KR101155416B1 - Composition for reducing the exudation of serum proteins - Google Patents

Abstract

The present invention relates to a composition for reducing the exudation of blood proteins, and more particularly to the reduction of skin and mucosal exudation of blood proteins (serum-proteins) to improve symptoms such as lung disease.

Description

Composition for reducing the exudation of blood proteins

The present invention relates to a composition for reducing the exudation of blood proteins, and more particularly to the reduction of skin and mucosal exudation of blood proteins (serum-proteins) to improve symptoms such as lung disease.

For the purpose of academic understanding of atopic diseases and for the relief and treatment of symptoms, many studies have been carried out in conjunction with the development of immunology and cytology to understand and use immunomodulatory mechanisms or cell signaling mechanisms. have. On the other hand, some scientists have steadily studied the causes of changes in modern civilization, such as changes in diet and exposure to pollutants.

A common finding in these various areas of atopic disease research is that atopy, whether it is interpreted as an immunological cause, a cause due to westernized food, or as a cause of exposure to chemicals, can be found. Blood proteins ooze out of the skin and mucous membranes of sexual disorders. However, no studies have yet been made to ascertain whether atopic diseases are caused by blood proteins leaking into the skin or mucous membranes or by blood proteins leaking.

Exudation of blood proteins in the epidermis or mucosa has been mostly observed with serum-albumin as a marker. In skin diseases, albumin exudation is known to correlate with the severity of the disease. Severe skin exudates of blood proteins cause hypoalbuminemia of the blood (Worm et al., 1981. Br. J. Dermatol. 104: 389-396 and Worm and Rossing, 1980. J. Invest. Dermatol. 75: 302-305). Patients with allergic asthma and rhinitis also showed symptoms of intestinal lymphangiectasia, which caused severe loss of albumin in the intestinal wall (Esenberh, 1976. Ann. Allergy, 36: 342-). 350). Loss of albumin due to atopic dermatitis in children also leads to inhibition of growth (Abrahamov, 1986. Eur. J. Pediatr. 145: 223-226). In addition to hypoalbuminism, oiguria and terminal cyanosis. (cyanosis) is also accompanied (Capulong et al. 1996. Pediatr. Allergy Immunol. 7: 100-102). In the case of atopic eczema and contact dermatitis, the degree of albumin release from the affected area has been reported to be correlated with the severity of symptoms (David et al., 1990. Br. J. Dermatol. 122: 485-489 and Wijsbek et al., 1991. Int. J. Microcirc. Clin.Exp. 10: 193-204).

Symptoms of asthma and chronic obstructive pulmonary disease have also been reported in the release of blood proteins, including albumin, from the sputum of patients (Schoonbrood et al. 1994. Am. J. Respir. Crit. Care Med. 150: 1519-1527 and Anderson & Persson 1988. Agents Actions Suppl. 23: 239-260), chronic cough has been reported to produce albumin effusion without symptoms of eosinophilia. (Pizzichini et al., 1999. Can. Respir. J. 6: 323-330).

Blood protein exudation is due to chemicals such as methyl salicylate, phenol, croton oil, benzalkonium (Patrick et al. 1985. Toxicol). Pharmacol. 81: 476-490) Toluene, m-xylene, cyclohexane, etc. (Iyadomi et al., 1998. Ind. Health 36: 40-51 ). 2,4-dinitrofluorobenzne is used in animal models to study skin irritation, which also causes the exudation of blood proteins (Nakamura et al., 2001. Toxical. Pathol. 29: 200-207). It is reported that not all organic solvents induce blood protein exudation, and the extent of exudation also varies with chemicals. Effusions of blood proteins are easily induced by aromatic ring chemicals, and organic solvents such as acetone have little effect on the effusion of blood proteins.

Studies that suggest that atopic diseases are caused by Western diets (Weiland et al., 1999. Lancet 353: 2040-2041 and von Mutis et al., 1998. Lancet 351: 862-866 and Dunder et al. , 2001. Allergy 56: 425-428) note the changes in lipid content and content that people consume. In the 1970s, the researchers found that unbalanced fatty acids and trans-oil, the main components of excessively ingested vegetable oils, lead to imbalances in human metabolism, leading to an increase in atopic diseases.

Unlike other organs and organs, the lungs of mammals, including humans, contain a lot of phospholipids with significantly higher bisaturated fatty acids. Especially, the surfactant on the surface of the lungs is called dipalmitoylphosphatidylcholine (DPPC). The content is very high. This component is known to play a role in lowering surface tension in the lungs. The reduction of surface tension by surfactants at the surface of the lung not only helps to breathe easier when you inhale, but also that the alveolar walls stick together or collapse when you exhale to the end. Prevents. About 90% of the lipids in the lungs are phospholipids (about 70% of these are bisaturated phospholipids) and about 10% are triglycerides (most of which are cholesterol). Jon Goerke 1998. Biochem. Biophy. Acta. 1408: 79-89 and Veldhuizen et al., 1998. Biochim. Biophys. Acta. 90-108).

Further scientific results to consider above are the macroscopic pathways in which lipids in the lung surfactant are synthesized. Most cholesterol in human lungs comes from blood. Cholesterol is only about 1% synthesized in the lungs and the rest must be supplied from the blood (Hass and Longmore, 1979. Biochim. Biophys. Acta 573: 166-174). Phospholipids, which make up most of the surfactant in the lung, are synthesized and secreted in epithelial cell Type II, but most of the fatty acids that make up phospholipids are derived from very low density lipoproteins (VLDL) in the blood. It is known to be supplied (Rama et al., 1997. J. Clin. Invest. 99: 2020-2029).

Surfactant Protein A (SP-A) is the main protein present in the surfactant in the lung and has been studied for over 30 years. SP-A is synthesized and secreted from type II epidermal cells present in the alveoli, as well as found in the small intestine surface, the Eustachian tube of the ear, and tears. The molecular weight is about 700 KDa (size by gel-filtration analysis), and 18 identical units of 32 KDa are collected to form a completed protein having one function. There are several known biological functions of this protein, but it can be broadly classified into two categories. First, SP-A is an immunological function that protects the lungs by binding to bacteria or viruses that enter the lungs during breathing, and other mites and pollen. Second, it maintains homeostasis of the surfactants in the lungs. (Tino and Wright 1998. Biochim. Biophys. Acta. 1408: 241-263 and Haagsman, Biochim. Biophys. Acta. 1408: 264-277 and Crouch & Wright, 2001. Annu. Rev. Physiol. 63: 521 -524 and Haagsman and Diemel, 2001 Compar. Biochem. Physiol. 129: 191-108).

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems and the above-mentioned necessity, and an object of the present invention is to provide a composition for treating, preventing and / or alleviating diseases related to the exudation of blood proteins.

In order to achieve the above object, the present invention provides a composition for treating or alleviating blood protein exudation-related diseases comprising a double saturated phospholipid as an active ingredient.

The double saturated phospholipids of the present invention are preferably extracted from animals, more preferably from cows or pigs, most preferably those from pulmonary lavage fluid or lysates of lung tissue.

In addition, the double saturated phospholipid of the present invention is preferably dipalmitoylphosphatidylcholine and / or dipalmitoylphosphatidylinositol.

In addition, the composition of the present invention preferably further comprises an organic acid containing calcium and carboxyl groups, the organic acid containing a carboxyl group is an organic acid that can be metabolized, that is, for example, but not limited to lactic acid, succinic acid, fumaric acid or citric acid Is most preferred. In addition, the composition of the present invention may further include an additive, for example, glycerol as necessary.

 In the composition of the present invention, the double saturated phospholipid is preferably present at a concentration of 0.1 mg / ml to 60 mg / ml. The concentration range was most preferable at the concentration of less than 0.1 mg / ml because the therapeutic or alleviating effect was weak and the emulsion formation was difficult at 60 mg / ml or more.

The blood protein effusion-related diseases of the present invention include, but are not limited to, atopic rhinitis, asthma, or chronic obstructive pulmonary disease.

Hereinafter, the present invention will be described.

The present invention is directed to a phenomenon in which blood proteins are exuded from the skin or mucous membranes due to the deterioration of the endothelial-epithelial barrier due to excessive intake of unsaturated fatty acids and trans oils present in plant extract oils. It was used as a common model. Plant extract oil was administered to the lungs of rats to artificially induce blood protein exudation, and it was found that it is possible to reduce or inhibit blood protein exudation by using safe biological components that are completely metabolized in vivo. And it was found that it works effectively in the affected areas (skin) of patients with atopic disease.

The present invention finds that SP-A protein in the lung lavage fluid or pulmonary crush solution of healthy animals forms a unique precipitation layer with ideal phospholipid components present in the animal lungs when agglutination by divalent cations occurs. It is ideal for healthy living organisms after removing the surfactant proteins (especially the organic solvent soluble proteins SP-B and SP-C), hydrophobic peptides, cholesterol and unsaturated phospholipids from this precipitation layer. It includes a method for obtaining a combined bisaturated phospholipid fraction intact.

Furthermore, based on the discovery that non-specific hydrophobic interactions are enhanced when SP-A protein is absent, a composition comprising a bisaturated phospholipid fraction is applied to the skin or mucous membrane of atopic diseases. When applied to inhibit blood protein exudation, a carboxyl group that can be metabolized in cells not only requires a certain concentration of calcium ions but also prevents bisaturated phospholipids from agglomerating by specific concentrations of calcium ions. Addition of a substance having a carboxyl group (citrate or citric acid) to the composition is also an important factor.

As can be seen from the above configuration, the composition containing the double saturated phospholipid of the present invention has an effective effect in the treatment or alleviation of atopic diseases caused by the exudation of blood proteins.

1 is a photograph confirming the double saturated phospholipid by TLC. In FIG. 1, the * indicates the double saturated phospholipid fraction.
Figure 2 shows an example of the results of steady-state protein pattern analysis after the induction of blood protein exudation in the lung of the rat, after inhibition by the composition. In Figure 2 (1) is a result of inducing blood proteins in the lungs of rats (2) is a result of administering the composition to the blood protein exudation-induced rats (3) is the state of the control rats. A is a peak containing the SP-A (˜700 KDa) protein. B represents a peak containing blood albumin (˜70 KDa), and the effusion inhibitory effect was observed by comparing the magnitudes of the two peaks.
Figure 3 shows an example of the results after application of atopic dermatological disease (2-4 weeks). The left side of the photo before the application of the composition. The right side of the photo is after applying the composition. The duration of application was 2-4, with the top photo showing atopic eczema, the upper back photo of atopic dermatitis including ulcers, the third photo of atopic erythema, and the bottom photo of atopic dermatitis. It is a photograph.

The present invention will be described in more detail with reference to the following Examples. However, the embodiment of the present invention is only for explaining the present invention and the scope of the present invention is not limited to the following examples.

Example 1 Extraction of Double Saturated Phospholipid Fraction from Swine Wash

(1) How to get waste washing liquid.

Lungs extracted from healthy pigs were washed internally by administering saline containing 5 mM calcium chloride (CaCl ₂ ) into the trachea. The washing was performed by using a pressure pump at room temperature to inject about 0.6 liters of solution into one lung and to drain the washing solution. Wash 15 liters per lung. The collected bronchial alveolar lavage was immediately transferred to an ice-water bath for cooling.

(2) A method for obtaining precipitates of surfactants using agglomeration of SP-A from waste washing liquid

When the waste washing solution containing calcium ions (5 mM) was left in an ice-water bath for 1 hour, the SP-A protein aggregated together with the lipids of the surfactant. This solution was centrifuged in a centrifuge (Hanil, Korea) having a low-acceleration function. It was centrifuged at 4 ° C. for 35 minutes with a centrifugal force of 4,500 g. After centrifugation the precipitate has three distinct layers. A small amount of bottom layer is cells and denatured proteins, while the highest amount of middle layer and a small amount of top layer are a combination of surfactants and surfactant proteins. The middle and top layers of the precipitate were collected separately and used for extraction of the bisaturated phospholipid fraction.

(3) Primary Organic Solvent Extraction

Distilled water twice the volume of the complex of surfactant proteins and surfactant lipids obtained above was added and turbid. A 2: 1 (volume ratio) mixed solvent of chloroform and methanol was added to the sample in the same volume and shaken at 30 ° C. for 30 minutes. The sample was centrifuged for 15 minutes with a centrifugal force of 1,000 g, and then the organic solvent layer was extracted.

(4) Extraction of Saturated Phospholipid Fractions Using Silica Column Chromatography.

The first organic solvent extracted sample was evaporated using an evaporator, and then dissolved in chloroform. This sample was loaded onto a 1: 5 (diameter: height ratio) column filled with silica (Merck, 230-400 mesh). Solvents designed to remove cholesterol and dissolved dissolved organic solvents from the sample and obtain bisaturated phospholipids were used in the following order. The silica column was washed with pure chloroform, and then pure chloroform-pure acetone-pure chloroform-chloroform: methanol (9: 1 by volume) mixed solvent -chloroform: methanol (4: 1 by volume) mixed solvent-chloroform: methanol: water (8: 6: 1 by volume) was used in the order of the mixed solvent. The organic solvent soluble surfactant proteins and hydrophobic peptides are eluted with a pure acetone-pure chloroform solvent, and the bisaturated phospholipid fraction, a component required in this invention, is eluted with the last solvent. Each phospholipid component of the obtained fractions was identified using 2D-TLC (two-dimensional thin-film chromatography) using standard lipids (purchased from Sigma Company) (FIG. 1). The main components of the extracted bisaturated phospholipid fractions were dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylinositol.

(5) Post-treatment of extracted double saturated phospholipid fractions.

The final sample extracted from the column was passed through a three-layer Whatman Filterpaper No. 1 paper filter, and then the solvent was removed using an evaporator. Pure ethanol was added to the sample from which the solvent was removed, and then filtered using a PVDF (polyvinylidene fluoride, 2μm pore-size, Millipore) filter. Ethanol was evaporated again using an evaporator. Ethanol washing was performed twice. The remaining amount of ethanol was removed using a freeze-drier. Powder form of the obtained bisaturated phospholipid fraction was stored in -70 ℃ in a sealed container filled with nitrogen.

Example 2 Extraction of Saturated Phospholipid Fraction from Bovine Waste Wash

The bisaturated phospholipid fraction was obtained from the waste washing solution of the cow through the procedure of (1)-(5) described in Example 1 except that the animal used was changed from pig to cow.

Example 3: Obtaining a Double Saturated Phospholipid Fraction from Lung Tissue Crushes of Healthy Pigs

(1) primary crushing of animal lung tissue

Remove 150g of tissue from the lungs extracted from healthy pigs and cut them into 2cm × 2cm. 700 ml of chilled saline containing 3 mM divalent cation (calcium chloride) was added to the sliced waste pieces, followed by homogenization with a metal-blade blander. The crushing was performed at a low speed of six rotations of 20 seconds, and the gap was cooled using an ice-water bath to prevent the temperature from rising. Initial crushing caused the lung tissue to be cut to the size of a soybean without complete crushing.

* (2) A method for removing blood from the primary crushed liquid without loss of surfactant lipid.

The primary lysate is left in an ice-water bath for 1 hour to allow blood to escape easily from crushed tissue with a large surface area, while at the same time the surfactant components are agglomerated by divalent cations (calcium ions, 3 mM). The phenomenon can be caused. The crushed liquid left for 1 hour was centrifuged at 4 ° C. for 40 minutes with a centrifugal force of 4,500 g using a low-acceleration centrifuge. After centrifugation, the blood-containing solution was removed, except for the sedimentation layer and suspended solids (some of the lung tissue that had not been completely shredded contained air and thus not suspended).

(3) Secondary crushing of lung tissue and precipitation method of surfactant.

500 ml of 75 mM sodium chloride solution (half the concentration of physiological saline) was added to the blood-derived primary lung tissue lysate, followed by a blender with a metal blade. The tissue was crushed finely with. This procedure used a hypotonic solution to easily obtain multi lamellar structures that act as reservoirs of surfactants present inside the type II epidermal cells of the lung. In order to prevent the temperature from rising during the crushing process, the high-speed rotating crushing was performed 6-8 times for 40 seconds, and the gap was cooled using an ice-water bath. The sample subjected to secondary crushing was allowed to stand at 4 ° C. for 1 hour to cause aggregation of the surfactant due to SP-A. 40 minutes was centrifuged by the centrifugal force of 4,500g at 4 degreeC using the low speed centrifuge. After centrifugation, the sample forms two sedimentary layers of distinct color and texture. The upper layer was obtained separately in the precipitated layer and subjected to an organic solvent extraction process to extract the bisaturated phospholipid. The remaining portion of the remaining layer was added again to the turbidity of 5mM calcium ion containing saline again, and then centrifuged in the same way, the mixture of some of the surface active lipids were separated again. The upper precipitated layer was combined with the previously obtained sample and subjected to organic solvent extraction.

(4) How to Obtain a Double Saturated Phospholipid Fraction

The bisaturated phospholipid fraction was obtained from lung tissue lysates using the same method as in (3), (4) and (5) described in Example 1 above.

Example 4 Method for Obtaining Saturated Phospholipid Fractions from Healthy Bovine Lung Tissues

A bisaturated phospholipid fraction was obtained from the lung tissue lysate of a cow by the same procedure as described in Example 3 except that the animal used was changed from pig to cow.

Experimental Example 1: Animal Experiment

1-1. Effusion of blood proteins in the lungs of animals

Corn oil (purchased from Sigma's reagent company) and saline were sterilized separately using a high temperature autoclave. 500 μl (microliter) of corn oil and 1,500 μl of saline were mixed and then very vigorously vortexed into a homogeneous suspension. The turbidity was administered to the lungs of mature Sprague-Dawley rats to induce blood protein exudation. Control rats with a placebo effect were given intrabronchial administration of sterile saline only. Two weeks later, rats were anesthetized using ketamine (Ketamine) and anesthetized using carbon dioxide. As soon as the experimental animals died, the lungs were immediately removed, and the lungs were lavaged with a total of 50 ml of saline (containing 3 mM calcium chloride) to collect the lung washing solution for each animal.

1-2. Inhibitory effect test of blood protein effusion and composition of used composition

After inducing blood protein effusion to the animal by the above-mentioned method, the composition containing the bisaturated phospholipid fraction obtained from Examples 1 to 4 was administered intrabronchially one week later. Lung extraction and lung lavage from experimental animals were performed one week after the time of administering the composition.

The composition used was mixed in distilled water to a concentration of 30 mg / ml bisaturated phospholipid fraction, 1.5 mM calcium chloride, 7.5 mM citrate trisodium salt, and 125 mM sodium chloride, and the pH of the solution was 6.0. Shake vigorously before administration to animals to make a homogeneous turbid solution.

1-3. Analysis of Exudation and Inhibition of Blood Proteins

(1) Preparation of analytical samples in each experimental animal group

Lung washes obtained from each experimental animal group were centrifuged at 4 ° C. for 30 minutes using a centrifugal force of 4,500 g using a low-acceleration centrifuge. In the obtained precipitate, only the layers of the surfactant aggregated by SP-A in the presence of divalent cations (calcium ions) were collected separately. About 3 times the volume of saline (containing 3 mM calcium chloride) of the collected precipitates was added again and turbid. This turbidity liquid was centrifuged with the same centrifugal force to precipitate. The washing process of the precipitate was repeated two more times to wash the precipitate. The turbidity of the final precipitate was divided into 1 ml small centrifuge tubes and partitioned so that the volume of the precipitate was 200 μl.

10 ml of Tris buffered solution (Tris buffered saline, pH 7.4, 10mM Tris-HCl, 140mM NaCl) containing 10mM of idieti (EDTA, ethylenediamineteteraacetic acid) was added to 200µl of the washed surfactant precipitate described above. A turbid detergent (CHAPS, Amresco, USA) was added to this solution to dissolve the turbidity (solubilization). The stock solution was used at 10% (about 162 mM concentration) and the final concentration of CHAPS was 65 mM.

(2) analysis

Take 1 ml from each sample (2 ml) prepared by the above procedure and apply it to the chromatography column filled with Sephacry S-400HR (1.5 cm × 20 cm, Amersham Biosciences) resin. ) Was analyzed. Chromatographic work was performed using GradiFrac (Pharmacia). The buffer used was 10 mM Tris buffer (pH 7.4) containing 5 mM EDTA, 1 mM CHAPS and 140 mM NaCl. From the UV absorption graph of the proteins eluted in the column, by comparing the size (quantity) of the protein peak containing SP-A with a molecular weight of 700 kDa and the albumin containing molecular weight with a molecular weight of 70 kDa The degree of exudation of blood proteins and the inhibition of exudation were measured, respectively (see FIG. 2).

1-4. Animal test results

Samples obtained from rats that induced blood protein exudation, samples of rats that were inhibited by the administration of the composition, samples obtained from saline-only rats, and normal rats that had not been treated. From the protein elution pattern graph, the ratio of the protein peak of the molecular weight 700KDa site | part and the protein peak of the molecular weight 70KDa site | part, ie, the ratio (size) of the two peaks, is summarized in the following Table 1.

From the above Table 1 and the results obtained, it was confirmed that the composition containing the bisaturated phospholipid fraction extracted from the lungs of healthy animals to reduce blood protein exudation. Only one intrabronchial administration reduced the size of the albumin-containing peaks by about 50% compared to those of blood protein exudates. This reduced amount is from a set criterion and the actual decrease is much larger than this. The reason for this is that 2-3 ml (precipitate volume / horses) is obtained on average when lung washing is obtained from normal rats. However, blood protein effusion-induced rats have large variation in each individual, but 3 to 5 times higher than normal rats. Many precipitates are obtained. However, from rats subjected to blood protein exudation by the composition of the present invention, precipitates of about twice the volume are obtained at least about the same amount as that of normal rats. In other words, the composition of the present invention is shown to significantly reduce the absolute amount of the precipitate compared to blood protein exudation-induced rats. However, the absolute difference in the amount of these deposits was not quantified because they can be changed by the experiment temperature, the flexibility of the lung tissue, and the hand technique of the experimenter. That is, the reduction of blood proteins shown in FIG. 2 and Table 1 does not show the total amount of protein but only a relative comparison value of the peak containing SP-A and the peak containing albumin. If considering the total amount of the peak containing albumin reduced by the composition of the present invention (see B in Fig. 2 (2)) it can be seen that the degree of reduction has a very significant effect.

The ideal bisaturated phospholipid composition that the living body has on the lung surface should be the most effective from the saturated saturated phospholipid fraction extracted from the lavage fluid. The same rate of exudation of blood proteins was shown.

Experimental Example 2: Applicants Experiment of Atopic Skin Disease

2-1. Compositions and Methods Used for Skin

(1) composition

Double-saturated phospholipid fractions obtained by pulverization of animal lungs and extraction by agglomeration of surfactants by divalent cations (calcium ions) (These components were 0.2 µm pore-sized PVDF PVDF during extraction. (Polyvinylidene fluoride filter, 0.2μm pore-size, Millipore product) After filtering by distilled water was added to the lyophilized state, high temperature and high pressure sterilization. Calcium chloride solution, citrate (citrate trisodium salt) solution and glycerol were also autoclaved separately. The sterilized components are mixed in distilled water under aseptic condition to obtain a concentration of 15 mg / ml bisaturated phospholipid, 1.5 mM calcium ion, 7.5 mM citrate trisodium salt, and 10% (volume / volume ratio) glycerol. It was. pH was 6.0. Glycerol was added to a total concentration of 10% to give viscosity to the solution so that the bisaturated phospholipids could easily spread by the physical force rubbed while the bisaturated phospholipids were applied to the skin. The mixed ingredients were vortexed and applied into a homogeneous turbid solution.

(2) Application method

For skin application, a drop (about 30 μl) was dropped on the affected area of about 2 cm × 2 cm and rubbed until the solution was completely smeared. Skin application was recommended at least twice a day. While using this composition, it is recommended to refrain from using fragrance-based cosmetics or soaps that may have compounds with aromatic rings.

2-2. Applicant's experiment results (visual observation)

Fifteen sites were tested from eight volunteers with atopic dermatitis (5 ~ 40 years old, average age 33 years old, 4 boys, 4 girls). The skin application period of the composition was 2 to 4 weeks. All of the volunteers showed improvement in atopic dermatitis so that the border between the affected area and the affected area was indistinguishable.

Skin crusts formed by drying exudate due to atopic skin disease were confirmed to not remodel on the skin surface from 2 days after application. After one week, volunteers with atopic erythema disappeared indistinguishable from the color difference between the affected area and the affected area. In the case of skin ulcer accompanied by 3.5 weeks (after about 25 days), the wound was completely regenerated (see FIG. 3).

Claims (8)

Cosmetic composition for improving atopic dermatosis comprising a bisaturated phospholipid, an organic acid having two or more carboxyl groups and calcium ions as an active ingredient. The cosmetic composition for improving atopic skin disease according to claim 1, wherein the double saturated phospholipid is extracted from an animal. According to claim 1, wherein the double saturated phospholipid is a cosmetic composition for improving atopic skin disease, characterized in that extracted from cattle or pigs. The cosmetic composition for improving atopic dermatosis according to claim 2 or 3, wherein the double saturated phospholipid is extracted from pulmonary lavage fluid or crushed tissue of lung tissue. The cosmetic composition for improving atopic dermatosis according to any one of claims 1 to 3, wherein the double saturated phospholipid is dipalmitoylphosphatidylcholine or dipalmitoylphosphatidylinositol. delete According to claim 1, wherein the composition is a cosmetic composition for improving atopic skin disease, characterized in that it further comprises glycerol. The cosmetic composition for improving atopic dermatosis according to claim 1, wherein the double saturated phospholipid is present at a concentration of 0.1 mg / ml to 60 mg / ml.

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