JP2950348B2 - Fat emulsion and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a fat emulsion and a method for producing the same, and more particularly to a fat emulsion for nutritional supplement with improved stability and a method for producing the same.

[0002]

2. Description of the Related Art Conventionally, in the maintenance of a patient's life, oral nutrition and tube feeding have been impossible or inadequate, or even if they are possible, the digestive and absorptive function of the patient is reduced. In cases where the condition is extremely poor or the passage of food through the digestive tract leads to an exacerbation of the underlying disease, an infusion is administered intravenously for nutritional supplementation. Examples of such infusion preparations include sugar infusions containing saccharides such as reducing sugars, amino acid infusions containing essential amino acids and the like, electrolyte infusions containing minerals, fat emulsions containing vegetable oil emulsions and the like, and mixed vitamin preparations. They are commercially available, and these infusion preparations are appropriately mixed and used at the time of use according to the symptoms of the patient.

[0003]

Of the various infusion preparations described above, the fat emulsion is usually prepared by dispersing a fat or oil such as a vegetable oil in water using an emulsifier to form an oil-in-water emulsion. Fat emulsions are unstable and tend to cause coarsening of fat particles over time during heat sterilization or storage. In addition, as described above, various infusions are mixed at the time of use, but mixing at the time of use of the infusion preparation is a complicated operation for workers, and above all, there is a problem of bacterial contamination during mixing. In view of such problems, infusion preparations in which a fat emulsion and another infusion preparation are mixed in advance have been studied.However, the fat emulsion is unstable, and the emulsion disintegrates, the fat and oil particles become coarse, and phase separation occurs due to mixing. Etc. are likely to occur, and there are various practical problems.
In particular, in a formulation in which a saccharide is blended with a fat emulsion, phase separation is likely to occur due to the difference in specific gravity between the two solutions. As mentioned above, fat emulsions have poor stability and lack compatibility with other infusions. In particular, in an infusion preparation in which a saccharide is mixed with a fat emulsion, phase separation of the fat emulsion easily occurs, and there is a problem that a stable preparation cannot be obtained for a long period of time. Therefore, a fat emulsion having excellent stability has been desired. In view of the above circumstances, the present inventors have conducted intensive studies on stabilization of a fat emulsion.As a result, by reducing the average particle size of the fat emulsion, the stability of the fat emulsion is significantly improved, and phase separation and the like are less likely to occur. Was found. The present invention has been made based on the above findings. In order to reduce the average particle size of the fat emulsion, the amount of the emulsifier used is usually increased. However, when the amount of the emulsifier such as phospholipid is increased, the free fatty acid content in the fat emulsion increases. Free fatty acids are
Since it may cause toxicity of the fat emulsion, the free fatty acid content in the fat emulsion must be reduced as much as possible, so that a large amount of emulsifier cannot be used. The present invention has been made to solve the above-mentioned problems of the prior art, and an object of the present invention is to provide a fat emulsion having excellent stability and a method for producing the same.

[0004]

Means for Solving the Problems In order to solve the above problems, the present inventors have intensively studied to obtain a nutritional supplement fat emulsion having a small average particle size. As a result, glycerin and / or glucose were prepared during the preparation of the fat emulsion. The present invention was found to be able to reduce the average particle size of the fat emulsion when coexisting, thereby significantly improving the stability of the fat emulsion and making it difficult to cause phase separation and the like. That is, the fat emulsion of the present invention is a nutritional supplement fat emulsion obtained by emulsifying fats and oils with an emulsifier, the emulsifier content is 0.01 to 5.0 W / V%, and the average particle size of the fat emulsion is 0.17 μm or less. belongs to. The method for producing a fat emulsion of the present invention is a method for producing the above-mentioned fat emulsion, and emulsifies fats and oils with an emulsifier together with one or two kinds selected from glycerin and glucose, and has an average particle diameter of 0.17 μm. The following fat emulsion is obtained.

The present invention has the above-mentioned constitution, and the fat emulsion of the present invention and the fat emulsion obtained by the production method of the present invention are:
An oil-in-water emulsion prepared by dispersing fats and oils in water using an emulsifier, and a nutritional supplement fat emulsion having an average particle size of 0.17 μm or less. As the above fats and oils, any fats and oils can be used as long as they are edible oils, for example, vegetable oils (for example, soybean oil, cottonseed oil, safflower oil, corn oil,
Palm oil, perilla oil, perilla oil, etc.), fish oil (eg, cod liver oil, etc.), medium-chain fatty acid triglycerides [eg, panassate (trade name), ODO (trade name), etc.] and chemically synthesized triglycerides [eg, 2- Linoleoyl-1,3-dioctanoyl glycerol (8L8), 2-linoleoyl-1,3-didecanoyl glycerol (10L10)
Chemically defined trig
lycerides] is preferably used. Phosphorus fat is used as an emulsifier.
Quality is used, and as the phospholipid, for example,
Quality, hydrogenated egg yolk phospholipid, soybean phospholipid, hydrogenated large
Bean phospholipids are exemplified, and one or more emulsifiers selected from these are preferably used. Particularly preferred is a fat emulsion using soybean oil as an oil and fat and egg yolk phospholipid as an emulsifier.

The fat emulsion of the present invention has an average particle size of 0.17 μm
It is preferably 0.15 μm or less, and has high stability because it is finer than the conventional fat emulsion having an average particle diameter of 0.2 to 0.3 μm. In addition, phase separation due to a difference in specific gravity can be suppressed.

The method for producing a fat emulsion according to the present invention is a method for producing a fat emulsion having the above-mentioned properties. One or two kinds selected from glycerin and glucose are added during the preparation of the fat emulsion, and the emulsion is emulsified. Particle size is 0.17μm or less, preferably 0.1
A fat emulsion having a size of 5 μm or less is prepared. Conventionally, fat emulsions have been prepared by adding oils and fats and an emulsifier to water, stirring to prepare a coarse emulsion, and then emulsifying the coarse emulsion by a high-pressure emulsification method. In the method, a fat emulsion having an average particle size of 0.2 to 0.3 μm is usually obtained. In order to further reduce the average particle size, it is necessary to use a large amount of an emulsifier and emulsify it under more severe conditions (for example, increase the number of times of passing through an emulsifier and emulsify at a high pressure). However, when emulsifying under severe conditions using a large amount of emulsifier, the free fatty acid content in the fat emulsion increases,
It cannot be used as a nutritional fat emulsion because of toxicity problems. Due to such problems, it has been difficult to reduce the average particle size of the fat emulsion for nutritional supplement. However, the inventors have found that glycerin and glucose have a specific action of promoting micronization, and according to the production method of the present invention, the average particle diameter is 0.17 μm.
m or less can be easily prepared.
The production method of the present invention can be carried out in various modes as long as one or two kinds selected from glycerin and glucose are added at the time of preparing an emulsion, and for example, an oil and fat and an emulsifier are added to water. After the addition, one or two selected from glycerin and glucose are added, and the mixture is stirred to prepare a crude emulsion, and then the crude emulsion is emulsified by a conventional method such as a high-pressure emulsification method to form a fat emulsion. Can be prepared. When the above emulsification is carried out by a high-pressure emulsification method, for example, using an emulsifier such as a Manton-Gaulin homogenizer, the coarse emulsion is subjected to about 5 to 50 times, preferably about 10 to 25 times under conditions of about ²⁰ to 700 kg / cm2. This is done by passing through to some extent. In this method, glycerin and / or glucose may be present at the time of emulsification. For example, glycerin and / or glucose may be added to a coarse emulsion prepared from fats and oils and an emulsifier to perform emulsification. The average particle size of the obtained emulsion can be measured by using a conventional measuring method such as a light scattering method.

In the above-mentioned production method, the amount of the fats and oils, emulsifier, glycerin and / or glucose used is such that the fat emulsion obtained is 0.1 to 30 W / V% of fats and oils (hereinafter, unless otherwise specified,% is W / V%), preferably about 2 to 10%, emulsifier 0.01 to 5.0%, preferably about 0.05 to 3%, glycerin and / or glucose about 30 to 70%, preferably about 40
It is adjusted so that it is composed of about 60% and water necessary to make the total amount 100.

The fat emulsion of the present invention thus obtained may be in any suitable form as desired, such as by diluting with water or adjusting the sugar concentration by adding saccharides. As the above saccharides, various saccharides can be used as long as they are saccharides used for infusion, and examples thereof include glucose, fructose, maltose, sorbitol, xylitol, and glycerin. Preferable examples of the composition of the fat emulsion in which the concentration of the saccharide is adjusted are fats and oils 0.1 to 30%, preferably 1 to 20%,
More preferably 2-10%, 0.01-5.0% of emulsifier, preferably
0.05-3%, more preferably 0.1-1%, glucose, fructose,
Maltose, sorbitol, xylitol and one or more saccharides selected from glycerin 5 to 60%, preferably 10 to 40%, more preferably 15 to 30%, and the total amount is 100
And a fat emulsion composed of water necessary for the above. Further, a pH buffering agent or a coloring inhibitor may be added to the fat emulsion of the present invention in order to prevent pH reduction and coloring during sterilization and storage. Examples of the pH buffer include, for example,
L-histidine, tris (hydroxymethyl) aminomethane and the like, and examples of the coloring inhibitor include thioglycerol and dithiothreitol. These p
The addition amounts of the H buffer and the coloring inhibitor are usually 1% each.
Degree or less. Further, vitamins (for example, vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin K, etc.) may be added. These various additives may be added to the coarse emulsion or may be added to the emulsified fat emulsion. As the liquid properties of the fat emulsion of the present invention, the pH is usually about 5.0 to 8.0, preferably
Adjusted to about 5.5-7.0.

[0010] The fat emulsion of the present invention and the fat emulsion obtained by the production method of the present invention can be heat-sterilized. For example, the heat-sterilization is performed by injecting the infusion solution into a glass container or plastic (for example, polypropylene, polyethylene, ethylene-ethylene glycol). Filling a container (eg, bag, bottle, etc.) with a vinyl acetate copolymer, polyvinyl chloride, etc., then replacing with an inert gas (eg, nitrogen gas, helium gas, etc.), sealing, and then subjecting it to a sterilization step This is done by: The sterilization step can be performed according to a conventional method, for example, high-pressure steam sterilization,
It can be performed by a method such as hot water immersion sterilization and hot water shower sterilization. When a plastic container is used, sterilization is preferably performed in an atmosphere substantially free of oxygen.

The fat emulsion of the present invention and the fat emulsion obtained by the production method of the present invention can be administered to a living body for the purpose of nutritional supplementation, and can be used as such or diluted with water. The mixture is mixed with other amino acid infusions, electrolyte infusions and the like, and administered intravenously to patients. Furthermore, it can be used for administration in oral or enteral administration forms.

[0012]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples. Example 1 Glycerin or various sugars (glucose, sorbitol, xylitol or fructose) were added to a dispersion containing soybean oil and egg yolk phospholipids, coarsely emulsified, and then subjected to manton-gorin homogenizer (manufactured by Gorin, Model 15M-8TA). Emulsification (pressure: 550 kg / cm ² , liquid temperature: 70 ° C. or lower) was performed to prepare a fat emulsion having the composition shown in Table 1 below. At this time, the average particle size of the emulsion during emulsification was measured with time. The average particle size was measured by adding 100 ml of water to 0.1 ml of the emulsion to prepare a sample solution.
(Manufactured by Malvern). As a control, a similar test was performed using the same amount of water instead of glycerin and saccharides. The result is shown in FIG. FIG.
In the graph, ● represents glycerin, Δ represents glucose, ○ represents sorbitol, □ represents xylitol, Δ represents fructose, and Δ represents control.

[0013]

As shown in FIG. 1, in the control system (system containing no glycerin and saccharide), the average particle diameter was about 0.2 μm even when the number of times of passing through the emulsifier was 30.
Also, in the system containing sorbitol, xylitol and fructose respectively, the average particle diameter at the time of passing 30 times of the emulsifier was about 0.18 to 0.2 μm. On the other hand, in the system containing glycerin and glucose, the average particle size is rapidly reduced in accordance with the number of times of passing through the emulsifier, and in the system containing glycerin, the number of times of passing through the emulsifier is about 8 times, In the above, the average particle diameter was 0.17 μm or less after passing through the emulsifier about 20 times. From this, it became clear that glycerin and glucose have a specific action of reducing the particle size.

Example 2 60 g of soybean oil, 7.2 g of egg yolk phospholipid and 500 g of glucose were added to water and coarsely emulsified, and then the total amount was made up to 1000 ml with water. The resulting coarse emulsion was emulsified by a Manton-Gaulin homogenizer (manufactured by Gorin, Model 15M-8TA) until the average particle size became 0.15 μm or less, to prepare a fat emulsion. This fat emulsion 50
500 ml of water was added to 0 ml. Table 2 shows the composition of the obtained fat emulsion.
Shown in This formulation was dispensed into a 50 ml glass container, replaced with nitrogen gas, stoppered, and then subjected to high-pressure steam sterilization at 115 ° C. for 30 minutes. The properties, pH and average particle size of the emulsion before and after sterilization were compared. Table 3 shows the results.

[0016]

[0017]

As shown in Table 3, sterilization lowered the pH slightly, but the formulation was stable.

Example 3 42.64 g of soybean oil and 6.14 g of egg yolk phospholipid were heated to 70 ° C.
After adding 429 ml of 0% glucose solution (70 ° C), the total amount is 500 with water.
It was adjusted to ml and coarsely emulsified. Next, the mixture was emulsified using a Manton-Gaulin homogenizer (manufactured by Gorin, Model 15M-8TA) (pressure: 550 kg / cm ² , liquid temperature: 70 ° C. or less), and the average particle diameter was 0.1%.
A fat emulsion of 7 μm or less was obtained.

Example 4 Water for injection was added to 150 ml of the fat emulsion obtained in Example 3 to make a total volume of 500 ml, dispensed into a 50 ml glass container, replaced with nitrogen gas, plugged, and then sealed. The autoclave was subjected to high-pressure steam sterilization at 30 ° C. for 30 minutes. The formulation thus obtained was able to maintain a good emulsified state for a long period of time.

Example 5 200 ml of the fat emulsion obtained in Example 3 was mixed with 304 ml of water for injection and
After adding 13.2 ml of 70% glucose solution, the mixture was dispensed into a 50 ml glass container, replaced with nitrogen gas, plugged, and then sealed.
The autoclave was subjected to high-pressure steam sterilization at 30 ° C. for 30 minutes. The formulation thus obtained was able to maintain a good emulsified state for a long period of time.

[0022]

As described above, the fat emulsion of the present invention is adjusted to have an average particle size of 0.17 μm or less, so that the stability of the fat emulsion during sterilization and storage can be remarkably improved, and at the same time, other infusion agents can be used. , A good emulsified state can be maintained for a long period of time. Further, according to the production method of the present invention, a fat emulsion having the above characteristics can be easily and reliably prepared without using a large amount of an emulsifier. Therefore, according to the present invention, it is possible to provide a fat emulsion excellent in stability and safety over a long period of time. Particularly, in an infusion preparation in which a saccharide is blended with a fat emulsion, phase separation due to a difference in specific gravity can be suppressed, and furthermore, it can be used. In some cases, an operation of blending the fat emulsion and the saccharide is not required, so that the operation is simplified, and there is an effect that bacterial contamination during mixing can be prevented.

[Brief description of the drawings]

FIG. 1 is a diagram showing the relationship between the number of times of passage through an emulsifier and the average particle size of a fat emulsion in the preparation of a fat emulsion of Example 1. In the figure, ● represents glycerin, Δ represents glucose, ○ represents sorbitol, □ represents xylitol, Δ represents fructose, and Δ represents control.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/045 A61K 31/045 31/23 31/23 31/70 ADD 31/70 ADD 47/06 47/06 H (72) Inventor Ryoichiro Murashima 2- 25-1, Odani Otani, Hirakata City, Japan Midori Cross Central Research Laboratories (72) Inventor Shunichi Abe 2-25-1, Odani Otani, Hirakata City Midori Cross Central Research Institute (72) Inventor Kazumasa Yokoyama 2-5-1 Otani Otani, Hirakata City Midori Cross Central Research Institute, Inc. (56) References JP-A-2-167217 (JP, A) JP-A-55-147228 (JP, A) 62-29511 (JP, A) JP-A-3-161430 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 9/107 A61K 47/06

Claims (5)

(57) [Claims] Claims: 1. A fat emulsion for nutritional supplement wherein an oil or fat is emulsified using an emulsifier, wherein the oil or fat is 0.1 to 30 W / V.
%, Phospholipid 0.01-5W / V%, glucose 30-7
0 W / V%, and the fat emulsion has an average particle size of 0.17
a fat emulsion having a particle size of not more than μm. 2. An emulsion obtained by emulsifying a fat or oil with an emulsifier.
A fat emulsion for nutritional supplementation, comprising 0.1 to 30 W / V of fats and oils.
%, Phospholipid 0.01-5W / V%, glucose, fructose,
Selected from maltose, sorbitol and xylitol
Fat milk containing 5 to 60 W / V%
Characterized in that the average particle size of the agent is 0.17 μm or less
Fat emulsion. 3. The method according to claim 1, wherein the fat or oil is a vegetable oil, a fish oil, or a medium-chain fatty acid.
Selected from glycerides and chemically synthesized triglycerides
One or two or more phospholipids such as egg yolk phospholipids, water
Egg yolk phospholipids, soybean phospholipids and hydrogenated soybean liquor
One or more selected from phospholipids.
Is the fat emulsion according to any of 2. 4. A fat and / or oil, together with glucose, a phospholipid.
Emulsified using a fat having an average particle size of 0.17 μm or less
Production of a fat emulsion for nutritional supplements characterized by obtaining an emulsion
Law. 5. Vegetable oil, fish oil, medium chain fatty acid triglyceride
One or more selected from cerides and chemically synthesized triglycerides
Is a mixture of two or more fats and oils, together with glucose,
Quality, hydrogenated egg yolk phospholipids, soybean phospholipids and hydrogenated
One or more phospholipids selected from soybean phospholipids
5. The fat emulsion for nutritional supplement according to claim 4, wherein the fat emulsion is emulsified by using.
Manufacturing method.