JPH10139678A - Antioxidant in organism - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an antioxidant for an organism useful as a medicine manifesting an effect on a disease caused by the in vivo oxidation, e.g. arterio sclerosis, myocardial infarction by formulating Muirapuama as an active ingredi ent. SOLUTION: This antioxidant for an organism is obtained by formulating Muirapuama (a root of shrub belonging to olacaceae family, the original plant of which is exemplified by Liriosma ovata sp.) as an active ingredient. For example, an extract obtained by dipping the thinly cut root of the original plant in 50-99% ethanol, further dipping the residue of the before dipped root in the 50-99 ethanol, and condensing the both extracting liquids to form the extract, is used as the antioxidant. for the organism. The daily dose of the extract is 0.2-3.0g/50kg expressed in terms of the amount of the original crude medicine for a general adult and is administered by dividing into one or several portions.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an antioxidant,
More particularly, the present invention relates to an antioxidant having an effect in vivo.

[0002]

2. Description of the Related Art In vivo, drugs, metals, ischemia-reperfusion,
Active oxygen and free radicals are generated by various causes such as stress. These are lipids, proteins,
Attacks sugar, DNA, etc., and causes the occurrence of arteriosclerosis, cancer, aging and the like. Therefore, in vivo antioxidants that have the effect of eliminating active oxygen and free radicals or preventing their generation have therapeutic effects on various diseases. As antioxidants effective in in vitro tests, vitamin C, tocopherol (vitamin E), crude drugs and the like have been reported (JP-A-4-5237).

[0003] The method of evaluating the antioxidant activity of a substance is based on the test substance Super Oxide Dismutase.
An in vitro method for measuring (ase, SOD) -like activity is known (JP-A-4-5237). However, many natural plants, which are considered to be antioxidants, contain a reducing agent, and thus directly reduce cytochrome C and NBT even without O2- (superoxide anion radical). Sometimes. Therefore, it is difficult to measure the true antioxidant power of the test substance by the in vitro method. In addition, since these methods are measurement systems using an enzyme reaction, depending on the test substance, the components may inhibit the enzyme. In fact, several plant extracts have NB
When the SOD-like activity was measured using the T method, there was a report that what was thought to be the SOD-like activity was actually merely inhibiting the enzyme (Yamaji et al., Food and Development, Vol. 31, 1, p. 45 (1996)).

[0004] Here, if there is an antioxidant effective in the living body, diseases caused by oxidation in the living body, such as arteriosclerosis,
It is expected to be effective in the treatment of myocardial infarction, stroke, cerebral infarction, cerebral hemorrhage, cerebral thrombosis, epilepsy, cataract, autoimmune disease, etc.To date, in vivo antioxidants that show efficacy in vivo are known. Therefore, a substance exhibiting antioxidant power in vivo has been desired.

[0005] Muirapuama is an oleraceae family (olaca) distributed from the Amazon basin of South America to northern Brazil and the like.
ceae) is the root of a shrub, and the base plant is Liriosma
ovata, Ptychopetalum olacoides, Ptychopetlum unci
There are natum species. These extracts are known as tonics and are known to be effective against duodenal hookworm, dysentery, chronic rheumatism, acute spinal gray matter, and the like. However, it was not known to have an antioxidant effect.

[0006]

SUMMARY OF THE INVENTION It is an object of the present invention to find an antioxidant which has an effect in vivo.

[0007]

As a result of various studies, the present inventors have found that muirapuama, a herbal medicine, is an antioxidant that is effective in vivo and completed the present invention.

[0008] That is, the present invention is an in vivo antioxidant characterized by containing muirapuama as an active ingredient.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, muirapuama refers to a crude drug powder, an extract, a dried extract, etc. of a root of a base plant. The extract can be produced by a usual method. As a preferable production method, a liquid obtained by immersing the cut pieces of the root of the root plant in 50% to 99% ethanol and a residue of the immersion liquid in 50% to 99% ethanol are preferably used. The concentrated solution is then combined and concentrated to obtain an extract.

The dose of muirapuama is 0.2 to 3.0 g / 50K per day for a general adult in terms of the amount of a crude drug.
g, more preferably 0.2 to 1.5 g / 5.
0 Kg, and the dose can be administered once or several times. In addition, the dose can be appropriately increased or decreased depending on the weight, age, and the like.

The in vivo antioxidant of the present invention can be produced in a usual oral administration dosage form such as a liquid, tablet, capsule, granule, powder and the like by a conventional method.

In the present invention, an antioxidant in vivo refers to a substance having an effect of eliminating or reducing active oxygen and free radicals generated in a living body, or a substance having an effect of preventing the generation itself of active oxygen and the like. That is.

The present invention provides vitamins (vitamin B1, vitamin B2, vitamin B6, vitamin B12, nicotinamide, etc.) and amino acids (pantothenic acid, carnitine chloride, taurine) as long as they do not inhibit the in vivo antioxidant activity of muirapuama. , Arginine hydrochloride, etc.), herbal medicines (such as Cistanche salsa, Japanese mustard, Toshishi, Eucommia, Kaikujin, Lokujo, Epimedium, Carrot, Sanyaku, Jio, Hampi, Sanshuyu, Gomishi, Bukuroku)
And the like.

The in vivo antioxidant power is measured by applying an X-band ESR or the like to the amount of radicals generated by applying a photo-induced radical product to the skin of a test animal to which a test substance has been orally administered and then irradiating with light. It can be measured by a method such as

Here, the photo-induced radical product is a product that generates a radical upon irradiation with light, and specifically, anthralin, 3,3 ′, 4 ′, 5-tetrachlorosalicylanilide, 4-methyl-N -Ethylpyrrolo [3,2-g] coumarin, 7-hydroxychloropromazine, bithionol, fenticrol, amiodarone, sulfanilamide, 4-aminobenzoic acid, porphyrin and the like. Of these, the most preferred is anthralin. Anthralin is 1,8-Dihy
Droxy anthrone, which is conventionally known as a psoriasis vulgaris treatment or photosensitizer.

As test animals, shaved rats, mice, rabbits and the like can be considered, and a hairless mouse is particularly preferable. The skin on the back is preferable as the skin site used for evaluation from the viewpoint of ease of operation.

Light irradiation means irradiating a light beam that radicalizes a photo-induced radical product, and specifically, irradiation with ultraviolet rays is preferred. UV light is 390nm ~ 200n
It is light having a wavelength of m. Also, the measurement of the amount of generated radicals
The skin can be measured by exfoliating the skin of the test animal after light irradiation, placing the skin in a tissue ESR measurement sample tube, and measuring with an X-band ESR. In addition, although measurement can be performed with L-band ESR, X-band ESR is more preferable for sensitivity. The radical strength can be calculated from the ratio to an internal standard such as Mn.

The antioxidant activity of the test substance can be evaluated based on the degree of decrease in the radical strength of the test substance based on the radical strength of a substance having no antioxidant action, such as physiological saline, as a reference substance. .

[0019]

The present invention will be described below in more detail with reference to examples and test examples.

Example 1 A root (380 kg) of a shredded base plant was immersed and extracted in a three-fold amount of 70% ethanol for 2 days, and filtered to obtain a filtrate (A). The residue was similarly extracted with three times the amount of 70% ethanol to obtain a filtrate (B). (A) and (B) were combined and concentrated under reduced pressure to obtain a muirapuama extract (19 kg).
30 mg of the obtained extract was suspended in 50 ml of purified water to obtain an oral solution for test.

Example 2 Muirapuama extract 15 mg, carrot 600 m
g, Draft 300 mg, Kokushi 300 mg, Jasushi 400 mg, Toshishi 200 mg, Eucommia 200 mg, Lokujo 400 mg, Inyokaku 1000 mg, Kaikujin 100 mg, Bakuryo 400 mg, Dashi 300 mg, Hampi 250 m
g, 5 mg of vitamin B1, 5 mg of vitamin B2, 65 mg of vitamin B, 500 mg of taurine, and 50 mg of caffeine were dissolved in purified water to make 50 ml, and an oral solution was obtained.

Test Example 1 The oral solution of Example 1 was used as a test substance, and a physiological saline solution having no antioxidant action was used as a reference substance.
Anthralin was used as a photo-induced radical product.

As test animals, hairless mice (weight around 20 g) were used in groups of 6 each.

Test substance and reference substance are 10 ml / kg
Was orally administered to test animals once a day for each group for 3 days. In each group, 5 minutes after the end of administration on the last day, 500 μl of 50 mM anthralin was applied to the skin on the back of the mouse, and
It was left under an ultraviolet sterilizing lamp (15 W, GL-15) having a height of 3 cm for 3 hours. Then the mice were sacrificed by cervical dislocation,
The skin on the back of the mouse was peeled off to prepare a skin section (2 × 0.3 cm). The prepared sample is placed in a tissue ESR measurement sample tube,
Radical strength was measured using X band ESR (JEOL, JES-RE1X). The peak height was defined as the radical intensity by taking the ratio with the peak height of Mn used for the internal standard.

ESR measurement conditions are microwave output: 5 m
W, microwave frequency: 9400 MHz, central magnetic field: 3
33.5 ± 10 mT, sweep time: 4 min, modulation frequency: 100 kHz, modulation width: 0.1 mT, amplification factor: 5 ×
100, time constant: 0.1 sec.

Results The anthralin radical intensity of each test solution administration group was calculated as a ratio to the reference substance administration group. As a result, in the group to which the liquid preparation of Example 1 was administered for 3 days, 70.23% (p <
0.005).

Since the amount of anthralin radicals generated in the skin of the group administered with the liquid preparation of Example 1 was significantly reduced as compared with the group administered with physiological saline, the liquid preparation of Example 1 had an antioxidant effect (inhibition of radical generation) in vivo. ).

From this, it was found that muirapuama was an in vivo antioxidant having efficacy in vivo.

[0029]

Industrial Applicability According to the present invention, there is provided a drug which is effective against diseases caused by in vivo oxidation, such as arteriosclerosis, myocardial infarction, stroke, cerebral infarction, cerebral hemorrhage, cerebral thrombosis, epilepsy, cataract, autoimmune disease and the like. It became possible.

──────────────────────────────────────────────────続 き Continued on front page (51) Int.Cl. ⁶ Identification symbol FI // A61K 9/08 A61K 9/08 E

Claims (1)

[Claims] 1. An antioxidant in vivo, comprising muirapuama as an active ingredient.