KR101527580B1 - Multi-layered lamellar granule and skin external application composition containing same - Google Patents

Abstract

The present invention relates to a multilayer lamellar granule and a composition for external application for skin containing the same, which comprises a nucleating agent, a pseudomorpholipidic lamellar layer present on the nucleating agent and containing a ceramide and a phospholipid, and a polymer layer on the pseudomorphic lipid lamellar layer The composition for external application for skin containing multilayer lamellar granules according to the present invention exhibits excellent moisturizing effect and barrier function healing effect when applied to skin.

Lamellar, similar keratin lipids, ceramides, phospholipids, fatty acids, cholesterol, molecular fixatives, barrier

Description

TECHNICAL FIELD [0001] The present invention relates to a multi-layer lamellar granule and a skin topical composition containing the same. [0002] MULTI-LAYERED LAMELER GRANULE AND SKIN EXTERNAL APPLICATION COMPOSITION CONTAINING SAME [0003]

The present invention relates to a multilayer lamellar granule which provides excellent moisturizing effect and barrier function (exfoliation function) healing effect when applied to skin, and a composition for external application for skin containing the multilayer lamellar granule.

The skin is largely divided into three layers: epidermis, dermis, and subcutaneous tissue in order from the outside. It functions to protect the internal organs of the body from changes in temperature and humidity, ultraviolet rays, and other physical and chemical external stimuli. In particular, the epidermis plays an important role in preventing water evaporation inside the human body. The epidermis is divided into the stratum corneum, granular layer, the superficial layer and the basal layer in order from the outside. Cells of the stratum corneum act like bricks, and interstitial lipids between keratinocytes act like mortar to constitute skin barrier (J. Invest. Dermatol 80 (Suppl.), 44-49, 1983). In addition, healthy keratinocytes contain a high concentration of natural moisturizing factor (NMF), which helps to retain moisture in the skin. For example, substances such as amino acids are water-soluble, (J. Invest. Dermatol. 54, 24-31, 1970).

However, as it is nowadays, there is a tendency to control the temperature of the air / heating due to changes in environment or life patterns, skin stress due to various stresses and environmental pollution occurring in the social life, frequent washing according to makeup habits, Due to various causes such as aging of skin and the like, moisture of the stratum corneum decreases, and the skin becomes dry, the surface becomes rough, the skin becomes loose, the luster is lost and the skin looks dull, and the necessity of the skin moisturizing agent is increased have.

Conventionally, a method of increasing moisture retention in the stratum corneum has been performed by using an occlusive moisturizer such as humectant or oil, wax or the like, which has a property of absorbing moisture for such a moisturizing function. Examples of the humectant include glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, sodium 2-pyrrolidone-5-carboxylate and the like. However, such a moisturizing raw material has a disadvantage that the ability to contain moisture is good, but the persistence to moisture is low. Moreover, in a dry environment, it can absorb moisture in the skin and make the skin more dry.

Another approach is to incorporate niacinamide, which enhances skin barrier function and promote homeostasis of skin, by promoting the expression of ceramide, pilar green and the like in external preparations for skin or introducing ceramide directly into external preparations for skin . These approaches are favored in recent years as a technique that helps to maintain homeostasis and is a fundamental approach to moisturizing (J. Invest. Dermatol. (5), 731-740, 1994) Ceramides are poorly soluble crystalline materials, and when they are incorporated in cosmetic formulations in large quantities, the amount of surfactant, oil, and other additives used increases, making it difficult for the stratum corneum components to form a structure similar to the skin stratum corneum. In addition, ceramides are easily gelated to reduce the stability of cosmetic formulations and thus have limitations in their use in amounts of 1% by weight or more.

Accordingly, it is an object of the present invention to provide a multilayer lamellar granule comprising a pseudomorphic lipid lamellar layer which is excellent in formulation stability and does not cause gelation and exhibits a structure similar to a stratum corneum layer.

Another object of the present invention is to provide a composition for external application for skin which contains the multilayered lamellar granules and exhibits excellent moisturizing effect and barrier function healing effect when applied to skin.

To achieve the above object, the present invention provides a multilayered lamellar granule comprising a nucleating agent, a pseudomorphic lipid lamellar layer present on the nucleating agent and containing ceramide and a phospholipid, and a polymer layer on the pseudomorphic lipid lamellar layer do.

In the multilayer lamellar granule of the present invention, the nucleating agent may be selected from the group consisting of sugar, salt, hyaluronic acid, alginic acid, chondroitin sulfate, chitosan, chitin, polylysine, collagen, gelatin, stearic acid, cetyl alcohol, stearyl alcohol, And the nucleating agent may be contained in an amount of 1 to 99% by weight based on the total weight of the multilayer lamellar granule.

The ceramide of the pseudomorpholine lamellar layer may be at least one selected from the group consisting of natural ceramide and pseudamide ceramide.

The phospholipid of the pseudomorpholine lipid layer may be selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylisoside, phosphatidic acid, and mixtures thereof.

The pseudomorphic lipid lamellar layer may contain ceramide and phospholipid in a weight ratio of 1: 0.1 to 1: 1.

In addition, the pseudomorphic lipid lamellar layer may be contained in an amount of 0.00001 to 99 wt% based on the total weight of the multi-layer lamellar granule.

The pseudomorpholine lipid layer may further comprise fatty acids, cholesterol or derivatives thereof, alcohols, molecular anchoring agents, or mixtures thereof, wherein the fatty acid is an unsaturated or saturated fatty acid having from 8 to 30 carbon atoms Wherein the cholesterol or derivative thereof is selected from the group consisting of cholesterol, cholesteryl chloride, cholesteryl octanoate, cholesteryl nonanoate, cholesteryl isoleuconate, cholesteryl isostearyl carbonate and mixtures thereof And the alcohol is an unsaturated or saturated alcohol having 8 to 30 carbon atoms, and the molecular fixer is a hydrophobic group having an alkyl or alkenyl group having 12 to 20 carbon atoms as a hydrophobic group and a succinimidyl ester as a hydrophilic group , Preferably [oleyloxy-poly (ethylene glycol) _n -succinyl-N- Idroxy succinimidyl ester] (n is an integer of 2 to 100). Preferably, the pseudomorpholine lipid layer comprises 1 to 50 parts by weight, 1 to 50 parts by weight, 1 to 50 parts by weight of a fatty acid, a cholesterol or a derivative thereof, an alcohol and a molecular fixer, based on 100 parts by weight of the ceramide, In an amount of 1 to 50 parts by weight.

In the multilayer lamellar granule of the present invention, the polymer layer may be contained in an amount of 0.01 to 90% by weight based on the total weight of the multilayer lamellar granule.

The multilayer lamellar granules of the present invention can be produced in a fluidized bed coater.

According to another aspect of the present invention, there is provided a composition for external application for skin comprising multilayer lamellar granules as described above.

In the composition for external application for skin of the present invention, the granules may be contained in an amount of 0.01 to 99% by weight based on the total weight of the composition.

The composition for external application for skin may be a cosmetic composition or a pharmaceutical composition.

The multilayer lamellar granule according to the present invention includes a pseudomorpholipidic lamellar layer simulating the components of the skin surface lipid (stratum corneum), which is the outermost layer of the skin, in the granule so that contact with oil, surfactant, A lamellar structure similar to the stratum corneum can be stably maintained. Accordingly, the composition for external application for skin containing multilayer lamellar granules of the present invention is excellent in formulation stability and exhibits excellent moisturizing effect and barrier function-treating effect upon application to skin without causing gelation, and thus can be usefully used in cosmetics and pharmaceuticals.

The present invention provides multilayer lamellar granules comprising a nucleating agent, a pseudomorphic lipid lamellar present on the nucleating agent and containing a ceramide and a phospholipid, and a polymer layer on the pseudomorphic lipid lamellar layer.

The nucleating agent used in the present invention is a colloid which is inactive and easily dissolves into external stimuli such as sugar, salt, hyaluronic acid, alginic acid, chondroitin sulfate, chitosan, chitin, polylysine, collagen, gelatin, stearic acid, Cetyl alcohol, stearyl alcohol, and mixtures thereof.

Such nucleating agents may be used in an amount of from 1 to 99% by weight based on the total weight of the multilayer lamellar granules. When the amount of the nucleating agent is used within the above range, not only the coagulation phenomenon that may occur during the coating of the pseudomorphic lipid layer, the polymer layer, and the like on the surface of the nucleating agent can be reduced and the coating rate can be increased, The structural stability of the lamellar granules can be improved.

A pseudomorphic lipid lamellar layer is located on the nucleating agent as described above. The stratum corneum of human skin consists of keratinocyte and intercellular lipid, and functions as skin barrier. The core function of this barrier function is intercellular lipid, and it has a lamellar structure of multilayer structure. The simulated keratinous lipid lamella layer, which is simulated substantially similar to the structure of intercellular lipids with lamellar structure.

The pseudomorphic lipid lamellar layer essentially comprises ceramides and phospholipids, and may further comprise fatty acids, cholesterol or derivatives thereof, alcohols, molecular anchoring agents or mixtures thereof, in addition to the above ceramides and phospholipids. have.

The ceramides contained in the pseudomorphic lipid lamellar layer as described above encompass both natural ceramides and pseudoceramides.

The natural ceramide may be at least one selected from the group consisting of ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6, ceramide 7, and ceramide 8.

Pseudoceramide is a synthetic substance having properties similar to those of natural ceramide, such as skin protecting action, water retention ability, etc., and may be selected from at least one of the compounds represented by the following formulas (1) to (6) It is not.

(Wherein,

R is C _{9 -} a saturated or unsaturated aliphatic chain of C _21),

(Wherein,

n is 1 or 2;

R and R 'are C _{9 -} a saturated or unsaturated aliphatic chain of C _21),.

(Wherein,

m and n are the same or different and are an integer of 1 to 3;

k and l are the same or different and are 1 or 2;

j is 0 or 1;

R and R 'are the same or different, which does not contain or contains a hydroxy group, C _{1 -} C ₃₁ straight chain or a branched-chain saturated or unsaturated alkyl group;

A ¹ , A ² and A ³ are the same or different and are hydrogen or any substituent of the following structure, provided that A ¹ , A ² and A ³ are simultaneously hydrogen:

Wherein M, M ¹ and M ² are selected from the group consisting of alkali metals, lysine, arginine, histidine, triethanolamine, ammonia, polyquaternium-4, polyquaternium-6, polyquaternium- , Polyquaternium-11, polyquaternium-16, lauryldimethylbenzylammonium chloride and stearyldimethylbenzylammonium chloride, and L is an alkaline earth metal,

(Wherein,

R and R 'are the same or different, which does not contain or contains a hydroxy group, C _{10 -} C ₃₂ linear or branched and saturated or unsaturated alkyl group;

R ³ and R ⁴ are the same or different, hydrogen or a C _{1 -} C ₄ alkyl group or hydroxy alkyl group of;

R ⁵ is -CH ₂ CH ₂ OA or a substituent of the following structure:

,

,

,

,

및

,

,

,

,

And

Wherein M, M ¹ and M ² are selected from the group consisting of alkali metals, lysine, arginine, histidine, triethanolamine, ammonia, polyquaternium-4, polyquaternium-6, polyquaternium- L is selected from the group consisting of polyquaternium-11, polyquaternium-16, lauryldimethylbenzylammonium chloride and stearyldimethylbenzylammonium chloride, and L is an alkaline earth metal)

(Wherein,

m and n are the same or different and are an integer of 1 to 4;

R and R 'are the same or different and are a linear or branched, saturated or unsaturated alkyl group of C ₁ -C ₃₁ , which contains or does not contain a hydroxyl group;

A ₁ and A ₂ are the same or different and each represent hydrogen or a substituent having the following structure:

,

,

,

,

및

,

,

,

,

And

Wherein M, M ¹ and M ² are an alkali metal or an organic base containing nitrogen and L is an alkaline earth metal,

(Wherein,

m and n are the same or different and are an integer of 1 to 3;

k and l are the same or different and are 1 or 2;

j is 0 or 1;

A ¹ , A ² and A ³ are the same or different and each is hydrogen or any one of substituents having the following structure:

,

,

및

,

,

And

Wherein M, M ¹ and M ² are an alkali metal or an organic base containing nitrogen and L is an alkaline earth metal;

R is a substituent having the structure:

[Wherein, B is a methyl group in the 5-, 7- or 8- position of tocopherol, m is an integer from 1 to 3, D is -CH ₂ (CH ₃₎ -CH- or -CH (CH ₃₎ = C-).

The above-mentioned compounds of the formulas (1) to (6) have excellent effects on skin moisturizing and skin barrier function recovery, and are commercially available as ceramide PC104, PC102, PC107 and the like.

In addition, the phospholipid contained in the pseudomorphic lipid lamellar layer significantly contributes to the stabilization of the ceramide, thereby suppressing the gelation of the ceramide. The phospholipid used in the present invention is produced by extracting from plant, soybean, egg or the like, or further purified therefrom, and is a species having a fatty acid chain having 12 to 24 carbon atoms. Specific examples thereof include phosphatidylcholine, phosphatidylethanolamine, Phosphatidylserine, phosphatidylglycerol, phosphatidylisoside, phosphatidic acid, and mixtures thereof. Preferably, the phospholipid used in the present invention is a mixture of saturated lecithin and unsaturated lecithin, which is extracted from soybean and contains 20 to 99% by weight of unsaturated lecithin having a phosphatidylcholine content of 10 to 99% by weight.

The pseudomorphic lipid lamellar layer may contain ceramide and phospholipid in a weight ratio of 1: 0.1 to 1: 1.

As the fatty acid contained in the pseudomorpholine lamellar layer, for example, unsaturated or saturated fatty acids having 8 to 30 carbon atoms may be used, and examples of the alcohol include unsaturated or saturated alcohols having 8 to 30 carbon atoms.

In addition, examples of the cholesterol or derivatives thereof contained in the pseudomorpholine lipid layer include cholesterol, cholesteryl chloride, cholesteryl octanoate, cholesteryl nonanoate, cholesteryl oleyl carbonate, cholesteryl Isostearyl carbonate, and mixtures thereof.

Pseudomorphic lipid The molecular anchoring agent contained in the lamellar layer chemically binds the lipid structure and the protein on the skin, thereby maintaining the lipid structure on the skin for a long time. The molecular fixer that can be used in the present invention is a substance having an alkyl or alkenyl group having 12 to 20 carbon atoms as a hydrophilic group and having a succinimidyl ester as a hydrophilic group and is preferably a [oleyloxy-poly (ethylene glycol) _n- -N-hydroxysuccinimidyl ester] (n is an integer of 2 to 100, more preferably an integer of 10 to 80).

Preferably, the pseudomorpholine lipid layer comprises 1 to 50 parts by weight, 1 to 50 parts by weight, 1 to 50 parts by weight of a fatty acid, a cholesterol or a derivative thereof, an alcohol and a molecular fixer, based on 100 parts by weight of the ceramide, In an amount of 1 to 50 parts by weight.

Such quasi- The lipid lamellar layer may be used in an amount of, for example, 0.00001 to 99 wt% based on the total weight of the multilayer lamellar granules of the present invention.

The polymer layer is located on the pseudomorphic lipid lamella layer as described above. The polymer layer surrounds the pseudomorphic lipid layer and protects the pseudomorphic lamellar layer, which greatly improves the structural stability of the multilamellar granule.

The polymer layer is not particularly limited as long as it is not easily dissolved in a solvent, for example, water or an organic solvent having polarity, and can be uniformly coated on the surface of a pseudomorphic lipid lamellar layer. The polymer layer may be a natural polymer, And may be a mixture of a natural polymer and a synthetic polymer.

Natural polymers constituting the polymer layer include, for example, hyaluronic acid, alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, chitin, polylysine, collagen and fibrin.

Polyethylene glycol-polylactic acid-polyethylene glycol (PEG-PLA-PEG), polyethylene glycol-poly (lactic-coglycolic acid) -polyethylene glycol (PEG-PLGA-PEG), and the like are examples of synthetic polymers constituting the polymer layer. (PEG-PCL-PEG), polyethylene-bis- (polylactic acid-acrylate) and phosphorus (isopropylacrylamide-co-acrylic acid), polyethylene glycol-polycaprolactone-polyethylene glycol .

(Polyethylene glycol-co-peptide), alginate-g- (polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO)), and the mixture of natural polymers and synthetic polymers constituting the polymer layer ), Phosphorus (poly (lactic-coglycolic acid) -co-serine), collagen-acrylate and alginate. Further, biodegradable hydrophobic aliphatic polyesters can be used as the above-mentioned polymers. Examples thereof include poly-L-lactic acid, poly-D, L-glycolic acid, poly-L- - copolymers made from lactic acid-co-glycolic acid, polycaprolactone, polyvalerolactone, polyhydroxybutyrate, polyhydroxyvalerate, polyorthoesters and monomers thereof, and mixtures thereof .

Examples of the polymer usable in the present invention include polystyrene, poly p- or m-methyl styrene, poly p- or m-ethyl styrene, poly p- or m-chlorostyrene, poly p- or m- (Meth) acrylate, poly (meth) acrylate, poly (n-butyl) (meth) acrylate, styrene sulfonic acid, poly p- or m- or t-butoxystyrene, polymethyl (Meth) acrylate, poly (isobutyl) (meth) acrylate, poly (t-butyl) (Meth) acrylate, methoxypolyethylene glycol (meth) acrylate, polyglycidyl (meth) acrylate, polyoxyethylene (meth) acrylate, Polydimethylaminoethyl (meth) acrylate (Meth) acrylate, poly (meth) acrylate, poly (meth) acrylate, polyvinyl acetate, polyvinyl butyrate, polyvinyl butyrate, polyvinyl ether, polyallyl butyl ether, polyallyl glycidyl ether, Unsaturated carboxylic acids such as maleic acid, polyalkyl (meth) acrylamide, and poly (meth) acrylonitrile.

The polymer layer may be used in an amount of 0.01 to 90% by weight based on the total weight of the multi-layer lamellar granule. When the amount of the polymer layer is used within the above range, the stability of the multilayered lamellar granule can be enhanced, and when the multilayer lamellar granule as the final product is applied to external preparations for skin such as cosmetics, a foreign body feeling is prevented.

The multilayer lamellar granules according to the present invention can be prepared by various coating methods, and preferably, for example, by using a fluidized bed coating method using a fluidized bed coater.

This will be described in more detail as follows.

First, the nucleating agent is put into a fluidized bed coater and vortexed.

Next, the surface of the vortexed nucleating agent is first spray-coated with a solution of a pseudomorphic lipid lamellar blend containing ceramides and phospholipids under a room temperature depressurized condition, followed by drying to form a pseudomorphic lipid lamella layer on the surface of the nucleating agent. At this time, other arbitrary components may be added to the solution together with the spray coating, and the ceramide and the phospholipid may be separately prepared as separate solutions and spray-coated sequentially. When using separate ceramide and phospholipid solutions, the optional components may be added in any solution.

The solvent for dissolving the pseudomorphic lamellar blend is volatile and is not particularly limited as long as it can dissolve the pseudomorphic lipid components.

The solvent used in the above process is any chemical substance capable of dissolving the selected keratinous lipid components. Specific examples thereof include linear alkanes such as hexane, heptane, octane, nonane, decane and the like; Linear or branched alcohols such as methanol, ethanol, propanol, butanol and the like; Alcohols having 4 to 10 carbon atoms such as pentanol, hexanol, heptanol, octanol, nonanol, decanol and the like; alkyl esters having 7 or more carbon atoms, such as n-hexyl acetate, 2-ethylhexyl acetate, methyl oleate, dibutyl sebacate, dibutyl adipate, 2-butyl carbamate and the like; Aliphatic ketones such as methyl isobutyl ketone, isobutyl ketone and the like; Aromatic hydrocarbons such as benzene, toluene, o- or p-xylene, etc .; Chlorine compounds such as methylene chloride, chloroform, carbon tetrachloride and the like can be used, but the present invention is not limited thereto.

Preferably, methanol, ethanol, methylene chloride, chloroform, or acetone, which has a low boiling point and easily evaporates to facilitate the coating, is preferably used.

The amount of the solvent to be used may be 10 to 99 parts by weight based on 100 parts by weight of the papermaking lamellar blend. When the amount of the solvent is used within the above range, the active ingredient can be dissolved effectively, and the spraying time is not long during the spray coating, thereby increasing the efficiency of the process.

Next, the multilayer lamellar granules according to the present invention can be prepared by spray coating the surface of the pseudomorphic lipid layer of the nucleating agent with a solution of the polymer in a secondary condition under reduced pressure at room temperature, followed by drying.

At this time, the solvent for dissolving the polymer is volatile, and all the chemicals having similar solubility parameters to the selected polymer. Specific examples are substantially the same as the solvents for the pseudomorphic lipid lamellar formulations described above.

The solvent may be used in an amount of 10 to 99 parts by weight based on 100 parts by weight of the polymer. When the amount of the solvent is used within the above range, the gelation of the polymer is prevented, and the spraying time is not long during the spray coating, thereby improving the process efficiency.

The present invention also provides a composition for external application for skin comprising the multilayer lamellar granules.

The external preparation for skin of the present invention may contain the multilayer lamellar granules in an amount of, for example, about 0.01 to 99% by weight, preferably about 0.01 to 5% by weight based on the total weight of the composition. When the above range is satisfied, there is an advantage in better formulation stability, feel on use, skin moisturizing and barrier restoration effect.

The composition for external application for skin of the present invention is not particularly limited in its formulation and may be, for example, a cosmetic composition having a formulation of softening agent, nutritional lotion, massage cream, nutritional cream, pack, gel or skin adhesive type cosmetic. Preferably, the cosmetic composition may be an oil-in-water emulsion or a solubilized gel formulation having excellent phase stability.

In addition, the multi-layer lamellar granule of the present invention may be present in a pharmaceutically acceptable carrier in a dispersed or dissolved state, and may be prepared by transdermal administration such as lotion, solution, gel, cream, emollient cream, ointment, patch or spray It can be used as a solvent. In the case of such a pharmaceutical composition, for example, atopic dermatitis, rashes, erythema, frostbite, skin diseases caused by diapers, contact dermatitis, seborrheic dermatitis, vidal saliva, eczema eczema, housewife eczema, sunburn dermatitis, , Psoriasis, erythema multiforme, epidermolysis, epidermolysis, lupus erythematosus, pemphigus vulgaris, lupus erythematosus, lupus erythematosus, Can be used for the treatment and prevention of diarrhea, pemphigus vulgaris, epidermal dermatitis, alopecia areata, alopecia areata, sarcoidosis, skin amylolithosis, keloid, hypertrophic wound, wound, pressure sores, hair loss, wool or hair growth have.

The composition for external application for skin of the present invention can also serve as a base for the delivery of other medicines and can improve the clinical response to medicines. Examples of such agents include anti-inflammatory agents (e.g., corticosteroids, colchicine, sulfasalazine and sulfone); Antibiotics such as quinolones, macrolides, penicillins, cephalosporins, sulfonamides and tetracyclines; Antiviral agents (e.g., acyclovit, euglydine, zidovudine, 2 ', 3'-dideoxyinosine (ddI), vidaribin and trifluridine); Antifungal agents such as ketoconazole, econazole, griseofulvin, cycloplex and naphthidine; Antihistamines (e.g., diphenhydramine, astemizole, hydroxyzine, doxepin, amitriptyline, cyproheptadine and sodium cromolyne); Antiperspirants (eg campo, menthol, phenol, benzocaine, benzyl alcohol, salicylic acid, dichlonin and pramoxin); Anti-neoplastic agents such as methotrexate, pyrithrex core, cisplatin, 5-fluorouracil, bleomycin, carmustine, hydroxyurea, azathioprine and nitrogen mustard; Carboxylic acid analogs such as 1-monolaurin, azelaic acid and dodecanedioic acid; Natural or synthetic vitamins and analogs thereof such as vitamin D, calcipitriol, 1,25-dihydroxycholecalciferol, retinol, retinyl palmitate, retinyl ascorbate, isotretinoin, esretinate, Nonsan); And artemisinin analogues (e.g., artesunate, arteether, artemether, dihydroartemisinin and artalene acid).

The composition of the present invention is not limited to the above-described components, and may include other components incorporated in a usual cosmetic composition or pharmaceutical composition, if necessary. For example, it is possible to use a water-soluble organic solvent such as a preservative, a humectant, an emollient, a surfactant, an organic or inorganic pigment, an organic powder, an ultraviolet absorbent, an antiseptic, a bactericide, an antioxidant, a plant extract, Cold agents, antiperspirants, purified water, and the like.

Hereinafter, the present invention will be described more specifically with reference to Examples and Comparative Examples, but the present invention is not limited to these examples.

Example 1: Preparation of multilayer lamellar granules containing pseudoceramide - (1)

Ceramide PC104 (Macrocare, Korea), a pseudoceramide, was used, and granules were prepared by the following procedure.

First, 500 g of sugar nucleating agent having an average size of 200 mm was put into a fluidized bed coater (Glatt, Germany) and vortexed. Next, 1000 g of Ceramide PC104 was completely dissolved in 5 kg of methylene chloride, and the surface of the nucleating agent was spray-coated under reduced pressure at room temperature with this solution. Subsequently, 100 g of phosphatidylcholine, 10 g of [oleyloxy-poly (ethyleneglycol) _20- succinyl-N-hydroxysuccinimidyl ester] and 50 g of stearic acid as a molecular fixer were dissolved in 500 g of methylene chloride, The surface of the coating was spray coated under reduced pressure at room temperature. Subsequently, the surface of the coating obtained above was spray-coated with a solution of 50 g of chitin dissolved in 95 g of water under reduced pressure at room temperature. The spraying speed was all 10 ml / min, and all processes were carried out at room temperature. The final recovered multilayer lamellar granules were sieved to remove fine residues and kept in an aluminum pack.

Example 2: Preparation of multilayer lamellar granules containing natural ceramides

Layer lamellar granules were prepared in the same manner as in Example 1 except that ceramide 1, a natural ceramide, was used instead of pseudoceramide (Doosan, Korea).

Example 3: Preparation of multilayer lamellar granules containing pseudoceramide - (2)

Layer lamellar granules were prepared in the same manner as in Example 1 except that no molecular fixer was used.

Test Example 1: Structural analysis of multilayer lamellar granules

The shapes of the multilayer lamellar granules prepared in Examples 1 and 2 were observed with an optical microscope, a polarizing microscope and an electron microscope, and an electron micrograph of the granules prepared in Example 1 is shown in Fig. From the photograph of FIG. 1, it can be seen that the multilayer lamellar granules prepared in Example 1 contain nuclei in the inside, and the lamellar layer and the polymer layer surround the periphery thereof. From the polarized light microscope, it can be seen that the lamellar layer exhibits a strong crystalline image, indicating that the ceramide and phospholipid coating layers form a lamellar structure.

In addition, the multilayer lamellar granules prepared in Example 2 showed the same shape as the microscopic image shown in Fig. 1, indicating that ceramides, molecular fixatives and fatty acids were arranged and immobilized in a lamellar structure together with phospholipids.

Formulation Example 1: Preparation of Solubilized Formulation - Formulation Stability Test

A solubilized formulation in the form of a clear gel (viscosity about 3,500 cps) having the composition shown in Table 1 below was prepared. At this time, the viscosity was measured at 30 캜 and 12 rpm using Brookfield (LVDVII +). In addition, all the granules were added in an amount of 5% by weight, and Ceramide PC104 or Ceramide 1 was added separately to compare the formulation stability. The formulations thus prepared were stored in an oven at 25 ° C and 45 ° C, respectively, and samples were taken after 2 weeks, 4 weeks and 8 weeks, and the degree of gelation was observed. The results are shown in Table 2 below.

It can be seen from Table 2 that the solubilization formulations of Formulation Examples 1-1 and 1-2, which only contain the ceramide as a pseudomorpholine lipid layer in the granules, do not cause gelation, whereas Formulation Example 1-3 And the solubilized formulations of 1-4 were gelated with time.

Formulation Example 2: Preparation of emulsified formulations - Formulation stability test

To examine the effect of preventing gelation in emulsified formulations, a lotion having the composition shown in Table 3 was prepared. Each oil phase and water phase was completely dissolved at 70 DEG C and emulsified at 7,000 rpm for 5 minutes to prepare an opaque gel type lotion. The viscosity of the lotion was about 3,000 cps. The formulations thus prepared were stored in an oven at 25 ° C and 45 ° C, respectively, and samples were taken after 4 weeks, 8 weeks and 16 weeks, and the degree of gelation was observed. The results are shown in Table 4 below.

It can be seen from Table 4 that the emulsion formulations of Formulation Examples 2-1 and 2-2, which only contain the ceramide as a pseudomorpholine lipid layer in the granules, do not cause gelation, whereas Formulation 2-3 And the emulsified formulations of 2-4 were gelated with time.

Reference Example 1: Effect of molecular fixer

The following test was conducted by verifying the effect of the molecular fixer in the prepared multilayer lamellar granule.

Each of the emulsified formulations prepared in Formulation Examples 2-1 and 2-5 was placed in an amount of 0.2 g on artificial skin, 0.01 g of a water-soluble dye, Red No. 227 1/1000 dilution, was added and mixed well. The photographs are shown in FIG. 2 (left: Formulation of Formulation Example 2-1, right: Formulation Example 2-5). ≪ / RTI > 2, the formulations of Formulation Example 2-1 in which the molecular fixatives were used remained mostly on the skin, whereas the formulations of Formulation 2-5 in which the molecular fixatives were not used were mostly washed out. This demonstrates that the use of a molecular fixer allows the multilayer lamellar granules to remain on the skin for longer periods of time.

From the above results, it was confirmed that the ceramide present in the multilayer lamellar granule according to the present invention exhibits excellent formulation stability even though it exists in a high content in cosmetic formulations. These results show that the use of ethanol, a surfactant, and other cosmetic additives remarkably lowered the stability of the formulation, so that the use of ceramides, whose use was limited, can be used in a larger amount.

1 is an electron micrograph of the granules prepared in Example 1,

FIG. 2 is a photograph showing the comparison of the amount of adsorbed colorant after washing the mixture of each of the emulsified formulations prepared in Formulation Examples 2-1 and 2-5 and the coloring matter for a predetermined time (Left: Formulation Example 2-1 , Right: Formulation of Formulation Example 2-5).

Claims (21)

Nucleating agents; A pseudomorphic lipid lamella layer present on the nucleating agent and containing ceramide and phospholipid; And The polymer layer on the pseudomorphic lamellar lamella layer Wherein the ceramide is hydroxypropyl bis-palmitamide monoethanolamide or ceramide 1 and the phospholipid is phosphatidylcholine. The method according to claim 1, Wherein the nucleating agent is selected from the group consisting of sugar, salt, hyaluronic acid, alginic acid, chondroitin sulfate, chitosan, chitin, polylysine, collagen, gelatin, stearic acid, cetyl alcohol, stearyl alcohol and mixtures thereof. The method according to claim 1, Wherein the nucleating agent is contained in an amount of 1 to 99 wt% based on the total weight of the multilayer lamellar granule. delete delete delete delete The method according to claim 1, Wherein the ceramide and the phospholipid are contained in a weight ratio of 1: 0.1 to 1: 1. The method according to claim 1, Wherein the pseudomorphic lipid lamellar layer is present in an amount of 0.00001 to 99 wt% based on the total weight of the multilayer lamellar granule. The method according to claim 1, The pseudomorphic lipid lamellar layer comprises a fatty acid; Cholesterol or derivatives thereof selected from the group consisting of cholesterol, cholesteryl chloride, cholesteryl octanoate, cholesteryl nonanoate, cholesteryl isoleuconate, cholesteryl isostearyl carbonate and mixtures thereof; A multi-layer lamellar granule further comprising an alcohol, a molecular fixative, or a mixture thereof. 11. The method of claim 10, Wherein the fatty acid is an unsaturated or saturated fatty acid having 8 to 30 carbon atoms. delete 11. The method of claim 10, Wherein the alcohol is an unsaturated or saturated alcohol having from 8 to 30 carbon atoms. 11. The method of claim 10, Wherein the molecular fixer is a material having an alkyl or alkenyl group having 12 to 20 carbon atoms as a hydrophobic group and having succinimidyl ester as a hydrophilic group. 15. The method of claim 14, Wherein the molecular fixer is [oleyloxy-poly (ethylene glycol) _n- succinyl-N-hydroxysuccinimidyl ester] (n is an integer from 2 to 100). 11. The method of claim 10, The fatty acid, the cholesterol or derivatives thereof, the alcohol and the molecular fixer are contained in an amount of 1 to 50 parts by weight, 1 to 50 parts by weight, 1 to 50 parts by weight, and 1 to 50 parts by weight, based on 100 parts by weight of the ceramide, Lamella granules. The method according to claim 1, Wherein the polymer layer is contained in an amount of 0.01 to 90% by weight based on the total weight of the multi-layer lamellar granule. The method according to claim 1, The multilayer lamellar granule is prepared in a fluidized bed coater. A composition for external application for skin comprising multilamellar granules according to claim 1. 20. The method of claim 19, Wherein the multilayer lamellar granule is present in an amount of 0.01 to 99% by weight based on the total weight of the composition. 20. The method of claim 19, Wherein the composition is a cosmetic composition or a pharmaceutical composition.

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