JPH0567679B2 - - Google Patents

Description

[Detailed description of the invention]

INDUSTRIAL APPLICATION FIELD The present invention relates to a liquid fatty oil-albumin complex, and more particularly to a water-insoluble powdered fatty oil-albumin complex in which liquid fatty oil and albumin are combined. BACKGROUND OF THE INVENTION Fatty oil is a substance stored by living organisms as a nutrient source, and is contained in all plant seeds and the bodies of animals. Therefore, there are many types, each with different properties and uses. Fatty oils can be classified into vegetable oils and animal oils depending on their raw materials, and they contain many types of fatty acids. Most animals require polyunsaturated fatty acids to maintain normal structure and function,
Moreover, they do not have the ability to make polyunsaturated fatty acids from saturated fatty acids and monounsaturated fatty acids, so they need to ingest such unsaturated substances. Furthermore, fish oils such as lamprey oil, sardine oil, and herring oil contain vitamins and various types of fatty acids, are nutritionally superior, and are useful as nutritional foods. Eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) is used for the prevention and treatment of myocardial infarction and thrombotic diseases, and is known to have serum cholesterol-lowering effects and is commercially available as soft capsules. has been done. Furthermore, it has recently been discovered that saturated fatty acids having 13 to 15 and 21 carbon atoms, oleic acid, linoleic acid, and linolenic acid have anticancer effects.
Since these fatty oils are unstable to oxidation, it has been difficult to formulate them for use in medicines and foods. Therefore, it has been used in the form of soft capsules or suspensions using various methods. However, aqueous solutions pose problems in transportation, storage, etc., and it has been desired to provide them as stable powders. As a method of using the above-mentioned suspension, a fat infusion preparation consisting of a fatty acid or ester, vegetable oil, an emulsifier, and water is known (Japanese Patent Application Laid-Open No. 1989-1999).
(Refer to Publication No. 237017). Furthermore, a method is known in which lecithin is added to eicosapentaenoic acid and docosahexaenoic acid in order to prevent unpleasant taste when ingesting highly unsaturated fatty acids (see Japanese Patent Application Laid-open No. 82070/1983). It is also known to add human serum albumin to solubilize drugs that are insoluble or poorly soluble in water (see Japanese Patent Application Laid-open No. 216126/1983). However, these are all solutions, and it has not been known to add albumin to liquid fatty oil and make it into a powder. Problems to be Solved by the Invention Human serum albumin described in the above-mentioned Japanese Patent Application Laid-Open No. 58-216126 facilitates the dissolution of water-insoluble or sparingly soluble drugs in water, whereas The resulting composite is water-insoluble, non-hygroscopic and has excellent storage stability. Most fatty oils are water-insoluble and contain highly unsaturated fatty acids, which are oxidized and decomposed by oxygen in the air, producing malodorous substances. Therefore, even when taken as a soft capsule, an unpleasant odor remains in the mouth along with burp, making it difficult to take. The present invention is to provide a water-insoluble fatty oil-albumin complex by combining a fatty oil with a sufficient amount of albumin to form a precipitate in order to powder the fatty oil. Means for Solving the Problems The present invention relates to a powdered fatty oil-albumin complex in which liquid fatty oil and albumin are combined. In the present invention, liquid fatty oil refers to any fat that is liquid at room temperature or that can be made liquid by heating or dissolving in a solvent.
Mention may also be made of fatty acids or animal or vegetable oils containing them. Examples of fatty acids include saturated fatty acids and unsaturated fatty acids. Examples of saturated fatty acids include fatty acids having 2 to 26 carbon atoms, with palmitic acid, stearic acid, lauric acid and myristic acid being particularly advantageous. Examples of unsaturated fatty acids include fatty acids having 10 to 22 carbon atoms, especially palmitooleic acid, oleic acid, linoleic acid,
Preference is given to linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid. Animal oils include sardine oil, herring oil, cod oil, shark oil, squid oil, whale oil, dolphin oil, crucian carp oil, carp oil,
Examples include eel oil, lamprey oil, krill oil, pupa oil and ox leg oil. Vegetable oils include sesame oil, olive oil, rapeseed oil, soybean oil,
Examples include cottonseed oil, rice oil, corn oil, evening primrose oil, safflower oil and castor oil. Examples of albumin include ovalbumin, serum albumin, plaque albumin, α-lactalbumin,
Examples include leucosin, cephalin, and levumelin, but it is preferable to use human-derived albumin, especially when the complex obtained by the present invention is applied to the pharmaceutical field where antigenicity is a problem. Further, by adding ascorbic acid or its fatty acid ester and vitamin E to these liquid fatty oils, the stability of the liquid fatty oil-albumin complex can be increased. Examples of fatty acid esters of ascorbic acid include vitamin C stearate and palmitate. The addition ratio of ascorbic acid or its fatty acid ester and vitamin E to the liquid fatty acid oil is not particularly limited, but is preferably 0.01 to 1.0%. Further, the ratio of ascorbic acid or fatty acid ester to vitamin E may be in the range of about 1:1 to about 1:10. The fatty oil-albumin complex of the present invention can be easily produced by first dissolving albumin in an aqueous solution, adding fatty oil to the solution, and bringing the two into contact with each other under high-speed stirring (approximately 5,000 to 30,000 rpm). . In order to add ascorbic acid or its fatty acid ester and vitamin E as a stabilizer, it is preferable to add the above-mentioned stabilizers to the fatty oil. The concentration of albumin aqueous solution when producing this complex is not particularly limited, but is at least 1%
(W/V) It can be used preferably at a concentration of 5 to 25% (W/V). The ratio of albumin to fatty oil is not critical and can be varied over a wide range as long as precipitation occurs during the reaction, but it is generally preferred to use a ratio of 5 to 700 parts of fatty oil to 100 parts of albumin. . Any aqueous solution can be used as long as it dissolves albumin without denaturing it, but water is most preferred. However, part of the water can also be replaced with a water-soluble solvent such as ethanol, propylene glycol, glycerin, etc. The reaction temperature and reaction time are not critical and can be varied depending on the albumin and fatty oil used, but generally both are stirred for about 1 to 30 hours at a temperature where the fatty oil is liquid and the albumin is not thermally denatured. It is advantageous to react below. The fatty oil and albumin react almost 100% regardless of the ratio of the two added, and depending on the ratio of the two added, a precipitate in which about 5 to 250% albumin is bound to the fatty oil can be obtained. The desired powdered fatty oil-albumin complex can be obtained by removing the solvent from the thus obtained precipitate using means such as air drying, vacuum drying, drum drying, spray drying, etc. The fatty oil-albumin complex of the present invention described above has the characteristics of not being hygroscopic, being water-insoluble, and being stable over time. Therefore, the obtained complex can be easily processed into various forms, such as tablets and sheets together with excipients, binders, disintegrants, lubricants, etc. commonly used in pharmaceuticals. I can do it. It is also possible to uniformly mix other powders into foods,
It can be widely used in fields such as cosmetics, medicine, and feed. The powdered fatty oil-albumin complex obtained by the present invention has extremely excellent stability over time. Powdered fatty oil-albumin complexes prepared in Examples 1 to 5 below were placed in an air-permeable bottle and heated at 40°C and humidity at 75°C.
The fatty oil content was measured as a weight change index when stored for 30, 60, and 90 days. Fatty oil extraction and quantitative method: Accurately weigh 1 to 3 g of the fatty oil-albumin complex into a 200 ml eggplant-shaped flask, add 2 to 6 ml of water,
Further, 50 to 150 ml of a chloroform-methanol (2:1) solution was added, and the mixture was heated with stirring on a water bath (60 to 65°C) for 1 to 2 hours under a nitrogen gas atmosphere with a Dimroth attached. After cooling, it was filtered, and the residue was washed 2 to 3 times with 25 ml of the above solution, and the washings were combined with the filtrate. The filtrate and washing liquid were heated under a nitrogen gas atmosphere.
It was concentrated under reduced pressure until it became a viscous liquid, and 50 ml of petroleum ether or ether was added to the residue. whatsman
After filtration using IPS filter paper (trademark), the solvent was distilled off from the filtrate under a nitrogen gas atmosphere, and its weight (g) was measured. The results are shown in Table 1 below. The numbers in the table represent the fatty oil content of the composites obtained by the methods shown in Examples 1 to 4 below.

[Table] Furthermore, among the powdered fatty oil-albumin complexes obtained in the present invention, the most susceptible to rancidity are 1) lamprey oil-albumin (0.5:1) complex, 2) lamprey oil-albumin complex (1) :1.Pour ascorbic acid stearate (containing 0.5% of vitamin E in lamprey oil) in a breathable bottle and store at 40℃ and 75% humidity for 30 days or 60 days.
After being stored for a day, it was extracted in the same manner as above, and its peroxide value, acid value, iodine value, and saponyl value were measured by the following methods. In addition, untreated lamprey oil stored under the same conditions for 30 or 60 days was used as a control. The results are shown in Tables 2 and 3.
Shown in the table. Method for measuring peroxide value (POV) 1 g of fatty oil obtained by the above fatty oil extraction method (hereinafter referred to as sample oil) was accurately weighed into a 200 ml stoppered flask, and acetic acid: carbon tetrachloride (3:2) was added. Add 25ml of
Furthermore, add 0.5 ml of saturated potassium iodide aqueous solution and shake gently for 2 minutes, then add 50 ml of water.
Titrate with 0.01N sodium thiosulfate test solution. POV=A×F/T×10 A: 0.01N sodium thiosulfate test solution (ml) F: Factor T: Sample oil (g) Method for measuring acid value Accurately weigh 1 g of sample oil into a 250 ml stoppered flask, and benzene: ethanol (1:1) Add 100ml of solution and 1 to 2 drops of phenolphthalein test solution, and add 0.1N
Titrate with sodium hydroxide/ethanol solution. Acid value = B x 5.611 x F/T B: 0.1N sodium hydroxide/ethanol (ml) F: Factor T: Sample oil (g) Method for measuring iodine value Pour 0.1 to 0.15 g of sample oil into a 500 ml stoppered flask. Weigh, add 10 ml of carbon tetrachloride, and shake.
Add exactly 25 ml of iodine trichloride test solution, cap tightly, and leave in a dark place for 1 hour with occasional shaking. Then add 20ml of potassium iodide solution and add 100ml of water.
ml and shake thoroughly, then titrate with 0.1N sodium thiosulfate solution. The indicator is 1ml of starch test solution.
Use. Perform a blank test under the same conditions. Iodine value = (A-B) x 1.269/T A: Amount of 0.1N sodium thiosulfate test solution during blank test (ml) B: Amount of 0.1N sodium thiosulfate test solution of sample oil (ml) T: Sample oil (g) Measuring method for saponification number: Accurately weigh 2 g of sample oil into a 250 ml hard flat-bottomed flask, add 25 ml of caustic potash alcohol solution (about 32 g of caustic potash is dissolved in the same amount of distilled water, and add alcohol to make 1), and cool under reflux. Attach the container and heat on a hot water bath for 30 minutes (just enough to bring the alcohol to a slight boil). During this time, gently shake the flask to promote saponification. After cooling, use phenolphthalein as an indicator.
Titrate the remaining amount of caustic potash with 0.5N hydrochloric acid. A blank test is performed without adding any material. Ken number = (A-B) x 28.05/T A: Amount of 0.5N hydrochloric acid test solution during blank test (ml) B: Amount of 0.5N hydrochloric acid test solution of sample oil (ml) T: Sample oil (g)

【table】

[Table] Example 1 10 g of ovalbumin was dissolved in 100 ml of water, and 5 g of lamprey oil was added to the solution and stirred at room temperature for 24 hours. After stirring, add ethanol to the reaction solution.
Add 100ml and dry under reduced pressure to obtain light brown powdered lamprey oil-egg albumin complex.
14.9 g (binding ratio 0.5:1) was obtained. Example 2 1 g of ovalbumin was dissolved in 100 ml of water, and 5 g of γ-linolenic acid was added to the solution, followed by stirring at room temperature for 24 hours. After stirring, drying using a spray dryer yields 4.3 g of γ-linolenic acid-egg albumin complex in white powder form (binding ratio 5:1).
I got it. Example 3 2.5 g of ovalbumin was dissolved in 100 ml of water, 5.0 g of olive oil was added to the solution, and the mixture was stirred at high speed for 15 minutes at room temperature. After stirring, add ethanol to the reaction solution.
After adding 50 ml, the solvent was distilled off and then dried under reduced pressure to obtain 7.4 g of an olive oil-egg albumin complex (binding ratio 2:1) in the form of a pale yellowish white powder. Example 4 After dissolving 5.0 g of ovalbumin in 100 ml of water, 3.0 g of evening primrose oil was added and stirred at high speed for 15 minutes at room temperature. After stirring, 50 ml of ethanol was added to the reaction solution and dried under reduced pressure to obtain 7.9 g of evening primrose oil-ovalbumin complex (binding ratio) in the form of pale yellowish white powder.
0.6:1) was obtained. Example 5 After dissolving 5 g of egg albumin in 100 ml of water, 5 g of lamprey oil, 25 mg of ascorbic acid stearate, and natural vitamin E were added to the solution.
(1:5) was added and stirred, and the mixture was stirred for 2.5 hours under ice cooling in a nitrogen stream to homogenize. The obtained aqueous solution was used in a spray dryer to obtain 9.8 g of lamprey oil-ovalbumin complex (binding ratio 1:1).

Claims (1)

[Scope of Claims] 1. A powdered fatty oil-albumin complex in which liquid fatty oil is combined with albumin. 2. The complex according to claim 1, wherein the albumin is ovalbumin. 3. The complex according to claim 1, wherein the liquid fatty oil is a saturated fatty acid having 6 to 24 carbon atoms. 4. The complex according to claim 1, wherein the liquid fatty oil is palmitooleic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid or docosahexaenoic acid. 5. The complex according to claim 1, wherein the liquid fatty oil is lamprey oil. 6 Claim 1 containing ascorbic acid or its ester and vitamin E as a stabilizer
The complex according to any one of items 5 to 6.