JPH03197408A - Stabilization of liposome and phospholipid dispersion - Google Patents

Abstract

PURPOSE:To obtain a liposome and phospholipid dispersion storable stably over a long period without causing the lowering of pH of the system and applicable to drugs, quasi-drugs, cosmetics, etc., by compounding a compound selected from cepharanthine, rutin, licorice extract and kojic acid. CONSTITUTION:A liposome or phospholipid dispersion can be stabilized by compounding one or more compounds selected from cepharanthine, rutin, licorice extract (preferably oil-soluble extract) and kojic acid. The liposome and phospholipid dispersion produced by this process is resistant to the pH lowering with time and has excellent stability over a long period. The effect of liposome and phospholipid can be fully exhibited by stably compounding the above dispersion to cosmetics, etc.

Description

[Detailed description of the invention] [Industrial application field] The present invention is suitable for pharmaceuticals, quasi-drugs, cosmetics, etc.

The present invention relates to a method for stabilizing liposomes and phospholipid dispersions used in the present invention.

[Conventional technology]

Liposomes, which are closed lipid vesicles, have originally been widely used as a biological membrane model, but in recent years, various applications have been made toward drug delivery systems (DO3). Phospholipids are also used in the cosmetics field for hair and
It was originally formulated as a skin nutrient, but in recent years, attempts have been made to use it as a surfactant and moisturizer.

When using liposomes and phospholipid dispersions in this way, it is important that these dispersions are stable in order to exhibit their effects as DO3, surfactants, and humectants.

However, liposomes and phospholipid dispersions are
Under the influence of heat, osmotic pressure, etc., it easily causes chemical and physical changes, and in particular, economically, it is easy to cause a decrease in the p++ of the system, such as hydrolysis of phospholipids, aggregation, sedimentation, and precipitation of precipitates. There have been problems with changes in appearance and deterioration of functionality due to

For this reason, a method of adding an electrolyte to the dispersion liquid and attempting to suppress the pH drop through its buffering effect (Japanese Unexamined Patent Publication No. 1983-1989)
263109), and attempts have been made to replace the air in a closed container with nitrogen gas and store these dispersions therein.

[Problem to be solved by the invention]

However, in the method of adding electrolyte, the p++
Adding a sufficient amount of electrolyte to suppress the pH drop will promote aggregation of liposomes and gelation of the system, and nitrogen gas replacement is not effective in reducing the pH of the system over time. However, it has the disadvantage that if the package is opened a few degrees, the effect of nitrogen gas replacement disappears, and it cannot withstand continuous use for a long period of time.

Therefore, there has been a desire for liposomes and phospholipid dispersions that do not cause a decrease in p+ of the system and have excellent long-term stability.

[Means for Solving the Problems] Under these circumstances, the present inventors conducted intensive research and found that if a compound selected from cephalanthine, rutin, 'iTj grass extract, and kojic acid is blended, the p11 of the system can be improved. The present invention was completed based on the finding that it is possible to obtain a ribotum and phospholipid dispersion that suppresses the deterioration and is stable for a long period of time.

That is, the present invention provides a method for stabilizing liposomes or phospholipid dispersions, which is characterized by incorporating one or more selected from cephalanthine, rutin, licorice extract, and kojic acid; The present invention provides phospholipid dispersions and cosmetics containing these dispersions.

Cephalanthine, rutin, licorice extract, and kojic acid used in the present invention can be extracted by conventional methods, and especially for licorice extract, oil-soluble ones are preferable. These can be used alone or in combination of two or more, and can be used in the dispersion in an amount of 00001 to 10% by weight (hereinafter referred to as
(simply expressed in %) is preferably included. In addition, these may be added during or after the preparation of the liposome dispersion or phospholipid dispersion. Particularly in the case of liposomes, it is preferably added at the time of preparing the dispersion.

Examples of the phospholipids used in the present invention include natural phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, lysophosphatidylcholine, sphingomyelin, egg yolk lecithin, and soybean lecithin, synthetic phospholipids such as dioleoylphosphatidylcholine, Alternatively, hydrogenated lecithin, in which the unsaturated carbon chain of a naturally occurring phospholipid is saturated with hydrogen, and other phospholipids extracted from microorganisms such as Escherichia coli, etc., may be used alone or in combination of two or more. I can do it. Furthermore, in order to improve dispersion stability, it is desirable that the composite lipid lamellar phase be electrically charged. In this case, phosphatidylserine, dicetyl phosphate, phosphatidic acid, stearylamine, etc. may be blended.

In the present invention, liposomes can be prepared using commonly known methods such as the portic swing method (A, D).

Bangham, J., Mo1. Biol...
13. 238 (1965)), sonication method (
C. Huang, Biochem, 8344
(1969)), the prevesicle method (l(, Traub
le.

Neurosci, Res, Prog, Bull
,, 9. 273 (1971)), ethanol injection method (S, BatzriBiochem, Biop
hys, Acta, 298.1015 (1973
)), French press extrusion method (Y, Barenhol
z, FBBSLett,, 99, 210 (1
979)), -]-ruic acid removal method (Y, Kagawa
, J. Biol.Chem., 246, 547
7 (1971)),) Lydon x-100 batch method (1
'1. J.

Gerritsen, [! ur, J, Bioch
em, 85, 255 (1978)), Ca2
+Fusion method (D, Papahadjopoulos, B
iocham, Biophys, Acta, 39
4. 483 (1975)), ether injection method (D,
Deazer, Biochem.

Biophys, octa, 443. 629 (
1976)), Ryo Nealing Method (R, Lawacze)
ck, Biochem, Biophys.

Acta, 443.313 (1976)), freeze-thaw fusion method (M, Kasahara, J, Bio
Chem, 252.7384 (1977))
, W10/W emulsion method (S.

Matsumoto, J., Co11oid I
interface 5ci162゜149 (1977
)), reverse phase evaporation method (F, 5zoka, ProcN
atl, Acad, Sci, USA, 75.41
94 (197B>), polyhydric alcohol method (Unexamined Japanese Patent Publication No. 1983
-7932) etc.

The amount of phospholipid added in the liposome and phospholipid dispersion is preferably in the range of 0.01 to 20%. If it is less than 0.00%, the effects of liposomes and phospholipids will not be obtained when this dispersion is used in cosmetics, etc., and if it exceeds 20%, the system will gel, which is not preferable.

Depending on the purpose, the liposomes and phospholipid dispersions of the present invention may include, for example, lower alcohols such as ethanol, propyl alcohol, and isopropyl alcohol; Alcohol; water-soluble substances such as sodium chondroitin sulfate and sodium hyaluronate; oil-soluble substances such as squalane and cholesterol; powders such as dyes and pigments, etc. can be appropriately blended.

The liposome and phospholipid dispersion of the present invention is particularly suitable when incorporated into cosmetics such as lotions, serums, emulsions, creams, and packs, as it is stable for a long period of time and can exert the effects of the liposomes and phospholipids. It is. In particular, when it contains kojic acid, the whitening effect of kojic acid is synergistically exhibited by encapsulating it in liposomes.
preferable.

Moreover, the liposome and phospholipid dispersion of the present invention are
(It is stable within the range of 6.5 to 8, and when it is blended into cosmetics etc., it is stable within the same range.

〔Example〕

Next, the present invention will be explained in more detail with reference to Examples.
The present invention is not limited to these examples.

Example 1 50 - 0.15 g of egg yolk lecithin in an eggplant-shaped flask.

After dissolving 0.02 g of cephalanthine and 110 ml of dicetyl phosphate in 10 g of chloroform, chloroform is distilled off using a rotary evaporator. This was dried in a vacuum desiccator for 2 hours to completely distill off chloroform. Add this to water 20rn1. was added and hydrated at 40°C for 30 minutes, followed by vigorous shaking using a portex mixer to form liposomes. After cooling, p+ was adjusted to 7.60±0. using IN sodium hydroxide.
05 to obtain the desired liposome solution.

Example 2 A liposome solution was produced in the same manner as in Example 1 except that 0.02 g of rutin was added.

Example 3 6.3 g of concentrated glycerin was heated to 75-80° C., and 1.55 g of partially hydrogenated lecithin and 109 μm of dicetyl phosphate were added thereto and stirred to uniformly swell. 0 for this
．． 0.01% aqueous kojic acid solution (200ml) was added and the mixture was further swollen at 60°C for 3 minutes. Finally, this solution was stirred for 3 minutes using a homomixer while keeping it at 60°C, then returned to room temperature, and the pH was adjusted to 7.60 ± 0.05 with IN sodium hydroxide to obtain the desired Lipotum solution. .

Example 4 A liposome solution was produced in the same manner as in Example 3, except that oil-soluble licorice extract was mixed with concentrated glycerin together with phospholipids.

Comparative Example Instead of cephalanthine in Example 1, berberine hydrochloride, I)-(
+)-Liposome solutions were prepared with or without catechin or quercetin.

Test Example The liposome solutions produced in Examples 1 to 4 and Comparative Examples were
It was stored at 0°C for 2 months and evaluated for pH changes and system stability. The results are shown in Table 1.

Below margin = 9-n Table 1 As is clear from Table 1, the liposome solution of the present invention is
No significant p++ decrease occurred over time, and the stability was also excellent.

Example 5 Lotion: (Ingredients) (%) (1
) Hydrogenated soybean lecithin 1.5 (2)
Squalane 0.2 (3) Chrycerin 50 (4)
1.3--butylene glycol 1.50 (5
) Methylparaben 01(6) Sodium pyrrolidone carboxylate 01(7) Collagen hydrolyzate 0.01(8) Di'Udic acid 01(9) Purified water Remainder (6゜(Production method) 8. Components (1) to (5) ) is heated and dissolved.

Mix and stir C1 components (6) to (9).

[Add day to A and mix evenly to obtain lotion).

The conversion product of the present invention obtained as described below 1. Immediately after production, the pl+ was 7.6, and after storage at 40°C for 2 months, the pn was 117.1, with no significant pn decrease over time, and it was excellent in stability.

Furthermore, when this lotion was examined for inhibition of dirosinase activity by B1.6 melanoma cells, a synergistic inhibitory effect was observed compared to a product containing kojic acid alone.

Example 6 Beauty serum (ingredients) (%) 1 2 (1) Hydrogenated egg yolk lecithin 18 (2
) Liquid paraffin 05 (3) Cephalanthine ol (4) Keso extract (oil-soluble) o, 1 (5) Fragrance 0.1 (
6) Glycerin 5.0 (7
) Polyethylene glycol 15 [1(
8) Carboxyvinyl polymer 0. ](9
) Sodium hydroxide 060100
Keltrol 0100 Purified Water Remaining Amount (Production Method) A. Heat and dissolve components (1) to (5).

B. Mix and stir components (6) to θD.

B was added to C and A and mixed uniformly to obtain a serum.

The serum of the present invention obtained as described above has a pH of 7.5 immediately after production, and after storage at 40°C for 2 months, it has a pH of 7.5 (pH 7.5).
, (1), there was no significant decrease in 29N over time, and the stability was excellent.

〔Effect of the invention〕

As detailed above, according to the present invention, it is possible to obtain liposomes and phospholipid limb fluids that do not cause a decrease in pH over time and are stable for a long period of time. It can be stably incorporated into foods, etc., and the effects of liposomes and phospholipids can be fully exhibited.

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Claims (1)

[Scope of Claims] 1. A method for stabilizing liposomes or phospholipid dispersions, which comprises blending one or more selected from cephalanthine, rutin, licorice extract, and kojic acid. 2. A stabilized phospholipid dispersion containing phospholipids and one or more selected from cephalanthine, rutin, licorice extract, and kojic acid. 3. A stabilized liposome dispersion containing one or more selected from cephalanthine, rutin, licorice extract, and kojic acid. 4. Phospholipid dispersion according to claim 2 and/or claim 3
A cosmetic containing the liposome dispersion described above.