KR102615130B1 - Composition for improving atopic skin of fermented product of colostrum - Google Patents

Abstract

The present invention relates to an anti-atophytic composition of a fermentation product of colostrum, and more specifically, to a new use of a fermentation product of colostrum obtained by fermenting colostrum. The fermentation product obtained by fermenting colostrum with fermentation bacteria such as lactic acid bacteria is used to treat atopic dermatitis. and a composition for anti-atopic dermatitis that can be used as a cosmetic composition used to improve atopic skin such as psoriasis or a pharmaceutical composition used for treatment and prevention.

Description

Composition for improving atopic skin of fermented product of colostrum}

The present invention relates to an anti-atophytic composition of a fermentation product of colostrum, and more specifically, to a new use of a fermentation product of colostrum obtained by fermenting colostrum. The fermentation product obtained by fermenting colostrum with fermentation bacteria such as lactic acid bacteria is used to treat atopic dermatitis. and a composition for anti-atopic dermatitis that can be used as a cosmetic composition used to improve atopic skin such as psoriasis or a pharmaceutical composition used for treatment and prevention.

The largest organ that humans have is the skin. The skin is composed of the epidermis and dermis. The epidermis cells continuously divide and create various types of layers. At this time, the outermost cells die and become hard, making it one of the most outstanding defense organs that protects the body from external stress. Even bacteria cannot penetrate this skin.

Since the skin has sebaceous glands and sweat glands, the sebaceous glands secrete sebum and the sweat glands secrete moisture, thereby creating a sebum film and protecting the stratum corneum. For this reason, human skin is always moist, shiny, and smooth. It becomes possible.

In the case of humans, the most ideal skin is when the moisture content of the stratum corneum reaches 20%, and this is a state where beauty stands out to the fullest. However, when the moisture content falls below 10%, the dead skin cells that are supposed to protect the skin cannot stay in place and fall off or the space between them widens, making it easier for foreign substances or bacteria to penetrate, causing inflammation, disease, allergies, etc. The probability of this occurring increases. Additionally, metabolism becomes impaired, further aggravating the above-mentioned irritation. In addition, the number of people with sensitive skin due to natural pollution, ultraviolet rays, and indoor environments is increasing. In the case of such sensitive skin, side effects occur when using popular skin cosmetic compositions, resulting in erythema, stinging, itching, and in severe cases, inflammatory reactions.

Cosmetics are intended to protect, decorate, and clean the skin from the outside, but if you look closely at the composition of cosmetics, you will see that, contrary to the original meaning, ingredients necessary for the formation of the product are included, and those ingredients may actually irritate the skin. there is. For example, emulsifiers, flavorings, and preservatives are included. Since these are mostly made through chemical reaction synthesis, in the case of sensitive skin, the probability of inflammatory reactions, allergies, and erythema increases.

Lactic acid bacteria refer to bacteria that decompose carbohydrates into lactic acid through metabolism. As lactic acid increases, acidity decreases, and the acidity causes the lactic acid bacteria to die on their own. Therefore, fermentation time is important, and making it resistant to oxidative stress is also a method.

Lactic acid produced by lactic acid bacteria plays many roles. It has anti-oxidant, anti-cancer, and anti-radiation properties as well as detoxifying properties and also has anti-inflammatory effects. In addition, it has the ability to increase moisture binding in the stratum corneum, improving fine wrinkles on the skin and making the skin soft.

Interleukin 1 (IL-1) is produced by various cells such as activated mononuclear phagocytes, epithelial cells, or vascular endothelial cells, and is a type of cytokine that mediates inflammatory responses. Another representative inflammatory component is the cytokine Tumor Necrosis Factor-α (TNF-α).

Conversely, there is also a cytokine that reduces inflammatory response, Interleukin-10. In the case of interleukin-10, it plays a role in suppressing the expression of enzymes related to inflammation such as inducible nitric oxide synthase (iNOS) and inducible cyclooxyganase (COX-2) present in macrophages. (Niiro, Hiroaki, et al, 1995 )

Because lactoferrin is present in existing colostrum, it has an anti-inflammatory effect. Lactoferrin is well known to play a role in regulating Tumor Necrosis Factor-α (TNF-α) and Interleukin 1 (IL-1) (Yamanaka, 2003).

Additionally, colostrum contains Insulin-like Growth Factor-1 (IGF-1), which is known to promote overall growth and has the ability to regulate cell growth and amplification (Uruakpa et al , 2002).

Casein, contained in colostrum, accounts for 3% of all milk components and approximately 80% of milk proteins, and has been found to be an ingredient that causes allergies in our bodies when ingested (G. H. Docena et al, 1996). Additionally, casein is used as a cosmetic ingredient, but research has not been sufficiently conducted.

In addition, colostrum contains exfoliating ingredients (Kwon Yu-bin, et al. 2007) and is also known to contain TGF-beta, which suppresses melanin pigment and causes a whitening effect (Martinez-Esparza M, et al. , 1997), and colostrum contains a lot of hyaluronic acid, which has been proven to have an excellent moisturizing effect (Pedersen, et al, 2014).

As an existing cosmetic composition using such colostrum, Korean Patent No. 10-0964831 proposes a cosmetic composition for promoting skin keratin differentiation containing colostrum as an active ingredient. Here, the colostrum component has anti-inflammatory, anti-allergy, and moisturizing effects. It explains the various usefulness of cosmetics applications, including the effectiveness of colostrum ingredients in promoting skin keratin differentiation.

In addition, Korean Patent No. 10-1003740 uses a novel Streptococcus thermophilus strain and fermented colostrum probiotic for pig farming to improve the weight gain of livestock and prevent the growth of harmful intestinal microorganisms such as E. coli and Salmonella. It is proposed to reduce antibiotic use and improve productivity by preventing bacterial diarrhea disease and suppressing livestock mortality. In addition, Korean Patent Publication No. 10-2002-0021908 discloses that it is a health supplement made by fermenting colostrum using lactic acid bacteria. The fermentation method using lactic acid bacteria reduces the content of harmful microorganisms present in colostrum and extracts various functional substances contained in colostrum. We are suggesting health supplements that can be used as is.

In addition, in Korean Patent No. 10-0619289, a method for manufacturing whitening cosmetics is known by combining the albumin of colostrum with arbutin, a whitening agent, and in Korean Patent Publication No. 10-2009-0071998, a method for producing skin keratin using colostrum as an active ingredient is known. A composition for promoting differentiation has been proposed, and US Patent No. 5750149 proposes a technology for cosmetics containing substances derived from horse colostrum.

In the above patented invention, the lactic acid bacteria fermentation technology of some colostrum is known, and various effects of colostrum components, a whitening effect by arbutin, and an absorption effect of colostrum's immune elements into the skin are proposed.

However, in particular, it cannot be said to be effective in improving atopic skin, and in fact, no cosmetics or medicines have been proposed that show a proper improvement in atopic skin without side effects.

Korean Patent No. 10-0964831 Korean Patent No. 10-1003740 Korean Patent Publication No. 10-2002-0021908 Korean Patent No. 10-0619289 Korean Patent Publication No. 10-2009-0071998 US Patent No. 5,750,149

The present invention solves the problems of the prior art as described above and is based on the results of research on the utility of colostrum, and aims to provide a new use for the fermentation product obtained by fermenting colostrum components.

Therefore, the purpose of the present invention is to provide a use for improving anti-atopy dermatitis of colostrum fermentation products obtained by fermenting colostrum.

In addition, another object of the present invention is, more specifically, to provide a cosmetic composition for moisturizing and anti-atopic dermatitis for the aerobic fermentation product of colostrum.

In addition, another object of the present invention is to provide, more specifically, a pharmaceutical composition for improving atopic skin using an aerobic fermentation product of colostrum.

In order to solve the above problems, the present invention provides an anti-atopic composition containing a fermentation product of colostrum as an active ingredient.

A preferred embodiment of the present invention includes an anti-atopic composition containing as an active ingredient an aerobic fermentation product of colostrum fermented under aerobic conditions.

According to a preferred embodiment of the present invention, the aerobic fermentation product of colostrum may be a fermentation product from which fat has been removed.

According to a preferred embodiment of the present invention, the aerobic fermentation product of colostrum is Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus ) and Lactobacillus rhamnosus GG ( Lactobacillus rhamnosus GG ), it is more preferable that it is fermented with a mixture of one or more lactic acid bacteria and Streptococcus thermophilus ( Streptococcus thermophilus ).

According to a preferred embodiment of the present invention, the aerobic fermentation product of colostrum from which the casein component has been removed can be preferably used.

According to the present invention, the composition for anti-atopic dermatitis can be used as a cosmetic composition for anti-atopic dermatitis.

Additionally, the composition for anti-atopy dermatitis of the present invention can be applied as a pharmaceutical composition for treating and preventing atopy dermatitis.

Additionally, the anti-atopic composition of the present invention can be applied as a pharmaceutical composition for treating and preventing psoriasis.

Additionally, the composition for anti-atopic dermatitis of the present invention can be applied as a health functional food for anti-atopic dermatitis.

The fermentation product of colostrum according to the present invention increases the specific active ingredients contained in colostrum through fermentation and is especially effective in improving atopic skin, so it is especially excellent for atopic skin compared to similar ingredients such as existing colostrum or milk. Demonstrates improvement effect.

In particular, the fermentation product of colostrum according to the present invention is simple and easy to manufacture, and since it is fermented using microorganisms conventionally used in food production, it is non-toxic to the human body and has high stability.

Therefore, when cosmetics are manufactured using the fermentation product of colostrum according to the present invention, it is useful as an anti-atopic cosmetic composition for improving atopic skin, unlike the effect expressed by existing colostrum ingredients.

In particular, according to the present invention, unlike other bacteria, colostrum is a fermentation product that is selectively fermented with specific complex bacteria, so when applied to the skin, it is difficult to treat and treat skin diseases such as atopy and psoriasis, which are chronic skin problems. It has a very useful effect in prevention.

Figure 1 is an experimental example of the fermentation product of colostrum according to the present invention, and shows the results of a comparative experiment on the cytotoxic effect of the colostrum fermentation product prepared in the Example, milk, milk fermentation product, and colostrum, according to the concentration of each sample. This graph shows the measurement results of 12-hour cell viability using MTT assay.
Figure 2 is an experimental example of the fermentation product of colostrum according to the present invention, showing the results of the AQP3 mRNA expression level confirmation test (aquaporin experiment) using keratinocytes for the colostrum fermentation product, milk, milk fermentation product, and colostrum prepared in the example. This is a graph showing the results of a comparative experiment measuring the mRNA expression level at each concentration of each sample.
Figure 3 is an experimental example of a colostrum fermentation product according to the present invention, and is a graph showing the PCR results for each sample of the colostrum fermentation product, milk, milk fermentation product, and colostrum prepared in the example.
Figure 4 is an experimental example of the fermentation product of colostrum according to the present invention. The NO production inhibitory activity was measured using THP-1 cells for the colostrum fermentation product prepared in the example and each sample of milk, milk fermentation product, and colostrum. As a result of the measurement, this is a graph showing the results of a comparative experiment on the NO production inhibition activity at each concentration of each sample.
Figure 5 is an experimental example of the fermentation product of colostrum according to the present invention, showing the inhibitory activity of Prostaglandin E2 production using THP-1 cells for each sample of colostrum fermentation product, milk, milk fermentation product, and colostrum prepared in the examples. As a result of the measurement, this is a graph showing the actual comparative results of the PGE2 production inhibition activity at each concentration of each sample.
Figure 6 is an experimental example of a colostrum fermentation product according to the present invention. IL-1β and TNF were measured using THP-1 cells for each sample of colostrum fermentation product, milk, milk fermentation product, and colostrum prepared in the example. This is a graph showing the results of comparative experiments measuring the mRNA expression levels of -α and IL-8.
Figure 7 is an experimental example of a colostrum fermentation product according to the present invention, showing the results of measuring Hyaluronidase inhibitory activity for each sample of the colostrum fermentation product, milk, milk fermentation product, and colostrum prepared in the Example, and the results of measuring the Hyaluronidase inhibitory activity of each sample. This is a graph showing the results of a comparative experiment on Hyaluronidase inhibitory activity by concentration.

Hereinafter, the present invention will be described in more detail as an embodiment as follows.

The present invention relates to a novel use of colostrum fermentation products as a more usable fermentation product obtained from colostrum.

The fermentation product obtained by fermentation of colostrum obtained in the present invention has an excellent effect on improving atopic skin, so it can be used to replace and supplement existing chemically synthesized cosmetic compositions or side effects drugs of steroid preparations.

According to a preferred embodiment of the present invention, the aerobic fermentation product of colostrum fermented under aerobic conditions can be preferably used.

According to a preferred embodiment of the present invention, the fermentation product of colostrum may be an aerobic fermentation product from which fat has been removed.

According to a preferred embodiment of the present invention, the aerobic fermentation product of colostrum preferably includes at least one of a fermentation broth, a fermentation broth from which casein has been removed, a sterilized fermentation broth, and a lactic acid bacteria-fermented colostrum extract in which any of the fermentation broths has been purified. It can be used easily.

According to a preferred embodiment of the present invention, the aerobic fermentation product of colostrum may be a Lactobacillus Streptococcus thermophilus colostrum fermentation dissolution filtrate or a fermentation extract obtained by filtering the lysate obtained after fermentation.

According to one embodiment of the present invention, the aerobic fermentation product of colostrum is Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus rhamnosus . GG ) and Streptococcus thermophilus ( Streptococcus thermophilus ) fermented with one or more bacteria can be preferably used.

According to a preferred embodiment of the present invention, the aerobic fermentation product of colostrum is Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp. bulgaricus ) and Lactobacillus rhamnosus GG (Lactobacillus rhamnosus GG ) or more preferably fermented with a complex mixture of lactic acid bacteria and Streptococcus thermophilus .

According to a more preferred embodiment of the present invention, the aerobic fermentation product of colostrum is Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus ), Lactobacillus rhamnosus GG , and Streptococcus thermophilus are used.

According to a more preferred embodiment of the present invention, when colostrum is fermented with specific lactic acid bacteria or a complex of Lactobacillus and Streptococcus and applied to atopic skin as a natural cosmetic and pharmaceutical composition, it has an anti-atopic effect and A new use was invented that shows effectiveness in preventing and treating itching in atopic dermatitis such as psoriasis.

According to one embodiment of the present invention, the fermentation product of colostrum can be preferably used as milk or colostrum fermentation dissolution filtrate or fermentation extract of Lactobacillus Streptococcus thermophilus obtained by filtering the lysate obtained after fermentation.

According to a preferred embodiment of the present invention, the fermentation product of colostrum is hydrated Lactobacillus and Streptococcus Thermophilus colostrum fermentation extract (Hydrolyzed Lactobacillus/Streptococcus Thermophilus / Colostrum Ferment Extract) can be preferably used.

The present invention uses colostrum as a fermentation raw material, for example, specific complex bacteria, and the fermentation product efficiently fermented by the synergistic effect of the complex bacteria can be used as a more preferable composition for improving atopic skin.

According to the present invention, the complex fermentation product of colostrum, especially the aerobic fermentation product, is a composition for improving atopic skin and exhibits unexpected excellent effects in anti-atopic cosmetic compositions showing skin improvement effects, atopic dermatitis, pruritus, psoriasis, etc. . This effect can be achieved by fermenting with specific complex bacteria selectively applied to achieve an even better synergistic effect.

According to a preferred embodiment of the present invention, the fermentation product of colostrum that can be used for the above purpose may include at least one of a fermentation broth obtained by fermenting colostrum with the specific complex bacteria, a fermentation broth from which casein has been additionally removed, and a sterilized fermentation broth. You can. More preferably, a fermented broth from which casein has been removed is good.

Colostrum used as a fermentation raw material in the present invention is preferably milk expressed within 3 days after delivery.

In the present invention, the colostrum used as a fermentation raw material is preferably bovine colostrum, and here, colostrum generally includes colostrum from livestock animals such as goats and goats, but is not limited thereto.

According to a preferred embodiment of the present invention, in order to use colostrum, for example, the colostrum is rapidly cooled and then pasteurized to prepare fermentation raw materials.

Low-temperature sterilization in the present invention can be performed by a normal low-temperature sterilization method.

According to a preferred embodiment of the present invention, colostrum from which fat has been removed can be preferably used. Fat removal can be performed by separation by density difference.

According to a preferred embodiment of the present invention, the fermentation raw material obtained in the above step may be inoculated with lactic acid bacteria and fermented to obtain a fermented broth.

According to a preferred embodiment of the present invention, lactobacillus fermentation involves Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus ) and Lactobacillus rhamnosus . Complex lactic acid bacteria mixed with Streptococcus thermophilus and one or more lactic acid bacteria selected from GG ) can be preferably used, and the selective use of such specific complex bacteria is important for achieving the desired purpose of obtaining a synergistic effect, for example. It is an element.

According to the present invention, for example Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus ) produces D-lactic acid during the fermentation process, which has a detoxifying and anti-inflammatory effect and can exert anti-atopic effects and skin texture improvement effects.

Additionally, Lactobacillus rhamnosus GG ) can be effective in preventing eczema and atopy, and prevents Staphylococcus aureus, a gram-positive bacterium, from settling in and growing in keratinocytes, or helps keratinocyte migration and cell proliferation to promote re-epithelialization (GG). It can have an effect that contributes to re-epithelialization.

Therefore, in the present invention, it is preferable to select and use among the above two bacteria among Lactobacillus .

Additionally, Streptococcus thermophilus can have desirable effects on the skin, such as forming the stratum corneum structure or increasing the amount of ceramides essential for this function.

Additionally, according to the present invention, for example, Lactobacillus rhamnosus GG ) and Streptococcus thermophilus produce interleukin-10 as a synergistic effect of their mixed use, providing excellent anti-inflammatory and anti-atopic effects and prevention and treatment effects of psoriasis, lichen, etc. It can be expressed.

According to the present invention, when the complex bacteria as described above are used, the anti-inflammatory and anti-atopic effects are enhanced along with the lactoferrin of colostrum, and a synergistic effect is shown in the treatment of atopic skin diseases such as psoriasis and lichen.

For example, as a preferred example, the use of Lactobacillus rhamnosus GG can be effective in preventing eczema and atopy, and prevents Staphylococcus aureus, a gram-positive bacterium, from settling in and growing in keratinocytes. , it can help keratinocyte movement and cell proliferation, contributing to re-epithelialization.

Additionally, Streptococcus thermophilus can have desirable effects on the skin, such as forming the stratum corneum structure or increasing the amount of ceramides essential for this function.

According to the present invention, Lactobacillus rhamnosus support as described above. When using a complex of GG ) and Streptococcus thermophilus , the therapeutic activity of atopy and skin psoriasis can be greatly increased through fermentation of colostrum, and various complex components such as lactoferrin in colostrum can treat atopic It can have a synergistic effect that further enhances the skin improvement effect.

However, although the above-mentioned various functional effects are aided by the complex fermentation bacteria used, they are essentially due to the effects of fermentation products obtained after fermentation of colostrum. In particular, fermentation of colostrum with the above-mentioned selective complex bacteria In this case, the effect appears as an even better synergistic effect.

According to the present invention, for example, Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricu s) and Streptococcus thermophilus , which are used as lactic acid bacteria, can protect themselves from oxidative stress by providing polyamines to each other. In that mixed use, a more desirable synergistic effect can be expected.

More preferably, Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus ), Lactobacillus rhamnosus When the above three types of bacteria, such as GG ) and Streptococcus thermophilus , are used together, a further enhanced synergistic effect can be achieved.

According to a preferred embodiment of the present invention, fermentation using the above complex bacteria is performed by inoculating the above complex bacteria into low-temperature sterilized colostrum, which is a fermentation raw material, and more preferably at a temperature of 30 to 50° C. under aerobic conditions. It can be fermented for 120 minutes.

According to a preferred embodiment of the present invention, after the fermentation process, the fermentation product of colostrum can be obtained by centrifuging the fermentation broth to obtain a fermentation broth.

According to a preferred embodiment of the present invention, the fermentation product of colostrum of the present invention may have casein removed.

Therefore, according to a preferred embodiment of the present invention, the fermentation product of colostrum by the specific complex bacteria as described above may preferably additionally include the step of obtaining a fermentation extract by using the fermentation broth with an enzyme.

According to the present invention, the step of obtaining a fermentation extract using an enzyme from the fermentation broth is preferably, for example, a coagulation process to purify the colostrum fermentation broth that has gone through the fermentation process.

Therefore, according to a preferred embodiment of the present invention, it may include the step of obtaining a fermentation product of colostrum in which casein is removed by coagulating the fermentation broth using an enzyme.

This process is intended to remove things that may have negative effects, such as casein, contained in the fermented broth obtained by lactic acid bacteria fermentation, and the content of functional ingredients can be increased by removing casein, which has a high content in milk proteins. Therefore, enzymes are added to remove components such as casein through agglutination reaction.

Therefore, according to a preferred embodiment of the present invention, after the addition of the enzyme, a purification process may be further included including centrifuging and filtering the enzyme additive. After going through this process, the fermentation product of colostrum can be obtained in the form of a more refined fermentation product, lactic acid bacteria fermented colostrum extract.

According to a preferred embodiment of the present invention, the enzyme used to remove casein, etc. may be, for example, an enzyme complex for the role of a coagulation enzyme, and specifically, for example, rennet may be preferably used.

Rennet, as exemplified here, refers to an enzyme complex found in the stomach of ruminants. In other words, rennet is a coagulation enzyme containing rennin, one of the proteolytic enzymes, and is known to be contained together with pepsin in the gastric juice of calves. This rennet acts on milk to form casein. It is known to have the property of precipitating , and cheese that is short-ripened using the cow's stomach enzyme rennet is known to have a good aroma and a smooth feel in the mouth.

The enzyme used in the present invention can be understood to include all enzymes that exhibit similar properties to the above-mentioned rennet.

According to the present invention, when using an enzyme represented by such rennet, it can be preferably used to remove casein by causing an agglutination reaction with casein contained in fermented colostrum obtained by fermentation with complex bacteria containing the above-mentioned lactic acid bacteria.

According to a preferred embodiment of the present invention, in the enzyme addition process, the fermented broth of colostrum obtained after complex bacterial fermentation may be flocculated for 30 to 120 minutes after adding the enzyme at 30 to 40 ° C.

In addition, according to a preferred embodiment of the present invention, in the enzyme addition process, the fermentation broth may be recovered by additionally performing a coagulation process for components such as casein, followed by centrifugation and filtration. By going through this process, it is possible to obtain a fermentation product of colostrum from which the casein component has been substantially removed. The fermentation product of colostrum obtained in this way can be manufactured, for example, in the form of a lactic acid bacteria-fermented colostrum extract from which casein has been removed.

Another embodiment includes a fermentation product of colostrum obtained by fermenting colostrum from which fat and casein has been removed under aerobic conditions with fermenting bacteria.

According to a preferred embodiment of the present invention, when casein is removed before fermentation as described above and then fermented using fermentation raw materials, the casein removal process as described above can be additionally performed even after fermentation.

Therefore, according to a preferred embodiment of the present invention, the fermentation product of colostrum of the present invention can be preferably obtained from casein removed before, after, or before and after fermentation of colostrum.

In another case, according to a preferred embodiment of the present invention, the fermentation product of colostrum can be treated with, for example, rennet or by other methods to produce a fermentation product of colostrum containing glycomacropeptide (GMP). .

According to a preferred embodiment of the present invention, a fermentation product of colostrum containing glycomacropeptide has never been manufactured. These glycomacropeptides are known to be produced during the cheese-making process, but because they are highly soluble in water, they are removed and discarded along with the cheese-making by-products.

In general, glycomacropeptides contain a significant amount of sugar, but they have the ability to neutralize toxins from microorganisms produced by Escherichia coli or Vibrio bacteria, increase immune activity, help the proliferation of intestinal bifidobacteria, and lower blood pressure. It has functions such as reducing blood clotting and facilitating blood flow. It is also good for dental health as it prevents cavity-causing bacteria from attaching to teeth.

In addition, the sialic acid component contained in glycomacropeptide is effective in developing brain function and improving memory according to animal experiments.

In addition, it also affects skin beauty by promoting digestive function, appetite control, secretion of digestive enzymes in the pancreas, and secretion of cholecystokinin in the small intestine. Additionally, it can be expected to be effective in improving atopic skin.

Therefore, according to a preferred embodiment of the present invention, the fermentation product of colostrum according to the present invention contains glycomacropeptide and is useful as a health functional food. It is also useful as a pharmaceutical composition for improving the symptoms.

According to a preferred embodiment of the present invention, the aerobic fermentation product of colostrum according to the present invention may contain 0.001-15% by weight of glycomacropeptide.

According to a preferred embodiment of the present invention, the fermentation product of colostrum can be produced through additional filtration and sterilization steps.

In this way, the lactic acid bacteria-fermented colostrum extract obtained according to the present invention can be used by filtering it twice or several times after production to remove any bacteria that may be present.

The lactic acid bacteria-fermented colostrum extract obtained through the above steps according to the present invention is a preferred example of a fermentation product of colostrum, and has been confirmed to exhibit very useful properties that are different from any existing components derived from colostrum.

Therefore, the fermentation product of colostrum according to the present invention is a fermented broth obtained by fermenting colostrum with complex bacteria containing specific lactic acid bacteria, a fermented broth from which casein has been substantially removed, a sterilized fermented broth, a fermented product in which the fermented broth has been purified, or lactic acid bacteria-fermented colostrum. It may contain one or more of the extracts. An example of the most preferred type of colostrum fermentation product according to the present invention may be a purified lactic acid bacteria-fermented colostrum extract obtained by purifying the fermentation broth and sterilizing it to contain no casein.

According to a preferred embodiment of the present invention, by fermenting colostrum with specific complex bacteria as described above, excellent effects can be exhibited, unlike in the past, and in particular, the specific lactic acid bacteria and Streptococcus thermophilus bacteria of the present invention are selected and combined. Because it exerts a synergistic effect when used, surprising results can be obtained in which an excellent synergistic effect can be expected, showing far superior activity compared to using a complex of other bacteria or a single lactic acid bacteria.

In this way, the fermentation product of colostrum according to the present invention can achieve a particularly useful effect in improving atopic skin, and when additionally purified, the disadvantages caused by casein, etc. are excluded and the content of functional ingredients is increased, thereby further improving the skin condition. Moisturizing and anti-atopic effects, which show desirable results, and treatment and prevention effects of atopic skin diseases such as atopic dermatitis, pruritus, psoriasis, and lichen can be achieved at the same time, resulting in an excellent synergistic effect that was previously unpredictable.

Meanwhile, in order to replace and supplement chemically synthesized cosmetic compositions, which are existing cosmetics, the present invention manufactures a natural cosmetic composition using the fermentation product of acetic acid according to the present invention, and contains it as an active ingredient for moisturizing and anti-atopic use. Includes provision of cosmetic compositions.

In addition, the fermentation product of colostrum according to the present invention, such as especially the colostrum fermentation extract, has a surprising effect of showing a synergistic effect in the treatment of psoriasis and lichen in addition to the skin moisturizing and atopic dermatitis treatment effect due to the fermentation of colostrum.

Accordingly, the present invention includes the provision of a pharmaceutical composition for the treatment and prevention of atopy or psoriasis.

When colostrum fermentation products go through a refining process, they exclude disadvantages such as casein and increase the content of functional ingredients. In particular, they have unpredictable excellent skin moisturizing properties compared to milk fermentation products or colostrum, while preventing atopic dermatitis such as atopy or psoriasis. This can show an effect on skin improvement.

Psoriasis is a disease that forms erythematous papules and plaques of various sizes with well-defined borders covered with silvery-white scales on the skin. Histologically, it is characterized by hyperproliferation of the epithelium and is a chronic inflammatory condition with repeated worsening and improvement. It is a skin disease.

The cause of psoriasis is generally thought to be genetic factors, environmental deterioration or triggers, and immunological factors, but it is not clear. Currently, it is known that psoriasis is caused by genetic factors, an individual's lifestyle, and environmental factors, and that immunological factors cause proliferation of keratinocytes and inflammatory reactions. Factors that worsen or cause psoriasis include skin trauma, infection, cold and dry climates such as winter, dry skin, stress, and medications, which are related to skin moisturization.

Psoriasis usually occurs symmetrically and occurs in areas that receive a lot of stimulation, such as the shins, elbows, knees, sacrum, scalp, and neck. Psoriasis initially causes small, red, millet-like rashes to appear on the skin, which gradually become larger. Additionally, new millet-like rashes appear around the area, and as they grow larger, they merge together. In the psoriasis area, white scale-like scales appear in layers, and when the scales are removed, petechial hemorrhages appear.

Lichen refers to a condition in which the skin becomes thickened. This is mainly due to frequent scratching of the skin, which causes the skin to become thick and wrinkled so badly that it looks like elephant skin. This is called the lichenification phenomenon, and the rash that appears when lichenification does not cause blisters, suppuration, or skin destruction, but in rare cases, blisters may occur.

In particular, lichen pilaris refers to small red or gray papules that protrude sharply from the pores. It is most common in people with dry skin and is most common on the arms, legs, elbows, and shoulders.

According to a preferred embodiment of the present invention, the colostrum fermentation product of the present invention has excellent anti-inflammatory and antibacterial effects, unlike existing milk or colostrum, and exhibits a skin moisturizing effect and excellent therapeutic activity for atopy and psoriasis, and is contained in the colostrum fermentation product. By significantly improving the atopic skin environment with various ingredients, it can be suitably used as a moisturizing and anti-atopic cosmetic composition of natural ingredients or a pharmaceutical composition for the treatment and prevention of atopy or psoriasis.

Therefore, according to a preferred embodiment of the present invention, it includes an anti-atopic cosmetic composition containing a fermentation product of colostrum, more preferably an aerobic fermentation product of colostrum, as an active ingredient.

According to a preferred embodiment of the present invention, a pharmaceutical composition for the treatment and prevention of atopy containing a fermentation product of colostrum, more preferably an aerobic fermentation product of colostrum, as an active ingredient.

According to a preferred embodiment of the present invention, a pharmaceutical composition for treating and preventing psoriasis containing a fermentation product of colostrum, more preferably an aerobic fermentation product of colostrum, as an active ingredient.

According to a preferred embodiment of the present invention, an anti-atopic health functional food containing a fermentation product of colostrum, more preferably an aerobic fermentation product of colostrum, as an active ingredient is included.

According to a preferred embodiment of the present invention, a health functional food for improving and preventing psoriasis containing a fermentation product of colostrum, more preferably an aerobic fermentation product of colostrum, as an active ingredient.

According to a preferred embodiment of the present invention, the fermentation product of colostrum in the cosmetic composition or pharmaceutical composition may be contained in an amount of 0.01 to 40% by weight based on the total weight of the composition. If it exceeds the lower limit of the above content range, the effect is significantly reduced, and if it exceeds the upper limit, it is difficult to manufacture it as a cosmetic or pharmaceutical formulation, or it is undesirable from an economic standpoint.

According to a preferred embodiment of the present invention, the fermentation product of colostrum prepared by the above method can be added to a cosmetic composition or pharmaceutical composition in various forms, for example, as a fermented colostrum extract, for example, in powder form, liquid form, nanocapsule, It can be added in the form of a complex, etc., and as a preferred example, it can be added in liquid form.

According to the present invention, the cosmetic composition containing the fermentation product of colostrum can be used in cosmetic formulations such as lotion (skin lotion), nutritional lotion, nutritional cream, massage cream, nutritional essence, cleanser, and mask pack, and is specifically limited thereto. It does not mean that it can be used in other hair preparations or skin preparations for various functional effects.

In the case of the cosmetic composition of the colostrum fermentation product according to the present invention, the raw material is colostrum and the fermenting bacteria used to ferment it are natural microorganisms that have been conventionally used in food production, so the extract itself is highly safe, and is used as an anti-atopic cosmetic or atopic or In terms of the treatment and prevention of psoriasis, it is far more effective than cow's milk, fermented milk, or colostrum.

In particular, by fermenting colostrum and using specific complex bacteria, it shows a remarkable atopic skin improvement effect that is more unpredictable due to the synergistic effect of selective complex fermentation compared to using other lactic acid bacteria and complex bacteria of other bacteria.

In this way, the colostrum fermentation product according to the present invention is applied as an anti-atopic cosmetic composition for use as a composition for improving atopic skin and used as a cosmetic on the skin, or as a pharmaceutical composition for the treatment and prevention of atopy or psoriasis. Therefore, for example, when used in cream form or skin ointment, synergistic effects such as improving atopic skin and treating atopic skin diseases can be expected, so it is expected to be very useful as a new concept cosmetic composition or pharmaceutical composition.

The cosmetic composition or pharmaceutical composition containing the colostrum fermentation product of the present invention as an active ingredient can be specifically applied by applying to the skin several times at 1-500 mg/ml.

According to a preferred embodiment of the present invention, it can be more preferably applied at 10-400 mg/ml.

According to a preferred embodiment of the present invention, cosmetics using the anti-atopy cosmetic composition containing the colostrum fermentation product according to the present invention as an active ingredient, or skin for the treatment and prevention of atopy or psoriasis containing the colostrum fermentation product as an active ingredient. The ointment can be manufactured and applied in various contents within the above content range, such as 50 mg/ml, 100 mg/ml, 200 mg/ml, and 400 mg/ml.

In addition, the health food or oral pharmaceutical composition according to the present invention can be administered orally 1-3 times a day as an oral agent, for example, at 50 mg, 100 mg, 200 mg, 400 mg, 500 mg, or 1,000 mg at a time.

According to a preferred embodiment of the present invention, if the colostrum fermentation product exceeds the lower limit of the above content range, the effect is significantly reduced, and if it exceeds the upper limit, it is difficult to prepare a composition or formulation for skin application, or it is difficult to prepare a composition or formulation for skin application, or It is not desirable from an economic perspective because the expected effect is not significantly improved.

Hereinafter, the present invention will be described in detail through examples, but the present invention is not limited by the examples.

Example 1

In order to prepare a fermented colostrum extract, which is a fermentation product from colostrum, the fermented colostrum extract was prepared through the following process.

Step 1: Preparation of raw materials

Freshly squeezed cow's colostrum is rapidly cooled, placed in a constant temperature water tank, sterilized for 30 minutes after the temperature of the colostrum reaches 63℃, and then lowered to 35℃ to prepare fermentation raw materials.

Step 2: Preparation of lactic acid bacteria fermentation broth

Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus , ATCC 11842), Streptococcus thermophilus ( ATCC 19258), and Lactobacillus rhamnosus GG (ATCC 53103) were inoculated into the fermentation raw material of the first stage and aerobically Fermented product (fermented liquid) is obtained by fermenting for 60 minutes at a temperature of 35°C.

Step 3: Preparation of fermented colostrum extract

The fermentation broth obtained in the second step is centrifuged at 2000 rpm for 20 minutes to remove suspended matter, and the supernatant excluding the sediment is recovered to obtain fermented colostrum liquid as a fermentation product of colostrum.

The fermented colostrum fluid is adjusted to 33°C, rennet is added, coagulated for 60 minutes, and the fermented colostrum product is recovered. The fermented colostrum product obtained above is centrifuged at 13000 rpm for 60 minutes, and the supernatant is obtained as a fermented colostrum extract, which is a fermentation product.

The supernatant was filtered a second time through filter paper of 0.4 ㎛ and 0.2 ㎛, and then a fermented colostrum extract was prepared as a final fermentation product of lactic acid bacteria.

Examples 2-6

Colostrum fermentation product was prepared in the same manner as in Example 1 by adjusting the bacteria or complex bacteria inoculated into the fermentation raw material in the first step in Example 1 as shown in Table 1 below.

division strain used Example 2 Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus , ATCC 11842) Example 3 Lactobacillus rhamnosus GG , ATCC 53103) Example 4 Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus , ATCC 11842)
+ Lactobacillus rhamnosus GG , ATCC 53103) Example 5 Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus , ATCC 11842)
+ Streptococcus thermophilus (ATCC 19258) Example 6 Lactobacillus rhamnosus GG , ATCC 53103)
+ Streptococcus thermophilus ( ATCC 19258)

Example 7

A fermentation product of colostrum was prepared in the same manner as in Example 1, except that Streptococcus thermophilus (ATCC 19258) was used alone as the bacteria used for fermentation.

Example 8

In the method of Example 2, Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . A fermented colostrum extract was prepared in the same manner as in Example 2, except that Lactobacillus acidophilus (ATCC 4356) was used instead of bulgaricus (ATCC 11842).

Example 9

Lactobacillus bulgaricus ( Lactobacillus delbrueckii subsp . bulgaricus , ATCC 11842), except that Lactobacillus acidophilus (ATCC 4356) and Streptococcus thermophilus (ATCC 19258) were used instead of Streptococcus thermophilus (ATCC 19258 ). Then, a fermented colostrum extract was prepared in the same manner as in the above example.

Comparative Example 1-9

Fermentation was carried out in the same manner as in Example 1-9, but the fermentation conditions were anaerobic rather than aerobic.

To confirm the above effects, check Hyaluronidase enzyme activity, IL-8 production inhibition effect, NO production inhibition effect, PGE2 production inhibition effect, moisturizing activity measurement (aquaporins), moisturizing ability measurement evaluation through water weight change, Corneometer moisture content Evaluation and TEWL change experiments were conducted. The following experimental examples show results showing excellent efficacy.

Experimental Example 1: Cytotoxicity experiment

For each sample, cell viability was measured using MTT assay.

MTT assa y is an experimental method widely used for cell proliferation or toxicity by measuring the number of living cells. Living cells are water-soluble within the mitochondria, and MTT, a yellow salt, is converted into a water-insoluble blue formazan derivative by succinate dehydrogenase. It uses the principle of reduction.

First, HaCaT cells were inoculated into a 6-well plate at a density of 1x10^5 cells/well and cultured at 37°C for one day. Afterwards, each sample (milk, milk fermentation, colostrum, and colostrum fermentation) was treated in each well at different concentrations (1, 10, and 20 ug/ml). After culturing at 37°C for 12 hours, the cells were treated with MTT solution, activated for 1 hour, and measured at 450 nm with an ELISA reader. Control was conducted with H2O2, and cell survival rate was shown compared to the control group.

The experimental results are shown in Table 2 and Figure 1, and it was confirmed that fermented colostrum, a fermented colostrum product, showed a superior survival rate compared to other comparison groups.

12H control 100 0.2 milk 1ug/ml 90 0.05 10ug/ml 118 0.1 20ug/ml 107 0.04 milk fermentation 1ug/ml 100 0.06 10ug/ml 105 0.18 20ug/ml 94 0.1 beestings 1ug/ml 81 0.1 10ug/ml 108 0.11 20ug/ml 106 0.07 Colostrum fermentation 1ug/ml 122 0.18 10ug/ml 126 0.14 20ug/ml 125 0.26

Experimental Example 2: Confirmation of AQP3 mRNA expression level using keratinocytes

There are 13 types of aquaporins (AQP0-AQ P12) in mammals. When examined with skin-related cells such as human keratinocytes, melanocytes, and skin fibroblasts, a total of 6 types of AQPs 1, 3, 5, 7, 9, and 10 can be found. Among them, AQP3 is found in Epidermis and plays a role in permeating both water and glycerol. In conclusion, AQP3 deletion shows normal skin structure, but has the effect of reducing moisture in the stratum corneum and reducing epidermal permeability to water and glycerol. Accordingly, the moisturizing effect was confirmed using the expression level of AQP3 mRNA.

As an experimental method, first, dispense keratino cytes into a 6-well plate at 4x10^5cells/well, and after culturing for 24 hours, each sample (milk, milk fermentation, colostrum, and colostrum fermentation) was mixed by concentration (0, 1, 10, 100ug). /ml). After 3 hours, the cells were collected, RNA was extracted, and cDNA was synthesized. Real-time PCR was performed with the produced cDNA to measure the expression level of mRNA, and the increase rate was shown compared to the no addition group.

The results are shown in Table 3 and Figure 2 below, and Figure 3 shows the PCR results for each sample.

As a result of the above test, no significant moisturizing effect was obtained from milk and colostrum. However, it was confirmed that the amount of mRNA expression increased in a concentration-dependent manner in milk fermentation and colostrum fermentation. In particular, in the colostrum fermentation group at 100ug/ml, the mRNA expression level increased by more than 8 times compared to the no-added group, confirming that the moisturizing effect was very excellent.

Experimental Example 3: Measurement of nitric oxide (NO) production inhibition activity

Lipopolysaccharide (LPS), which is mainly used as an inflammation model, activates macrophages. Activated macrophages produce pro-inflammatory cytokine TNF-α. Increases the expression amount of IL-1β, IL-12, and IFNγ. Pro-inflammatory cytokines produce nitric oxide (NO). Therefore, the anti-inflammatory effect was evaluated by reducing the amount of NO expression.

As an experimental method, THP-1 cells were placed in a 12-well plate at a rate of 1 It was cultured for more time. After incubation, 100 ㎕ of cell supernatant and 100 ㎕ of Griess reagent are mixed, reacted for 10 minutes in a 96 well plate, and absorbance is measured at 540 nm. The amount of NO produced was measured in the form of NO2- present in the cell culture using Griess reagent, and sodium nitrite (NaNO2) was used as a standard.

The LPS-only treatment group induced NO production, and the NO production inhibition activity for each sample was measured.

The result values are shown in Figure 4.

Experimental Example 4: Confirmation of the effect of suppressing prostaglandin (Prostaglandin E2) production

We investigated the effect of inhibiting the production of prostaglandin E2 (PGE2), which is known to play an important role in causing inflammation. Cyclooxygenase (COX) is an enzyme that converts arachidonic acid into prostaglandin and is classified into COX-1 and COX-2. COX-1 acts on normal biological functions in the body, such as the formation of platelets, protection of the stomach lining, and maintenance of kidney function, while COX-2 forms PGE2, an inflammatory mediator. PGE2 is known to be deeply involved in the development of cancer, including promoting inflammatory responses, immune responses, and angiogenesis.

As an experimental method, THP-1 cells were dispensed at a rate of 1 Cultured for another 24 hours. The amount of PGE2 produced was expressed by calculating the value measured using the PGE2 ELISA kit using the following equation (1). The control group was an experimental group treated with LPS alone. The PGE2 production inhibition rate was calculated using the following equation, and the results are shown in Figure 5.

[Equation 1]

(In the above formula, S is the amount of PGE2 in the sample treatment, and C is the amount of PGE2 in the experimental group treated with LPS alone.)

Significance was verified through a test. (P<0.01)

Experimental Example 5: Confirmation of inflammatory factor mRNA expression level using monocytes

Confirmation of increased concentrations of IL-1β, TNF-α, and IL-8, which are essential factors involved in the migration activation of neutrophils during an acute inflammatory response, is used as an indicator of the inflammatory response. Accordingly, the inflammatory response was confirmed by confirming changes in the mRNA expression levels of IL-1β, TNF-α, and IL-8.

As an experimental method, first, monocyte THP-1 cells were dispensed at 1x10^6cells/well in a 12 well plate, and after culturing for 24 hours, each sample (milk, milk fermentation, colostrum, colostrum fermentation) was divided by concentration (0, 1, 10). , 100%). After 24 hours, cells were collected, RNA was extracted, and cDNA was synthesized. Real-time PCR was performed with the produced cDNA to measure the expression level of mRNA, and the increase rate was shown compared to the no addition group.

The result values are shown in Figure 6.

Experimental Example 6: Measurement of inhibitory effect on inflammation-related enzyme (hyaluronidase) activity

Hyaluronidase is an enzyme that hydrolyzes hyaluronic acid and causes inflammation. Additionally, since hyaluronic acid is an ingredient that increases moisturizing power, decomposing it causes a decrease in moisturizing power. Hyaluronidase inhibitory activity is measured by converting N-acetylglucosamine formed from sodium-hyaluronic acid (HA) added as a substrate into a glucoxazoline derivative and reacting with p-dimethylamino benzaldehyde (DMAB) added as a coloring agent. The enzyme inhibition effect was measured by measuring the degree of decrease in absorbance of the color developed.

The experimental method was to mix 0.05ml of hyaluronidase (7,900 unit/mL) dissolved in 0.1M acetate buffer (pH 3.5) and 0.1ml of sample solution (milk, milk fermentation, colostrum, colostrum fermentation) and incubate at 37°C for 20 minutes. After reaction, 0.1 ml of 12.5mM calcium chloride (CaCl2) was added, mixed, and reacted for another 20 minutes. In the control group, 0.05 ml of hyaluronidase (7,900 unit/mL) and 0.1 ml of distilled water were mixed instead of the P. chinensis extract, and hyaluronic acid (HA; 12 mg/mL) dissolved in 0.1M acetate buffer (pH 3.5) was added as a substrate. After reacting for another 40 minutes, 0.1 ml of 0.4N potassium tetraborate and 0.4N NaOH solution were added to 0.1 ml of the reaction mixture, heated on a water bath for 3 minutes, and then completely cooled.

To the cooled reaction product, 3 mL of p-dimethylamino benzaldehyde (DMAB) reagent (4 g of p-dimethylamino benzaldehyde dissolved in 350 ml of 100% acetic acid and 50 ml of 10 N hydrochloric acid) was added and reacted at 37°C for 20 minutes. Next, the inhibitory activity was calculated by measuring the absorbance at 585 nm. Hyaluronidase inhibitory activity was calculated using the formula below, and the significance of the experimental results was verified through Student's T test.

[Equation 2]

(In the above formula, S is the absorbance of the reaction solution containing the sample and enzyme, and C is the absorbance of the solution without the sample.)

The result values are shown in Figure 7.

Claims (16)

The aerobic fermentation product obtained by fermenting colostrum under aerobic conditions contains the active ingredients Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus rhamnosus GG, and Streptococcus thermophilus. An anti-atopic dermatitis composition containing as an active ingredient an aerobic fermentation product of colostrum obtained after fermentation with mixed complex bacteria, and containing 0.001-15% by weight of glycomacropeptide (GMP).
delete delete delete The composition for anti-atopic dermatitis according to claim 1, wherein the aerobic fermentation product of colostrum is a fermentation broth from which fat and casein has been removed, or a fermentation broth that has been further sterilized and fermented under aerobic conditions.
delete delete delete delete delete A cosmetic composition for anti-atopic dermatitis containing the composition for anti-atopic dermatitis according to claim 1 or 5 as an active ingredient.
A pharmaceutical composition for the treatment and prevention of atopy containing the anti-atopic composition according to claim 1 or 5 as an active ingredient.
A pharmaceutical composition for the treatment and prevention of psoriasis containing the aerobic fermentation product of colostrum according to claim 1 or 5 as an active ingredient.
A skin ointment for the treatment of atopic skin disease containing the aerobic fermentation product of colostrum according to claim 1 or 5 as an active ingredient.
A health functional food for improving and preventing atopy containing the aerobic fermentation product of colostrum according to claim 1 or 5 as an active ingredient.
A health functional food for improving and preventing psoriasis containing the aerobic fermentation product of colostrum according to claim 1 or 5 as an active ingredient.