KR101086503B1 - Pharmaceutical composition comprising lactobacillus and pharmaceutical composition of gold with culturing with lactobacillus for therapy against atopy dermatitis - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing and treating atopic dermatitis, which comprises lactic acid bacteria as an active ingredient and is administered to the skin, and a pharmaceutical composition comprising gold cultured with the bacteria. When the composition according to the present invention is administered to the skin, it is possible to improve the prevention, symptom relief and therapeutic effect of atopic dermatitis due to the fundamental change of the body's immune system, as well as resistance by using microorganism strains harmless to the human body. Side effects of the chemical agent can be prevented and safety is secured.

Lactic acid bacteria, atopy, dermatitis, gold, composition

Description

Pharmaceutical composition comprising lactobacillus and pharmaceutical composition of gold with culturing with lactobacillus for therapy against atopy dermatitis}

The present invention relates to a pharmaceutical composition comprising lactic acid bacteria for treating atopic dermatitis and a pharmaceutical composition comprising pure gold cultured with the bacteria. More specifically, the present invention can improve the prevention, symptom relief and therapeutic effect of atopic dermatitis as a fundamental change in the body's immune system when applied to the skin, as well as resistance to conventional chemicals using microbial strains that are harmless to the human body. It relates to a pharmaceutical composition comprising lactic acid bacteria for the treatment of atopic dermatitis, which can prevent side effects of and to ensure safety, and a pharmaceutical composition comprising pure gold cultured with the bacteria.

In modern society, allergic diseases are increasing every year due to the increase of natural environment pollution, the change of dietary life, and the weight of stress due to industrial development. Allergy is a biochemical phenomenon that shows a specific and modified response to a foreign substance (antigen, Allergen), and the resulting disease is called an allergic disease. Allergic diseases include various diseases including autoimmune diseases and collagen diseases, but in general, allergic diseases refer to classic allergic diseases in which atopic diseases are the main. This includes anaphylactic shock, allergic rhinitis, pollinosis, bronchial asthma, pharmaceutical allergies, plant allergies, rashes, eczema, atopic dermatitis, and allergic contact dermatitis.

Atopic dermatitis is an incurable disease that cannot be precisely defined by modern medical techniques. It is known that the immune system induces hypersensitivity reactions to external stimuli. It is known that secretion of histamines induces itching and inflammation, mainly by increasing the concentration of IgE in the blood. However, due to the various and complex causes, no suitable treatment is currently developed.

On the other hand, the recent development of atopic dermatitis from children to adults in a wide range of domestic and international development of urgent treatment is urgent. Currently, steroidal atopic dermatitis inhibitors are used as therapeutic agents. Commercially available methods of applying ointments such as steroids are often used when severe symptoms such as inflammation, steroids are a kind of corticosteroids, but the effect is very good, but caution should be used. If the symptoms are not severe, it is desirable to refrain from using it. When the symptoms of the skin are very severe or scratched or wounded or inflamed, it is possible to minimize the side effects. And common side effects for steroids include skin atrophy, vasodilation, discoloration, and purpura, and worsen skin. This worsened skin may reveal capillaries. In addition, there is a case in which the resistance of the germ to the drug is generated, the less effective the use, and there is a rebound phenomenon (recurrence) due to discontinuation of use. Therefore, steroid preparations show temporary alleviating effects rather than the original solution of atopic dermatitis, and at the same time, there is a known side effect of developing resistance.

On the other hand, lactic acid bacteria are called lactic acid bacteria and refers to bacteria that produce a significant amount of lactic acid as the final product. Lactic acid bacteria are one of the microorganisms that have been used by whales in human diet, and are widely used in fermented foods such as kimchi in Korea and dairy fermented foods in the West. Recently, researches on lactic acid bacteria have been actively conducted, and the range of application is being widened, such as not only general foods but also used as health functional foods and medicines. , The genus Leuconostoc, the genus Lactobacillus (Latobacillus), the sporolactobacillus (Sporolactobacillus) and the genus Bifidobacterium (Bifidobacterium).

Such a role of lactic acid bacteria has been reported to inhibit the growth of pathogens in the intestine, to produce substances that control the immune capacity of intestinal epithelial cells and immune cells, and to compete with pathogens to inhibit the growth of pathogens. Lactobacillus is a lactic acid bacterium that has strong acid resistance and is known to act on intestinal and anticancer effects, lowering blood cholesterol and synthesizing vitamin B group. In other words, lactic acid bacteria inhibit the growth of harmful bacteria in the intestine, promote digestion, increase immunity in the intestine, and soften the stools. In particular, Lactobacillus asidophilus adheres to the intestinal mucosa, causing pathogens and carcinogens. It is reported that the effect of excretion in vitro is excellent. In addition, it is reported that the lactic acid bacteria preparation is effective as an agent for preventing and treating antibiotic-associated diarrhea, or an inhibitor of rotavirus infection. However, no composition for preventing and treating atopic dermatitis through skin administration has been reported.

The present invention has been made to solve the problems of the prior art, an object of the present invention is to provide a biological preparation containing lactic acid bacteria that shows excellent preventive and therapeutic effects for atopic dermatitis upon skin administration and does not have any side effects.

Another object of the present invention is to provide a novel functional cosmetic preparation that shows excellent preventive and therapeutic effects against atopic dermatitis upon skin application and has no side effects.

Other objects and advantages of the present invention will become apparent from the following detailed description, claims and drawings.

According to an aspect of the present invention, the present invention provides a pharmaceutical composition for preventing and treating atopic dermatitis, which comprises lactic acid bacteria as an active ingredient and is administered to the skin.

The present inventors apply lactic acid strains to the skin of a biologic formulation for skin application and apply the same to the skin of mice (NCNGa) that induced atopic dermatitis, thereby inhibiting inflammation and alleviating dermatitis by a control group not administered with the strain. The present invention has been achieved by comparing and confirming the effect.

According to a specific aspect of the present invention, the lactic acid bacteria are Lactobacillus acidophilus La5 (Lactobacillus acidophilus La5), Bifidobacterium lactic Bb12 (Bifidobacterium lactic Bb12), Streptococcus thermophilus, Lactobacillus vulgaris and It may be selected from one or more of the group consisting of oligoflutose (Lactobacillus bulgaricus and oligofructose).

The strains are known strains can be prepared by a culture method commonly used in the art, and can be easily obtained on the market. The present inventors purchased a commercially available strain from CHR-Hansen (Denmark). When the strain is administered in the form of oral administration, which is a common lactic acid bacterium, it has been shown that little effect on atopic dermatitis occurs.

Therefore, the composition according to the present invention is preferably administered to the skin or subcutaneous injection. The pharmaceutical compositions of the present invention are not oral preparations such as tablets, capsules, granules, suspensions, and are not administered in the form of injections or other suitable pharmaceutical forms in the form of ampoules for intravenous and intramuscular injection.

In addition, the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier in addition to the above components as an active ingredient. In addition, the compositions of the present invention may further comprise physiologically resistant excipients and / or diluents and / or adjuvants conventionally used in pharmaceutical formulations. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995), to which reference may be made.

The composition of the present invention is administered in a therapeutically effective amount. The term “therapeutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, the effective amount being the severity, age, sex, time of administration, administration of the disease. Route and rate of release, duration of treatment, factors including concomitant medications, and other factors well known in the medical arts. For example, the pharmaceutical composition of the present invention may be administered to the adult 10 ³ viable cells / times to 10 ¹⁰ viable cells / times based on the lactic acid strain of the active ingredient, can be increased or decreased depending on the severity of atopic dermatitis. .

When two or more kinds of the lactic acid bacteria are selected, they are administered sequentially or simultaneously.

The composition is characterized in that it is a liquid or solid formulation in the form of a solution, suspension or emulsion in an oil or aqueous medium.

According to another aspect of the present invention, the present invention provides a pharmaceutical composition for the prevention and treatment of atopic dermatitis comprising a bacterial coating gold obtained by culturing the lactic acid bacteria with gold as an active ingredient.

 According to a specific aspect of the present invention, the lactic acid bacteria are Lactobacillus acidophilus La5 (Lactobacillus acidophilus La5), Bifidobacterium lactic Bb12 (Bifidobacterium lactic Bb12), Streptococcus thermophilus, Lactobacillus vulgaris and It may be selected from one or more of the group consisting of Lactobacillus bulgaricus and oligofructose.

The strains are known and can be prepared and cultured by a culture method commonly used in the art, and can be easily obtained on the market. The present inventors purchased a commercially available strain from CHR-Hansen (Denmark).

The gold is preferably pure gold, and the particle size of gold is preferably 1mm * 1mm * 0.0001mm, but is not limited thereto. In addition, the culture conditions may be cultured by a culture method commonly used in the art (Ref. Journal of Microbiology and Biotechnology, Vol. 14, No. 3, 503-508).

The composition comprising the bacterial coating gold of the present invention has the advantage of synergistic effects and commercial preparations due to the efficacy of the gold itself beneficial to the human body, such as more effective stimulation on the skin surface with the efficacy of the lactic acid bacteria. Anti-magnetic properties of gold include the effects of preventing skin aging through promoting blood circulation due to ionic effects, skin activation by promoting hormone secretion, preventing skin inflammation and acne healing by detoxification, and strengthening immune function. have.

The pharmaceutical composition of the present invention is preferably administered to the skin or administered by subcutaneous injection, but is not limited thereto.

In addition, the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier in addition to the above components as an active ingredient. In addition, the compositions of the present invention may further comprise physiologically resistant excipients and / or diluents and / or adjuvants conventionally used in pharmaceutical formulations. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995), to which reference may be made.

The composition of the present invention is administered in a therapeutically effective amount. The term “therapeutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, with the effective amount being the severity, age, sex, time of administration, administration of the disease. Route and rate of release, duration of treatment, factors including concomitant medications, and other factors well known in the medical arts. For example, the pharmaceutical composition of the present invention may be administered to the adult 10 ³ viable cells / times to 10 ¹⁰ viable cells / times based on the lactic acid strain of the active ingredient, and can be increased or decreased depending on the severity of atopic dermatitis. .

When two or more kinds of lactic acid bacteria are selected, the composition is administered sequentially or simultaneously.

The composition is characterized in that it is a liquid or solid formulation in the form of a solution, suspension or emulsion in an oil or aqueous medium.

According to another aspect of the present invention, it provides a cosmetic for improving atopic dermatitis, comprising lactic acid bacteria as an active ingredient, or a bacterial coating gold obtained by culturing the lactic acid bacteria with gold as an active ingredient and applied to the skin. .

 According to a specific aspect of the present invention, the lactic acid bacteria is Lactobacillus acidophilus La5 (Lactobacillus acidophilus La5), Bifidobacterium lactic Bb12 (Bepdobacterium lactic Bb12), Streptococcus thermophilus, Lactobacillus vulgaris and It may be selected from one or more of the group consisting of oligoflutose (Lactobacillus bulgaricus and oligofructose).

The cosmetic may be contained as one or more selected from diluents, softeners, moisturizers, emulsifiers, surfactants, bioactive substances and purified water known in the art in addition to the components. In addition, the cosmetics may be contained in addition to at least one selected from viscosity regulators, neutralizing agents, chelating agents, astringents, preservatives, decontaminants known in the art. Since the specific component composition can be easily manufactured by a person skilled in the art as needed, detailed description is abbreviate | omitted.

On the other hand, it can be formulated according to a method that can be easily carried out by those of ordinary skill in the art. The formulations can then be prepared in the form of solutions, suspensions or emulsifiers in oils or aqueous media, with sprays, lotions, creams, skins and the like which are easy to apply to the skin.

Cosmetics of the present invention can be administered to the adult 10 ³ viable cells / times to 10 ¹⁰ viable cells / times based on the lactic acid strain which is the active ingredient, depending on the type of cosmetics adjusted according to the severity of atopic dermatitis can do.

In the present invention, microorganisms of lactic acid strains (Lactobacillus acidophilus La5, Bifidobacterium lactic Bb12, Streptococcus thermophilus, Lactobacillus bulgaricus and oligofructose: CHR-Hansen, Denmark), which are not substances that lower the immune system, are used as biological agents. It is a technology that induces improvement of atopic dermatitis by activating the immunological environment of the skin when the prepared probiotics are applied to the skin. It is a fundamental change of the body's immune system to prevent, relieve symptoms and treat effects of atopic dermatitis. In addition to using the microbial strain that is harmless to the human body can prevent side effects of conventional chemical agents, such as resistance and ensure safety.

As described above, the lactic acid strain and the bacterial coating gold composition according to the present invention induce a change in the cytokine in the skin during application of the skin to increase the expression of interferon-gamma, which is one of the inhibitors of atopic dermatitis, and simultaneously Inhibition of the expression of the factor IgE was shown. As a result, it is possible to induce atopic dermatitis relief and to alleviate the symptoms of itching and dermatitis, which are symptoms of atopic dermatitis. Therefore, according to the composition according to the present invention, it is possible to exert an excellent therapeutic effect on an atopic skin disease without an appropriate therapeutic agent, and there is no side effect such as resistance induction by using a microbial strain that is harmless to the human body.

In addition, the present invention exhibits a therapeutic effect when applied to the skin, and thus has high utility as a functional cosmetic preparation.

As a result, the composition using the lactic acid bacteria of the present invention can be very useful in the pharmaceutical industry and the cosmetic industry as a treatment and auxiliary preventive agent for atopic diseases in which an appropriate therapeutic agent is absent as an intractable disease.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example 1 Preparation of Lactic Acid Bacteria Mitigating Atopic Dermatitis

First, lyophilized bacteria of Lactobacillus acidophilus La5, Bifidobacterium lactic Bb12, Streptococcus thermophilus, Lactobacillus bulgaricus and oligofructose: CHR-Hansen, Denmark, which are readily available in the art, were diluted in distilled water. Diluted Lactobacillus cells were used to apply 200 ul of diluent in an amount of 10 mL per 2 g to the skin.

Example 2: Preparation of Bacterial Coated Pure Gold Composition

Preparation of pure gold coated with lactic acid bacteria was carried out as follows.

Pure gold powder (1mm * 1mm * 0.0001mm, goldkorea.co, Korea) was incubated at the same time when culturing fungi in lactic acid culture. At this time, the culture conditions were 37 ℃, 24 hours. After 24 hours of incubation, centrifugation was performed at 1000 rpm for 10 minutes. Thereafter, the supernatant was discarded to obtain only a gold component, after which 10 ml of PBS was added, and after 10 minutes of centrifugation, the supernatant was discarded.

Example 3: Confirmation of the atopic dermatitis inhibitory effect of the lactic acid strain of the present invention

1) Chemical Dermatitis Composition in Animal Models

The back of the Nc / Nga mouse (SLC. Japan), 5-6 weeks old, was epilated and left for 24 hours to heal fine wounds on the skin.

Thereafter, a reaction mixture of 1% DNCB (Sigma, USA) was prepared in a solution in which acetone and olive oil were mixed 3: 1, and 200ul of the mixed solution was applied to the back. After 4 days, 150ul of 0.2% DNCB solution was applied to the back area 2-3 times a week. Dermatitis was induced after 4-5 weeks of treatment. In this state, 10 ⁵ viable cell counts / times were administered orally with lactic acid strain and bacterial coating gold, and skin coating was performed. Was observed.

2) IgE expression inhibition and cytokine expression change by administration of Lactobacillus preparations

Two weeks after oral administration of lactic acid strains and bacterial coatings of the present invention, oral administration of gold, and skin application, blood was collected from the eyes of rats, and the expression patterns of IgE were measured, and the changes of cytokines were the same. (Reference: Shibayagi ELISA KIT protocol, Shibayaki.co.Japan).

Figure 1a shows the inhibition of IgE expression in oral administration of lactic acid strains and bacterial coated gold and skin-coated dermatitis rats Figure 1b shows atopic dermatitis in the dermatitis rat body after oral administration and lacquer application of lactic acid strains and bacterial coated gold The expression patterns of the caine were compared. 1A and 1B show that the probiotic formulation of the present invention has an effect of increasing the expression of Interferon-gamma, which is one of the inhibitors of atopic dermatitis, and simultaneously inhibiting the expression of Immunoglobulin E (IgE). Can be. In particular, the composition of the present invention was shown to have an excellent inhibitory effect of immunoglobulin E (IgE) to increase the dermatitis during skin application.

3) Alleviation of symptoms of dermatitis by administration of Lactobacillus preparations in mice

Also, two weeks after oral administration of lactate strain and bacterial coating gold of the present invention and dermatitis, sensory evaluation was performed using clinical visual evaluation of Nc / Nga mouse dermatitis.

Figures 2a and 2b was presented by comparing the drawings observed the symptoms of alleviation of dermatitis in rats by lactic acid strain and bacterial coating gold of the present invention. Figure 2a is the effect of the formulations applied to the skin, the dermatitis relief effect was expressed in the bacterial formulations and gold and gold coating gold. On the other hand, in the case of Figure 2b oral administration of the usual route of administration of lactic acid bacteria, it was confirmed that the effect may be insignificant or rather increased dermatitis. As a result, it can be seen from FIG. 2A and FIG. 2B that in the mice induced with atopic dermatitis, the mice coated with the skin of lactic acid strain and bacterial coated gold significantly alleviated the symptoms of dermatitis compared to the control mice. The effect was minimal.

In Figure 3, the number of scratching (number of scratching: the number of times the mouse scratches the body with atopic disease, Dermatitis score: the degree of disease assessed by visually assessing atopic dermatitis on the skin of the mouse; Reference: International Achives of Allergy and Immunology, Improvement of Atopic Dermatitis in NC / Nga Mice by Topical Application of CpG Phosphodiester-ODN, Vol 144, No. 4. 2007), are presented to the skin coating of lactic acid strain and bacterial coating gold of the present invention. Atopic dermatitis inhibitory effect was suggested. 3, it can be seen that in the mice induced with atopic dermatitis, the dermatitis index was significantly lowered when skin administration of lactic acid strain and bacterial coating gold was applied to the skin compared to the control mice. Unlike the above results, the effects of oral administration were insignificant.

As described above, the lactic acid strain and the bacterial coating gold composition according to the present invention induces a change in the cytokine in the skin during application of the skin, thereby enhancing the expression of interferon-gamma, which is one of the inhibitors of atopic dermatitis, and simultaneously being an active factor. It has been shown to suppress the expression of IgE. As a result, it is possible to induce dermatitis relief and to reduce the symptoms of itching and dermatitis, which are symptoms of atopic dermatitis.

The present invention described above is not limited to the above-described embodiments and drawings, and various substitutions, modifications, and changes can be made without departing from the technical spirit of the present invention. It will be apparent to those who have

Figure 1a is a diagram showing the lowering effect of immunoglobulin E (IgE) that causes dermatitis after applying the composition of the present invention to the skin in mice induced atopic dermatitis.

Figure 1b is a diagram showing the change in the expression of anti-inflammatory cytokine interferon gamma having a dermatitis improvement effect after applying the composition according to the invention to the skin induced mice with atopic dermatitis.

Figure 2a is a diagram showing the effect of reducing the inflammation of the skin after the administration of the composition according to the invention in the mouse induced atopic dermatitis.

Figure 2b is a diagram showing the effect of reducing the inflammation of the skin after oral administration of the composition according to the invention in mice induced atopic dermatitis.

3 is a view showing the relief effect of the indicator showing the symptoms of dermatitis after administration of the composition according to the present invention in mice induced atopic dermatitis.

Claims (12)

It contains lactic acid bacteria as an active ingredient and is in the form of a liquid, gel or ointment applied to the skin or in the form of an injection administered to the skin, Bifidobacterium lactic Bb12 (Bifidobacterium lactic Bb12), Lactobacillus bulgaricus and oligofructose (Lactobacillus bulgaricus and oligofructose) is a lactic acid bacterium selected from the group consisting of pharmaceuticals for the prevention and treatment of atopic dermatitis Composition. delete delete delete Bacterial coating gold obtained by culturing the lactic acid bacteria with gold as an active ingredient, a liquid, gel or ointment applied to the skin or in the form of an injection administered to the skin, Bifidobacterium lactic Bb12 (Bifidobacterium lactic Bb12), Lactobacillus bulgaricus and oligofructose (Lactobacillus bulgaricus and oligofructose) is a lactic acid bacterium selected from the group consisting of pharmaceuticals for the prevention and treatment of atopic dermatitis Composition. delete delete 6. The pharmaceutical composition for preventing and treating atopic dermatitis according to claim 5, wherein the gold is pure gold. It contains lactic acid bacteria as an active ingredient and is applied to the skin in the form of a spray, lotion, cream, skin or shampoo. Bifidobacterium lactic Bb12 (Bifidobacterium lactic Bb12), Lactobacillus vulgaricus (Lactobacillus bulgaricus and oligofructose) Cosmetics for improving atopic dermatitis, characterized in that one of the lactic acid bacteria selected from the group consisting of. delete In the form of a spray, lotion, cream, skin or shampoo applied to the skin containing the bacterial coating gold obtained by incubating the lactic acid bacteria with gold as the active ingredient, Bifidobacterium lactic Bb12 (Bifidobacterium lactic Bb12), Lactobacillus vulgaricus (Lactobacillus bulgaricus and oligofructose) Cosmetics for improving atopic dermatitis, characterized in that one of the lactic acid bacteria selected from the group consisting of. delete

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