KR100964831B1 - Topical agent composition containing colostrum - Google Patents

Abstract

The present invention relates to a topical skin composition comprising colostrum as an active ingredient and applied to the skin. More specifically, as an active ingredient, colostrum includes both dark and yellow liquids or powdered cases coming out of the mammary glands within 72 hours after the birth of the mother. The present invention is an external composition for skin containing colostrum containing factors that help increase immunity and overcome various diseases such as immunoglobulins, growth factors, vitamins, minerals, various enzymes, bifidus lactic acid bacteria, albumin, complex amino acids, etc. It provides anti-allergic effect, anti-inflammatory effect, keratin differentiation effect, skin moisturizing effect, skin barrier function, skin wrinkle improvement effect and wound healing effect of colostrum by using surplus colostrum to provide skin external composition for skin improvement In addition, industrial added value can be expected.

Colostrum, cosmetics, external skin preparations, anti-inflammatory, skin barrier function enhancement, wrinkle improvement, skin moisture, wound healing

Description

Topical agent composition containing colostrum

The present invention relates to a topical skin composition comprising colostrum as an active ingredient and applied to the skin.

Colostrum includes both dark and yellow liquids or powdered cases from the mammary gland within 72 hours of the birth of the mother. Compared to normal oil, the difference in ingredients is remarkable, and it is not used as a dairy product at present. However, when the axial axis is born and exposed to various infectious agents from the outside, it contains various bioactive substances and functions that are necessary to protect the individual of the axial axis (Ishizaka S. 1998; Mustoe TA et al., 1987; van Vlasselaer et al., 1992 .; Nader de Macias et al., 1993; Uruakpa et al., 2002; Playford et al., 2000; Pakkanen R and Aalto J., 1997; Huppertz et al., 1999) .

To date, lactoferrin, a component of colostrum in the skin area, is known to be deeply involved in the inflammatory response. Lactoferrin is one of the substances normally produced and secreted in the skin as well as colostrum and is important for the regulation of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α). It is known to play a role.

Currently in Korea, colostrum secreted from cows is about 15 kg per head per day, and calf is fed about 5 kg per day. The remaining 10 kg of surplus colostrum is forbidden to be discarded on the ranch. Although there is no established system of domestic colostrum due to lack of interest in cow colostrum, colostrum milk powder and health foods made with colostrum are imported at a high price. It is necessary to establish a proper use system and to find out the characteristics of domestic colostrum to utilize domestic resources. As of 2003, domestic milk head was 278,500 kg, producing 15 kg of colostrum per head per day. If 5 kg of this is consumed, surplus colostrum is estimated to be 2,785,000 kg. Therefore, when producing products that can be industrialized using surplus colostrum, not only dairy farmers but also companies that produce products can produce profits by producing high value-added products. Conventional cosmetic development using colostrum according to the Republic of Korea Application No. 10-2005-0078393, it is known about the manufacturing method of the whitening cosmetics by linking the colostrum albumin with the whitening agent arbutin, but the simplicity of the colostrum component and the previously known whitening agent Various effects of colostrum ingredients have not been revealed through the prior art, except for the whitening effect of arbutin and the absorption of colostrum into the skin by mixing. In addition, cosmetics added with colostrum lactoferrin have been released, but colostrum contains not only lactoferrin but also a large number of immune substances, growth factors, etc., but their dermatological use is almost none.

As a result of conducting research on the condition and preservation method of colostrum in Korea (Anseong, Gyeonggi-do), the inventors found that 30% of the colostrum produced is discarded, and the value of colostrum is inferior to that of foreign colostrum. Appeared. A study on colostrum characteristics and usability in Korea was conducted mainly on human colostrum, and studies on the physiological characteristics of cow's lactoferrin (Nam et al., 1994), and the contents of immunoglobulin G and colostrum components of Korean cattle , 1991), the study on the molecular composition and fractionation of colostrum casein according to the inorganic period (Han et al., 1997), the report on the colostrum productivity of cows and the storage period by adding organic acid to colostrum (Kwon et al., 1991), etc. There is this. Kirihara (1990) said that by 3 days milking an average of 60 kg of colostrum and feeding the calf 15 kg, 45 kg of colostrum is available. Meylan et al. (1996) found that LTLT heat treatment (65 ° C, 30) resulted in a loss of 12.3% of IgG and delayed development of Mycobacterium paratuberculosis bacteria, but could not be completely removed by sterilization. A study on the use of colostrum was conducted. Pedersen (2002) et al. Confirmed that there is clinical improvement in inflammatory diseases such as lichen planus using colostrum containing oral cleanser in dermatology. Therefore, the applicability to the skin inflammatory diseases can be considered, but the effect research through the application to the skin itself has not been made yet.

Cosmetics are products used to protect the skin and to beautify and cleanse the skin, but the composition inevitably includes ingredients that are different from the purpose of protecting the skin. Examples of such ingredients are surfactants, preservatives, fragrances, sunscreens, pigments and various ingredients for adding efficacy or effects. However, these ingredients are known to cause various side effects such as inflammation or edema in the skin. In addition, sebum and sweat emitted from the body and fatty acids, higher alcohols and proteins contained in cosmetics are decomposed into highly toxic substances by skin flora, causing skin irritation and skin inflammation caused by ultraviolet rays. May be induced. Inflammatory reactions are manifested in five phenomena: erythema, tingling, burning, edema and tissue changes, which are part of the physiological response to protect the living body from the harmful environment of the surroundings, such as invasion and mechanical damage of foreign foreign substances such as bacteria. . As a result of inflammation, many types of polymorphonuclear leukocytes and immune substances are increased, and cells perform treatment and defense by releasing various kinds of proteolytic enzymes and cytokines, which are inflammatory cell products. However, this action can also cause harmful damage to adjacent tissue cells and noncellular components. Thus, under appropriate conditions, normal function is restored after the initial stage of inflammation, but if the irritant that stimulates inflammation is not removed or continues to be produced, chronic inflammation will result, resulting in more serious tissue damage. A key substance in the inflammation production process is arachidonic acid, which is converted from cell membrane lipids by phospholipase A2 (PLA2) activated by stimulation. Arachidonic acid mediates various inflammatory reactions by metabolizing prostaglandins and leukotrienes, which are inflammation mediators through two pathways, cyclooxygenase (COX) or lipoxygenase. In recent years, studies on methods for reducing skin irritation and inflammation have been actively conducted. As a result of the previous studies, nerve peptides such as substance P (Substance P) secreted from nerve cells and tissues by stimulation And various cytokines and prostaglandin E2 (PGE2) formed by kinins, such as bradykinin, which are activated in the plasma, or by the COX pathway, are involved in edema formation and vasodilation, causing inflammation and pain. It is known that this becomes. Accordingly, as anti-inflammatory agents, neuropeptide antagonists such as substance P, bradykinin antagonists, COX inhibitors, and the like have been proposed, but the anti-inflammatory agents known to date have most problems in terms of safety to the skin and stability when incorporated into the product. The situation is limited to its use.

The present inventors developed industrialization technology using surplus colostrum remaining after calf ingesting colostrum secreted from cows, and developed an external skin agent having anti-inflammatory effect utilizing the same by revealing the functionality of colostrum to prevent skin disease and problem. We want to develop products that can be applied to the skin and industrialized.

Therefore, the object of the present invention is not cytotoxic and contains colostrum that shows anti-allergic effect, anti-inflammatory effect, keratinization effect, skin moisturizing effect, skin barrier function, wrinkle improvement and wound healing effect as active ingredients It is to provide an external composition for skin, characterized in that the coating.

The present invention relates to a topical skin composition comprising colostrum as an active ingredient and applied to the skin. Skin external preparation using colostrum is characterized in that it is used in cosmetic compositions and other skin external preparations based on the results of the following biological activity studies.

In order to achieve the above object, the external preparation composition for skin according to the present invention contains colostrum as an active ingredient in an amount of 0.001 to 30% by weight based on the total weight of the composition to inhibit inflammation and relieve skin irritation, and excellent skin moisturizing effect. And a wound healing effect. The present invention also provides a cosmetic composition comprising colostrum as an active ingredient.

Hereinafter, the present invention will be described in detail.

At this time, if there is no other definition in the technical terms and scientific terms used, it has a meaning commonly understood by those of ordinary skill in the art.

In addition, repeated description of the same technical configuration and operation as in the prior art will be omitted.

The composition of the present invention relates to an external preparation composition for skin, characterized by anti-allergy, anti-inflammatory, keratin differentiation promotion, skin moisturization, skin barrier enhancement, wrinkle improvement or skin improvement of wound healing.

The composition is made of colostrum alone or by adding one or more auxiliary agents selected from excipients, diluents and antioxidants, such as softening longevity, nutrient longevity, nutrition cream, spray, warning agent, granules, lotion, essence, powder, syrup, liquid Formulations include, but are not limited to, aerosols, ointments, fluid extracts, emulsions, suspensions, dips, tablets, injections, capsules or pills. In addition, according to the anti-inflammatory agent, anti-allergic agent, skin moisturizer, anti-wrinkle agent, wound healing agent and the purpose of use, it is good to adjust the content of the active ingredient appropriately.

Examples of the excipients that can be mixed include glycerin, starch, lactose, water, alcohol, propylene glycol, salicylic acid, dahyroacetic acid or physiological saline, but are not limited thereto. Anti-inflammatory agents, anti-allergic agents, skin moisturizers, anti-wrinkle agents, wound healing agents can be used orally or parenterally, preferably parenteral, more preferably transdermal administration.

Colostrum according to the present invention can be used in cosmetic compositions because it has the effect of relieving skin irritation due to the stimulating ingredients contained in the cosmetic composition as well as the anti-inflammatory effect. The cosmetic composition may contain colostrum in an amount of 0.001 to 30% by weight, but it is preferable to properly adjust according to the content of the other ingredients contained in the formulation or cosmetic composition. When the amount of colostrum in the cosmetic composition is less than 0.001%, it may be difficult to expect a substantial anti-inflammatory effect in the cosmetic composition, and when it exceeds 30% by weight, it may be uneconomical compared to the efficacy depending on the physical properties or the cost increase.

The cosmetic composition of the present invention may be provided for the use of basic cosmetics, makeup cosmetics, body cosmetics, hair cosmetics, scalp cosmetics, shaving cosmetics or oral cosmetics. Examples of the basic cosmetics include creams, lotions, packs, massage creams, emulsions, etc. The makeup cosmetics include foundation, makeup base, lipstick, eyeshadow, eyeliner, mascara, eyebrow pencil, and the like. Examples include soaps, liquid cleansers, baths, sunscreen creams and sun oils. Hair care products include shampoos, rinses, hair treatments, hair mousses, hair liquids, pomades, hair colorants, hair bleaches, and colorants. There are rinses, hair tonics and scalp treatments as scalp cosmetics, aftershave and shaving creams as shaving cosmetics, and toothpaste and mouth washes as oral cosmetics.

As described above, the present invention provides a skin external preparation composition containing colostrum as an active ingredient, anti-allergic effect, anti-inflammatory effect, keratin differentiation promoting effect, skin moisturizing effect, skin barrier function, skin wrinkle improvement effect and By exposing the wound healing effect, it is possible to provide an external skin composition for skin improvement by using excess colostrum, and can also expect industrial added value.

Hereinafter, the present invention will be described in more detail with reference to specific examples. However, the present invention is not limited to the following examples, and it will be apparent to those skilled in the art that various changes or modifications can be made within the spirit and scope of the present invention.

Example 1 Colostrum Preparation

Colostrum used in the present invention, after recovering the dark yellow liquid from the mammary gland within 24 hours of the birth of the mother place, and then denitrified (delipidization) and powdered through a conventional treatment method. In order to evaluate the effect of colostrum using a cell culture system, first, the colostrum component was compared with the general milk component by electrophoresis method, and the results are shown in FIG. 1. In particular, since the sterilization of colostrum is required to be applied to the cell culture system, the purpose of this study was to determine whether the colostrum component changes during sterilization by filter. A 0.45 μm low protein binding membrane was used for the sterilization of colostrum. As a result of electrophoresis, colostrums 0, 1 and 2 collected immediately after delivery contained more protein of 50 kd molecular weight and other higher molecular weight proteins than normal milk. In addition, little change in protein composition was observed after sterilization with a 0.45 μm low protein binding membrane.

Example 2 Cytotoxicity Test

In this embodiment, to measure the toxicity of colostrum and colostrum components to skin cells, HaCaT cells and skin fibroblasts, which are keratinocytes, were used. Each cell was inoculated to 1 × 10 ⁴ cells in a 24-well plate and cultured for one day, and the colostrum and the fractions of the colostrum components were further cultured for one day. In order to evaluate the survival rate of the cells, the MTT reagent was treated with 1 mg / ml, followed by further 4 hours of incubation, and the culture medium was removed, followed by DMSO treatment to insoluble MTT. The cytotoxicity was evaluated by measuring the absorbance at 450 nm. The results are shown in Table 1 below.

TABLE 1

As shown in Table 1, the colostrum of Example 1 showed little cytotoxicity up to 0.1% treatment concentration.

Example 3 Antiallergic Evaluation Using Mast Cells

In this example, to investigate the anti-allergic effect of colostrum, we tried to determine whether allergen induction is inhibited by inhibiting the activity of the mast cells using MHC-1 cells, which are mast cell lines. 0.25 μM A23187 (calcium inophore) and 0.05 μM PMA were used to activate MHC-1 cells. After colostrum was treated for 30 minutes, incubated for 30 minutes, and after the addition of A23187 and PMA, the expression of inflammatory mediators IL-4, IL-5 and TNF-α was affected. Transcription-PCR, RT-PCR) was performed. The primer set used at this time is as follows.

IL-4

Forward primer: 5′-TGAACAGCCTCACAGAGCAG-3 ′ (SEQ ID NO: 1)

Reverse primer: 5′-CTCTGGTTGGCTTCCTTCAC-3 ′ (SEQ ID NO: 2)

IL-5

Forward primer: 5′-GAGACCTTGGCACTGCTTTC-3 ′ (SEQ ID NO: 3)

Reverse primer: 5′-ATCTTTGGCTGCAACAAACC-3 ′ (SEQ ID NO: 4)

TNF-α

Forward primer: 5′-AGCCCATGTTGTAGCAAACC-3 ′ (SEQ ID NO: 5)

Reverse primer: 5′-ATGTTCGTCCTCCTCACAGG-3 ′ (SEQ ID NO: 6)

The results are shown in Table 2 below.

TABLE 2

As shown in Table 2, colostrum of Example 1 inhibited inflammatory mediated cytokine expression in mast cells in a concentration-dependent manner.

Example 4 Evaluation of Antiallergic Effect of Colostrum

In this example, acute allergic reaction induced by compound 48/80 was induced in male Sprague-Dawley rats in order to verify the effect on mast cell dependent allergic inflammation in an animal model. Indicated. After colostrum was administered orally or once percutaneously for 3 days, 0.1% compound 48/80 solution was injected into the dermis. After about 30 minutes, 1% Evans blue solution was injected into the tail vein, and 1 hour later, the rats were slaughtered to extract skin. The antiallergic efficacy of colostrum was visually determined. Colostrum showed significant anti-allergic effect in both oral and transdermal administrations compared to the control group. In particular, the experimental group administered orally through sonde for 3 days showed a significant anti-allergic effect.

Example 5 Evaluation of Anti-inflammatory Effect of Colostrum Using Macrophages

In this example, Raw 264.7 cells, macrophages, were cultured in DMEM (Dulbecco's modified Eagle's medium) to analyze the anti-inflammatory effects of colostrum. Lipopolysaccharide (LPS) was treated for macrophage activity. Macrophages are important immune cells that mediate allergic inflammatory responses, and the expression of inflammatory mediators such as Cox-2, IL-6, TNF-α, and iNOS increases markedly when stimulating external antigens such as lipopolysaccharides. Could know. The effect of colostrum on the expression of these inflammatory mediators of cytokines in macrophages was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). The results are shown in Table 3 below.

[Table 3]

As shown in Table 3, colostrum of Example 1 inhibited inflammatory mediated cytokine expression in macrophages in a concentration-dependent manner.

Example 6 Evaluation of the Effect of Colostrum on Keratin Differentiation

In this example, we examined the potential of colostrum to affect the differentiation of keratinocytes and to confirm its potential as a functional material applicable to atopic dermatitis. To this end, the concentration of colostrum was treated in keratinocytes isolated from human epidermis and the expression of genes of Involucrin, Keratin10 and Filaggrin, which are structural proteins that increase when keratinocyte differentiation occurs. Was examined by reverse transcription polymerase chain reaction. The results are shown in Table 4 below.

[Table 4]

As shown in Table 4, colostrum of Example 1 increased the expression of keratinocyte differentiation-related genes in a concentration-dependent manner. These results were analyzed using Western blot as shown in Figure 3, it was observed that the increase in the protein level.

Example 7 Evaluation of the Effect of Colostrum on Glycerol Absorption

In this example, it was confirmed how colostrum promotes the absorption of glycerol into keratinocytes. The results of measuring the amount of glycerol absorbed into the cells after treatment with keratinocytes incubated with the radioisotope labeled glycerol are shown in Table 5 below.

TABLE 5

As shown in Table 5, colostrum of Example 1 promoted the absorption of keratinocytes of glycerol in a concentration-dependent manner. As a result, colostrum stimulates the absorption of glycerol, which is involved in moisturizing in keratinocytes, and enhances the function of skin barrier against dry skin and severe pruritus caused by abnormal keratinization of atopy. I could see that.

Example 8 Evaluation of the Effect of Colostrum on Elastase Activity

In this example, the effect of colostrum on the elastase activity was evaluated. 40 seconds after the mixing of elastease, elastin and colostrum, the absorbance was measured by a spectrophotometer combined enzyme immunoassay and the numerical value was obtained by substituting the following equation.

[Equation 1]

The results are shown in Table 6 below.

TABLE 6

As shown in Table 6, since the colostrum of the present invention inhibits the elastinase, it can be seen that the expression of elastin is also suppressed by the elastease, thereby improving skin wrinkles.

Example 9 Evaluation of the Effect of Colostrum on Wound Healing

The biopsy punch was used to cut a 8 mm wound inside the rabbit's ear, and then the skin was peeled off with tweezers, coated with 1% and 2% colostrum and wrapped with tape. And the results of observing the process of healing the wound for 7 days are shown in Table 7 and Figure 4 below.

TABLE 7

As shown in Table 7, it can be seen that the wound healing is faster at the portion where the colostrum of the present invention is applied.

Example 10 Preparation of Emulsion Containing Colostrum

An emulsion composition containing colostrum was prepared with the composition of Table 8 below in weight percent. In the emulsion production method of the present embodiment, a conventional production method is applied.

[Table 8]

[ Example  11] Skin moisturizing effect of colostrum containing cosmetics

The upper and lower parts of the subjects were measured with a corneometer and a tewameter before and after the application of colostrum-containing cosmetics. The results are shown in Table 9 and Table 10 below.

TABLE 9

As shown in Table 9, the skin moisture was increased in the portion of the colostrum-containing cosmetic of the present invention.

TABLE 10

As shown in Table 10, the transdermal moisture evaporation before the application of colostrum-containing cosmetics of the present invention was lowered to 21.8% in the total cosmetics.

Figure 1 shows the results of electrophoresis analysis of the components of colostrum and ordinary milk.

Figure 2 shows the effect of colostrum on the acute allergic reaction induced by compound 48/80.

Figure 3 shows the effect of colostrum on the synthesis of structural proteins increased during keratinocyte differentiation.

Figure 4 shows the effect of colostrum on wound healing.

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Claims (5)

Cosmetic composition for promoting keratin differentiation containing colostrum as an active ingredient in an amount of 0.001 to 30% by weight based on the total weight of the composition. delete delete The method of claim 1, The composition is characterized in that the colostrum is formulated as softeners, nutrients, nutrition creams, sprays, warning agents, granules, lotions or essences by incorporating one or more auxiliary agents selected from alone or excipients, diluents and antioxidants, etc. A cosmetic composition for promoting skin keratinization. delete

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