung 28(3), 347
-350 (1978), Rev. Room. Med. V
irol. , 32(3), 213-215 (1981)
].

[0004] Respiratory syncytial viruses belong to the Paramyxoviridae family.
Syncytial virus (RS virus) is a causative agent of lower respiratory tract infections in infants, sometimes resulting in fatal infections. Currently, a vaccine against this virus has not yet been developed, and ribavirin is a known chemotherapeutic agent [N. Engl. J. Med. ,308,1443
-1447 (1983)].

[0005]

[Problems to be Solved by the Invention] Ribavirin has several problems, including the fact that it cannot be administered orally due to its strong toxicity and must be administered locally by aerosol spray, and that resistant viruses have emerged. An object of the present invention is to provide an anti-RS virus agent with less toxicity.

[0006]

[Means for Solving the Problems] The present invention is an anti-RS virus agent containing rutin or a derivative thereof as an active ingredient.

Rutin or its derivatives, which are the active ingredients of the anti-RS virus agent of the present invention, can be natural products or chemically synthesized products. Derivatives of rutin include, for example, compounds obtained by methoxylating some or all of the hydroxyl groups of the aglycone moiety of rutin, and compounds obtained by transglycosylation of the glycoside moiety of rutin.

Examples of plants containing rutin include Fagopyrum esc.
ulentum), Nicotiana tabacum (Nicot
iana tabacum), Forsythia suspensa, Viola sp., Eucalyptus macroryncha
etc. are known.

[0009] Rutin can be extracted and purified from plants by a combination of known solvent extraction methods and various chromatographic methods.

The chemical synthesis of rutin was carried out by Zh. Obshch.
Khim. , vol. 32, 390 (1962), Chem
ical Abstract Volume 58, 1426e (1
This can be done by a known technique such as 963).

[0011] In the method of methoxylating the hydroxyl group of the aglycone moiety of rutin, rutin is dissolved in water, sodium hydroxide and dimethyl sulfate are added, and the mixture is reacted at 30 to 50°C for 5 to 10 hours. After the reaction, the mixture was neutralized to pH 6.0 with 1N hydrochloric acid and extracted with a mixed solvent of chloroform and ethanol. Isolation and purification can be performed by combining known methods.

[0012] The method for transglycosylation of the glycoside moiety of rutin is as follows:
It can be obtained by dissolving rutin and dextrin in water and reacting them in the presence of a glycosyltransferase such as glucose transferase.

The anti-RS virus agent of the present invention can be used as a pharmaceutical for inactivating RS virus in the form of a composition containing an effective and non-toxic amount thereof. The anti-RS virus agent of the present invention can be used in the form of an oral preparation, an injection drug, or an external preparation such as an ointment, a lotion, or a liniment.

[0014] When used as an oral preparation, it is preferable to administer 100 to 6000 mg per adult in divided doses several times a day, depending on the age, weight, and severity of the disease of the patient.

[0015]

Effects of the Invention The anti-RS virus agent of the present invention exhibits an anti-RS virus effect equivalent to that of known anti-RS virus agents, and is safe because it contains less toxic rutin, which has already been used as a vasodilator, as an active ingredient. It can be made into a highly effective drug.

[0016]

[Example] In the following, percentages represent weight %. (Example 1) HeLa cells grown in Eagle's MEM medium containing 10% fetal bovine serum and 1.6% glucose were cultured in a 24-well multitray for 24 to 48 hours to form a monolayer. A certain amount of respiratory syncytial virus (RS Lo)
ng) was added for virus infection. In each 24-well multi-tray, maintenance medium containing 0.7% methylcellulose (Eagle MEM containing 2% fetal bovine serum, 1.6% glucose, and 4x glutamine) containing 4-fold serial dilutions of rutin starting at 200 μg/ml was added. Culture medium) was added and cultured. On the 4th day of culture, remove the maintenance medium, add maintenance solution containing 0.2% neutral red, keep warm at 37°C for 1 hour, remove maintenance solution containing neutral red, and add 0.2% maintenance solution containing neutral red.
It was fixed with formalin-containing phosphate buffer (pH 7.2) for 30 minutes. The number of plaques in the groups administered each concentration of drug was counted. EC50 is the concentration at which the number of plaques in the drug administration group is suppressed by 50% compared to the number of plaques in the control group to which no rutin is added.
It was expressed as The results are shown in Table 1.

[0017]

[Table 1]

(Example 2) RS virus was transformed into RS FM
EC50 was determined according to Example 1 except that the value was 58-8. The results are shown in Table 2. (Reference Example 1) EC50 was determined according to Example 2 except that ribavirin was used instead of rutin. The results are shown in Table 2.

[0019]

[Table 2]

(Formulation Example 1) Tablet Rutin
100 parts by weight lactose
235 parts by weight starch
50 parts by weight Polyvinylpyrrolidone 50 parts by weight Magnesium stearate 5 parts by weight

0
[021] Rutin, lactose and starch were mixed and wet granulated with an aqueous polyvinylpyrrolidone solution. After drying and sieving, the granules were kneaded and compressed with magnesium stearate to obtain tablets of 500 mg/tablet.

(Formulation Example 2) Suspension syrup rutin 0.25
g Sorbitol 1.5 g Glycerol 0.005 g Dispersible cellulose 0.005 g Sodium benzoate 0.010 ml Water
5 liters

002
3] Sorbitol and glycerol were added to 3 liters of water and mixed. Sodium benzoate was dissolved in water and added to the above aqueous solution. Next, cellulose and rutin were added to the aqueous solution and dispersed to adjust the volume.

Claims (1)

[Claims] Claim 1: Anti-RS virus agent containing rutin or its derivative as an active ingredient