KR20040058851A - Composition for repression of phagocytosis containing Saururus chinensis extract - Google Patents

Abstract

PURPOSE: Provided is a composition for inhibiting phagocytosis containing Saururus Chinesis(Lour) Bail extract that effectively inhibits the phagocytosis of the keratinocyte activated by exposure to ultraviolet rays. Further, provided is a pharmaceutical composition which prevents and treats various kinds of diseases associated with phagocytosis. CONSTITUTION: A phagocytosis inhibiting composition is characterized by containing, as an active ingredient, Saururus Chinesis(Lour) Bail extract in the amount of 0.0001-10 wt.%. It is used for prevention and treatment of phagocytosis related diseases.

Description

Composition for repression of phagocytosis containing Saururus chinensis extract}

The present invention relates to the use of trichophytium extract for inhibiting phagocytosis of cells. More specifically, it is to provide a composition that can improve or prevent the phagocytosis-related diseases or conditions by using the three hundred sec extract according to the present invention to inhibit the phagocytosis of keratinocytes.

Phagocytosis is the action of digesting intracellular digestion by trapping not only debris of old tissue, old blood cells or waste tissue, but also pathogens and particulate matter from outside. Typically, it refers to an intracellular process in which cells pick up solid particles from the environment to separate or destroy them. In vertebrates, cells with this function are cells belonging to various leukocytes and reticulo endothelial cells, reticular cells, tissue cells, vascular epithelial cells, astrocytic cells, lymphocytes, leukocytes, liver Kube cells Plasma cells, and the like. Phagocytosis acts as an important body defense mechanism against infection by microorganisms or occlusion of mucosal surfaces and tissues by foreign particles and tissue debris. Phagocytosis is distinguished from pinocytosis, which is the uptake of fluid by cells through invagination and contraction of the plasma membrane. Here, the terms 'phagogy' and 'intracellular digestion' are used interchangeably.

When the phagocytic function of the stomach cells distributed in different organs is reduced or excessively increased, various kinds of diseases, including the immune system, occur. Representative immunological and inflammatory diseases include pulmonary emphysema associated with the phagocytosis of neutrophils, and immunological lung diseases such as allergic lung organ bronchopulmonary aspergillosis. And periodontitis is associated with the attachment and infection of opsoninous Staphylococcus aureus by polymorphonuclear cells ('PMN's'), and secondary infections frequently occur in patients undergoing organ transplantation and valve replacement or cancer treatment. It is also involved in phagocytosis. Pulmonary polymorphonuclear leukocytes derived from diabetic patients show reduced phagocytosis both at the level of bacterial uptake and removal compared to healthy people. In particular, in the immune response, these patients often suffer from undesirable infections because diabetes is a condition in which abnormal effects such as chemotaxis, phagocytosis and adhesion are impaired. Atherosclerotic plaques, which are absorbed in a form that is not regulated by macrophage phagocytosis, include cholesterol-rich particles, causing cardiovascular disease. Central nervous system disease is also associated with phagocytic abnormalities. Microglial cells found around amyloid plaque cores phagocytize and remove old plaque cores. The ability of these microglia is inhibited by the removal of aging plaques when inhibited by an astrocyte-secreted diffusable factor, which allows for continued Alzheimer's disease and other neuropathological degenerative progression. Neutrophil phagocytosis was also found to be reduced in mentally depressed patients. Regarding skin diseases, there are various forms of aging and partial types of pigmented diseases due in part to the phagocytosis of wrinkles and morphologically normal elastic tissues. Such pigmented diseases can be inherited (eg, vitiligo), acquired acquired (eg, post-inflammatory pityriasis alba, spontaneous antagonistic hypomelanosis). hypomelanosis, mellasma], and infection.

Knowledge of the chemical and enzymatic basis of melanogenesis as a mechanism for regulating skin color is well known. Melanocytes migrate from the embryonic neural crest to the skin to produce melanosomes that produce melanin, the particles they secrete. The key enzyme in melanogenesis is tyrosinase, which causes a reaction cascade that converts tyrosine into raw polymer melanin. Two tyrosinase-related proteins (TRP's) are known as TRP-1 and TRP-2. These proteins share about 40% homology with tyrosinase and have a catalytic activity as well as a regulatory role in melanogenesis. Melanin occurs in an organelle called melanosome, in which the enzymes are distributed, and melanocytes containing melanin are later delivered to keratinocytes (keratinocytes) through melanocyte dendrites. . The mechanisms of regulation of keratinocyte-melanosite interactions and melanosomal transfer to keratinocytes have not been accurately known to date. However, there is a lot of evidence that melanoma is very likely to be delivered to keratinocytes in connection with the phagocytic function of keratinocytes in the melanocyte secreted from melanocytes.

Although there have been previous reports that white extract extracts have a whitening effect by acting as a tyrosinase inhibitor on skin melanocytes, there is no known effect on phagocytosis of keratinocytes.

The present inventors have extensively researched and studied to develop a substance that effectively inhibits the process of delivering melanocytes from the skin to melanocytes. As a result, it was found that the extract of 300 seconds inhibits the phagocytosis of keratinocytes.

Accordingly, it is an object of the present invention to provide a novel use of the extract of three hundred seconds that has the effect of inhibiting phagocytosis of keratinocytes. On the other hand, it is an object of the present invention to improve or prevent phagocytosis-related diseases or conditions through this. By regulating the activity of phagocytosis at the cellular level, various diseases affected by phagocytosis, specifically immune system-related emphysema, allergic pulmonary organ Aspergillosis, periodontitis and atherosclerotic plaques It is an object of the present invention to provide a pharmaceutical composition for treating or preventing cardiovascular disease, secondary infection of cancer patients, immune related diseases of diabetic patients, Alzheimer's disease, depression, aging and the like. In particular, it aims to suppress melanin from depositing on skin by inhibiting the transfer of melanocytes from melanocytes to keratinocytes through phagocytosis.

Figure 1a is a graph showing the phagocytosis promoting effect of keratinocytes by UVA. The graph shows the degree of phagocytosis after UV, 0, 2, and 24 hours after irradiating UVA, 5, 10, and 15J, respectively, per unit area.

Figure 1b is a graph showing the phagocytic effect of the keratinocytes by UVB. The graph shows the degree of phagocytosis after UV, B, 0, 2, and 24 hours after irradiating 0 (control), 10, 20, and 30 mJ, respectively, per unit area.

Figure 2a is a graph showing the effect of UVA on the proliferation and death of keratinocytes. The graph shows the results of measuring the cell growth rate after 0, 2, 24 hours after irradiating UV (A), 5, 10, 15J per unit area of UVA, respectively.

Figure 2b is a graph showing the effect of UVB on the proliferation and death of keratinocytes. The graph shows the results of measuring the cell growth rate after 0, 2, 24 hours after irradiating UVB B (control group), 10, 20, 30mJ per unit area, respectively.

Figure 3 is a graph showing the effect on the phagocytosis of keratinocytes exposed to ultraviolet light of three hundred seconds extract according to the present invention. The graph shows the inhibition of phagocytosis induced by treatment of 300 sec extract for 24 hours after irradiation with UVB 20mJ keratinocytes.

Figure 4 is a graph showing the effect of the three hundred seconds extract according to the present invention on the killing of keratinocytes. The graph shows the results of measuring the cell growth rate of keratinocytes after treatment with 300 sec extract for 24 hours after irradiation with ultraviolet B 20mJ.

Figure 5 is a photograph showing the effect of the extract of three hundred seconds according to the present invention on the acquisition of melanin or melanosomal in vitro of keratinocytes. The picture is a picture showing the melanin absorption degree measured after treatment with melanosome UV B 20 mJ / cm ² and then treated with 300 seconds extract for 24 hours.

In order to achieve the above object, the composition according to the present invention is characterized by containing three hundred seconds extract.

Hereinafter, the present invention will be described in more detail.

First, some terms used in the present specification are defined as follows to further clarify the present specification.

"Phagocytosis" is the action of internal digestion by trapping not only debris of old tissue, old blood cells or waste tissue, but also pathogens and particulate matter from outside. Typically, it refers to an intracellular process in which cells pick up solid particles from the environment to separate or destroy them. Phagocytosis is distinguished from pinocytosis, which is the uptake of fluid by cells through invagination and contraction of the plasma membrane. Here, the terms 'phagogy' and 'intracellular digestion' are used interchangeably.

"Treatment" here is an approach for obtaining beneficial or desirable clinical results. Beneficial or desirable clinical outcomes for the purposes of the present invention, whether or not detectable or not, may be partial or total, relief of symptoms, reduction of disease extent, stabilization of disease (i.e. not worse). Conditions, delayed or slowed disease progression, amelioration or temporary alleviation and alleviation of disease states, but are not limited thereto. "Treatment" also means prolonged survival as compared to survival expected when treatment is not accepted. "Treatment" is an intervention that is performed with the intention of preventing the development or alteration of a lesion of a disease. Thus, "treatment" refers to both therapeutic and prophylactic aspects. Those that need to be treated include those that already have the disease as well as those that should be prevented.

Here, "three hundred sec extract" is a leaching solution of the perennial Saururus chinensis, a perennial herbaceous plant, which is a tricot herbaceous plant. It includes, but is not limited to, stagnation, premises, periodical, fluid extracts (hereinafter referred to as extraction extracts) produced by drying water, and chemicals which exert their main effects in herbal medicines themselves.

The present invention relates to an effect of inhibiting activated phagocytosis of keratinocytes induced by UV rays from the tritical herb extract, which is effective for reducing the distribution of melanocytes from melanocytes in the keratinocytes. It features.

Sambaekcho is a perennial herb, also called Cheonseongcho, Arboretum, Trifolium baekcho, Baekseokgol, Baekgolgol, Waterside Sambaekcho, and Saur. Stems contain water-soluble tannins and leaves contain methyl-en-norylketoons. It is also known to contain Cuerceti, Cuercitri, Isoquercitrin, Abiclarin, Hyperin, Ruchin and Water-soluble Tannins. The roots contain various amino acids, organic acids, sugars, and leaves and stems. There is water-soluble tannin, which is 0.48%. Three hundred seconds is surprisingly diverse and excellent pharmacological action. It is known to have a remarkable effect on the prevention and treatment of various adult diseases such as constipation, diabetes, liver disease, cancer, high blood pressure, heart disease, gynecological diseases, kidney disease. Prabon-based substances such as quercetin, quercitzin, sisotuercitri, and ruchin, which are identified as effective substances of 300 seconds, clear the blood more than ginkgo leaf prabon-based substances and supply a lot of blood deeply throughout each tissue of the whole body. It strengthens and protects the arteries, and studies have shown that water-soluble tannins have a strong anti-carcinogenic effect by blocking DNA (gene) mutations.

The composition according to the present invention is preferably from 0.0001 to 10% by weight based on the three hundred sec extract. This is because the effect cannot be expected at 0.0001% by weight or less, and at 10% by weight or more, there are difficulties in safety and formulation stability. Considering the effective effects and safety and formulation stability, it is most preferable that it is 0.01 to 1% by weight.

The phagocytic inhibitor composition according to the present invention can be administered orally, parenterally, rectally, vaginally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously. The most preferred route of administration is transdermal administration. The dosage of the active compound will of course depend on the subject to be treated, the particular disease or pathology to be treated, the severity of the disease or pathology, the route of administration, and the judgment of the prescriber. Dosage determination based on these factors is within the level of skill in the art. In general, the dosage will range from approximately 0.001 mg / kg / day to approximately 2000 mg / kg / day. Preferred dosages are from 0.5 mg / kg / day to 2.5 mg / kg / day.

Phagocytic inhibitors according to the present invention may be formulated into pharmaceutical compositions with pharmaceutically acceptable carriers. See Remington's Pharmaceutical Sciences, latest edition, by E.W. Martin (Merck Publ. Co., Easton, Pa.) Describes typical carriers and methods of preparing conventional pharmaceutical compositions that can be used to prepare the compositions of this invention. The composition may also be administered in conjunction with other compositions and procedures for the treatment of the disease, for example, surgery, laser or chemotherapy may be combined with administration of the composition according to the invention.

Depending on the intended dosage form, the pharmaceutical composition may be in solid, semisolid, or liquid dosage form. Examples of dosage forms include, but are not limited to, tablets, pills, capsules, suppositories, small bags, granules, powders, creams, lotions, ointments, plasters, liquid solutions, suspensions, and dispersions, emulsions, syrups, and the like. The active ingredient may be encapsulated in liposomes, microparticles, microcapsules or the like. However, the most preferred formulations are formulations for transdermal administration such as creams, lotions, ointments, liquid solutions, suspensions, dispersions or emulsions.

Conventional non-toxic carriers are agents of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talc, cellulose, glucose, sucrose, dextrose, glycerol, magnesium carbonate, triglycerides, oils, solvents, sterile water, and isotonic saline Including but not limited to grades. Solid compositions such as tablets, pills, granules and the like may be coated for convenience. Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer and include local anesthetics to relieve pain at the injection site. If desired, the medicament may also contain small amounts of non-toxic auxiliary substances such as wetting agents, emulsifiers, pH buffers and the like. Examples of such auxiliary materials include, but are not limited to, sodium acetate, sorbitan monolaurate, triethanolamine, and triethanolamine oleate. The composition of the present invention may comprise excipients such as stabilizers, antioxidants, binders, colorants, flavors, preservatives, and thickening agents.

Hereinafter will be described a method for preparing the extract of three hundred seconds according to the present invention.

Method of Preparation of Triticale Extract

It is possible to use a well-known method as a manufacturing method of the three hundred sec extract according to the present invention. For example, after drying three hundred seconds by any method such as natural drying or forced drying, and finely chopped, polar solvents such as water, ethanol, butanol and acetone; Nonpolar solvents such as ether, hexane, benzene, chloroform and ethyl acetate; A mixed solvent of the nonpolar solvent and the polar solvent; Using a solvent such as alkaline water, or vegetable oils such as soybean oil and sesame oil, the leaching treatment is carried out by any method such as cold sedimentation, percolation, and warm sedimentation to obtain a leaching substance containing the active ingredient. The leaching treatment is about 12 to 96 hours for cold needle and percolation, and depending on the type and temperature of solvent used for warm needle, but suitably for about 0.5 to 24 hours at a temperature close to the reflux temperature of the solvent. Good to do. In particular, it is preferable to use a tincture, a liquid extract or an extract that has leached into the hydrous alcohol.

The present inventors used a human keratinocyte line system to study the phagocytic activity of keratinocytes. In the experiments on the phagocytosis inhibition of the three hundred sec extract according to the present invention in the following examples, after treatment with cells 20mJ / cm ² UV treatment of the three hundred sec extract prepared according to the above method for 24 hours and then fluorescent microspheres Incubated for 3 hours. Beads absorbed by the cells were measured using a fluorometer.

Hereinafter, the present invention will be described in more detail with reference to Examples and Examples. However, the present invention is not limited thereto.

Example

<Test Example 1. Evaluation of the phagocytosis promoting effect of keratinocytes by ultraviolet light>

The present inventors experimented as follows to determine whether the phagocytosis of keratinocytes is promoted by ultraviolet light. In this test example, the human keratinocyte line HaCaT was used as an in vitro model system to study the effect of ultraviolet light on the phagocytosis of keratinocytes.

Phagocytic activity of keratinocytes was determined by culturing fluorescent microspheres for 3 hours and measuring the brightness of the fluorescent beads absorbed into the cells. First spread the cells in 96-well culture dishes to 1 X 10 ⁴ cells and leave them on the floor for one day. Cells were washed twice with PBS (phosphate buffered saline), 100 μl of PBS was filled in each well, and UVA was irradiated with 0 (control), 5, 10, and 15J per unit area, and UVB was 0 (control group) per unit area. ), 10, 20, 30mJ was investigated to determine the phagocytic activity of keratinocytes according to the respective dose. And in order to test how the phagocytosis of keratinocytes is maintained after UV irradiation, phagocytic activity after 0, 2 and 24 hours was also measured for each dose of ultraviolet rays A and B by the same system. The measurement method is incubated under the addition of DMEM medium for the desired time after UV irradiation, and the cells are exposed to FITC fluorescent microspheres (diameter 1-0.5 μm, excess microspheres / cells) at 37 ° C. for 3 hours. Microspheres were derived from molecular probes (Eugene, OR) and the process proceeded according to the manufacturer's instructions. After the treatment, the cells were treated with trypan blue for 1 minute to remove beads not ingested by keratinocytes and the fluorescence of the cells was measured with a fluorometer. That is, the brightness of fluorescence is proportional to the amount of beads ingested and the results are shown in FIGS. 1A and 1B.

As shown in Figure 1a, 1b, the phagocytic activity after UV irradiation in the human keratinocyte line HaCaT, compared to the control group not irradiated with ultraviolet radiation in the group irradiated with ultraviolet radiation, according to the dose, that is, the fluorescence microsphere A significant increase in intake was observed. The results of the test according to the irradiation amount of the ultraviolet ray A and the elapsed time after irradiation are shown in FIG. As shown in FIG. 1A, the amount of microspheres absorbed by the ultraviolet ray A was significantly increased immediately after the irradiation, compared to the non-irradiated control group, but the effect was lost after 2 hours. As shown in FIG. 1B, the phagocytosis of keratinocytes increased proportionally with the amount of UV irradiation, and its activity was continued for 24 hours.

Test Example 2 Effect of UV on Proliferation and Death of Keratinocytes>

The inventors of the present invention examined whether the increased phagocytic activity of keratinocytes exposed to ultraviolet light is related to the effects of transient proliferation of keratinocytes and the extent of death of keratinocytes according to the UV irradiation dose. The same experiment was performed. Human keratinocyte line HaCaT cells were attached and cultured under the same conditions and system as in Test Example 1, and irradiated with ultraviolet rays A and B. After incubation in DMEM culture medium for a desired time after UV irradiation, 50 μl of tetrazolium dye was added and incubated at 37 ° C. for 4 hours. The amount of formazan produced by the living cells was added to 150 µl of the lysis solution and dissolved, and the absorbance was measured at 570 nm, thereby measuring the number of living cells by time (0, 2, 24 hours) according to the irradiation dose. . Absorbance by lysed formazan is proportional to the number of living cells.

Test results for the effect of UV A on keratinocyte growth is shown in Figure 2a, the results of the test for ultraviolet B is shown in Figure 2b.

As shown in Figures 2a and 2b, it can be seen that in the case of ultraviolet A, the cell number was reduced by about 10% in all doses. Similarly, the test results for ultraviolet B showed a decrease of 10% in the cell number for all doses. Therefore, it was proved that the increase in phagocytic activity of keratinocytes by ultraviolet rays was not due to the increase in the number of keratinocytes. No other changes were observed compared to the control except for such a slight decrease in cell numbers. Thus, UV rays do not appear to significantly affect the proliferation and death of cells compared to the control. From the above results, it can be seen that the increase in phagocytosis of keratinocytes caused by ultraviolet light is not caused by the transient proliferation of cells to each ultraviolet light, but the increase in phagocytic activity itself, thus increasing phagocytic activity by ultraviolet light. The importance of inhibiting substances has been demonstrated.

Example 1: Effect of the Triticale Extract on Phagocytosis of Keratinocytes Irradiated with UV Light

The present inventors have confirmed that from the test examples 1 and 2, the phagocytic activity itself of keratinocytes is increased by ultraviolet light, based on this, the three hundred sec extract according to the present invention is to increase the phagocytic activity by the above ultraviolet light In order to confirm whether the inhibition was performed the following experiment.

In this example, 20mJ of UVB B, which effectively increased the phagocytosis of keratinocytes without affecting cell death, was used.The treatment time of the inhibitor capable of inhibiting the increased phagocytosis was 24 hours after UVB irradiation. Determined by. 24 hours after irradiation is a time that the phagocytic activity of keratinocytes induced by ultraviolet light B is steadily maintained, and therefore, the treatment resulted in decreased cell phagocytosis activity reduced by the treatment of 300 seconds according to the present invention compared with the activity of the untreated group. Condition that can measure the amount.

Human keratinocyte line HaCaT cells were laid in the same manner as described in Example 1, and UV-B was irradiated at 20 mJ per unit area to induce an increase in phagocytosis. , 10, 100 μg / ml was treated for each concentration, and after 24 hours to determine the inhibition of phagocytosis by three hundred seconds by treatment with fluorescent microspheres. The results measured by the fluorometer are shown in Table 1 and FIG. 3.

Triticale Extract (μg / ml) Inhibition of Phagocytosis (%) Control 0 One 36.0 10 44.5 100 60.5

As shown in Table 1 and Figure 3, the extract of three hundred seconds inhibited the phagocytosis of keratinocytes depending on the concentration, when 1% treatment reduced the phagocytosis to the level before UV irradiation.

<Example 2: Effect of the extract of three hundred seconds on the death of keratinocytes irradiated with ultraviolet light>

The present inventors examined whether the decrease in phagocytosis of keratinocytes by the extract of 300 sec was directly related to the death of keratinocytes exposed to ultraviolet rays through the following test. This Example was carried out in the same system as in Test Example 2, and was also used the same UV and treatment time used in the system for evaluating phagocytic efficacy. That is, three hundred sec extract was irradiated with UVB 20mJ and treated by concentration, and after 24 hours, the degree of cytotoxicity was determined by quantifying formazan. Toxicity of keratinocytes by the extract of three hundred seconds is shown in Table 2 and FIG.

Triticale Extract (μg / ml) Cell proliferation (%) Control 100 One 96.6 10 98.0 100 105.1

As can be seen in Table 2 and Figure 4 below, the 300 seconds extract did not show any toxicity for keratinocytes exposed to UVB for 24 hours. Therefore, it can be seen that the effect of inhibiting phagocytosis of keratinocytes by the extract of trichophytium is not caused by the direct toxicity of trichophytium to the cells.

<Example 5: Effects of three hundred sec extract on melanoma acquisition of keratinocytes>

This example tests the ability of keratinocytes to acquire in vitro melanin or melanosomes, i.e. to test the function of a simplified system in which melanosomes are absorbed from the skin. Keratinocytes were incubated in the chamber slide glass, UVB was irradiated at 20mJ / cm ² . Then, a culture solution containing 1% of 300 seconds was added thereto, followed by incubation for 24 hours, and then melanosomes separated from melanocytes were added. Cells were washed with PBS and stained with Fontana-Mason ('F &M'). F & M is a method for identifying melanin inside keratinocytes by staining silver nitrate-reducing molecules. The results are shown in Figures 5a and 5b.

Figure 5a is a photograph of the untreated control group after irradiating UVB 20mJ, Figure 5b is a photograph treated with 100μg / ml three hundred seconds extract after UV irradiation for 24 hours. As can be seen in the following figures, the untreated keratinocytes absorbed melanin from the culture medium from the culture medium, while the cells treated with the 300 sec extract showed a significant decrease in external melanin uptake. Can be. Table 3 quantifies the staining results of Fontana-Mason through image analysis.

Triticale Extract (μg / ml) External melanin absorption rate (%) Control 100 100 65.3

From the above results, it can be seen that the extract of 300 seconds according to the present invention effectively inhibits phagocytosis of cells. This proved that the Triticale extract has an excellent effect in improving or preventing diseases or conditions related to phagocytosis. In particular, it is possible to block the transfer of melanin to the epidermis by effectively inhibiting the transfer of melanosomes from melanocytes to keratinocytes (keratinocytes).

The three hundred sec extract-containing composition according to the present invention has an excellent effect of effectively inhibiting phagocytosis while being very safe for keratinocytes. Therefore, secondary diseases of various diseases related to phagocytosis of cells, specifically immune system-related emphysema, allergic lung organ aspergillosis, periodontitis, cardiovascular disease caused by atherosclerotic plaque, and cancer patients It can be used as a composition that can treat or prevent infections, immune-related diseases of diabetics, Alzheimer's disease, depression, aging and the like. In particular, by effectively inhibiting the transfer of melanocytes from the melanocytes to keratinocytes can be expected to control the skin color and can treat and prevent hyperpigmentation, freckles, blemishes, spots and the like by ultraviolet rays.

Claims (7)

Phagocytosis inhibitor composition, characterized in that containing three hundred seconds extract as an active ingredient. The method of claim 1, wherein the content of the three hundred seconds extract is phagocytic inhibitor composition, characterized in that 0.0001 to 10% by weight. The method of claim 2, wherein the content of the three hundred seconds extract is phagocytic inhibitor composition, characterized in that 0.01 to 1% by weight. According to claim 1, wherein the composition is a phagocytosis inhibitor composition of the cell, characterized in that it is used for the treatment and prevention of phagocytic diseases. According to claim 4, The phagocytosis-related diseases of the cells, immune system-associated emphysema, allergic pulmonary organ Aspergillosis, periodontitis, cardiovascular disease caused by atherosclerotic plaque, cancer patients Phagocytosis inhibitor composition of the cell, characterized in that the secondary infection, immune related diseases of diabetics, Alzheimer's disease, depression, aging or skin pigmentation disease. According to claim 1, wherein the cells are keratinocytes, the composition is a phagocytosis inhibitor of the cell characterized in that the melanocytes from the melanocytes through the inhibition of phagocytosis by keratinocytes from being delivered to keratinocytes Composition. 7. The cell phagocytosis composition of claim 6, wherein the composition prevents and treats excessive deposition of melanin on the skin.