Cochelates using phosphatidylserine/anionic surfactant/calcium chloride

Abstract

The present invention relates to cochleates using phosphatidylserine/anionic surfactant/calcium chloride and, more specifically, to cochleates comprising phosphatidylserine, an anionic surfactant, calcium chloride, an active ingredient, and water.

Claims

1. A cochleate consisting essentially of 0.1 to 20% by weight of phosphatidylserine, 0.001 to 5% by weight of anionic surfactant, 0.0001 to 2% by weight of calcium chloride, 0.0005 to 50% by weight of an active ingredient and 30 to 96% by weight of water, wherein the anionic surfactant is selected from the group consisting of sodium stearoyl glutamate, disodium stearoyl glutamate, sodium lauryl glucose carboxylate and sodium methyl cocoyl taurate, and wherein the cochleate does not contain a lipid other than phosphatidylserine.

2. The cochleate according to claim 1, which consists essentially of 0.5 to 18% by weight of phosphatidylserine, 0.01 to 3% by weight of anionic surfactant, 0.0005 to 1.8% by weight of calcium chloride, 0.001 to 45% by weight of the active ingredient and 40 to 95% by weight of water.

3. The cochleate according to claim 2, which consists essentially of 1 to 15% by weight of phosphatidylserine, 0.1 to 2% by weight of anionic surfactant, 0.001 to 1.5% by weight of calcium chloride, 0.002 to 40% by weight of the active ingredient and 50 to 94% by weight of water.

4. The cochleate according to claim 1, wherein the anionic surfactant is sodium stearoyl glutamate.

5. The cochleate according to claim 1, wherein the active ingredient is one or more selected from the group consisting of a moisturizer, a whitening agent, an anti-wrinkle agent, a UV blocking agent, a hair growth promoter, vitamin or a derivative thereof, amino acid or peptide, an anti-inflammatory agent, an acne therapeutic agent, a microbicide, female hormone, a keratolytic agent and a natural product.

6. The cochleate according to claim 5, wherein the moisturizer is one or more selected from the group consisting of creatine, polyglutamic acid, sodium lactate, hydroproline, 2-pyrrolidone-5-carboxyclic acid sodium salt, hyaluronic acid, sodium hyaluronate, ceramide, phytosteryl, cholesterol, sitosterol, pullulan and proteoglycan.

7. The cochleate according to claim 5, wherein the whitening agent is one or more selected from the group consisting of arbutin and a derivative thereof, kojic acid, bisabolol, niacinamide, vitamin C and a derivative thereof, placenta and allantoin.

8. The cochleate according to claim 5, wherein the anti-wrinkle agent is one or more selected from the group consisting of retinol, a retinol derivative, adenosine, licorice extract, red ginseng extract and ginseng extract.

9. The cochleate according to claim 5, wherein the UV blocking agent is one or more selected from the group consisting of benzophenone derivative, para-aminobenzoic acid derivative, methoxycinnamic acid derivative and salicylic acid derivative.

10. The cochleate according to claim 5, wherein the hair growth promoter is a blood circulation promoter or a hair follicle stimulant.

11. The cochleate according to claim 10, wherein the blood circulation promoter is one or more selected from the group consisting of an extract of Swertia japonica Makino, cepharanthin, vitamin E and a derivative thereof, and gamma-oryzanol.

12. The cochleate according to claim 10, wherein the hair follicle stimulant is one or more selected from the group consisting of capsicum tincture, ginger tincture, cantharides tincture and nicotinic acid benzyl ester.

13. The cochleate according to claim 5, wherein the vitamin or a derivative thereof is one or more selected from the group consisting of vitamin A and a derivative thereof, vitamin B1, vitamin B2, vitamin B6, vitamin E and derivatives thereof, vitamin D, vitamin H, vitamin K, pantothenic acid and derivatives thereof, biotin, panthenol, coenzyme Q.sub.10 and idebenone.

14. The cochleate according to claim 5, wherein the amino acid or peptide is one or more selected from the group consisting of cysteine, methionine, serine, lysine, tryptophan, amino acid extract, epidermal growth factor (EGF), insulin-like growth factor (IGF), fibroblast growth factor (FGF), copper tripeptide-1, tripeptide-29, tripeptide-1, acetyl hexapeptide-8, nicotinoyl tripeptide-35, hexapeptide-12, hexapeptide-9, palmitoyl pentapeptide-4, palmitoyl tetrapeptide-7, palmitoyl tripeptide-29, palmitoyl tripeptide-1, nonapeptide-7, tripeptide-10 citrulline, sh-polypeptide-15, palmitoyl tripeptide-5, diaminopropionoyl tripeptide-33 and r-spider polypeptide-1.

15. The cochleate according to claim 5, wherein the anti-inflammatory agent is one or more selected from the group consisting of beta-glycyrrhetinic acid, glycyrrhetinic acid derivative, aminocaproic acid, hydrocortisone, β-glucan and licorice.

16. The cochleate according to claim 5, wherein the acne therapeutic agent is one or more selected from the group consisting of estradiol, estrogen, ethinyl estradiol, triclosan and azelaic acid.

17. The cochleate according to claim 5, wherein the microbicide is one or more selected from the group consisting of benzalkonium chloride, benzethonium chloride and halocalban.

18. The cochleate according to claim 5, wherein the female hormone is one or more selected from the group consisting of estradiol, ethinyl estradiol and isoflavone.

19. The cochleate according to claim 5, wherein the keratolytic agent is one or more selected from the group consisting of sulfur, salicylic acid, alpha-hydroxy acid (AHA), beta-hydroxy acid (BHA), and resorcin.

20. The cochleate according to claim 5, wherein the natural product is one or more selected from the group consisting of an extract of Japanese witch-hazel, an extract of Lamium album var. barbatum, an extract of Hedyotis diffusa, an extract of Rheum palmatum, an extract of licorice, an extract of aloe, an extract of chamomile, an extract of rose hip, an extract of horse chestnut, an extract of ginseng, an extract of Luffa aegyptiaca, an extract of cucumber, an extract of laver, an extract of sea mustard, an extract of Dioscorea batatas, an extract of snail, an extract of fruit of Dioscorea polystachya, hinokitiol and beta-carotene.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is an electron microscopy photograph of cochleate.

(2) FIG. 2 is a schematic diagram representing the structure of cochleate.

(3) FIG. 3 is a result of measuring the diameter of cochleate by the use of Photal ELS-Z.

(4) FIG. 4 is a cryo-electron microscopy photograph of particles of cochleates.

(5) FIG. 5 is a result of measuring zeta potential by the use of Photal ELS-Z to measure the stability of cochleate.

(6) FIG. 6 is a result of measuring the stability of cochleate by the use of Turbiscan.

DETAILED DESCRIPTION

(7) Hereinafter, the present invention is explained in more detail with the following examples. However, it must be understood that the protection scope of the present invention is not limited to the examples.

Examples 1 to 18: Preparation of Cochleate Containing Various Active Ingredients

(8) According to the constitutional compositions of Tables 1 to 18, cochleates were prepared by continuously passing the ingredients five (5) times through a high-pressure microfluidizer at 1,000 bar.

Example 1: Preparation of Cochleate Containing Plant Natural Product

(9) TABLE-US-00001 TABLE 1 Ingredient Content (% by weight) Phosphatidylserine 3 Sodium stearoyl glutamate 0.5 Calcium chloride 0.1 Ginkgo leaf extract 20 Distilled water 76.4 Total amount 100

Example 2: Preparation of Cochleate Containing Marine Natural Product

(10) TABLE-US-00002 TABLE 2 Ingredient Content (% by weight) Phosphatidylserine 3 Sodium stearoyl glutamate 0.5 Calcium chloride 0.1 Kelp extract 10 Distilled water 86.4 Total amount 100

Example 3: Preparation of Cochleate Containing Oil

(11) TABLE-US-00003 TABLE 3 Ingredient Content (% by weight) Phosphatidylserine 5 Sodium stearoyl glutamate 0.6 Calcium chloride 0.05 Olive oil 20 Camellia oil 2 Macadamia nut oil 2 Castor oil 2 Sunflower oil 2 Jojoba oil 2 Almond oil 2 Apricot seed oil 2 Green tea oil 2 Meadowfoam seed oil 2 Argan oil 2 Distilled water 72.35 Total amount 100

Example 4: Preparation of Cochleate Containing Wax

(12) TABLE-US-00004 TABLE 4 Ingredient Content (% by weight) Phosphatidylserine 2 Sodium stearoyl glutamate 0.1 Calcium chloride 0.05 Beeswax 5 Candelilla wax 5 Distilled water 87.85 Total amount 100

Example 5: Preparation of Cochleate Containing Butter

(13) TABLE-US-00005 TABLE 5 Ingredient Content (% by weight) Phosphatidylserine 6 Sodium stearoyl glutamate 0.8 Calcium chloride 0.001 Shea butter 5 Mango butter 5 Green tea butter 5 Distilled water 78.199 Total amount 100

Example 6: Preparation of Cochleate Containing Paraffin

(14) TABLE-US-00006 TABLE 6 Ingredient Content (% by weight) Phosphatidylserine 3 Sodium stearoyl glutamate 0.5 Calcium chloride 0.1 Paraffin 20 Distilled water 76.4 Total amount 100

Example 7: Preparation of Cochleate Containing Higher Fatty Acid

(15) TABLE-US-00007 TABLE 7 Ingredient Content (% by weight) Phosphatidylserine 1 Sodium stearoyl glutamate 0.1 Calcium chloride 0.1 Stearic acid 6 Distilled water 92.8 Total amount 100

Example 8: Preparation of Cochleate Containing Ester

(16) TABLE-US-00008 TABLE 8 Ingredient Content (% by weight) Phosphatidylserine 8 Sodium stearoyl glutamate 0.9 Calcium chloride 0.5 Cetyl ethylhexanoate 20 Distilled water 70.6 Total amount 100

Example 9: Preparation of Cochleate Containing Silicone

(17) TABLE-US-00009 TABLE 9 Ingredient Content (% by weight) Phosphatidylserine 6 Sodium stearoyl glutamate 0.1 Calcium chloride 0.4 Dimethicone 30 Distilled water 63.5 Total amount 100

Example 10: Preparation of Cochleate Containing Moisturizer

(18) TABLE-US-00010 TABLE 10 Ingredient Content (% by weight) Phosphatidylserine 5 Sodium stearoyl glutamate 0.5 Calcium chloride 0.1 Ceramide 5 Hyaluronic acid 0.5 Polyglutamic acid 0.1 Proteoglycan 0.0001 Distilled water 88.7999 Total amount 100

Example 11: Preparation of Cochleate Containing Whitening Agent

(19) TABLE-US-00011 TABLE 11 Ingredient Content (% by weight) Phosphatidylserine 6 Sodium stearoyl glutamate 0.7 Calcium chloride 1 Arbutin 20 Distilled water 72.3 Total amount 100

Example 12: Preparation of Cochleate Containing UV Blocking Agent

(20) TABLE-US-00012 TABLE 12 Ingredient Content (% by weight) Phosphatidylserine 8 Sodium stearoyl glutamate 1 Calcium chloride 0.15 Octyl methoxycinnamate 20 Distilled water 70.85 Total amount 100

Example 13: Preparation of Cochleate Containing Vitamin

(21) TABLE-US-00013 TABLE 13 Ingredient Content (% by weight) Phosphatidylserine 5 Sodium stearoyl glutamate 0.8 Calcium chloride 0.5 Macadamia nut oil 10 Vitamin A (retinol) 5 Distilled water 78.7 Total amount 100

Example 14: Preparation of Cochleate Containing Amino Acid and Peptide

(22) TABLE-US-00014 TABLE 14 Ingredient Content (% by weight) Phosphatidylserine 5 Sodium stearoyl glutamate 0.7 Calcium chloride 0.3 Cysteine 10 Epidermal growth factor (EGF) 0.0001 Insulin-like growth factor (IGF) 0.001 Distilled water 83.9989 Total amount 100

Example 15: Preparation of Cochleate Containing Peptide

(23) TABLE-US-00015 TABLE 15 Ingredient Content (% by weight) Phosphatidylserine 5 Sodium stearoyl glutamate 0.7 Calcium chloride 0.3 Palmitoyl pentapeptide-3 0.0001 Hexapeptide-9 0.001 Palmitoyl tetrapeptide-7 0.00001 Nonapeptide-7 0.0001 Dipeptide-8 0.001 Distilled water 93.99779 Total amount 100

Example 16: Preparation of Cochleate Containing Anti-Inflammatory Agent

(24) TABLE-US-00016 TABLE 16 Ingredient Content (% by weight) Phosphatidylserine 8 Sodium stearoyl glutamate 0.5 Calcium chloride 0.3 Hydrocortisone 5 Distilled water 86.2 Total amount 100

Example 17: Preparation of Cochleate Containing Acne Therapeutic Agent

(25) TABLE-US-00017 TABLE 17 Ingredient Content (% by weight) Phosphatidylserine 3 Sodium stearoyl glutamate 0.7 Calcium chloride 0.3 Azelaic acid 20 Distilled water 76 Total amount 100

Example 18: Preparation of Cochleate Containing Microbicide

(26) TABLE-US-00018 TABLE 18 Ingredient Content (% by weight) Phosphatidylserine 10 Sodium stearoyl glutamate 0.7 Calcium chloride 0.5 Halocalban 30 Distilled water 58.8 Total amount 100

Comparative Example: Preparation of General Liposome Containing Retinol

(27) According to the constitutional composition of Table 19, the ingredients were introduced into a vessel. The resulting mixture was continuously passed five (5) times through a high-pressure microfluidizer at 1,000 bar, followed by cooling and deaeration to obtain liposome.

(28) TABLE-US-00019 TABLE 19 Ingredient Content (% by weight) Saturated lecithin 3 Sodium stearoyl glutamate 0.8 Macadamia nut oil 10 Retinol 5 Distilled water 81.2 Total amount 100

Experimental Example 1: Measurement of Particle Size Distribution

(29) The particle size distribution of the cochleates prepared in Example 2 was measured by the use of Photal ELS-Z, and the result is represented in FIG. 3. From the result of the measurement, it can be known that the average particle size of the cochleates is 359.3 nm.

Experimental Example 2: Cryo-Electron Microscopy

(30) Photographs of the cochleates prepared in Example 2 were taken. Due to very fine particle size, it was impossible to take photographs by a general optical microscope. Therefore, cryo-electron microscopy photographs (JEM 1010, JEOL Ltd., Japan) were taken (FIG. 4). From FIG. 4, it can be known that the cochleates are well formed.

Experimental Example 3: Measurement of Stability of Cochleate

(31) To measure the stability of the cochleates prepared in Example 2, zeta potential was measured by the use of Photal ELS-Z. From the result of the measurement, it can be known that the potential of particle is −75.36 mV, and the cochleates are stable (FIG. 5).

Experimental Example 4: Measurement of Stability of Cochleate

(32) The stability of the cochleates prepared in Example 2 was measured by the use of Turbiscan. As a result, the stability of the cochleates was confirmed (FIG. 6).

Experimental Example 5: Test for Promoting Transdermal Absorption

(33) The artificial skin, Neoderm (Tego Science, Korea) was mounted to a Franz-type diffusion cell (Lab Fine Instruments, Korea). 50 mM phosphate buffer (pH 7.4, 0.1M NaCl) was added to a receptor cell (5 ml) of the Franz-type diffusion cell. A diffusion cell was then mixed and diffused at 600 rpm, 32° C., and 50 μl of the cochleate containing retinol prepared in Example 13 and the liposome of the Comparative Example, respectively, were added to donor cells. Absorption and diffusion were carried out according to the predetermined time, and the area of the skin where the absorption and diffusion were carried out was 0.64 cm.sup.2. After finishing the absorption and diffusion of the active ingredient, the residues-which were not absorbed and remained on the skin-were cleaned with dried Kimwipes™ or 10 ml of ethanol. The skin in which the active ingredient was absorbed and diffused was homogenized by the use of a tip-type homogenizer, and retinol absorbed into the skin was then extracted with 4 ml of dichloromethane. The extract was then filtrated with a 0.45 μm nylon membrane filter. The content was measured by high-performance liquid chromatography with the following conditions, and the results are represented in Table 20.

(34) TABLE-US-00020 TABLE 20 Transdermal absorption (μg) Rate of increase Cochleate of 0.3888 16.82% Example 13 Liposome of 0.2312 — Comparative Example A) Column: C18 (4.6 × 200 mm, 5 μm) B) Mobile phase: methanol:hexane = 2:1 C) Flow rate: 0.8 ml/min D) Detector: UV 275 nm