JPH01307438A - Safe lipid composition having high surface activity - Google Patents

Abstract

PURPOSE:To increase the permeability and wettability of a lipid compsn. as well as the safety by blending lysophosphatidylcholine with monoglyceride of unsatd. fatty acid having a specified number of carbon and fatty acid to prepare the lipid compsn. CONSTITUTION:Lysophosphatidylchloline (A) is blended with monoglyceride (B) of 16-22C unsatd. fatty acid and 9-13C fatty acid (C) as essential components to prepare a lipid compsn. The weight ratios among the components A-C are B/A=10/90-90/10, C/B=20/100-200/100 and C/(A+B)=10/100-200/100. In case of (B+C)/A>5, bile acids and/or alkali salts of bile acids are added by 5-100wt.% of the total amt. of the components A-C. The lipid compsn. has very high safety and superior surface activity.

Description

[Detailed Description of the Invention] [Field of Industrial Application] The present invention provides a lipid-based composition that is extremely safe and has surfactant effects such as high permeability, wettability, and spreadability. Regarding.

(Problems to be solved by conventional techniques and inventions) Currently,
Highly safe surfactants used in the fields of food, feed, cosmetics, toiletry products, pharmaceuticals, and agricultural chemicals include glycerophospholipids (lecithin) and their fractions, hydrogenated products, partially enzyme-treated products, and , natural or synthetic glycerin fatty acid monoester, sorbitan fatty acid ester, sucrose fatty acid ester, propylene glycol fatty acid ester, polyglycerin fatty acid ester, tartaric acid, malic acid, acetic acid, lactic acid, succinic acid derivatives of glycerin fatty acid monoester, poly Glycerin condensed lysylinate, fatty acid salt, stearoyl-2-lactylate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, sodium dioctyl sulfosuccinate, sodium dodecyl sulfate, mono- and acylphosphatidate, etc. These surfactants are considered to be relatively safe and are used in various countries. However, surfactants containing glycerophospholipid f1 (lecithin) and mono- and diglycerides of fatty acids,
The reality in each country is that the permissible intake per day is determined, and the substances that can be used are often restricted, and unlimited use is not permitted.

In addition, soybean phospholipids (lecithin) can be treated with phospholibase A.
Monoacylglycerophospholipids, especially lysophosphatidylcholine, and highly purified sucrose monofatty acid esters obtained by treatment with It cannot be said that it has sufficient effects such as wetting and spreading.

Also, Japanese Patent Publication No. 59-51241, U.S. Patent No. 3,
No. 388,999, Danish Patent No. 101,6
No. 49, U.S. Pat. No. 3,661.795 and U.S. Pat. No. 3,549.382 describe various compositions having surfactant action, but none of the compositions The effect is also insufficient.

In addition, in published patent publication No. 1982-502891, (a
) At least one type of fatty acid having 14 to 18 carbon atoms, Φ)
At least one of glycerin and a fatty acid having 14 to 18 carbon atoms
(C) lysophosphatidylcholine containing a fatty acid component having 14 to 18 carbon atoms; and (d) a drug as an optional component, for promoting the absorption into the body of an orally administered substance. things are listed. The above-mentioned published patent publication describes palmitoleic acid, oleic acid, linoleic acid, lylunic acid, and carbon atoms 14 to 18 as the fatty acids constituting the components (a), (b), and (C).
of saturated fatty acids are listed.

However, the composition described in the above-mentioned published patent publication is a composition for dispensing an orally administered substance, and its main purpose is not to obtain surface activity.

Therefore, sufficiently strong activity cannot be obtained within the range of the composition described in the above-mentioned published patent publication.
The composition using saturated fatty acid No. 8 has extremely poor surface activities such as penetrating power, wetting power, and spreading property.

Therefore, an object of the present invention is to provide a lipid-based composition that is extremely safe and has surfactant effects such as high permeability, wettability, and spreadability.

[Means to solve the problem]

As a result of various studies, the present inventor found that a composition consisting of a glycerophospholipid partially decomposed by phospholipase-2 and a monoglyceride of an unsaturated fatty acid and/or a monoglyceride of a medium-chain fatty acid is highly safe. They found that these compositions had a strong surfactant effect and could be obtained at low cost, and filed applications for these compositions (Japanese Patent Application Nos. 62-207093 and 62-24020).
No. 5), but these compositions were not necessarily sufficient in penetration and spreading effects.

As a result of further various studies, the present inventors discovered that the following lipid composition achieves the above object of the present invention, and arrived at the present invention.

That is, the present invention provides the following lipid composition.

Contains as essential constituents, ■ lysophosphatidylcholine, ■ monoglycerides of unsaturated fatty acids having 16 to 22 carbon atoms, and ■ fatty acids having 9 to 13 carbon atoms, and contains the above components ■ ~
The ratio (weight ratio) of ■ is: ■/■=10/90 to 90/10 ■/■=20/100 to 200/100■/(■+■)
= 10/100 to 200/100 and (■+■)/■ exceeds 5, ■bile acids and/or alkali salts of bile acids are added to the component (
1. A lipid composition that is safe and has a high degree of surface activity, characterized in that it contains 5 to 100% of the weight of

The safe and highly surface-active lipid composition of the present invention will be described in detail below.

Lysophosphatidylcholine, which is one of the essential components of the composition of the present invention, can be obtained from natural products such as soybean phospholipids, rapeseed phospholipids, corn embryo phospholipids, and egg yolk phospholipids.
Phospholibase A-2 or Phospholibase A-
2 to form lysophospholipids, and the decomposition products are further fractionated by means such as fractionation with a solvent or column chromatography. In addition, it can be produced from any choline phosphatide that is chemically synthesized or produced by biological transesterification using various phospholipases (A, B, C, D). It is also possible to use a As the acyl group of lysophosphatidylcholine, one type or a mixture of two or more types selected from linoleic acid, oleic acid, lylunic acid, arachidonic acid, palmitic acid, myristic acid, stearic acid, etc. is suitable. The above acyl group is glycerin 1
It may be bonded to either the position or the 2nd position. The above (1) lysophosphatidylcholine preferably consists essentially of a moacyl form, but if the weight ratio is within about 20%, it may contain a diacyl form of phosphatidylcholine or a small amount of phosphatide other than choline phosphatide. You can.

If the content of the diacyl phosph-1tidylcholine and other phosphatides in the above (1) lysophosphutidylcholine increases to 20% or more, the solubilizing power of the entire composition in water decreases, which is undesirable.

In addition, one of the essential components of the composition of the present invention is
As a monoglyceride of an unsaturated fatty acid having 16 to 22 carbon atoms, the constituent fatty acid is one selected from unsaturated fatty acids such as palmitoleic acid, oleic acid, linoleic acid, ryleic acid, arachidonic acid, and eicosapencitric acid. that's all,
A mixture of these unsaturated fatty acids and saturated fatty acids with an iodine value of 50 or more is preferred, and those derived from vegetable oil and/or animal oil within the above range are used.

Further, as for the unsaturated fatty acid monoglyceride mentioned above, one having a monoester content of 70% or more is preferable, and a highly purified product such as distilled monoglyceride is suitable. Furthermore, the bonding position of the unsaturated fatty acid may be any of the 1st, 2nd, and 3rd positions of glycerin.

If the degree of saturation of the fatty acids constituting the unsaturated fatty acid monoglyceride increases, the solubility of the entire composition in water decreases, which is undesirable. Unsaturated fatty acids have 1 carbon atom
Those below 5 and above 23 are rare in nature.

In addition, one of the essential components of the composition of the present invention is
Examples of fatty acids having 9 to 13 carbon atoms include lauric acid and capric acid. If the number of carbon atoms is 8 or less or 14 or more, strong surface activity with excellent penetration and spreading power, which is the main objective of the present invention, cannot be obtained.

In the composition of the present invention, the content ratio between the above-mentioned (1) lysophosphatidylcholine converted into a pure product, the above-mentioned (1) unsaturated fatty acid monoglyceride, and the above-mentioned (3) fatty acid is in a weight ratio of ■/■ = 10/90. ~90/10 ■/■=20/100~200/100■/(■+■)
-10/100~200/100 preferably, ■/■-20/80~80/20 ■/■-40/100~150/100■/(■+■)
=25/100 to 140/100.

The weight ratio (■/
If the ratio (2) is less than 10/90, the effect of the present invention is insufficient, and if it exceeds 90/10, the water solubility of the composition decreases, which is not preferred.

Furthermore, if the weight ratio (■/■) of the above-mentioned (■) fatty acid to the above-mentioned (1) unsaturated fatty acid monoglyceride is less than 20/100, the effect of the present invention will be insufficient, and if it exceeds 200/100, the surfactant effect will be reduced. Not only does it not increase, but also the water solubility of the composition decreases, which is undesirable.
/(■10)] is less than 10/l O0, the effect of the present invention will be insufficient, and if it exceeds 200/100, not only will the surfactant effect not be improved, but the water solubility of the composition will be reduced.・The composition of the present invention contains ■
Bile acids and/or alkali salts of bile acids may further be added. In particular, in each component composition of (1), (2) and (2) above,
When (■10■)/■ exceeds approximately 5, it is necessary to add (2) bile acids and/or alkali salts of bile acids (hereinafter MIC, simply referred to as bile acids).

The above-mentioned bile acids may be any mammalian bile acids; for example, one or a mixture of two or more bile acids selected from bile acids such as cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid, particularly preferably these. Conjugated bile acid obtained by reacting bile acid with taurine and/or glycine,
Alternatively, alkali metal salts of these bile acids may be mentioned. The amount of (1) bile acids added is 5 to 100% of the total weight of (1) lysophosphatidylcholine, (2) unsaturated fatty acid monoglyceride, and (2) fatty acid. If it is less than 5%, there is no solubilizing effect on the composition, and even if it is added more than 100%, the solubility state will not improve, so there is no need to add any more. It is determined as appropriate depending on the composition of the product and the type of bile acids.

The composition of the present invention can be produced, for example, as follows.

(1) If the amounts of unsaturated fatty acid monoglycerides and fatty acids are relatively large, they can be mixed with lysophosphatidylcholine, and if bile acids are used, they can be added together and heated to make them compatible. The composition of the invention is obtained as an oily paste.

(2) When the amount of lysophosphatidylcholine is relatively large and unsaturated fatty acid monoglyceride is added to zophosph 1
When the total amount of tidylcholine is relatively large, bile acids or the like may be added as necessary, and each component may be dissolved in water in order of water solubility, and this may be used as a composition as it is. Alternatively, the composition can be obtained by simply adding each component to water and heating it to form an aqueous colloidal solution using ultrasonic waves or the like, or by using a mixer with rotating blades, a pressurized homogenizer, or the like to obtain the composition as an aqueous solution. Furthermore, water can be removed from these aqueous solutions under reduced pressure to obtain a composition as an aqueous paste.

(3) To easily obtain the composition of the present invention, each component is added to a mixed solution of hexane, ethanol, ether, etc. and dissolved under pressure, and then the solvent is removed under reduced pressure to form a paste composition. There is a way.

The composition of the present invention may contain other surfactants as long as they do not impair the purpose; however, care must be taken as other surfactants may impair the effects of the composition of the present invention. be.

The fourth component of the composition of the present invention is the above-mentioned bile acids,
Although it does not have much effect on improving surface activity in itself,
Helps solubilize the composition. Furthermore, the addition of bile salts tends to slightly reduce the surface tension lowering ability of the aqueous composition solution, has little effect on the contact angle, and tends to slightly improve the penetrating power.

Among the above-mentioned (1) lysophosphatidylcholine, (1) unsaturated fatty acid monoglyceride, and (1) fatty acid which are the constituent components of the composition of the present invention, the one which is water-soluble and has penetrating and moisturizing effects is zophosphatidyl. Although only choline and the other two components are substantially insoluble in water, the former solubilizes the latter two.

A micellar solution prepared by dissolving the composition of the present invention in water exhibits surface activities such as strong penetrating action and wetting action.

Does a composition consisting of two components, lysophosphatidylcholine and unsaturated fatty acid monoglyceride and/or saturated fatty acid monoglyceride, have an improvement in the penetration and moisturizing effect beyond that exhibited by lysophosphatidylcholine itself at the same concentration as the composition? , or at least very little. However, when a medium chain fatty acid having 9 to 13 carbon atoms is added to this system as in the composition of the present invention, the above-mentioned surface activity increases dramatically.

The composition of the present invention is safe to dig, has strong surfactant ability, and can be used as a penetrating agent, a wetting agent, and a spreading agent. It can also be used as an aqueous emulsifier, a solubilizer for hydrophilic substances in an oil phase, and a solubilizer for lipophilic substances in an aqueous phase.

Specifically, by taking advantage of these properties, it can be used as a penetrating/wetting agent to improve the wettability of powdered foods, feeds, cosmetics, pharmaceuticals, etc., as a hair rinse agent, and as chemicals for plants and insects. For example, oil-in-water and water-in-oil emulsification of edible oils, vegetable essential oils, paraffins, and other oily substances. , dispersion of cocoa powder, instant food powder, spice powder, antifungal agents such as butyl roseoxybenzoate, various pigment powders, etc., wetting and dispersion in water, and emulsification of the above substances under acidic conditions to the extent necessary. Examples include use for dispersion, solubilization of insoluble substances in fats and oils, etc.

Furthermore, the composition of the present invention leaches proteins such as enzymes from cell membranes of animals and plants. In this field, polyoxyethylene nonylphenol ether is often used as a strong surfactant, but this surfactant may denature some proteins.

Although lysophosphatide J. lecorin can also be used for this purpose, its efficacy is not always sufficient; on the other hand, the composition of the present invention is safe and potent.

In fact, an important use of the composition of the present invention is that it is effective to utilize its high permeability to promote the absorption of drugs through the enteral, transdermal, and transmucosal routes. Eicosapentaenoic acid, T, which has physiological activity in the composition itself
- The composition of the present invention itself can also be used as a drug by incorporating polyunsaturated fatty acids such as lylunic acid, odd-numbered acids such as pentadecanoic acid. Furthermore, the composition of the present invention can be used in an oil-fat emulsion and used in combination with other nutrients as a 5-digestible enteral nutrient.

Promotion of drug absorption can be applied not only to mammals but also to a wide range of animals such as insects and plants such as agricultural crops.

The composition of the present invention exhibits amphipathic properties that allow it to easily form micelles and dissolve in both water and non-polar solvents such as oils and fats.

[Example] The present invention will be described in more detail by referring to Examples below, but the present invention is not limited to the following Examples.

"%" and "part" in the examples are "%" and "part" unless otherwise specified.
% by weight" and 1 part by weight".

Example 1 Commercially available soybean phospholipids were defatted with acetone and fractionated with hydroalcohol to obtain 70% phosphatidylcholine.
We obtained phosphatide containing . After treating this product with lysopholibase A-2 (Recitase 1O-L, manufactured by Novo), fatty acids were removed by acetone treatment, and further treated with hydrous alcohol and silica gel chromatography using hydrous alcohol. A phosphatide containing 97% zircholine was obtained. This phosphatide was used as lysophosphatidylcholine.

In addition, as unsaturated fatty acid monoglycerides, monoglycerides mainly consisting of linoleic acid: Emulgy MU manufactured by Riken Vitamin ■ (74% linoleic acid, 13% oleic acid)
, 8% palmitic acid, 2.6% stearic acid, etc.
Monoester content: 95%, iodination: 116), Emulgy MO manufactured by the same company (contains linoleic acid: 47%, oleic acid: 14%, palmitic acid: 37%, etc., monoester content: I: 93%)
, iodinated 72), and the company's Emulgy OL (oleic acid 74%,
Contains 5% linoleic acid, 5% palmitoleic acid, 4% valmitic acid, and 193% monoester.

Iodination67) was used.

Further, as the fatty acids, lauric acid was used as NAA-122 (purity 99%) manufactured by NOF Corporation, and as capric acid, Lunatsuku 10-95 manufactured by Kao Corporation (purity 95%) was used.

As the bile salts, sodium taurocholate (purity 70%) manufactured by Difco Laboratories was used.

For comparison, as a composition component outside the scope of the present invention, myristic acid, NAAI42 (purity 99
%), caprylic acid manufactured by Kao ■, Lunatsuk 8-95 (purity 95%) was used.

Each of the formulations shown in Table 1 below was added to a mixture of hexane alcohol (1:1) in an amount three times the total weight, heated to make them compatible, and the solvent was removed under reduced pressure to obtain each composition. Ta.

An aqueous solution having a concentration of 0.2% for the portion excluding sodium taurocholate from each composition was prepared, and various surface activity tests described below were conducted.

(1) Surface tension reducing ability: Kyowa Science ■ type surface tension system CBV
A platinum plate piece was attached to Model PA-3, and the surface tension at 35°C was measured.

(2) Campus disk sedimentation method: Using a thick campus cloth with a diameter of 1 inch, “Industrial Book ■ Surfactant Handbook, 1
960, the penetration power was 37° by the method described on page J860.
Measured at 25°C and 25°C.

(3) Contact angle measurement: ■ The contact angles for beeswax and wooden wax at 30''C were measured using a contact angle measuring device manufactured by Elmer (Elmer 13 model).

(4) Spreading test on plant leaves; composition with a concentration of 0.1% by volume excluding bile acids, 0.06% by volume of xanthan gum (Merck & Co., Ltd., Echo Gum), and food coloring blue 1
A spreading test was carried out as follows using each aqueous solution (spreading liquid) containing a small amount of No. Brilliant Blue FCF (manufactured by Sanei Chemical Industry Co., Ltd.).

Make a test piece of 1O x 6cm from the part other than the petiole of the 6th to 8th leaf from the outside of the cabbage, and add 30cm of spreading solution at 25°C.
After being immersed in M for 10 seconds, it was dried on a filter paper and the state of spread of the blue dye was observed.

Evaluation: 5 points, 7 points for plants with 90% or more of the leaf surface colored blue
0-90%: 4 points, 50-70%: 23 points,
There were 22 items with 30-50% and 11 items with 10-30%.

The test results are shown in Table 1 below.

(Hereinafter, blank space) Example 2 Commercially available soybean phospholipids were defatted with acetone, and fractionated with hydrous alcohol to obtain 70% phosphatidylcholine.
A phosphatide containing the following was obtained. After treating this product with phospholipase A-2 (Recitase 10L manufactured by Novo), fatty acids were removed by acetone treatment, and further treated with hydrous alcohol and silica gel chromatography using hydrous alcohol. A phosphatide containing 87% was obtained.

A composition was obtained in the same manner as in Example 1 using 17 parts of pure lysophosphatidylcholine, 33 parts of Emulcy MU, 50 parts of lauric acid, and 20 parts of crystalline glycocholic acid manufactured by Sigma. Aqueous solutions with concentrations of 0.2% and 0.5% of the portion of this composition excluding glycocholic acid were prepared, and the same surface activity test as in Example 1 was conducted. The results of the test were as follows.

For 0.2% aqueous solution: Surface tension 26.7 dyne/cm, penetration time 27.3 seconds at 37°C, contact angle for beeswax 35°, contact angle for wax wax 41° For 0.5% aqueous solution: Penetration time at 37°C: 6.7 seconds Example 3 A water paste of egg yolk phospholipid (egg yolk lecithin manufactured by Asahi Kasei Industries, Ltd.) was treated in the same manner as in Example 1 to form a phosphatide containing 98% of lysophosphatidylcholine. I got it.

A composition was obtained in the same manner as in Example 1 by blending 17 parts of this phosphatide, 33 parts of Emulcy MU, 50 parts of capric acid, and 30 parts of sodium taurocholate. A surface activity test similar to that in Example 2 was conducted on this composition. The results of the test were as follows.

Surface tension: 27.2 dyne/ca+, penetration time at 37°C: 27.1 seconds, contact angle with beeswax: 38°, contact angle with wax: 41" Example 4 The ratio of each component used in Example 3 was changed, and the A surface activity test similar to that in Example 3 was conducted on a composition containing phosphatidylcholine/Emulgy MU/capric acid/sodium taurocholate in a weight ratio of 20:40:40:40.The test results are as follows. It was on the street.

Surface tension: 27.8 dyne/c+w, penetration time at 37''C: 32.1 seconds, contact angle to beeswax: 40°, contact angle to wax: 43° Application Example 1 Regarding the compositions of Examples 1-1 and 1-2 , a dispersion test for the inorganic pigment titanium white, a wetting test for cocoa, and an easy dispersion test for cocoa.

[Dispersion test of inorganic pigment titanium white] 0.
Make a 25% (W/Vol) aqueous solution, and 20 d of this aqueous solution
and titanium white for pigments (Teikoku Kagyo type JR-701
) Ig was placed in a Nessler tube, shaken vigorously up and down to disperse it, and then left indoors for 1 and 3 days to observe the sedimentation state of the particles. The results are shown in Table 2 below.

Table 2 When simply dispersing in water, the particles almost completely settle out after one hour, but when using the composition of the present invention, even if the particles settle after the second day, a large amount of the powder remains at the top. remains.

[Cocoa wetness test]

An aqueous solution is prepared so that the concentration of the part of each composition excluding bile acids is 0.2%, and the solution is dispensed into a beaker using 100 #dl. While each aqueous solution was heated to 20°C and stirred at a constant speed on a magnetic stirrer to form a slightly concave surface on the top, 1 g of cocoa powder (Fujiya Co., Ltd., Versi Cocoa) was floated on the water surface until the powder was completely absorbed. The time required for the particles to disperse in water was measured. Test results for each composition (3
The average of the examples is shown in Table 3 below, and promotion of cocoa wetting was observed.

Table 3 (Cocoa dispersibility test) 3 g of the composition of Example 1-1 was dissolved in 40 g of ethyl alcohol, and this and 147 g of cocoa powder (Fujiya A-Ko, Versi Cocoa) were cooled in a Kenland mixer. The mixture was thoroughly stirred and mixed to make it homogeneous.Then, the alcohol was removed under reduced pressure and the mixture was dried, and the mixture was ground in a mortar to obtain instant cocoa (2).

In addition, instant cocoa (2) was obtained in the same manner using Ritsuto Wester S-1670-3.

2g each of these instant cocoa ■ and ■,
The instant cocoa was gently transferred to the surface of a 50 ml beaker containing 50 ml of water at 20° C., and the time required for substantially all of the instant cocoa to submerge from the water surface was measured.

The same sample was measured four times and the average value was taken. The results are as follows. Moreover, the instant cocoa using the composition of the present invention can be easily obtained by stirring when added to cold water. showed that.

Instant cocoa ■ 2 minutes 20 seconds Instant cocoa ■ 7 minutes 02 seconds [Effects of the present invention] The composition of the present invention is extremely safe and has surface active effects such as high permeability, wettability, and spreadability. It is a lipid-based composition having the following properties.

That is, the composition of the present invention is composed of all natural lipids; therefore, if an aqueous solution thereof is administered to the endothelium or outer skin of a living body, its effect on the living body is mild and safe unless it is administered into the blood or cells. In addition, ■It has a high degree of penetrating and moisturizing effect, ■It spreads well on the surfaces of animals and plants, ■It allows for good dispersion of minute solid particles in water, and ■It is also used effectively for emulsifying oil-based substances. It has excellent surfactant ability.

Claims (1)

[Scope of Claims] As essential constituents, (1) lysophosphatidylcholine, (2) monoglycerides of unsaturated fatty acids having 16 to 22 carbon atoms, and (3) fatty acids having 9 to 13 carbon atoms. The ratio (weight ratio) of the above components (1) to (3) is (2)/(1)=
10/90~90/10 (3)/(2)=20/100~200/100 (3)/((1)+(2))=10/100~200/
100 and ((2)+(3))/(1) exceeds 5, (4) Bile acids and/or alkali salts of bile acids are added to the component ((1)+(2)+ (3) A lipid composition that is safe and has a high degree of surface activity, characterized by containing 5 to 100% of the weight of (3)).