JPH06263647A - Inhibitor against lipoperoxide - Google Patents

Abstract

PURPOSE:To obtain an inhibitor against lipoperoxide having high safety to organisms having excellent inhibiting effect on lipoperoxide, hardly having side effect, capable of being administered by various methods. CONSTITUTION:An inhibitor against lipoperoxide comprises a carotene mixture extracted from a palm oil as an active ingredient. The palm oil extract is obtained by subjecting a palm oil to alcoholysis with a lower monoalcohol, diluting the prepared fatty acid lower alkyl ester with a hydrophilic solvent (e.g. methanol, ethanol or acetone), adding water to give a precipitate and purifying the precipitate by using distillation under reduced pressure and a column of silicic acid and is composed of 30-40% alpha-carotene, 55-66% beta-carotene and 5-15% other components such as carotenoids. The inhibitor is applicable by various administration methods such as oral medication, intravenous injection, hypodermic injection, intermuscular injection or suppository.

Description

Detailed Description of the Invention

[0001]

The present invention relates to a lipid peroxide inhibitor.

[0002]

2. Description of the Related Art Generally, lipid peroxide is induced by an enzyme (lipoxygenase) in the body using highly unsaturated fatty acid as a substrate or by various factors such as ultraviolet rays in the atmosphere. Non-enzymatically produced by the generated singlet oxygen and radicals. The hydroxyperoxy structure in lipid peroxides is generally unstable and often cleaves. It is believed that the resulting -O., -O-O. Or .OH, .H to it causes a chain of radical reactions and causes cytotoxicity in the living body. Furthermore, it is known that various organ tissues and immune functions are affected as a result of cell damage.
Further, peroxidation of the lipid membrane changes the permeability of the membrane, as a factor of various vascular lesions, further, hepatitis, cirrhosis, extinction system diseases such as gastric ulcer, retinal degeneration, ophthalmic diseases such as corneal ulcer, It is considered to be a factor of various diseases such as diabetes, rheumatism, gout, sunburn, melanosis, pregnancy poisoning, cancer and aging obesity.

Conventionally, as a drug for suppressing the production of lipid peroxide in vivo, that is, as a lipid peroxide inhibitor,
Female hormones such as estrone, estradiol, estriol, tocopherols, ascorbic acid, lipoflavin, antioxidant vitamins such as β-carotene, glutathione, superoxide desmutase,
In-vivo proteins such as catalase and glutathione peroxidase are known, but they all have the problem of side effects with respect to the dose, or the problem that the lipid peroxide inhibitory action against the dose is not sufficient, and they are always satisfactory. Was not.

Therefore, it has been desired to develop a novel lipid peroxide inhibitor which is free from the above-mentioned drawbacks, is highly safe, and can effectively inhibit lipid peroxide.

The present invention has been made in view of the above circumstances and has an excellent lipid peroxide inhibitory effect, almost no side effects, and various administration methods are possible, which is highly safe for living organisms. The purpose is to provide a lipid inhibitor.

[0006]

Means and Actions for Solving the Problems As a result of intensive studies to achieve the above-mentioned object, the present inventor has found that a carotene mixture extracted from palm oil surprisingly shows remarkable inhibition of lipid peroxide of biological lipids. The carotene mixture has various effects, and is highly safe for living organisms, and there are no side effects.
Due to its high lipophilicity, it has good human absorption and is orally administered,
It was found that a lipid peroxide inhibitor applicable to any of the administration methods such as intravenous injection, subcutaneous injection, intramuscular injection and suppository can be obtained, and the present invention has been completed.

Therefore, the present invention provides a lipid peroxide inhibitor containing a carotene mixture extracted from palm oil as an active ingredient.

The present invention will be described in more detail below. The lipid peroxide inhibitor of the present invention contains a palm oil extract having an antioxidant ability as an active ingredient. The palm oil extract is usually a mixture containing 30 to 40% α-carotene, 55 to 66% β-carotene, and 5 to 15% other components such as carotenoids.

As a method for preparing the palm oil extract (carotene mixture), a known method can be adopted. For example, palm oil is subjected to alcoholysis with a lower monoalcohol, and the resulting fatty acid lower alkyl ester is diluted with a hydrophilic solvent, specifically, methanol, ethanol, isopropanol, or acetone, and then water is added to form a precipitate. And then purifying the precipitate by vacuum distillation, using a silicic acid column, and the like.

Regarding the safety of the extract, when it was administered to mice and its toxicity was examined, no toxicity was observed up to 10 g / kg body weight, and the safety is high.

The lipid peroxide inhibitor according to the present invention comprises the above-mentioned palm oil extract as an active ingredient, and this palm oil extract is used alone or in combination with other lipid peroxide inhibitors as necessary. Then, it can be administered by various methods such as intravenous injection, subcutaneous injection, intramuscular injection, oral administration, and rectal administration by suppository. In addition, since the dose can be controlled by the route and frequency of administration, it can be varied over a wide range according to the condition, for example, 15 μg to 3 g / kg body weight or 1 mg to 10 g per day for an adult.

[0012] The lipid peroxide inhibitor according to the present invention is formulated by formulating an effective amount of the above palm oil extract with an appropriate amount of a non-toxic carrier and administering it by any conventional formulation method. Can be prepared. That is, when prepared for oral administration, prepared into soft capsules, hard capsules, tablets, granules, fine granules, powders, sustained-release active ingredient release agents, solutions, suspensions, etc. Is prepared as an injection, drip, suppository, or the like.

In this case, in formulating, a non-toxic carrier, for example, sucrose fatty acid ester, fatty acid monoglyceride, propylene glycol fatty acid ester, sorbitan fatty acid ester, surfactant such as lecithin, arabia gum, gelatin, sorbit, tragacanth gum, polyvinyl. Binders such as pyrrolidone, sucrose, lactose, starch,
Crystalline cellulose, mannite, light anhydrous silicic acid, magnesium aluminate, magnesium metasilicate magnesium aluminate, synthetic aluminum silicate, excipients such as calcium carbonate, sodium hydrogen carbonate, calcium hydrogen phosphate, carboxymethyl cellulose calcium, magnesium stearate , Lubricants such as talc, hydrogenated oil, salt, saccharin, orange oil, licorice extract, citric acid, glucose, menthol, eucalyptus oil, malic acid and other flavoring agents, flavoring agents, coconut oil, olive oil, sesame oil, peanut oil ，
Soybean oil, medium-chain fatty acid triglyceride, safflower oil, soybean phospholipids and other suspending agents, wetting agents, cellulose such as cellulose acetate phthalate (CAP), carbohydrate derivatives such as sugars, methyl acrylate / methacrylic acid copolymer Acrylic acid copolymers such as methyl methacrylate and methacrylic acid copolymers, polyvinyl derivatives such as dibasic acid monoesters, other film forming agents, coating aids, etc. It is prepared and put to use.

Formulations for mucosal application and injections are also prepared by a conventional method. When a method of suspending or emulsifying in distilled water for injection is adopted, the suspending agent is
Soybean oil, peanut oil, medium chain fatty acid triglyceride and the like can be used, and sucrose fatty acid ester, fatty acid monoglyceride, propylene glycol fatty acid ester, sorbitan fatty acid ester, lecithin and the like can be used as an emulsifier.

[0015]

INDUSTRIAL APPLICABILITY The inhibitor of lipid peroxide of the present invention contains, as an active ingredient, a carotene mixture extracted from palm oil having antioxidant ability, and thus has an effect of suppressing the amount of lipid peroxide in vivo. It is an excellent one. Furthermore, there are no problems in terms of safety and there are no concerns about side effects. Further, since various administration methods are possible, the administration method and dose can be adjusted according to the medical condition, and a large amount can be used. Therefore, it is effective in preventing and treating health and beauty disorders,
In addition to pharmaceuticals, it can be applied to food and drink, cosmetics and the like.

[0016]

EXAMPLES The present invention will be specifically described below by showing experimental examples and examples, but the present invention is not limited to the following examples.

[Experimental Example 1] HOS female hairless mice (4 weeks old) were fed with a palm oil extract of 0.005% concentration emulsified and suspended in 4% peanut oil in the form of drinking water for 15 weeks. The drug was administered by ingestion. On the other hand, in the control group,
Ordinary drinking water with only the emulsifier added was given. Furthermore, a β-carotene administration group (0.005% concentration) was similarly freely taken as a comparison group.

After administration for 15 weeks, ultraviolet rays (5 J
/ Cm ² ) was applied to the back. Before, immediately after, and 24 hours after the irradiation, the level of lipid peroxide in the skin on each back was measured by the thiobarbituric acid method [Uchiyama,
M. : "Anal. Biochem.", 86, 27.
1-278 (1978)]. The results are shown in Table 1.
Shown in.

The composition of the palm oil extract used in this example is 35% α-carotene, 60% β-carotene, and 5% other components.

[0020]

[Table 1]

From the results shown in Table 1, the level of lipid peroxide in the palm oil extract-administered group was clearly lower than that in the control group before and after irradiation with ultraviolet rays, and before and 24 hours after irradiation. Was lower than that in the β-carotene administration group, and it was found that the administration of the palm oil extract significantly suppressed the lipid peroxide amount.

During the above test period, all the mice were alive and in good health.

Experimental Example 2 Experimental Example 1 in which Hartley female guinea pigs (4 weeks old) were emulsified and suspended in 4% peanut oil.
Administration was carried out by freely ingesting the same palm oil extract with a concentration of 0.05% in the form of drinking water for 12 weeks. As a control group, ordinary drinking water containing only an emulsifier was administered. Further, a β-carotene administration group (0.05% concentration) was similarly freely taken as a comparison group. After administration, the back of the guinea pig was shaved and exposed to ultraviolet rays (5 J / c
m ² ) was applied to the back. The peroxidation level of squalene in sebum was measured before, immediately after, and 3 hours after, the irradiation with UV.
L-HPLC method [T. Miyazawa. , "Ana
l. Lett. ,, 20, 915 (1987)]. The results are shown in Table 2.

[0024]

[Table 2]

From the results shown in Table 2, the sebum squalene peroxidation level of the palm oil extract-administered group after irradiation with ultraviolet rays was clearly lower than that of the control group, and also compared with that of the β-carotene administration group. However, it was low. From this, it was revealed that the palm oil extract administration clearly suppressed the increase in the peroxidation level.

During the above test period, all guinea pigs were alive and were in good health.

Examples will be shown below. Specific examples of the embodiment of the present invention include injections and suppositories having the following compositions, but are not limited thereto.

[Example 1] Injection Palm oil extract 100 g Stearic acid monoglyceride 100 g Peanut oil 200 g Sucrose glycerin stearate 50 g Ascorbic acid stearate 20 g Distilled water for injection 9530 g An injection was prepared with the above composition, and 1 ampoule 10 ml was prepared. Fill each one.

Example 2 Suppository Methyl salicylate 0.0350 g Famasol T-115 (trade name, manufactured by Nissan Kagaku Co.) 2.0000 g Palm oil extract 0.0100 g A suppository having the above composition is prepared. In addition, in the said Example, the thing similar to Experimental example 1 was used as a palm oil extract.

Claims (1)

[Claims] 1. An inhibitor of lipid peroxide, which comprises a carotene mixture extracted from palm oil as an active ingredient.