JPS60150826A - Liquid dispersion of vehicle having surface charge - Google Patents

Abstract

PURPOSE:To improve dispersion stability and adsorbing property of vehicle particles by imparting surface charge to vehicle particles formed by adding an appropriate amt. of an ionic surface active agent to a nonionic surface active agent. CONSTITUTION:To an aq. dispersion of nonionic surface active agent vehicle consisting of (A) 100pts.wt. at least one kind of ethoxylate selected from polyoxyethylene castor oil ether and polyoxyethylene hydrogenated castor oil ether, and (B) 3-30pts.wt. sorbitan polyester of long chain fatty acid, is further incorporated (C) an ionic surface active agent. Surface charge is imparted to the thus formed vehicle particles, and the dispersion stability and the adsorption property of the vehicle particles are both improved.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides an aqueous dispersion of surface-charged vesicles using an easily available nonionic surfactant, more specifically, a hydrophilic active ingredient or a hydrophobic active ingredient is prepared in an aqueous dispersion using an easily available nonionic surfactant. The present invention relates to an aqueous dispersion of vesicles with improved dispersion stability and adsorption of vesicle particles, which can be blended in a state separated from a medium.

It has been known that amphipathic substances form vesicles, ie, endoplasmic reticulum, in water. For example, vesicles such as ribosomes made of phospholipids and ufasomes made of unsaturated fatty acids also exist in natural products. Since this type of vesicle is a stable dispersion, it is being applied to cosmetics, pharmaceuticals, etc. However, the naturally occurring vesicles described above are expensive, even if they have no safety issues. Therefore, it was unsuitable for mass consumption.

However, recently, vesicles using nonionic surfactants, ie, nioseems, have been discovered, and the formation of vesicle dispersions using readily available raw materials, for example, the general formula % formula % (where R is aliphatic hydrocarbon group having 12 to 3 carbon atoms, n
is an integer of 1 to 6) (Japanese Unexamined Patent Publication No. 52-6375), formation of vesicles by an ethylene oxide adduct of glycerin dialkyl ether and an ethylene oxide adduct of myristic acid stearylamide Formation of vesicles (:r, colloid engineering inter-face
Sci, J, Vol. 82, No. 2, No. 401-417.
page) etc. have been reported.

On the other hand, it is known that polyoxyethylene hydrogenated castor oil ether and polyoxyethylene sorbitol tetraoleate form concentric lamellar liquid crystals (1).
Japan Chemical Journal J, 1981, No. 11, No. 1691~
1696 pages).

In other words, a vesicle can be said to be a special form of concentric lamellar liquid crystal, and its difference is that the surfactant forms a bimolecular film or multilayer film, and a substantial hydrophilic cavity is formed inside the vesicle. However, it contains water or an aqueous solution. Therefore, in order to form this pair, it is necessary to orient the surfactant molecules so as to form a lamellar bilayer film having a curvature that facilitates the formation of pairs.

However, although the polyoxyethylene hydrogenated castor oil ether forms a concentric lamellar liquid crystal, as is well known, it is a mixture of multiple compounds with different numbers of added moles of ethylene oxide. The state of the liquid crystal is not uniform, and no clear vesicle structure is observed.

The present inventors have conducted extensive research in order to develop a vesicle dispersion using a surfactant that is approved for use in food products, cosmetics, etc. by public institutions, and is easily available. As a result, by first using nonionic polyoxyethylene castor oil ether or polyoxyethylene hydrogenated castor oil ether as a surfactant, and adding sorbitan polyester, a long chain fatty acid, at a predetermined ratio, discovered that vesicles are easily formed by orienting the surfactant with a curvature that facilitates the formation of vesicles, and filed a patent application.

However, the vesicles formed in this way do not have a surface charge, and their dispersion stability is not always satisfactory.

Therefore, as a result of further intensive research, the present inventors found that by adding an appropriate amount of ionic surfactant to the nonionic surfactant, a surface charge is imparted to the formed vesicle particles, resulting in stable dispersion. It was discovered that the adsorption property of vesicles was improved at the same time as the adsorption properties of the vesicles were improved, and based on this finding, the present invention was completed.

That is, the present invention provides at least one ethoxylate selected from (A) polyoxyethylene castor oil ether and hyphoryoxyethylene hydrogenated castor oil ether.
00 parts by weight and (B) 3 to 30 parts by weight of long-chain fatty acid sorbitan polyester, and further contains (C) an ionic surfactant. The present invention provides a vesicle dispersion having a surface charge of .

The nonionic surfactant constituting the vesicle membrane, which is used as a component of the vesicle dispersion of the present invention, is polyoxyethylene castor oil ether or polyoxyethylene hydrogenated castor oil ether, and is generally expressed by the following formula. It is an ethoxylate with the structure shown.

These ethoxylates may be used alone or in combination of two or more, and the average number of added moles of ethylene oxide (in the above formula, t0m+n+x+y+z
) is preferably in the range of 7 to 20, particularly 8 to 15.

Regarding the long-chain fatty acid sorbitan polyester used as component (B) in the vesicle dispersion of the present invention, those in which the long-chain fatty acid residue has 14 to 18 carbon atoms, particularly 1
6 to 18 are preferred. Also, its degree of esterification is 2
．． A range of 5 to 3.5, particularly a range of 2.8 to 3.2 is preferred. Examples of such substances include sorbitan tripalmitate, sorbitan triolate, sorbitan tallow fatty acid triester, and the like.

The ratio of component (A) and component (B) in the vesicle dispersion of the present invention is preferably in the range of 3 to 30 parts by weight of component D (B) per 100 parts by weight of component (A). Preferably, the ratio is between 100:5 and 1.00:25.

When component (A) is used alone, although concentric lamellar liquid crystals are formed, no vesicle formation is observed by electron microscopy.

However, when a small amount of component (B) is added, the surfactant is oriented with a curvature that facilitates the formation of vesicles, and vesicles are formed. When the ratio of component (A) to component (B) is within the range of the present invention, almost all of the aggregates formed by the surfactant used form vesicles. Further, a preferable range is selected in consideration of the stability of the vesicle and the ability to retain various drugs (active ingredients) carried thereon.

The ionic surfactant used as component (C) in the vesicle dispersion of the present invention imparts a surface charge to the formed vesicle particles, and includes cationic surfactants and anionic surfactants. Examples of the cationic surfactant include palmitylamine, stearylamine, hardened tallow alkylamine, etc. having 14 to 22 carbon atoms.
Long chain alkyl amines and their salts, di-long chain alkyl amines having 14 to 22 carbon atoms such as civalmitylamine, distearylamine, di-cured tallow alkylamine and their salts, valmityltrimethylammonium salt, stearyltrimethylammonium Carbon salts such as monoalkyl type quaternary ammonium salts having an alkyl group having 14 to 22 carbon atoms such as oleyl trimethyl ammonium salts, hardened tallow alkyl trimethyl ammonium salts, distearyl dimethyl ammonium salts, and di-hardened tallow alkyl dimethyl ammonium salts. Dialkyl type quaternary ammonium salt having two alkyl groups of number 14 to 22, long chain alkyl amines having 14 to 22 carbon atoms, such as bishydroxyethylstearylamine, bishydroxyethyl hardened tallow alkylamine, polyoxyethylene stearylamine, etc. 2 having an alkyl group having 14 to 22 carbon atoms, such as alkylene oxide adducts and salts thereof, and quaternized products of dehydration cyclization products of stearic acid and hydroxyethylethylenediamine.
-Alkyl-substituted imidazolinium salts, alkyldimethylbenzyl ammonium salts having an alkyl group of 8 to 12 carbon atoms, alkylpyridinium salts of an alkyl group having 12 to 22 carbon atoms, and quaternary ammonium having a hydroxyl group, an ether bond, and an amide bond. salts, bisguanide compounds represented by chlorhexidine and its salts, and cationic phospholipids such as dipalmitoylphosphatidylethanolamine. These cationic surfactants may be used alone or in combination of two or more.

In addition, as an anionic surfactant, for example, carbon number 1
Phosphoric acid monoesters and diesters of long chain alcohols with 4 to 22 carbon atoms and salts thereof, phosphoric acid monoesters and diesters of alkylene oxide adducts of long chain alcohols with 14 to 22 carbon atoms and salts thereof, carbon atoms 14 to 22 Alkyl sulfate, polyoxyethylene alkyl ether sulfate of alcohol with 14 to 22 carbon atoms, 1 carbon number
Examples include anionic glues/lipids such as alkanesulfonates having 4 to 22 carbon atoms, olefin sulfonates having 14 to 22 carbon atoms, and dipalmitoylphosphatidylserine. These anionic surfactants may be used alone or in combination.

The blending amount of the ionic surfactant as the component (C) in the vesicle dispersion of the present invention is as follows:
It is necessary that the nonionic surfactant component be in an amount sufficient to inhibit the formation of vesicles. If this amount is too large, mixed micelles will be easily formed, and the formation of vesicles will not be confirmed.

Table 1 shows polyoxyethylene hydrogenated castor oil ether (
p=10): weight ratio of sorbitan triolate is 9:1
Type and blending ratio of ionic surfactants and vesicles in a system in which a predetermined amount of various ionic surfactants are added to a nonionic surfactant mixture and dispersed at a concentration of 10% by weight. Shows the relationship with formability.

In addition, confirmation of vesicle formation was performed using a polarizing microscope or an electron microscope, and those in which vesicle formation was confirmed were marked as ○.

As can be seen from this table, the blending ratio at which vesicle formation is inhibited clearly differs depending on the type of ionic surfactant, and dialkyl (C14
-22) Type quaternary ammonium salts form vesicles in an arbitrary ratio with a nonionic surfactant.

In addition, monoalkyl (014-2゜) type quaternary ammonium salts, alkyl (C8-12) dimethylbenzylammonium salts, alkyl (01□-2□) pyridinium salts, long-chain alkyl (Ω14-2□) amines, salts thereof, di-long chain alkyl (C14-22) amines and salts thereof, alkylene oxide adducts of long-chain alkyl (C14-22) amines and salts thereof, 2-alkyl (014-22) substituted imidazolinium salts, and In the case of quaternary ammonium salts having a hydroxyl group, an ether bond, and an amide bond, vesicles are formed at a blending ratio of 10% by weight or less based on the total amount of the surfactant.

On the other hand, for cationic and anionic phospholipids, the blending ratio is 50% by weight or less based on the total amount of surfactant, and for chlorhexidine, which is a typical bisbiguanide compound, the blending ratio is 5% by weight or less. each form a vesicle.

Furthermore, phosphoric acid monoesters and diesters of alkylene oxide adducts of long chain alcohols (014-2□) and their salts, phosphoric acid monoesters and diesters of alkylene oxide adducts of long chain alcohols (014-22) and these In anionic surfactants such as salts of , 1 for the total amount of surfactant
Vesicles are formed at a blending ratio of % by weight or less.

Next, FIG. 1 shows an example in which the surface charge of nonionic surfactant vesicle particles changes by blending an ionic surfactant. Note that the change in the surface charge of the vesicle particles was determined by measuring the electrophoretic mobility of the vesicle particles.

FIG. 1 is a graph showing the relationship between the concentration of dipalmitoylphosphatidylseri, an aqueous substance of ionic surfactant vesicles, and the electrophoretic mobility of vesicle particles. The horizontal axis is the concentration of ionic surfactant in all the surfactants, and the vertical axis is the electrophoretic mobility (μm/sec/v/6n).
It is. In addition, the concentration of the nonionic surfactant in the dispersion liquid is polyoxyethylene hydrogenated castor oil ether (
p=10) and 1% by weight of sorbitant IJ oleate.

As is clear from Figure 1, when benzethonium chloride, a cationic substance, is used, the positive surface charge on the vesicle particles increases as the amount of benzethonium chloride increases, while when using dipalmitoylphosphatidylserine, an anionic substance, It can be seen that when used, the negative surface charge on the vesicle particles increases as the amount incorporated increases.

Incidentally, an increase in the viscosity of a vesicle dispersion generally corresponds to aggregation of vesicle particles, and when the degree of aggregation progresses significantly, phase separation occurs. Therefore, in a vesicle dispersion system with good dispersion stability, there is little change in viscosity over time.
Moreover, phase separation does not occur even during long-term storage.

Table 3 shows an example of the effect of blending an ionic surfactant on the dispersion stability of the nonionic surfactant Vencl.

That is, vesicle dispersions having the compositions shown in Table 2 were prepared, and each of the vesicle dispersions was stored at room temperature for a long period of time to determine the viscosity change and phase when the viscosity at the time of preparation was 1 and OO. The state of separation was observed and the results are shown in Table 3.

Note: ○, no phase separation observed, × phase separation observed. Furthermore, no phase separation was observed even if the sample was stored at room temperature for 24 months. In contrast, in the vesicle dispersion containing only a nonionic surfactant (sample ■), the
The viscosity becomes approximately twice as high as that immediately after preparation after being stored for a month, and clear phase separation is observed after 6 months.

For these reasons, it is possible to create a vesicle dispersion with good dispersion stability by adding a cationic or anionic ionic surfactant to the nonionic surfactant in an amount that does not inhibit vesicle formation. It is clear that the scales are prepared.

Such vesicle dispersions can contain various active ingredients in the internal aqueous phase or membrane of the vesicles and can therefore be used as carriers for active ingredients, in which case the adsorption properties of the vesicle particles It has an important meaning for the effectiveness of

It is generally believed that the surface of a living body is negatively charged due to sialic acid residues present at the terminal ends of sugar proteins contained in cell membranes. Therefore, if a positive surface charge is given to vesicle particles, the adsorption ability of the vesicle particles to the biological surface will improve, and the concentration of the active ingredient encapsulated in the vesicles on the biological surface will increase, thereby increasing the biological It can be expected that the utilization rate will improve.

Next, an example of the amount of vesicles adsorbed to biological tissues in a vesicle dispersion containing only a nonionic surfactant and a vesicle dispersion containing a cationic surfactant is shown in the second section.
As shown in the figure. Figure 2 shows the amount of adsorption of nonionic surfactant alone in vesicles using a golden hamster cheek pouch as a model of a biological surface, and the adsorption amount of vesicles to which a positive surface charge was imparted by adding benzethonium chloride. It is a figure showing comparison with adsorption amount.

As is clear from FIG. 2, by imparting a positive surface charge to the vesicle particles, the adsorption amount increases approximately twice.

Further, FIG. 3 shows an example of the amount of vesicle adsorption and the amount of active ingredient absorbed into living tissue in a vesicle dispersion containing only a nonionic surfactant and a vesicle dispersion containing a cationic surfactant.

Figure 3 uses flufenamic acid as a model active ingredient and rabbit red blood cells as model cells, and shows the amount of adsorption of vesicles to the red blood cells and the amount of flufenamic acid adsorbed to the red blood cells depending on whether distearyldimethylammonium salt is mixed with a non-ionic surfactant. FIG. 3 is a diagram showing a comparison of absorption amounts.

As is clear from Figure 3, when distearyldimethylammonium salt is added to impart a positive surface charge to vesicle particles, the adsorption amount of the vesicles increases, and at the same time, the absorption amount of flufenamic acid encapsulated within the vesicles also increases. do.

In this way, the adsorption of nonionic surfactant vesicles to biological tissues can be improved by incorporating an amount of cationic surfactant that does not inhibit vesicle formation into an aqueous dispersion of nonionic surfactant vesicles. Moreover, this vesicle dispersion is excellent as a carrier for increasing the amount of active ingredients absorbed into living tissues, since its main component is a nonionic surfactant that is inexpensive and highly safe.

Furthermore, it is easy to understand that when the adsorbent is positively charged, a similar effect can be obtained by incorporating an anionic surfactant to give the vesicle particles a negative surface charge. .

The vesicle dispersion of the present invention is obtained by first mixing components (A), (B), and (C) to form a homogeneous phase, and then mixing the mixture with a large amount of water. In this case, (A)
The total amount of the components (B) and (C) is preferably in the range of 0.1 to 50% by weight based on the total loss of the dispersion. Further, the obtained vesicle dispersion can be diluted to an arbitrary concentration. Furthermore, there are no restrictions on the method of mixing components (A), (B), and (C) and the method of mixing them with water, and any method may be used. For example, as a method for mixing component (A), component (Bl), and component (C) with water, a mechanical stirring method or an ultrasonic treatment method can be used, and normally the shearing force is relatively small like mechanical stirring. In this case, the particle size of the vesicles is about 1 to 5 microns, while in the case of ultrasonication, the particle size is about 0.5 microns.
Vesicles with a size of about 1 to 10 microns are obtained.

In the vesicle dispersion of the present invention, lipophilic or hydrophilic drugs as active ingredients can be incorporated into the vesicles depending on the intended use. Examples of lipophilic substances include lipophilic drugs used as active ingredients in pharmaceuticals such as β-glycyrrhetinic acid, fatty acid esters, oils and oils effective as sebum substitutes such as squalane, and polar substances such as chlorhexidine. Examples of hydrophilic substances include lipophilic substances having groups such as β-
Hydrophilic drugs used as active ingredients in pharmaceuticals such as dipotassium glycyrrhizinate, amino acids that have a moisturizing effect on the skin, PiCI IJtoncarboxylate,
Examples include humectants such as hyaluronic acid, and water-soluble substances that may react with components in the aqueous phase outside the vesicles, and these are used in amounts within a range that does not inhibit vesicle formation.

To incorporate each of the above components into the vesicle, for example, components (A), (B), (C) and the components to be incorporated may be mixed in advance to form a homogeneous phase, and then mixed with a large amount of water. .

The vesicle dispersion of the present invention contains various active ingredients in the internal aqueous phase or membrane of the vesicles, so it can be used as a carrier for active ingredients. Since it is a strong surfactant, the vesicles themselves have the effect of an oily component in cosmetics, etc., and can therefore be suitably used in pharmaceuticals or emulsion-type cosmetics such as creams and milky lotions.

When using the vesicle dispersion of the present invention for such purposes, the vesicle dispersion itself obtained by adding necessary components during production of the dispersion may be used, or the vesicle dispersion obtained in this way may be used. The dispersion liquid may be used by adding an appropriate amount to an aqueous solution or aqueous dispersion containing other necessary components, or it may be used by simply diluting it with water.

The vesicle dispersion of the present invention has excellent long-term stability and adsorption to biological tissue, and is extremely inexpensive, safe, and uses a surfactant that is easily available, making it practical. is extremely high.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 In a 100 ml beaker, 9 f of polyoxyethylene hydrogenated castor oil ether (p=1o) (component A), 12 of sorbitan trioleate (component B), and 2 of distearyldimethylammonium chloride (component C) were added.
9 was weighed out and mixed while heating.

Next, 88'y of water was added and sufficiently mixed using a magnetic stirrer to obtain a fluid, slightly transparent, milky white vesicle dispersion.

The formation of vesicles in this dispersion was confirmed by electron microscopy, and the particle size was within the range of 0.1 to 5 microns. In addition, the electrophoresis test showed that the obtained vesicle particles had a positive surface charge, and the static storage test showed that the obtained vesicle particles had a positive surface charge.
It was confirmed that the vesicles were extremely stable even after 24 months at room temperature.

Example 2 Example 1 except that polyoxyethylene castor oil ether (p=10) was used instead of component A in Example 1.
A vesicle dispersion was obtained in the same manner as above.

This dispersion had the same appearance, surface charge, stability, particle size, etc. as the vesicle dispersion obtained in Example.

Example 3 Component A97 used in Example 1, component Blf, and 0.22 of benzethonium chloride (component C) were weighed out and mixed in a 100-capacity beaker. Next, 89.81 i' of water was added and thoroughly mixed using a magnetic stirrer to obtain a fluid, slightly transparent, milky white vesicle dispersion.

The formation of vesicles in this dispersion was confirmed by electron microscopy, and the particle size was within the range of 0.1 to 5 microns. In addition, an electrophoresis test showed that the obtained vesicle particles had a positive surface charge, and a static storage test showed that the obtained vesicle particles had a positive surface charge.
It was confirmed that the vesicles were extremely stable even after more than 24 months at room temperature.

Example 4 100m7! Component A92 used in Example 1 for the beaker
and component B111' and benzalkonium chloride (component C)
0.2f was weighed out and mixed. Next, 89.82 g of water was added and thoroughly mixed using a magnetic stirrer so that the mixture became homogeneous to obtain a fluid, slightly transparent, milky white Beakle dispersion.

The formation of vesicles in this dispersion was confirmed by electron microscopy, and the particle size was within the range of 1 to 5 microns. Further, it was confirmed by an electrophoresis test that the obtained vesicle particles had a total positive surface charge, and by a static storage test, the vesicles were extremely stable even after 24 months at room temperature.

Example 5 Component A9 used in Example 1, component BIS' and chlorhexidine hydrochloride (component C) 0 in a 100m6 beaker
．． 21 was weighed out and mixed. Next, 89.87 g of water was added and thoroughly mixed using a magnetic stirrer so that the mixture became homogeneous to obtain a slightly transparent milky white vesicle dispersion having fluidity.

The formation of vesicles in this dispersion was confirmed by electron microscopy, and the particle size was within the range of 0.1 to 5 microns. Furthermore, it was confirmed by an electrophoresis test that the obtained vesicle particles had a positive surface charge, and by a static storage test, the vesicles were extremely stable even after 24 months at room temperature.

Example 6 Component A9 used in Example 1, component Bly, and sodium lauryl sulfate (component C) 0 in a 00 d beaker
．． 19 were weighed out and mixed. Next, 89.99 g of water was added and thoroughly mixed using a magnetic stirrer so as to be uniform, to obtain a slightly transparent milky white vesicle dispersion having fluidity.

The formation of vesicles in this dispersion was confirmed by electron microscopy, and the particle size was within the range of 0.1 to 5 microns. Furthermore, it was confirmed that the obtained vesicle particles had a negative surface charge in an electrophoresis test, and that the vesicles were extremely stable even after 24 months at room temperature in a static storage test.

Example 7 Component A9f and component B1 used in Example 1 for 100 m/vol.
4 and benzethonium chloride 22 were weighed out and mixed.

Next is water 89.8'? was added and mixed to homogenize [7.

The entire vesicle dispersion obtained was irradiated with ultrasonic waves.

The final mixture was translucent and the vesicles had a particle size of 0.1-1 micron. Furthermore, it was confirmed by an electrophoresis test that the obtained vesicle particles had a positive surface charge, and by a static storage test, the vesicles were extremely stable even after 24 months at room temperature.

Reference Example 1 As a vesicle dispersion, the concentration of a nonionic surfactant with a weight ratio of polyoxyethylene hydrogenated castor oil ether (p-1o):sorbitan triolate of 9:1 was 0.1% by weight.
and 0 for the nonionic surfactant.
．． Using a product containing 2% by weight of benzethonium chloride, - Using a Golden Mustard teak pouch as a model of the surface of a real body, the temperature was 35°C, the adsorption reaction time was 1 hour, and the cheek pouch weight was 0.3 to 0. , 52 and a vesicle adsorption test on the cheek pouch was conducted at a ratio of about 10 times the bath ratio. The results are shown in FIG.

Note that the interval estimation in the figure is based on a 95-coefficient confidence limit.

As is clear from FIG. 2, the amount of vesicle adsorption in the case containing benzethonium chloride is about twice that of the case in which only a nonionic surfactant is used. This is because the inclusion of benzethonium chloride imparted a positive surface charge to the di-nonionic surfactant vesicle particles.

Reference Example 2 As a vesicle dispersion, polyoxy hydrogenated castor oil ether (p-1o): sorbitan triolate weight ratio 9:1
The concentration of nonionic surfactant is 1.6%,
A product containing 200% by weight of distearyldimethylammonium salt based on the ionic surfactant was prepared.

4 me of physiological saline was added to 1 ml of the above vesicle dispersion, flufenamic acid was used as a model active ingredient, and 6.6 x 109 rabbit red blood cells were used as model cells, and the mixture was incubated at a temperature of 40°C for 1 hour. ,
The amount of vesicles adsorbed to the red blood cells was determined.

Next, after washing five times with 2% HCO-60 physiological saline, distilled water was added to lyse the blood and the remaining amount of flufenamic acid was measured, and the amount of flufenamic acid absorbed by the red blood cells was calculated.

These results are shown in FIG.

As is clear from Figure 3, when vesicle particles are given a positive surface charge by containing distearyldimethylammonium salt, the adsorption amount of the vesicles increases, and at the same time, the absorption amount of flufenamic acid encapsulated in the vesicles also increases. .

[Brief explanation of the drawing]

Figure 1 shows an example of the relationship between the content ratios of cationic and anionic surfactants and the electrophoretic mobility of vesicle particles in a system in which an aqueous dispersion of nonionic surfactant vesicles contains cationic and anionic surfactants. Figure 2 is a graph showing the vesicle dispersion containing only a nonionic surfactant and the vesicle dispersion containing a cationic surfactant.
Figure 3 showing an example of the amount of vesicles adsorbed to biological tissues.
The figure shows an example of the amount of vesicle adsorption and the amount of active ingredient absorbed into living tissue in a vesicle dispersion containing only a nonionic surfactant and a vesicle dispersion containing a cationic surfactant. Patent Applicant Lion Co., Ltd. Agent Akira Agata Figure 1: Most of the Ioso-columns are 1 thick (9% of the total amount of dirt) Figure 2: 16 years old, 1 piece Toni Hiroshi

Claims (1)

[Scope of Claims] 1 (A) 100 parts by weight of at least one ethoxylate selected from polyoxyethylene castor oil ether and polyoxyethylene hydrogenated castor oil ether;
) having a surface charge characterized by further containing (C) an ionic surfactant in an aqueous dispersion of nonionic surfactant vesicles consisting of 3 to 30 parts by weight of long-chain fatty acid sorbitan polyester Vesicle dispersion. 2 Ethoxylate has an average number of added moles of ethylene oxide 7~
20. The dispersion according to claim 1, which is an ethoxylate of No. 20. 3. The dispersion according to claim 1, wherein the sorbitan polyester is a sorbitan polyester of a long chain fatty acid having 16 to 18 carbon atoms. 4. Claim 1, wherein the ionic surfactant is at least one selected from dialkyl-type quaternary ammonium salts having two alkyl groups having 14 to 22 carbon atoms.
Dispersion liquid as described in Section. 5 The ionic surfactant is a monoalkyl type quaternary ammonium salt having an alkyl group having 14 to 22 carbon atoms, an alkyldimethylbenzyl ammonium salt having an alkyl group having 8 to 12 carbon atoms, and an alkyl group having 12 to 22 carbon atoms. The dispersion according to claim 1, wherein the dispersion is at least one selected from alkylpyridinium salts, and the proportion of the ionic surfactant is 10% by weight or less based on the total weight of the surfactant. liquid. 6. The ionic surfactant is at least one type selected from quaternary ammonium salts having a hydroxyl group, an ether bond, and an amide bond, and the proportion of the ionic surfactant is based on the total weight of the surfactant. 10. The dispersion according to claim 1, wherein the dispersion is 10% by weight or less. 7 The ionic surfactant is a long-chain alkylamine having 14 to 22 carbon atoms and its salt, a di-long-chain alkylamine having 14 to 22 carbon atoms and its salt, and an oxidizing agent of a long-chain alkylamine having 14 to 22 carbon atoms. Kylene adduct and its salt, carbon number 1
At least one type selected from 2-alkyl-substituted imidazolinium salts having 4 to 22 alkyl groups,
The dispersion according to claim 1, wherein the ionic surfactant is contained in a proportion of 10% by weight or less based on the total weight of the surfactant. 8 The ionic surfactant is at least one type selected from bisbiguanide compounds, and the blending ratio of the ionic surfactant is 5% by weight based on the total weight of the surfactant.
The dispersion according to claim 1, which is as follows. 9. The dispersion according to claim 8, wherein the bisbiguanide compound is chlorhexidine and its salt. io A patent in which the ionic surfactant is at least one type selected from cationic phospholipids, and the proportion of the ionic surfactant is 50% by weight or less based on the total weight of the surfactant. The dispersion according to claim 1. 11 The ionic surfactant is a phosphoric acid monoester or diester of a long-chain alcohol having 14 to 22 carbon atoms, a diester thereof, or a salt thereof; selected from salts of , alkyl sulfates having 14 to 22 carbon atoms, polyoxyethylene alkyl ether sulfates of alcohols having 14 to 22 carbon atoms, alkanesulfonates having 14 to 22 carbon atoms, and olefin sulfonates having 14 to 22 carbon atoms. The dispersion according to claim 1, which contains at least one kind of anionic surfactant, and the blending ratio of the anionic surfactant is 1% by weight or less based on the total weight of the surfactant. 12 The ionic surfactant is at least one type selected from anionic phospholipids, and the blending ratio of the ionic surfactant is 50% based on the weight of the total surfactant.
% or less by weight of the dispersion according to claim 1.