JPH059111A - Fat emulsion and its production - Google Patents

Abstract

PURPOSE:To obtain a fat emulsion, excellent in stability in sterilization, preservation and mixing with other transfusion solutions and useful for supplying nutriments, and a method for producing the aforementioned fat emulsion. CONSTITUTION:A fat emulsion is obtained by including 0.01-5.0wt./vol.% content of an emulsifying agent and regulating the average particle diameter to >=0.17mum. Furthermore this method for producing the fat emulsion of this invention is to produce the aforementioned fat emulsion by the coexistence of glycerol and/or glucose in preparing the emulsion. According to this invention, the average particle diameter of the fat emulsion is regulated to <=0.17mum and the stability of the fat emulsion is remarkably improved. A good emulsified state can simultaneously be kept in mixing with other transfusion solutions. The fat emulsion having the above-mentioned characteristics can simply and surely be prepared according to the method for production of this invention.

Description

Detailed Description of the Invention

[0001]

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 having improved stability and a method for producing the same.

[0002]

2. Description of the Related Art Conventionally, in maintaining the life of a patient, oral nutrition and tube feeding are impossible or inadequate, or even if they are possible, the digestive absorption function of the patient is In the case of extremely poor conditions, or in the case of a pathological condition in which the passage of food through the digestive tract leads to aggravation of the original disease, intravenous administration of an infusion is performed for nutritional supplementation. Such infusion preparations include sugar infusions containing sugars such as reducing sugars, amino acid infusions containing essential amino acids and the like, electrolyte infusions containing minerals, fat emulsions containing vegetable oil emulsions, mixed vitamin preparations and the like. It is 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 above various infusion preparations, a fat emulsion is usually prepared by dispersing an oil or fat such as vegetable oil in water using an emulsifier to obtain an oil-in-water emulsion. The fat emulsion is unstable, and the fat and oil particles are likely to coarsen with time during heat sterilization and during storage. Further, as described above, various infusion agents are mixed and used at the time of use, but mixing at the time of use of the infusion preparation is a complicated operation for a worker, and above all, there is a problem of bacterial contamination at the time of mixing. Due to these problems, infusion preparations in which fat emulsions and other infusion preparations have been mixed in advance have been studied, but fat emulsions are unstable, and emulsions are disintegrated by mixing, coarsening of oil and fat particles, and phase separation. And so on, and there are various problems in practical use.
In particular, in a preparation in which a saccharide is mixed with a fat emulsion, phase separation easily occurs due to the difference in specific gravity between the two liquids. As described above, the fat emulsion is inferior in stability and lacks compatibility with other infusion agents. In particular, in an infusion preparation in which a saccharide is mixed with a fat emulsion, there is a problem that phase separation of the fat emulsion easily occurs and a stable preparation cannot be obtained for a long period of time. Therefore, a fat emulsion having excellent stability has been earnestly desired. In view of the above circumstances, the present inventors have diligently studied stabilization of a fat emulsion, and as a result of reducing the average particle diameter of the fat emulsion, the stability of the fat emulsion is significantly improved and phase separation and the like are less likely to occur. Found. The present invention has been made based on the above findings. In order to reduce the average particle size of the fat emulsion, usually, the amount of the emulsifier used is increased. However, if the amount of the emulsifier such as phospholipid used is increased, the free fatty acid content in the fat emulsion increases. Free fatty acids are
It is necessary to reduce the free fatty acid content in the fat emulsion as much as possible, since it may cause toxicity of the fat emulsion, and therefore a large amount of emulsifier cannot be used. The present invention was devised 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]

In order to solve the above problems, the inventors of the present invention have conducted extensive studies to obtain a fat emulsion for nutritional supplementation having a small average particle size, and as a result, glycerin and / or glucose were prepared at the time of preparation of the fat emulsion. The present invention has been completed based on the finding that the coexistence of (1) and (2) can reduce the average particle size of the fat emulsion, thereby significantly improving the stability of the fat emulsion and making phase separation less likely to occur. 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 diameter of the fat emulsion is 0.17 μm or less. belongs to. Further, the method for producing a fat emulsion of the present invention is the method for producing a fat emulsion described above, wherein fats and oils are emulsified with an emulsifier together with one or two selected from glycerin and glucose, and the average particle diameter is 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, which is a fat emulsion for nutritional supplement having an average particle size of 0.17 μm or less. As the above-mentioned oil and fat, any oil and fat can be used as long as it is an edible oil, for example, vegetable oil (for example, soybean oil, cottonseed oil, safflower oil, corn oil, coconut oil, perilla oil, perilla oil, etc.), fish oil (for example, Cod liver oil, etc.), medium-chain fatty acid triglycerides [eg, panacetate
(Trade name), ODO (trade name), etc. and chemically synthesized triglycerides [for example, 2-linoleoyl-1,3-dioctanoylglycerol (8L8), 2-linoleoyl-1,3-didecanoylglycerol (10L10 ) Etc. Chemically defined trigly
Cerides], one or more kinds of fats and oils are preferably used. Further, as the emulsifier, any emulsifier can be used as long as it is an emulsifier used in pharmaceutical preparations, for example, egg yolk phospholipids, hydrogenated egg yolk phospholipids, soybean phospholipids, hydrogenated soybean phospholipids and nonionic interfaces. One or more emulsifiers selected from activators [for example, Pluronic F68, HCO-60 (both are trade names), etc.] 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.
The following is preferably 0.15 μm or less, and has high stability because it is finely divided as compared with the average particle diameter of a conventional fat emulsion of 0.2 to 0.3 μm, and in particular, in an infusion preparation containing a saccharide in a fat emulsion, The phase separation due to the 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 characteristics. When the fat emulsion is prepared, one or two kinds selected from glycerin and glucose are added and 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, for the preparation of a fat emulsion, a method of adding a fat and oil and an emulsifier to water, stirring to prepare a coarse emulsion, and then emulsifying the coarse emulsion by a high pressure emulsification method or the like is used. 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 diameter, it is necessary to use a large amount of an emulsifier and emulsify it under more severe conditions (for example, increasing the number of times of passage through an emulsifier and emulsifying at high pressure). However, when a large amount of emulsifier is used and emulsified under severe conditions, the free fatty acid content in the fat emulsion increases,
It cannot be used as a nutritional fat emulsion as it causes toxicity problems. Due to such problems, it was 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 size is 0.17 μm.
A fat emulsion having a size of 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 preparation of the emulsion. One example thereof is water containing fats and oils and an emulsifier. After adding 1 or 2 kinds selected from glycerin and glucose together with stirring, a crude emulsion is prepared by stirring, and then the crude emulsion is emulsified by a conventional method such as a high pressure emulsification method to form a fat emulsion. It can be prepared. When the above emulsification is carried out by a high-pressure emulsification method, for example, using an emulsifying machine such as Manton-Gaulin homogenizer, the crude emulsion is under conditions of about ²⁰ to 700 Kg / cm ^2, about 5 to 50 times, preferably 10 to 25 times. It is carried out by passing a degree. In this method, glycerin and / or glucose may be present at the time of emulsification, and for example, glycerin and / or glucose may be added to a crude emulsion prepared from fats and oils and an emulsifier for emulsification. The average grain size of the obtained emulsion can be measured by using a conventional measuring method such as a light scattering method.

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

The thus obtained fat emulsion of the present invention may be in any suitable form such as dilution with water or addition of sugars to adjust the sugar concentration. As the saccharide, various saccharides can be used as long as they are used for infusion, and examples thereof include glucose, fructose, maltose, sorbitol, xylitol and glycerin. Suitable examples of the composition of the fat emulsion in which the concentration of sugars is adjusted, fats and oils 0.1 to 30%, preferably 1 to 20%,
More preferably 2-10%, emulsifier 0.01-5.0%, preferably
0.05-3%, more preferably 0.1-1%, glucose, fructose,
One or more sugars selected from maltose, sorbitol, xylitol and glycerin 5 to 60%, preferably 10 to 40%, more preferably 15 to 30%, and the total amount is 100.
A fat emulsion composed of water necessary for Further, the fat emulsion of the present invention may be added with a pH buffering agent or an anti-coloring agent in order to prevent the pH from lowering or coloring during sterilization and storage. As the pH buffering agent, for example,
L-histidine, tris (hydroxymethyl) aminomethane and the like, and examples of the color preventive agent include thioglycerol, dithiothreitol and the like. These p
The addition amount of H buffer and anti-coloring agent is usually 1% each.
It is considered to be below the level. Further, vitamins (eg, vitamin A, vitamin Bs, vitamin C, vitamin Ds, vitamin Es, vitamin Ks, etc.) may be added. These various additives may be added to the crude emulsion or the emulsified fat emulsion. The liquid property of the fat emulsion of the present invention is usually about pH 5.0 to 8.0, preferably
Adjusted to around 5.5-7.0.

The fat emulsion of the present invention and the fat emulsion obtained by the production method of the present invention can be sterilized by heating. For example, the sterilization is carried out by subjecting the infusion solution to a glass container or a plastic (eg polypropylene, polyethylene, ethylene- (Vinyl acetate copolymer, polyvinyl chloride, etc.) Fill a container (eg, bag, bottle, etc.), then replace with an inert gas (eg, nitrogen gas, helium gas, etc.), seal, and then sterilize It is done by The sterilization step can be performed according to a conventional method, for example, high pressure steam sterilization,
It can be carried out by a method such as hot water immersion sterilization or hot water shower sterilization. When using a plastic container, it is preferable to sterilize in an atmosphere containing substantially no 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 may be used as it is or diluted with water, or alone or as needed. It is mixed with other amino acid infusions, electrolyte infusions, etc. and administered intravenously to the patient. Furthermore, it can be used for administration in a dosage form such as oral administration and enteral administration.

[0012]

The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited to these examples. Example 1 Glycerin or various sugars (glucose, sorbitol, xylitol, or fructose) was added to a dispersion liquid containing soybean oil and egg yolk phospholipid, and the mixture was coarsely emulsified. The emulsion was emulsified (pressure: 550 Kg / cm ² , liquid temperature: 70 ° C. or lower) 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 over time. The average particle size was measured by adding 100 ml of water to 0.1 ml of emulsion to prepare a sample solution, and using this sample solution, Malvern Autosizer 2C
(Manufactured by Malvern Instruments Ltd.). As a control, the same test was conducted using the same amount of water instead of glycerin and saccharides. The result is shown in FIG. Note that FIG.
Middle, ● indicates glycerin, ◆ indicates glucose, ○ indicates sorbitol, □ indicates xylitol, ▽ indicates fructose, and △ indicates control.

[0013]

As shown in FIG. 1, in the control system (system not containing glycerin and saccharide), the average particle size was about 0.2 μm even when the number of passages through the emulsifying machine was 30 times.
Further, also in the systems containing sorbitol, xylitol and fructose, the average particle size after passing through the emulsifying machine 30 times was about 0.18 to 0.2 μm. On the other hand, in the system containing glycerin and glucose, the average particle size was rapidly decreased in accordance with the number of times the emulsifier passed, and in the system containing glycerin, the system containing glucose was about 8 times passed through the emulsifier. In the above, the average particle diameter became 0.17 μm or less after passing through the emulsifying machine about 20 times. From this, it became clear that glycerin and glucose have a specific action of reducing the particle size.

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

[0016]

[0017]

As shown in Table 3, sterilization resulted in a slight decrease in pH 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 (70 ° C) of 0% glucose solution, bring the total volume to 500 with water.
It was adjusted to ml and coarsely emulsified. Then emulsified using a Manton Gorin homogenizer (manufactured by Gorin Co., 15M-8TA type) (pressure: 550 Kg / cm ² , liquid temperature: 70 ° C. or lower), the average particle diameter is 0.1.
A fat emulsion of 7 μm or less was obtained.

Example 4 150 ml of the fat emulsion obtained in Example 3 was added with water for injection to make a total volume of 500 ml, dispensed in a 50 ml glass container, replaced with nitrogen gas, capped and then 115 High-pressure steam sterilization was performed at 30 ° C for 30 minutes. The preparation thus obtained was able to maintain a good emulsified state for a long period of time.

Example 5 To 200 ml of the fat emulsion obtained in Example 3, 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, and then stoppered, then 115
High-pressure steam sterilization was performed at 30 ° C for 30 minutes. The preparation 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, and the stability of the fat emulsion during sterilization and storage can be remarkably improved and other infusion solutions can be obtained. Even when mixed with, 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 prepared simply and reliably 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 for a long period of time, and particularly in an infusion preparation in which a saccharide is mixed with a fat emulsion, phase separation due to a difference in specific gravity can be suppressed, and use Since the operation of blending the fat emulsion and the saccharide is not necessary at the time, the operation is simplified and the effect of preventing bacterial contamination during mixing can be obtained.

[Brief description of drawings]

FIG. 1 is a graph showing the relationship between the number of passages through an emulsifying machine and the average particle size of a fat emulsion in the preparation of the fat emulsion of Example 1. In the figure, ● indicates glycerin, ◆ indicates glucose, ○ indicates sorbitol, □ indicates xylitol, ▽ indicates fructose, and △ indicates control.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Office reference number FI technical display location A61K 31/045 8413-4C 31/23 8413-4C 31/70 ADD 8314-4C 47/06 H 7329 −4C (72) Inventor Ryoichiro Murashima Invited 2-25-1 Otani, Hirakata City, Midori Cross Central Research Institute Co., Ltd. (72) Inventor Shunichi Abe Invited 2-25 Otani, Hirakata City Central Research Institute, Midori Cross Co., Ltd. (72) Inventor Kazumasa Yokoyama 2-25-1 Otani, Hirakata-shi, Midori Cross Central Research Institute

Claims (6)

[Claims] 1. A fat emulsion for nutritional supplementation, in which fats and oils are emulsified with an emulsifier, and the emulsifier content is 0.01 to 5.0 W / V%.
And the mean particle size of the fat emulsion is 0.17 μm or less. 2. The fat emulsion comprises 0.1 to 30 W / V% of oil and fat, 0.01 to 5 W / V% of emulsifier, 30 to 70 W / V% of one or two kinds selected from glucose and glycerin, and the total amount is 100. A fat emulsion according to claim 1 consisting of the required water. 3. The fat emulsion comprises one or more selected from oils and fats 0.1 to 30 W / V%, emulsifiers 0.01 to 5 W / V%, glucose, fructose, maltose, sorbitol, xylitol and glycerin, and 5 to 60 W /. The fat emulsion according to claim 1, which comprises V% and water necessary to bring the total amount to 100. 4. A fat and oil selected from vegetable oil, fish oil, medium chain fatty acid triglyceride and chemically synthesized triglyceride.
Or 2 or more, and the emulsifier is 1 or 2 or more selected from egg yolk phospholipids, hydrogenated egg yolk phospholipids, soybean phospholipids, hydrogenated soybean phospholipids and nonionic surfactants. The fat emulsion according to any one of 1 to 3. 5. An oil and fat is emulsified with one or two kinds selected from glycerin and glucose using an emulsifier,
A method for producing a fat emulsion for nutritional supplementation, which comprises obtaining a fat emulsion having an average particle size of 0.17 μm or less. 6. Egg yolk phospholipid, hydrogen together with 1 or 2 or more kinds of fats and oils selected from vegetable oil, fish oil, medium chain fatty acid triglyceride and chemically synthesized triglyceride, together with 1 or 2 kinds selected from glycerin and glucose. The production of a fat emulsion for nutritional supplementation according to claim 5, which is emulsified with one or more emulsifiers selected from added egg yolk phospholipids, soybean phospholipids, hydrogenated soybean phospholipids and nonionic surfactants. Law.