JPH0539217A - Fat transfusion solution containing refined perilla oil blended therein - Google Patents

Abstract

PURPOSE:To obtain a pervenous fat transfusion solution useful as a nutriment supply agent by including refined perilla oil containing a specific amount of alpha-linolenic acid as a constituent fatty acid in a fat transfusion solution consisting essentially of a vegetable oil, an emulsifying agent, glycerol and water. CONSTITUTION:A pervenous fat transfusion solution is obtained by using refined perilla oil containing, especially, 51-70wt.% alpha-linolenic acid as a constituent fatty acid at 2.5-7.0wt.% ratio of the alpha-linolenic acid content to the linoleic acid content in a fat transfusion solution consisting essentially of a vegetable oil, an emulsifying agent, glycerol and water. The refined perilla oil is obtained by subjecting crude oil available from natural perilla oil to degumming, deacidifying, decoloring, deodorizing, dewaxing and treatment with active carbon. The aforementioned new fat transfusion solution is useful as a nutrient supply agent for patients under low nutritive conditions in various diseases such as cancer, hypertension, diabetes or thrombotic diseases or before or after operation.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a fat transfusion agent, and more particularly to a fat transfusion agent for intravenous administration using refined perilla oil.

[0002]

2. Description of the Related Art Intravenous fat transfusions are widely used for the purpose of supplementing essential fatty acids and nutrients together with amino acid solutions, sugar / electrolyte solutions during various diseases or before and after surgery. When intravenously administering fat, fat transfusions using natural vegetable oils having a high linoleic acid concentration such as safflower oil and soybean oil have been used. However, recent studies have shown that there is a very good correlation between dietary linoleic acid content and the incidence of breast cancer (Cancer Research, Vol. 45, p. 1997, 1985), as well as colorectal cancer, lung cancer or myocardial infarction. Whether the onset of illness or an increase in allergies is due to the excessive intake of linoleic acid, a large intake of linoleic acid as a fat source has been reviewed. Therefore, unlike linoleic acid, which is an ω-6 fatty acid, the role of ω-3 type α-linolenic acid, which competes metabolically, in the living body has been noted.

From the above, fats obtained by adding ethyl ester or triglyceride of α-linolenic acid to conventional soybean oil or safflower oil so that the concentration of α-linolenic acid in the total fat is 10 to 50% by weight. Infusion solutions have been proposed (JP-A-60-130519). Further, although it is an oral preparation, an oil and fat composition containing 20% or more of α-linolenic acid exhibits tumor cell metastasis inhibition (JP-A-63-154626).
No.) or a stroke attack or deterioration of discrimination ability at an old age and having a life-prolonging effect (JP-A-64-3117).

[0004]

According to Japanese Patent Laid-Open No. 60-130519, a fat transfusion containing a high concentration of α-linolenic acid is useful not only as a conventional nutritional supplement but also as an antithrombotic preparation. Has been shown to be. However, fat has about twice the amount of heat per unit weight of sugar and is excellent as a heat source, and as an essential source of essential fatty acid, fat is used for nutritional management for undernourished patients. Often. However, there are many problems in using this product for general nutritional supplementation.

Unlike sugar, most of the fat ingested into the body is once converted into body fat and then gradually metabolized into energy. Therefore, even if a large amount of fat transfusion is administered in a short period of time, it is not sufficiently utilized as an energy source, and side effects such as suppression of immune function due to fat accumulation in the liver or spleen become problems. Also, ω-6 in the living body
It is said that there are unsaturated fatty acids of ω-3 type and ω-3 type, and the balance of these two is important for maintaining the function of the living body. However, the conventional fat transfusion using soybean oil for patients with undernutrition. It is known that even if it is administered daily, the balance is not restored.

As described above, conventional fat transfusions have not always been satisfactory in terms of nutritional effects, side effects and the like. Therefore, the object of the present invention is that the fat to be administered is rapidly metabolized in vivo and is well utilized as a heat source, and
An object of the present invention is to provide a fat transfusion agent in which the balance of the fatty acid composition is not disturbed.

[0007]

Means for Solving the Problems The present inventors have investigated the nutritional effects of various fatty acid compositions, particularly fatty acid compositions containing a high concentration of α-linolenic acid, in detail by animal experiments.

As a result, perilla oil containing 51% by weight or more of α-linolenic acid as a constituent fatty acid and having a weight ratio of α-linolenic acid content to linoleic acid content of 2.5 to 7.0 is a conventional fat. The blood triglyceride concentration is low compared to the case where an infusion solution is administered, and since the triglyceride content in the liver and spleen is not increased, it is rapidly metabolized in vivo and is well utilized as an energy source. It was found that the weight gain in rats was greater than that of conventional fat transfusions using soybean oil, and the fatty acid composition was superior in nutritional effect. Further, they have found that a well-balanced fatty acid composition can be maintained by reducing the ω-3 fatty acid, icosapentaenoic acid (EPA), by administering the fat transfusion of the present invention, and completed the present invention.

On the other hand, in order to confirm the safety of the fat transfusion using the sesame oil, when the sesame oil purified by the usual industrial method was continuously administered to the rat intravenously, a clear swelling of the liver and spleen was observed. In addition, pathological examination of both organs showed an increase in reticuloendothelial cells. Therefore, as a result of earnestly studying the improvement of the refining method, each step of the steam refining method, that is, degumming, deoxidizing, decolorizing and deodorizing steps, was added a dewaxing step and an activated carbon treatment step, and each treatment condition was further changed to the optimum condition. By doing so, toxic impurities can be removed.

Specifically, a low temperature wintering process is performed in the dewaxing process, and the activated carbon process is carried out with respect to perilla oil.
2 w / v% or more, preferably 0.5 to 10 W / V% of activated carbon is used. 1 w / per sesame oil in decolorization process
v% or more, preferably 2 to 10% of activated clay is used. The deodorizing step is 250 ° C. or lower, preferably 200 to 240
Blow steam under high vacuum at ℃. Hydrophilic chlorophyll, glycolipid, lipophilic carotenoids, etc. can be removed by the above purification steps and conditions, and the toxic effects of impurities disappear. In order to prevent the oxidation of perilla oil during the refining process, citric acid is added as a metal deactivating acid for stabilization, and in order to prevent the effect on the living body due to the residual citric acid, a filter is used in the final step. To remove citric acid. Further, by adding tocopherol, which has been known as an antioxidant, it is possible to obtain stable refined perilla oil.

That is, the first aspect of the present invention is a fat transfusing agent containing vegetable oil, an emulsifier, glycerin and water as main components, containing 51 to 70% by weight of α-linolenic acid as a constituent fatty acid, and α-linoleic acid based on α-linoleic acid content. A fat transfusion agent characterized by using refined perilla oil having a linolenic acid content weight ratio of 2.5 to 7.0, the second of which is:
Refined perilla oil relates to a fat transfusion agent characterized in that crude oil obtained from natural perilla oil is refined by a steam refining method, which comprises degumming, deoxidation, decolorization, deodorization, dewaxing and activated carbon treatment steps. ..

[0012]

EXAMPLES The refined perilla oil used in the following examples was refined by performing a low temperature wintering treatment in the dewaxing process at a treatment condition of 0 ° C. for 24 hours.
10 g of activated carbon was used per 00 g, and 25 g of activated clay was used in the decolorization step. The temperature condition of the deodorizing process is 23
It was carried out at 0 to 240 ° C.

Example 1 To 100 g of purified perilla oil, 7.5 g of purified soybean lecithin, 12.5 g of glycerin and 1 g of tocopherol were added,
After stirring vigorously while heating and dissolving, a proper amount of distilled water for injection was added and stirred with a homogenizer to prepare a crude emulsion. This crude emulsion was further subjected to high pressure emulsification with a Microfluidizer M-110Y type (manufactured by Microfluidizer), and distilled water for injection was added to bring the total amount to 500.
ml. The infusion solution obtained here was filled in a glass bottle, and after substituting with nitrogen, the bottle was sealed. This was subjected to high-pressure steam sterilization to prepare a fat transfusion for intravenous administration containing 20% of purified perilla oil.

EXAMPLE 2 Purified perilla oil (50 g), purified soybean lecithin (6.0 g) and glycerin (12.5 g) were used in the same manner as in Example 1 to prepare a 10% purified perilla oil for intravenous administration.

[0015]

[Test example]

1. Fatty acid composition of refined perilla oil As for the fatty acid composition of refined perilla oil, the variation between lots was examined. As a result, the variation in fatty acid composition of each lot was as shown in Table 1.

[Table 1]

2. Safety test by animal experiment Using male SD rats weighing about 220 g, under normal breeding, physiological saline (control), soybean oil-containing fat transfusion (trade name: Benolipid Morishita Pharmaceutical) and conventional industrial purification method A fat transfusion (Reference Example) prepared by the same method as in Example 1 was applied to the perilla oil obtained in (1) and was administered into the tail vein at 20 ml / Kg (4 g / Kg as fat) for 1 week. After the final administration, the animals were fasted overnight, and liver and spleen weights and pathological examinations were performed. The results are shown in Table 2.

[Table 2]

According to the same test method as the above-mentioned safety test, physiological saline (control), soybean oil-containing fat infusion (trade name: Benolipid Morishita Pharmaceutical Co., Ltd.) under normal breeding and Example 1 were used.
For the fat transfusion containing the purified perilla oil, the organ weight and the pathological examination of the liver and spleen were performed. The results are shown in Table 3.

[Table 3]

According to the above safety test, the fat infusion solution of the present invention was safely used without any noticeable toxicity observed in the infusion solution containing perilla oil refined by the conventional industrial refining method (reference example). It turned out to be possible.

3. Drug efficacy test 1) Comparison of lipid metabolism Using SD male rats weighing about 270 g, central venous catheter implantation was performed under pentobarbital Na anesthesia. After administration of physiological saline at 1 ml / hr for 1 day, soybean oil-containing fat infusion (trade name: Benolipid Morishita Pharmaceutical)
Then, the fat transfusion containing the purified sesame oil of Example 1 was replaced with a continuous infusion at 1 ml / hr for 1 day. It should be noted that during the administration of the infusion, the food and water were fasted. Before and after administration of fat infusion 24
Blood triglyceride concentration up to time, and liver and spleen triglyceride contents at the end of administration were measured. The results are shown in Tables 4 and 5.

[Table 4]

[Table 5]

The fat transfusion containing the purified perilla oil of the present invention is
Compared with soybean oil-containing fat transfusion, the blood triglyceride concentration was significantly decreased, and the liver and spleen triglyceride contents were not increased. That is, it was revealed that the fat transfusion containing the purified perilla oil of the present invention was rapidly metabolized in the living body and was well utilized as an energy source.

2) Effect on nutritional effect and blood fatty acid composition A male SD rat having a body weight of about 280 g was subjected to central venous catheter indwelling under anesthesia with pentobarbital Na, and a liquid containing sugar, electrolyte and amino acid. At the same time, the purified perfumed oil infusion solution and soybean oil-containing fat infusion agent (trade name: manufactured by Benolipid Morishita Pharmaceutical Co., Ltd.) of Example 1 corresponding to 15% of non-protein calories were continuously infused at 2.5 ml / hr for 4 days. .. Body weight gain, nitrogen balance, blood biochemistry, liver protein synthesis activity, and blood fatty acid composition were measured after infusion. The results are shown in Tables 6, 7 and 8.

[Table 6]

[Table 7]

[Table 8]

The fat transfusion containing the purified perilla oil of the present invention is
The weight gain was better than that of the fat transfusion containing soybean oil, and there was no difference in nitrogen balance. In addition, the purified perilla oil-containing fat infusion solution of the present invention had a low blood triglyceride concentration in a blood biochemical test, and no abnormalities were observed in the GPT value. The protein content in the liver showed a high value in the fat transfusion containing the purified perilla oil, which was due to the protein / DNA ratio and the RNA / RNA ratio.
Similar results were obtained by comparing the DNA ratios, and it was revealed that the fat transfusion containing the purified perilla oil of the present invention enhanced the protein synthesis activity. In the blood fatty acid composition, administration of a soybean oil-containing fat infusion solution increased ω-6 fatty acid arachidonic acid (AA) and decreased ω-3 fatty acid icosapentaenoic acid (EPA). When an oil-containing fat infusion was administered, a clear increase in EPA was observed, and it was found that a well-balanced fatty acid composition can be maintained without a decrease in ω-3 fatty acids.

4. Stability test The refined perilla oil-containing fat infusion solution of Example 1 was heated and abused at 40 ° C. for 6 months, and its peroxide value (POV) was measured. As a result, the peroxide value was low at 2.74 mEq / l, It was found that the fat transfusion of the present invention is stable.

[0024]

INDUSTRIAL APPLICABILITY The present invention is a fat transfusion agent containing refined perilla oil, which is rapidly metabolized in vivo and is well utilized as an energy source. Moreover, an excellent nutritional effect can be expected due to the enhancement of protein synthesis activity. Furthermore, maintaining a well-balanced fatty acid composition in the body under malnutrition,
It does not cause adverse effects on biological function maintenance due to deficiency of system fatty acids.

[0025]

INDUSTRIAL APPLICABILITY The present invention is a new fat superior to conventional fat transfusions as a nutritional supplement for patients with various nutritional conditions (cancer, hypertension, diabetes, thrombotic diseases, etc.) before and after surgery. An infusion solution can be provided.

Claims (2)

[Claims] 1. A fat infusion agent containing a vegetable oil, an emulsifier, glycerin and water as main components, wherein α is used as a constituent fatty acid.
-Containing 51 to 70% by weight of linolenic acid, the weight ratio of α-linolenic acid content to linoleic acid content is 2.5 to 7.
A fat transfusion agent characterized by using refined perilla oil of 0. 2. The refined perilla oil is characterized in that crude oil obtained from natural perilla oil is refined by a steam refining method comprising degumming, deoxidizing, decolorizing, deodorizing, dewaxing and activated carbon treatment steps. The fat transfusion agent according to claim 1.