JPS6052126B2 - anti-inflammatory agent - Google Patents

Description

[Detailed description of the invention] The present invention relates to anti-inflammatory agents.

That is, the present invention provides an anti-inflammatory agent containing liquiritin represented by the following formula (Iiquiritin) as a component.

This liquiritin is derived from licorice (Glycy).
aLinne' var, granduliferaR
egel5Herder, Glycyrrhi2aur
Alensis Fisher is also known as a compound contained in the roots and stolons of other congenerous plants, but little is known about its effects.

As a result of researching the anti-inflammatory active ingredient of licorice, the present inventor happened to discover that the main substance is liquiritin.

I discovered that. The present invention is based on this discovery. This liquiritin is second to licorice, for example.

You can get it. Licorice in a non-polar solvent. A crude product obtained by diluting the residue obtained by extracting No. 15 with a hydrophilic lower alcohol and distilling off the solvent of the extract.

Counter-current distribution of fluorophores produces fluxes with strong anti-inflammatory activity. The powder obtained by distilling off the solvent from this fraction is dissolved in a small amount of water, and a fraction having a kd of 15.5 to 19.5 is collected by chromatography using water as an eluent.
By distilling off this fraction and re-evaporating the resulting powder using ethanol, liquiritin with m, p, and 214°C can be obtained. A specific example of its production is given below (as shown in 25).Crush 600y of licorice, put it in an ultrasonic extractor, add 3600ml of benzene, perform ultrasonic extraction in the usual manner at room temperature, and filter the resulting extract. to separate the residue.

Add 3,600ml of methanol to this residue, put it in an ultrasonic extractor, perform ultrasonic extraction in the usual manner at room temperature, and extract the extract at 40ml.
Evaporate under reduced pressure at °C to obtain a rough scratch of 50 da. This rough machining scratch was dissolved and dispersed in 1000 ml of n-butanol, 1000 ml of water was added thereto, and transferred 4 times by the usual method.
Countercurrent distribution is performed to obtain fractions r=0 to r=4. When the anti-inflammatory activity of the powder obtained by distilling off the solvent from each fraction was measured by the carrageenan edema method, strong anti-inflammatory activity was observed in the powder obtained from the r=2 fraction. This powder was dissolved in 100ml of water and subjected to column chromatography using Sephadex G-15 as a packing material (column diameter 3.4C7I).
1 length 30Crf11 elution solvent (water) is used to separate the eluate, and the eluate begins to flow out from the bottom of the young ram.
A 2750ml fraction is collected and dried under reduced pressure at 40°C.
Add 50 ml of ethanol to this and dissolve by heating.
The precipitated crystals were filtered and dried under ventilation at room temperature to obtain M.C. p. 2l Liquiritin 200m at 4℃
I got a 9. When the anti-inflammatory activity of liquiritin was measured by an anti-inflammatory test using the carrageenin edema method, it was found to be 30m9/K9.
It has 45% activity at administration of Although it is usually said to be an anti-inflammatory agent, the anti-inflammatory activity measured by the carrageenan edema method is said to be 40-60% when administered at 2m9 to 100m9/K9. It is quite useful as a. The anti-inflammatory test using the Naori lagenin edema method is as follows. Measure the anti-inflammatory activity. Specifically, a drug was administered to Wister rats, and after 3 bouts, λ-carrageenan was injected into the rat's paws as an inflammatory substance, and the rate of increase in paw volume (V
1) Measure. Similarly, 0.9% raw instead of drugs. After administering saline to the same rats as above, the rate of increase in paw volume (VO) of the rats inflamed with λ-carrageenan was measured,
Calculate the carrageenan edema suppression rate using the following formula and use it as the anti-inflammatory activity of the drug. The larger this value is, the higher the anti-inflammatory activity is. In addition, anti-inflammatory activity can also be evaluated using a cotton pellet method, an adjuvant arthritis method, etc. as an anti-inflammatory test. In addition, the acute toxicity LD5O of liquiritin was 1650m9 in an oral administration test using mice.
/K9, which is extremely safe.

Next, considering the data on anti-inflammatory activity, the effective dose of liquiritin is 20 m9 to 100 m9 per dose for intravenous injection.
For oral administration, the dose is 50 mg/200 mg per dose, and the dose may be adjusted as appropriate depending on the symptoms.

There are no particular limitations on the use of liquiritin as an anti-inflammatory agent, and it can be administered in a variety of ways depending on the form.

For example, powders, tablets, pills, solutions, suspensions, emulsions, granules, and capsules are administered orally. In the case of an injection, it is administered intravenously alone or mixed with a normal replacement fluid such as glucose or amino acids, and if necessary, it is administered alone intramuscularly, intradermally, subcutaneously, or intraperitoneally.
Further, in the case of an ointment, it is used externally, and in the case of a suppository, it is administered rectally. The above formulations are prepared by adding excipients, additives, auxiliaries, preservatives, coloring agents, etc. to liquiritin as necessary.
It can be manufactured according to conventional methods for manufacturing pharmaceutical preparations.

Next, examples of the present invention will be shown.

Example 1 Liquiritin 45 da, lactose 209.1y1 microcrystalline cellulose (avicel) 45y1 magnesium stearate 0
．． Put a total of 300y of 9y1 into a dice type mixer and make 15
After mixing for a minute, the tablets were compressed using a single-shot tablet machine.
200 m9 tablets were obtained per tablet.

One tablet contains 30m9 of liquiritin. Example 2 16 da of liquiritin and 364 f of lactose were put into a dice-type mixer, mixed together, and then put into a container with a capacity of 2 e.

After adding 100 ml of a 20% hydroxypropyl cellulose ethanol solution and kneading it, a diameter of 0. gIf
Place on an extruder granulator equipped with a 0ft screen.
The thus obtained cylindrical material was dried in a dryer at 60° C., and sieved through 12 mesh and 60 mesh sieves to obtain granules 280y of 12 to 60 mesh. This granule 1.0f1 contains 40 Tng of liquiritin.
Example 3 50y of liquiritin and 150y of lactose were mixed together in a dice-type mixer, and then filled with a vibrator-type capsule filling machine loaded with No. 1 capsules to make 30g of lactose.
0 mg capsules were obtained.

One capsule contains 75 mg of liquiritin. Example 4 70 ml of purified water is heated to 90 mC, 10 y of liquiritin is added thereto, one powder is stirred and dissolved, and then the temperature is set to 75°C.

Add 24 f of propylene glycol and 3 g of sodium lauryl sulfate to this and dissolve. Mix this solution in advance with 50 y of white petrolatum and 44 y of stearyl alcohol.
y was dissolved on a water bath and stirred and maintained at 74 °C to 78 °C, and the mixture was cooled with thorough stirring and solidified to obtain an ointment. This ointment 1y contains 50m9 of liquiritin. Example 5 Liquiritin 5y1 4.5y of sodium chloride was dissolved in 500ml of distilled water for injection, and filtered.

Claims (1)

[Claims] 1 formula ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ The active agent is liquiritin, which is expressed as .