JPH0375214B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention involves blending an aqueous dispersion of surface-charged vesicles using an easily available ionic surfactant, and more specifically, a hydrophilic active ingredient or a hydrophobic active ingredient separated from the aqueous dispersion. The present invention relates to an aqueous dispersion of vesicles with improved dispersion stability and adsorption of vesicle particles. It has been known that amphipathic substances form vesicles, that is, endoplasmic reticulum in water, and for example, vesicles such as liposomes 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 or niosomes using nonionic surfactants have been discovered, and the formation of vesicle dispersions from readily available raw materials, such as those with the general formula R(-OCH ₂ CHOHCH ₂ )-OH or

[Formula] (R in the formula is an aliphatic hydrocarbon group having 12 to 30 carbon atoms,
Formation of vesicles by an ionic surfactant (where n is an integer of 1 to 6) (Japanese Unexamined Patent Publication No. 52-6375), an ethylene oxide adduct of glycerin dialkyl ether and an ethylene oxide adduct of myristic acid stearylamide Formation of vesicles (“J.Colloid Interface
Sci., Vol. 82, No. 2, pp. 401-417). On the other hand, it is known that polyoxyethylene hydrogenated castor oil ether and polyoxyethylene sorbitol tetraoleate form concentric lamellar liquid crystals (Japanese Kagaku Zasshi, 1981, Vol.
11, pp. 1691-1696). By the way, 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 membrane or a multilayer membrane, and a substantial hydrophilic cavity is formed inside the vesicle.
The point is that it contains water or an aqueous solution. Therefore,
In order to form these vesicles, it is necessary that the surfactant molecules be oriented to form a lamellar bilayer film having a curvature that facilitates the formation of vesicles. 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 sharp 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 necessarily 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 knowledge, the present invention was completed. That is, the present invention provides (A) 100 parts by weight of at least one ethoxylate selected from polyoxyethylene castor oil ether and polyoxyethylene hydrogenated castor oil ether, and (B) 3 to 3 parts by weight of sorbitan polyester of long chain fatty acids. The present invention provides a vesicle dispersion with a surface charge characterized by further containing (C) an ionic surfactant in an aqueous dispersion of nonionic surfactant vesicles consisting of 30 parts by weight. . The nonionic surfactant constituting the vesicle membrane used as component (A) 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 having the structure shown below.
These ethoxylates may be used alone or in combination of two or more, and the average number of added moles of ethylene oxide (l in the above formula)
+m+n+x+y+z) is 7 to 20, especially 8
A range of ~15 is preferred. Regarding the long-chain fatty acid sorbitan polyester used as component (B) in the vesicle dispersion of the present invention, it is preferable that the long-chain fatty acid residue has 14 to 18 carbon atoms, particularly 16 to 18 carbon atoms. Further, the degree of esterification is preferably in the range of 2.5 to 3.5, particularly preferably in the range of 2.8 to 3.2. Examples of such substances include sorbitan palmitate, sorbitan triolate, and sorbitan tallow fatty acid triester. The ratio of component (A) and component (B) in the vesicle dispersion of the present invention is 3 to 3 parts of component (B) per 100 parts by weight of component (A).
The amount should be in the range of 30 parts by weight, preferably in the range of 100:5 to 100:25. When component (A) is used alone, concentric lamellar liquid crystals are formed, but 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 surfactants 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 long-chain alkylamines having 14 to 22 carbon atoms such as palmitylamine, stearylamine, hardened tallow alkylamine, salts thereof, dipalmitylamine,
Di-long chain alkyl amines having 14 to 22 carbon atoms such as disterylamine and di-hardened tallow alkyl amine, and their salts, palmityltrimethylammonium salt, stearyltrimethylammonium salt, oleyltrimethylammonium salt, and hardened tallow alkyltrimethylammonium salt. Number 14-22
Dialkyl-type quaternary ammonium salts having two alkyl groups having 14 to 22 carbon atoms, such as monoalkyl-type quaternary ammonium salts having alkyl groups, distearyldimethylammonium salts, and dicured beef tallow alkyldimethylammonium salts. ammonium salt,
Bishydroxyethylstearylamine, bishydroxyethyl hardened beef tallow alkylamine, polyoxyethylene stearylamine, etc. with 14 or more carbon atoms
2-alkyl-substituted imidazolytes having an alkyl group having 14 to 22 carbon atoms, such as alkylene oxide adducts of 22 long-chain alkyl amines and their salts, and quaternized products of cyclized dehydration products of stearic acid and hydroxyethylethylenediamine. In addition, alkyldimethylbenzyl ammonium salts having an alkyl group having 8 to 12 carbon atoms, alkylpyridinium salts having an alkyl group having 12 to 22 carbon atoms, quaternary ammonium salts having a hydroxyl group, an ether bond, and an amide bond, chlorhexidine, and its like. Examples include bisguanide compounds represented by salts, and cationic phospholipids such as dipalmitoylphosphatidylethanolamine. These cationic surfactants may be used alone or in combination of two or more. Examples of anionic surfactants include phosphoric acid monoesters and diesters of long-chain alcohols having 14 to 22 carbon atoms, and salts thereof, and salts thereof.
Phosphoric acid monoesters and diesters of alkylene oxide adducts of long-chain alcohols and their salts, alkyl sulfates with 14 to 22 carbon atoms, and 14 to 22 carbon atoms
Examples include polyoxyethylene alkyl ether sulfates of 22 alcohols, alkanesulfonates having 14 to 22 carbon atoms, olefin sulfonates having 14 to 22 carbon atoms, and anionic phospholipids such as dipalmitoyl phosphatidylserine. These anionic surfactants may be used alone or in combination of two or more. 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 amount of the nonionic surfactant (B) component does not inhibit the formation of vesicles. If this amount is too large, mixed micelles are likely to form, making it impossible to confirm the formation of vesicles. Table 1 shows that in a nonionic surfactant mixture with a weight ratio of polyoxyethylene hydrogenated castor oil ether (=10):sorbitan triolate of 9:1,
In a system in which a predetermined amount of various ionic surfactants are added and dispersed at a concentration of 10% by weight,
The relationship between the type and blending ratio of the ionic surfactant and vesicle forming property is shown.

【table】

[Table] In addition, vesicle formation was confirmed 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; In salts, vesicles are formed in any ratio with nonionic surfactants. In addition, monoalkyl (C _14-22 ) quaternary ammonium salts, alkyl (C _8-12 ) dimethylbenzylammonium salts, alkyl (C _12-22 ) pyridinium salts, long-chain alkyl ((C _14-22 )) Amines and their salts, di-long chain alkyl ( _C14-22 ) amines and their salts, alkylene oxide adducts of long-chain alkyl ( _C14-22 ) amines and their salts, 2-alkyl ( _C14-22 )
For substituted imidazolinium salts and quaternary ammonium salts having a hydroxyl group, ether bond, and amide bond, 10% by weight based on the total amount of surfactant.
Vesicles are formed at the following blending ratios. 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, a typical bisbiguanide compound, the blending ratio is 5% by weight or less. each form a vesicle. Furthermore, phosphoric acid monoesters, diesters and salts thereof of alkylene oxide adducts of long chain alcohols ( _C14-22 ), phosphoric acid monoesters, diesters and diesters of alkylene oxide adducts of long chain alcohols ( _C14-22 ) These salts, alkyl ( _C14-22 ) sulfates, polyoxyethylene alkyl ( _C14-22 ) ether sulfates, alkane ( _C14-22 ) sulfonates and olefins ( _C14-22 )
Anionic surfactants such as sulfonates form vesicles at a blending ratio of 1% by weight or less based on the total amount of surfactants. 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 surface charge of the vesicle particles was determined by measuring the electrophoretic mobility of the vesicle particles. Figure 1 shows that a cationic substance benzethonium chloride (A) and an anionic substance dipalmitoyl phosphatidylserine (B) are added to an aqueous dispersion of nonionic surfactant vesicles as ionic surfactants. ) is a graph showing the relationship between their concentration and the electrophoretic mobility of vesicle particles in a system containing each of them, where the horizontal axis is the concentration (%) of the ionic surfactant in the total surfactant, The vertical axis is electrophoretic mobility (μm/sec/v/cm). The concentrations of the nonionic surfactants in the dispersion are 9% by weight of polyoxyethylene hydrogenated castor oil ether (=10) and 1% by weight of sorbitan triolate. As is clear from Figure 1, when the cationic substance benzethonium chloride is used, the positive surface charge on the vesicle particles increases as the amount of benzethonium chloride increases, while the anionic substance dipalmitoylphosphatidyl It can be seen that when serine is used, the negative surface charge on the vesicle particles increases as the amount of serine 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, and phase separation does not occur even during long-term storage. Table 3 shows an example of the effect of blending ionic surfactants on the dispersion stability of nonionic surfactant vesicles. 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 at the time of preparation.
The change in viscosity and the state of phase separation were observed when the temperature was set to 1.00, and the results are shown in Table 3.

【table】

[Table] Note ○: No phase separation observed, ×: Phase separation observed. As can be seen from Table 3, in the vesicle dispersion liquid of the present invention (sample, , ), the viscosity changes extremely over time. Moreover, no phase separation is observed even if it is stored at room temperature for 24 months. On the other hand, in the case of a vesicle dispersion (sample) containing only a nonionic surfactant, the viscosity was approximately twice that immediately after preparation after being stored for 3 months at room temperature, and the viscosity was approximately twice as high after 6 months. Phase separation is observed. From these reasons, nonionic surfactants,
Furthermore, it is clear that a vesicle dispersion with good dispersion stability can be prepared by incorporating a cationic or anionic ionic surfactant in an amount that does not inhibit vesicle formation. 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 by sialic acid residues present at the terminal portions of glycoproteins contained in cell membranes. Therefore, if we give a positive surface charge to the vesicle particles,
Since the adsorptivity of the vesicle particles to the biological surface is improved, the concentration of the active ingredient encapsulated in the vesicles on the biological surface is increased, and an improvement in bioavailability can be expected. Next, FIG. 2 shows an example of the amount of vesicles adsorbed to biological tissue in a vesicle dispersion containing only a nonionic surfactant and a vesicle dispersion containing a cationic surfactant. Figure 2 shows the amount of adsorption of vesicles with a nonionic surfactant alone and the amount of adsorption of vesicles given a positive surface charge by adding benzethonium chloride, using a golden hamster cheek pouch as a model of a biological surface. FIG. 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 shows the adsorption amount of vesicles and the absorption of flufenamic acid to the red blood cells depending on the presence or absence of distearyl dimethyl ammonium salt added to the nonionic surfactant using flufenamic acid as a model active ingredient and rabbit red blood cells as model cells. FIG. 3 is a diagram showing a comparison of 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, by incorporating a cationic surfactant in an amount that does not inhibit vesicle formation in an aqueous dispersion of nonionic surfactant vesicles, the adsorption of nonionic surfactant vesicles to biological tissue can be improved. In addition, this vesicle dispersion is excellent as a carrier for increasing the amount of active ingredients absorbed into living tissues, since the main component of this vesicle dispersion is an inexpensive and highly safe nonionic surfactant. It is also easy to understand that when the adsorbent is positively charged, a similar effect can be obtained by adding an anionic surfactant to give the vesicle particles a negative surface charge. It can be done. 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, the total amount of components (A), (B) and (C) is preferably in the range of 0.1 _to 50% by weight based on the total amount of the dispersion. Further, the obtained vesicle dispersion can be diluted to an arbitrary concentration. Furthermore, there is no restriction on the method of mixing components (A), (B), and (C) with water, and any method may be used. For example, as a method for mixing components (A), (B), and (C) with water, a mechanical stirring method or an ultrasonic treatment method can be used, and unlike mechanical stirring, the shearing force is relatively low. In the case of small particles, the particle size of the vesicles is about 1 _to 5 microns, while in the case of ultrasonication, vesicles with a particle size of about 0.1 _to 1 micron 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 groups such as chlorhexidine. On the other hand, examples of hydrophilic substances include hydrophilic drugs used as active ingredients of pharmaceuticals such as dipotassium β-glycyrrhizinate;
Moisturizing agents such as amino acids, pyrrolidone carboxylate, and hyaluronic acid that have a moisturizing effect on the skin;
Alternatively, water-soluble substances that may react with components in the aqueous phase outside the vesicles may be used, and these are used in amounts within a range that does not inhibit vesicle formation. The above-mentioned components can be incorporated into vesicles by, for example, mixing component (A), component (B), component (C), and the incorporated component in advance to form a homogeneous phase, and then mixing the mixture with a large amount of water. The vesicle dispersion of the present invention can contain various active ingredients in the internal aqueous phase or membrane of the vesicle, so
It can be used as a carrier for active ingredients, and since the membrane component that forms the vesicle is a highly lipophilic surfactant, the vesicle itself has the effect of being an oily component of cosmetics, etc. It can be suitably used in pharmaceuticals, emulsion-type cosmetics such as creams and emulsions, and the like.
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 tissues, etc., and uses a cheap, stable, and easily available surfactant, so it is practical. Extremely high. Next, the present invention will be explained in more detail with reference to Examples. Example 1 Weigh out 9 g of polyoxyethylene hydrogenated castor oil ether (=10) (component A), 1 g of sorbitan trioleate (component B), and 2 g of distearyldimethylammonium chloride (component C) in a 100 ml beaker, Mixed while heating.
Next, 88 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 with 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, an electrophoresis test confirmed that the obtained vesicle particles had a positive surface charge, and a static storage test confirmed that the vesicles were extremely stable even after 24 months at room temperature. Example 2 A vesicle dispersion was obtained in exactly the same manner as in Example 1, except that polyoxyethylene castor oil ether (=10) was used in place of component A in Example 1. This dispersion was the same as the vesicle dispersion obtained in Example 1 in terms of appearance, surface charge, stability and particle size. Example 3 9g of component A used in Example 1 in a 100ml beaker
and component B1g and benzethonium chloride (component C)
0.2g was weighed out and mixed. Next, 89.8 g 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. Furthermore, an electrophoresis test confirmed that the obtained vesicle particles had a positive surface charge, and a static storage test confirmed that the vesicles were extremely stable even after more than 24 months at room temperature. Example 4 9g of component A used in Example 1 in a 100ml beaker
and component B1g and benzalkonium chloride (component C)
0.2g was weighed out and mixed. Next, 89.8 g of water was added and thoroughly mixed using a magnetic stirrer to obtain a milky white vesicle dispersion with fluidity and a slightly transparent feel. 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, electrophoresis tests showed that the obtained vesicle particles had a positive surface charge.
And static storage tests confirmed that the vesicles were extremely stable even after 24 months at room temperature. Example 5 9g of component A used in Example 1 in a 100ml beaker
1 g of component B and 0.2 g of chlorhexidine hydrochloride (component C) were weighed out and mixed. Next, 89.8g 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, electrophoresis tests showed that the obtained vesicle particles had a positive surface charge.
And static storage tests confirmed that the vesicles were extremely stable even after 24 months at room temperature. Example 6 Ingredient A9 used in Example 1 in a 100ml beaker
g, 1 g of component B, and 0.1 g of sodium lauryl sulfate (component C) were weighed out and mixed. Next is water 89.9
g was added thereto and sufficiently mixed using a magnetic stirrer so as to be 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 that the vesicle particles obtained by electrophoresis tests had a negative surface charge, and that the vesicles were extremely stable even after 24 months at room temperature by static storage tests. Example 7 9g of component A used in Example 1 and components in 100ml volume
1 g of B and 0.2 g of benzethonium chloride were weighed out and mixed. Next, 89.8 g of water was added and mixed to homogenize. 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. Also,
An electrophoresis test confirmed that the obtained vesicle particles had a positive surface charge, and a static storage test confirmed that the vesicles were extremely stable even after 24 months at room temperature. Reference Example 1 As a vesicle dispersion, a nonionic surfactant concentration of 0.1% by weight with a weight ratio of polyoxyethylene hydrogenated castor oil ether (=10):sorbitan trioleate of 9:1, and a nonionic surfactant in addition to this Using a surfactant containing 0.2% by weight of benzethonium chloride, on the other hand, using a golden hamster cheek pouch as a model of a biological surface, the temperature was 35°C, the adsorption reaction time was 1 hour, and the cheek pouch weight was 0.3~ An adsorption test of vesicles to the cheek pouch was conducted under conditions of 0.5 g and a bath ratio of about 10 times. The results are shown in FIG. Note that the interval estimates in the figure are based on 95% confidence limits. 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 nonionic surfactant vesicle particles. Reference Example 2 As a vesicle dispersion, a concentration of a nonionic surfactant with a weight ratio of polyoxy hydrogenated castor oil ether (=10):sorbitan triolate of 9:1 was used.
One containing 1.6% by weight of distearyldimethylammonium salt and another containing 20% by weight of distearyldimethylammonium salt based on the ionic surfactant were prepared. Using 4 ml of physiological saline added to 1 ml of the above vesicle dispersion, flufenamic acid as a model active ingredient, and 6.6 x 10 ⁹ rabbit red blood cells as model cells, incubation was performed 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 determined. 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 drawings]

Figure 1 shows the relationship between the content ratio 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.
Graph showing an example. Figure 2 is a diagram showing 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.
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.

Claims (1)

[Claims] 1 (A) At least one ethoxylate selected from polyoxyethylene castor oil ether and polyoxyethylene hydrogenated castor oil ether 100
part by weight and (B) 3 to 30 parts by weight of long-chain fatty acid sorbitan polyester, further comprising (C) an ionic surfactant. A vesicle dispersion with a surface charge. 2. The dispersion according to claim 1, wherein the ethoxylate has an average number of added moles of ethylene oxide of 7 to 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. The dispersion according to 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. 5 Monoalkyl type quaternary ammonium salts in which the ionic surfactant has an alkyl group having 14 to 22 carbon atoms, alkyldimethylbenzyl ammonium salts in which the alkyl group has 8 to 12 carbon atoms, and alkyl groups having 12 to 22 carbon atoms in the ionic surfactant. At least one kind selected from alkylpyridinium salts, and the blending ratio of the ionic surfactant is 10% based on the total weight of the surfactant.
% or less by weight of the dispersion according to claim 1. 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. Claim 1 which is 10% by weight or less based on
Dispersion liquid as described in Section. 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 alkylene oxide addition of a long chain alkylamine having 14 to 22 carbon atoms. at least one selected from 2-alkyl-substituted imidazolinium salts having an alkyl group having 14 to 22 carbon atoms, and the proportion of the ionic surfactant is greater than the total amount of the surfactant. The dispersion according to claim 1, which contains not more than 10% by weight. 8 Claims in which the ionic surfactant is at least one type selected from bisbiguanide compounds, and the blending ratio of the ionic surfactant is 5% by weight or less based on the total weight of the surfactant. The dispersion according to item 1. 9. The dispersion according to claim 8, wherein the bisbiguanide compound is chlorhexidine and its salt. 10 A patent claim in which the ionic surfactant is at least one type selected from cationic phospholipids, and the blending ratio of the ionic surfactant is 50% by weight or less based on the total weight of the surfactant. The dispersion according to item 1. 11 Ionic surfactants include phosphoric acid monoesters, diesters and salts thereof of long chain alcohols with 14 to 22 carbon atoms, phosphoric acid monoesters, diesters and salts of alkylene oxide adducts of long chain alcohols with 14 to 22 carbon atoms. These salts, 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 is at least one selected 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 A patent in which the ionic surfactant is at least one type selected from anionic phospholipids, and the blending ratio of the ionic surfactant is 50% by weight or less based on the weight of the total surfactant. The dispersion according to claim 1.