JPS59128329A - Antiviral agent - Google Patents

Abstract

PURPOSE:An antiviral agent useful for remedying viral diseases such as herpes, chicken water pox, etc., having low side effect, containing 1,2,3,4,6-pentagalloylglucose as an active ingredient. CONSTITUTION:The titled agent containing 1,2,3,4,6-pentagalloylglucose shown by the formula as an active ingredient. The active ingredient is obtained by extracting Moutan radicis cortex (plant of raw material, Paeonia suffruticosa), Paeoniae radix (plant of raw material, Paeonia albiflora), etc. as a crude drug with a hydrophilic organic solvent or a mixture of it and water, purifying the extract by using difference of solubilities of the extract in various kinds of solvents, and difference of affinity for adsorbents, etc. An antiviral agent containing the component can be used as a drug for oral administration or for injection, but it is especially preferably useful as a drug for external application.

Description

[Detailed description of the invention] TECHNICAL FIELD This invention relates to antiviral agents.

Compared to medicines for bacterial diseases, the development of medicines for viral diseases has lagged significantly.

Among chemically synthesized substances, there are many that have antiviral activity or that have severe side effects that make them difficult to put to practical use. Therefore, the emergence of an antiviral agent without side effects is desired.

The inventor focused on the fact that herbal medicines generally have few side effects, and as a result of searching for those that had antiviral activity among herbal medicine ingredients, he discovered peony rootbar (peony rootbar).
outan Cortex), peony r
oot.

1,2゜3,4,6-pentagalloyl gluconis contained in crude drugs such as Paeoniae Radix),
They discovered that it has excellent antiviral activity and completed this invention.

That is, this invention provides 1.2. '3.4.6-It is an antiviral agent containing 6-pentagalloylglucose as an active ingredient.

1,2.3.4.6-Pentagaloylglucose is present in the Chemical and Pharmaceutical Industry (Chem.

Pharm, Bull, (Tokyo), Vol. 28, p. 2850 (1980), and its structural formula is as follows.

1, 2.3.4.6-Bentagaloylgelcose, Botanpi as a crude drug (original plant I'aeonia 5
uff-ruticosa), herbal medicine (Paeonia albiflora) or the raw counterpart of these original plants, or gallic (Nutg.
alls = Gallabalepensis),
Chinese Nutgalls.

Ga1la Rhois) etc. are extracted with hydrophilic organic solvents such as j'9/-JL/, ethanol, acetone, etc., or a mixture of these and water, and the extracts are analyzed for differences in solubility in various solvents and affinity for various adsorbents. It can be obtained by refining using the difference in

Since the 1,2.3.4.6-pentagalloylglucose thus obtained has antiviral activity, it can be used to treat viral diseases such as herpes, water cavities, and warts. For example, 1.2.3.4. ``The results of testing the antiviral activity of 6-pentagalloylglucose against herpes simplex virus are as follows.

[Test method]

24 hours before the start of the antiviral test, form a monolayer of dispersed FL cells in a 35 mm diameter IJ dish, and when starting the test, remove the medium from the vessel and add the medium to the vessel. Herpes simplex virus-containing solution 1.e was added. After incubating the sterile in a humidified, 5% MoO2-containing egg container at 36°C for 1 hour, add 1 ml of medium and 1°2, 3.4.6-
An aqueous solution containing pentagalloylglucose was added. 24
After a period of time, the number of multinucleated giant cells was examined, and the minimum concentration at which no multinucleated giant cells appeared was defined as the antiviral activity. The results are as follows.

The acute toxicity of 1,2,3,4,6-pentagalloylglucose was investigated using rats, and it was found that the toxicity was extremely low.

Although the antiviral agent of the present invention can be used as an orally administered drug or an injectable drug, it is particularly suitable for use as an external drug. External preparations include ointments (oil-based ointments,
This includes hydrophilic ointments), lotions, liniments, etc. When manufacturing external preparations, the carriers (bases) are liquid trough-in, Isopar, vaseline, silicone oil,
Aliphatic higher fluorols (palmityl alcohol, oleyl alcohol, etc.), higher fatty acids (Mi11, 2. thiaic acid, stearic acid, etc.), fatty acid esters (microcrystalline wax, inpropyl myristate, etc.)
, Lanolin, Plastibase (mixture of fluid graphin and polyethylene), Polyethylene IJ Coal,
It is normal to use water etc. In addition, if necessary, emulsifiers (fatty acid monoglyceride, sorbitan fatty acid ester, polyoxyethylene lauryl ether, etc.), wetting agents (glycerin, propylene glycol, sorbitol, etc.), preservatives (methyl or propyl paraoxybenzoate, etc.), Antioxidants (Bl-IA, etc.), pH adjusters (citric acid, etc.), Kendaku Kitagawa (CMC, etc.), and other drugs (
Anti-pruritic agents, analgesics, etc.) may be added. The above-mentioned external drugs also include those intended for transdermal absorption. Drugs for oral administration and drugs for injection are each manufactured by conventional methods.

The content of the active ingredient 1, 2, 3, 4, 6-pentagalloylglucose varies depending on the dosage form, patient's age, condition of the affected area, etc., but in the case of external drugs, it is generally 0.001
~0.5% is suitable, and 0.01~0.1% is preferable.

Next, a production example of 1.2.3.4.6-pentagalloylglucose and an example of the present invention will be shown. In addition, in the Examples, 1,2,3,4.6-pentagalloylglucose was abbreviated as "active ingredient."

Production Example 1 Peony bark 50/m2 was immersed in methanol 500 me for one week and extracted. The extract was concentrated to dryness, and ether and water were added to the residue. The aqueous layer was separated and extracted with ethyl acetate. The ethyl acetate layer was concentrated and the residue was lyophilized. Dissolve this in methanol, Sephadex L'l-l-2
After adsorption onto a 0 column, methanol was passed through the column at a rate of 30 me/hr, and the eluate was divided into fractions of 20 d each. 50 .mu.l of each fraction was taken, diluted with 2.5 ml of methanol, and the absorption value at 254 nm was measured to obtain the results shown in Figure 1. Fractions indicated by A in FIG. 1 were collected, concentrated and freeze-dried to obtain 140 mg of crude 1.2.3.4.6-pentagalloylcurcose.

Production Example 2 Crude 1.2.3.4 obtained in Production Example 1 above. ' 6-Pentagaloylcurcose was dissolved in 20 me of 25% methanol, and the 5 me was adsorbed on a Likloprep RP-IB column, and then 25% methanol was passed through the column at a rate of 1 min. Measure the adsorption value of the eluent at 254 nm,
The results shown in FIG. 2 were obtained. This column chromatography was repeated four times. The portion indicated by B in FIG. 2 was collected, concentrated and lyophilized to obtain 125 mg of purified 1.2.3.4.6-pentagalloylglucose. The crystal was identified as the standard product by nuclear magnetic resonance spectroscopy.

Production Example 3 Purified 1.2.3.4.6-pentagalloylcurcose was obtained in the same manner as in Production Examples 1 and 2 using Xun Yao 100f. It was almost the same as product No. 2.

Example 1 (A) Active ingredient o, osy isopropyl myristate 5y (B) Plastibase 94.95
yA was mixed, and this was gradually added to B while stirring, and the mixture was homogenized to obtain an oily ointment.

Example 2 (A) Active ingredient 0.0! M
'Isopropyl myristate 5.95y (B)
Isopropyl myristate 10g Vaseline
66y Liquid Paraffin 5y Microcrystalline Wax 13yB was melted by heating, and the premixed A was added thereto at 45 to 50°C, and the mixture was stirred and homogenized until solidified to obtain an oily ointment.

Example 3 (A) Active ingredient o, osy
Polyethylene glycol (400) 11.9 5 y Tetrapolyethylene glycol (400) 2 y Polyethylene glycol (4000) 6P Melt B at 70°C, and add 50
°C, and stirred and homogenized until solidified to obtain a hydrophilic ointment. Additionally, Carbopol 934 may be added to the hydrophilic ointment.

Example 4 (A) Active ingredients 0.01" isopropyl myristate, 5.99P stearic acid 19ccetyl alcohol 4g (B) Polyoxyethylene lauryl ether v chrycerin monostearate 0.5y propylene glycol 4 citric acid 0.05P(C) Distilled water 64.351?Methyl paraoxybenzoate 0.05y Paraoxybenzoic acid 0.05yB at 80℃
To this, C heated and melted at 85°C was added, and further heated and melted A was added at 55°C, and the mixture was homogenized by stirring to form a cream.

Example 5 (A) Active ingredients 0.001p Propylene glycol 12y Polyoxyethylene lauryl ether y Isostearic acid 1y Octyldodecanol 4y Glycerin 32 Citric acid 0.075y (B)
Distilled water 78.924yA 4
After dissolving at 0°C and stirring, B was processed into a lotion.

Example 6 (A) Active ingredient 0.05g
Hydrocortisone acetate 0.5g! Diphenhydramine 0.59 white petrolatum
4.85y(B) White petrolatum
95f8 was melted by heating and mixed uniformly with -13 to prepare an ointment.

[Brief explanation of the drawing]

1 and 2 are ultraviolet absorption curves at 254 nm of the fractions obtained in Production Examples 1 and 2, respectively. Patent Applicant 1) Yasuo Naka, 1 representative attorney, patent attorney Seihaku Bo, and 1 other person °Figure 1 Figure 2

Claims (1)

[Claims] 1, 2.3.4.6-An antiviral agent containing bentagaloyl gelcose as an active ingredient.