KR101424105B1 - Composition for improvement of pruritus containg bee venom - Google Patents

Abstract

The present invention relates to a composition for improving skin pruritus including bee venom.
The composition for improving skin pruritus containing bee venom of the present invention is characterized by containing bee venom as an active ingredient having an effect of suppressing and alleviating itching of skin.
The present invention provides a composition for improving skin pruritus containing bee venom which is excellent in safety to human body and effective in suppressing and alleviating itching, thereby overcoming the problems in treating skin pruritus due to side effects and resistance to existing medicines , A pharmaceutical composition having excellent skin pruritus improvement and therapeutic effect, a cosmetic composition and a functional food composition.

Description

Technical Field [0001] The present invention relates to a composition for improving skin pruritus including bee venom,

The present invention relates to a composition for improving skin pruritus including bee venom, and more particularly to a composition for improving skin pruritus including bee venom which is harmless to the human body and is effective in suppressing and alleviating itching of the skin.

Skin pruritus is basically a symptom of itching itself, and itching is only perceived in the skin, mucosa and cornea.

Itching is a sensation commonly associated with pain in most skin conditions, and is defined in the clinic as an unpleasant sensation that causes the urge to scratch.

The cause of such skin pruritus varies, and particularly itching and generalized skin pruritus are caused by many external factors and internal conditions.

The most common causative agents are environmental factors, including climate, particulate matter, detergents, skin infections of fungi and bacteria, insects and intravital infiltrates, and the second most common cause is biliary obstruction or kidney failure.

Specifically, skin diseases in which itching is a major problem include urticaria, dry skin, seborrheic dermatitis, psoriasis and insect bites.

The skin pruritus also includes itching caused by dermatitis due to inflammatory dermatitis, roughness of the skin, rash, rash, frostbite, contact dermatitis due to diaper, psoriasis or wounds.

As shown in the above categorization of causes and symptoms, itching is the primary cause of bacterial or fungal infections or the infestation of insect pests or environmental toxins, and secondly the immune system Which is a series of phenomena leading to inflammation and swelling, and perception of itching.

Therefore, antibiotics, antibiotics, or antidotes are injected, or immunosuppressive agents are used. In fact, corticosteroids, antihistamines, immunosuppressants, capsaicin and the like have been used as therapeutic agents for itching.

However, they have substantial side effects, and their resistance may cause problems in the treatment of skin pruritus.

Korean Patent No. 10-0875075 (registered on Dec. 12, 2008, entitled " Plant Extraction Composition for Mitigating Skin Pruritis ") and Korean Patent No. 10-0557801 (registered on Feb. 27, 2006) Day, name: treatment for pruritus).

It is an object of the present invention to provide a composition for improving skin pruritus including bee venom which is harmless to the human body and effective for alleviating and suppressing itching in order to overcome the problems caused by side effects and resistance of drugs for improving skin pruritus such as steroids and antihistamines .

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are not intended to limit the invention to the particular embodiments that are described. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are not restrictive of the invention, There will be.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for improving and treating skin pruritus, which comprises bee venom as an effective ingredient for inhibiting and alleviating itching of the skin, wherein the bee venom is a honey bee having at least 15 days of age, And is characterized in that sugar and volatile substances are removed and water-soluble.

The bee venom is characterized by comprising 10 ^-5 to 10 ^-7 % by weight based on the total weight of the composition.

The composition may further comprise a pharmaceutically acceptable carrier, diluent, or excipient or a combination thereof.

The cosmetic composition for the treatment of skin pruritus according to the present invention is characterized by containing bee venom having an effect of suppressing and alleviating itching of the skin as an active ingredient. The bee venom is derived from a beeswax of more than 15 days old, It is water-soluble.

The bee venom is characterized by comprising 10 ^-5 to 10 ^-7 % by weight based on the total weight of the composition.

The functional food composition for improving skin pruritus according to the present invention is characterized by containing bee venom as an active ingredient having the effect of suppressing and alleviating itching of the skin, wherein the bee venom is derived from a beeswax of more than 15 days old of a Western species bee and the saccharides and volatile substances are removed And is water-soluble.

The bee venom is characterized by comprising 10 ^-5 to 10 ^-7 % by weight based on the total weight of the composition.

In addition, the method for treating skin pruritus of the present invention is characterized in that a pharmacologically effective amount of the pharmaceutical composition for the treatment and improvement of skin pruritus is administered to mammals other than humans.

The present invention provides a composition for improving skin pruritus containing bee venom which is excellent in safety to human body and effective in suppressing and alleviating itching, thereby overcoming the problems in treating skin pruritus due to side effects and resistance to existing medicines , A pharmaceutical composition having excellent skin pruritus improvement and therapeutic effect, a cosmetic composition and a functional food composition.

FIG. 1 is a graph showing changes in composition of bee venom isolated from beeswax of less than 15 days old of beeswax.
FIG. 2 is a graph showing the components contained in beeswax isolated from beeswax at the age of 15 days of the beeswax of the present invention.
FIG. 3 is a graph showing inhibitory effects on skin scratches of bee venom for 60 minutes in a skin pruritus-induced animal model.
FIG. 4 is a graph showing the inhibitory effect on the vascular permeability of bee venom in a skin pruritus-induced animal model.
FIG. 5 is a graph showing the inhibitory effect of bee venom on histamine in a skin pruritus-induced animal model.
FIG. 6 is a graph showing the effect of decreasing TNF-α expression level of bee venom in a skin pruritus-induced animal model.
FIG. 7 is a graph showing the effect of decreasing IL-4 expression level of bee venom in a skin pruritus-induced animal model.
FIG. 8 is a graph showing the effect of reducing the amount of IL-1β expression in bee venom in a skin pruritus-induced animal model.

The terms, techniques, and the like described in this specification are used in the meaning commonly used in the technical field to which the present invention belongs, unless otherwise specified.

The bee venom of the present invention is characterized by containing bee venom having an itching inhibiting and mitigating effect as an active ingredient. Particularly, the bee venom is characterized in that the bee venom is water-soluble derived from a beeswax of more than 15 days old and has saccharides and volatile substances removed.

The bee venom, which is contained in the bee venom, is composed of about 40 substances and has been used for the treatment of diseases of the human body since BC.

Currently, studies on the action and mechanism of bee venom component, sensitivity and toxicity of bee venom, immunotherapy and treatment of diseases such as arthritis, herpes simplex, multiple sclerosis and tumor have been reported. Especially, It is known.

In the present invention, bee venom having the above-mentioned effect is separated from bees of western species and separated from bees having a disease age of 15 days or more that does not show change of toxin even after a lapse of ages, The use of bee venom having pure water solubility obtained by removing the saccharides and volatile substances that are caused is safe in the human body even if it is used for pharmaceutical use, cosmetic use or functional food use.

The inventor of the present invention has found that bee venom as described above shows inhibitory and mitigating effects on skin itching in addition to the usual efficacy, and it provides a composition for improving skin pruritus in various fields including it as an effective ingredient.

The bee venom is preferably contained in an amount of 10 ^-5 to 10 ^-7 % by weight, more preferably 10 ^-7 % by weight, based on the total weight of the composition.

This is because if the content of the bee venom is less than the above-mentioned weight percentage, the effect of suppressing or alleviating the itchiness of the target is deteriorated, and if it exceeds the above-mentioned weight percentage, it may lead to cytotoxicity rather than the cosmetics, medicines and foods There is a possibility that the product is manufactured in an unsuitable state for use as a product.

As described above, since the composition of the present invention contains bee venom as an active ingredient which is safe to the human body and has no toxicity, side effects, and inhibits or alleviates skin itching, the composition can be reconstituted It is possible to obtain skin pruritus suppression or alleviation effect.

Specifically, in order to use the composition for improving skin pruritus according to the present invention as a pharmaceutical composition, it is preferable to use the dried bee venom granule obtained by granulating bee venom with a pharmaceutically acceptable carrier, diluent or excipient or a combination thereof Or may be prepared in unit dosage form by injection or by intrusion into a multi-dose container.

In this case, the formulation is in the form of powder, granule, capsule, or injection. Particularly, in the case of injection, it is injected into a subject causing skin pruritus in accordance with a pharmacologically effective amount, thereby attenuating and treating the skin pruritus.

It may further comprise a dispersant or stabilizer. This may be selected without difficulty by those skilled in the art depending on the purpose of use, and the addition amount thereof may be selected within a range that does not impair the objects and effects of the present invention.

Examples of the pharmaceutically acceptable carriers include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline Cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and also pharmaceutically acceptable excipients Include, but are not limited to, lubricants, wetting agents, sweeteners, flavoring agents, emulsifying agents, suspending agents, preservatives and the like.

In order to use the composition for improving skin pruritus of the present invention as a cosmetic composition, the bee-to-digest structure obtained by granulating the bee venom and the other beverages, which can give rise to a synergistic effect of the main effect, The present invention can be applied to any shape such as liquid, cream, paste, or solid form using additives such as fragrance, pigment, fungicide, antioxidant, preservative, moisturizer, thickener, inorganic salt, emulsifier and synthetic polymer The product is made to be applied to the skin such as cream, skin lotion, pack, make-up base, etc. At this time, the addition amount of the additive is selected and used within a range not to impair the object and effect of the present invention.

In order to use the composition for improving skin pruritus according to the present invention as a functional food composition, the bee venom is dried in the form of a bee venom granule. In addition, glutinous rice, wheat flour, honey, crystalline cellulose, silicon dioxide, Starch, starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogenphosphate, lactose, mannitol, sugar, arabic Starch glycolate, sodium starch glycolate, carnauba wax, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, calcium stearate, dextrose, sorbitol, sodium carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylcellulose, Talc and the like are used together to make it easy to ingest.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples, but the scope of the present invention is not limited thereto.

≪ Example 1 > The bee venom isolation

1) Beholding

The bee venom was collected using a bee venom collecting device of the western bees ( Apis meliffera L.). Only the bee venom of the bees of more than 15 days old was collected.

Categories
(Class of Molecules) Component
(Component) Content in dry bee venom
(% of dry venom) Enzymes Phospolipase A2 10-12 Hyaluronidase 1-3 Acid phosphomonoesterase Lysophopholipase a-glucosidase Other Proteins and Peptides Melittin 50 Apamine 1-3 Mast Cell Degranulating Peptide (MCD) 1-2 Secapin 0.5 to 2.0 Procamine 1-2 Adolapin Protease inhibitor Tertiapine * 0.1 Small peptides (with less than 5 amino acids) 13 ~ 15 Physiologically Active Amines Histamine 0.5 to 2.0 Dopamine 0.2 to 1.0 Noradrenaline 0.1 to 0.5 Amino Acids t -aminobutyric acid 0.5 a-amino acids 1.0 Sugars Glucose and fructose 2 Phospholipids 5 Volatile compounds 4 to 8

The bee venom constructed as shown in Table 1 was used for the present invention by having pure water-soluble bee venom composed of ingredients as shown in Table 2 below, by removing sugars and volatile compounds through a simple purification method of bee venom.

Categories
(Class of Molecules) Component
(Component) Content in dry bee venom
(% of dry venom) Enzymes Phospolipase A2 10-12 Hyaluronidase 1-3 Acid phosphomonoesterase Lysophopholipase a-glucosidase Other Proteins and Peptides Melittin 45 ~ 65 Apamine 1-3 Mast Cell Degranulating Peptide (MCD) 1-2 Secapin 0.5 to 2.0 Procamine 1-2 Adolapin Protease inhibitor Tertiapine * 0.1 Small peptides (with less than 5 amino acids) 13 ~ 15 Physiologically Active Amines Histamine 0.5 to 2.0 Dopamine 0.2 to 1.0 Noradrenaline 0.1 to 0.5 Amino Acids t -aminobutyric acid 0.5 a-amino acids 1.0 Phospholipids 5

<Example 2> Production of medicines (injection) containing bee venom having the skin itching inhibiting effect and mitigation effect of the present invention

First, the raw materials shown in Table 3 below were prepared.

Raw material Example 2 (% by weight) Comparative Example 1 (% by weight) One The bee venom of Example 1 10 ^-7 - 2 Mannitol 76.2 76.2 3 Na ₂ HPO ₄ .12H ₂ O 11 11 4 Distilled water Balance Balance

The raw materials were mixed and bottled and sterilized by heating at 20 ° C for 30 minutes to prepare each injection.

<Example 3> Production of cosmetic (lotion) containing bee venom having the skin itching inhibition and relaxation effect of the present invention

First, the raw materials shown in Table 4 below were prepared.

Raw material Example 3 (% by weight) Comparative Example 2 (% by weight) One The bee venom of Example 1 10 ^-7 - 2 glycerin 3.0 3.0 3 Butylene glycol 2.0 2.0 4 Propylene glycol 2.0 2.0 5 Polyoxyethylene (60) Hardened castor oil 1.0 1.0 6 ethanol 10.0 10.0 7 Triethanolamine 0.1 0.1 8 antiseptic a very small amount a very small amount 9 Pigment a very small amount a very small amount 10 Spices a very small amount a very small amount 11 Purified water Balance Balance

After the raw material 5 was melted by heating at about 60 ° C, the raw material 10 was stirred and charged into the raw material 11.

Finally, the raw materials 1, 6, 7 and 9 were added, stirred thoroughly, passed through a high-pressure homogenizer, and aged to prepare respective lotions.

<Example 4> Production of food (beverage) containing bee venom having the skin itching inhibiting effect and relaxation effect of the present invention

First, the raw materials shown in Table 5 below were prepared.

Raw material Example 4 (% by weight) Comparative Example 3 (% by weight) One The bee venom of Example 1 10 ^-7 - 2 Vitamin C 29.8 29.8 3 Powdered Vitamin E 14.9 14.9 4 Iron lactate 39.2 39.2 5 Zinc oxide 6.9 6.9 6 Nicotinic acid amide 6.9 6.9 7 Vitamin A 0.4 0.4 8 Vitamin B1 0.5 0.5 9 Vitamin B2 0.6 0.6 10 water Suitable amount Suitable amount

Each of the raw materials was mixed to prepare each beverage.

<Experimental Example 1> Analysis of compositional change of bee venom with time

The bee venom isolated in Example 1 was analyzed by liquid chromatography for changes in the composition with time.

The bee venom isolated from the beeswax of less than 15 days old was used for comparison.

As a result, as shown in Fig. 1, bee venom isolated from beeswax of less than 15 days of western species of bees was found to have a change in bee venom components as the age (age) passed. On the other hand, as shown in FIG. 2, it was confirmed that the bee venom of Example 1 isolated after 15 days of age did not change in composition over time. In other words, there was no significant difference in the composition of bee venom isolated at 15th or later age.

In other words, as shown in Table 6 below, the bee venom isolated from the worker bees less than 15 days old showed 0.065 mg per one dog within 1 hour, 0.166 mg within 5 days, 0.211 mg during 6-10 days, The bee venom of Example 1 of the present invention isolated from a 15-day old or older bees containing 0.294 mg of the bee venom did not change its content even after the passage of time.

Compared to (15 days old) Invention Example 1 in 1 hour Within 5 days 6 to 10 days 15 days Poisoning (mg / grain) 0.065 0.166 0.211 0.294

As a result of the above experiment, since there is no change in the toxic component in the beeswax of 15 days old or more of the western species of bees, it is possible to accurately measure the content usable safely in the human body by using the bee venom (Example 1) , Cosmetics, medicines, functional foods, and the like.

&Lt; Experimental Example 2 > Measurement of inhibitory effect on skin scratches of bee venom

1. Experimental Method

1) Bee venom samples: Bee venom prepared in Example 1 was diluted in physiological saline, and 0.01 mg / kg and 0.1 mg / kg were prepared according to the bee venom concentration.

② Skin pruritus animal model: 5-week-old Balb / c male mice were given a free diet of water and feed, which was stabilized for 1 week and used in the experiment.

The above-prepared 5-week-old Balb / c male mice were subcutaneously injected with compound 48/80 (50 μg / μl) to prepare an animal model of skin pruritus induced skin pruritus.

③ Observation method: The state of the animal was photographed 24 hours, and the number of scratches was observed using the hind legs.

2. Experimental results

As shown in FIG. 3, the animal model (control) injected with Compound 48/80 alone showed an average number of scratching times of 196.5 times, whereas bee venom 0.01 mg / kg was administered together In the experimental group, the average number of scratches was 48.7, and the average number of scratches was 24 in the group treated with bee venom 0.1 mg / kg.

In other words, it was found that bee venom had a mitigating effect on skin itching. In particular, the amount of bee poisoning was decreased in proportion to the bee venom concentration, Treatment of pruritus is also expected.

Experimental Example 3 Measurement of inhibitory effect on vascular permeability of bee venom

1. Experimental Method

The skin of an animal model in which skin pruritus was induced was prepared, and the skin was then stained using evans blus stainging, and vascular permeability was measured.

2. Experimental results

As shown in FIG. 4, in the experimental group administered with bee venom 0.01 mg / kg on the basis of 100% of the vascular permeability factor of the animal model (control) subcutaneously injected with Compound 48/80 alone, 70% , And 20% of the vascular permeability factors were measured in the group treated with bee venom 0.1 mg / kg.

In other words, compound 48/80, which causes skin itching, increases the permeability of the capillary to cause itching. Thus, the fact that the bee venom permeability factor is measured less by bee venom as the above experimental results means that the bee venom prevents the activity of compound 48/80 which causes skin itching, thereby alleviating the skin itching reaction. Especially, it was predicted that treatment of skin pruritus would be possible because the vascular permeability factor was the lowest in the experimental group treated with bee venom 0.1 mg / kg in proportion to the bee venom concentration and the effect rate of suppressing the skin itching reaction was the highest.

Experimental Example 4 Measurement of inhibitory effect of bee venom on histamine

1. Experimental Method

Mast cells (inflammatory cells important for allergic reactions) of the animal model in which skin pruritus was induced were reacted in a physiological solution for 10 minutes, and then the bee venom obtained in Example 1 was added And the reaction was terminated with ice.

The reaction solution thus obtained was centrifuged at 200 x g for 15 minutes and the amount of histamine released was measured.

2. Experimental results

As shown in FIG. 5, in the test group administered with bee venom 0.01 mg / kg based on the amount of histamine released from the animal model (control) injected with compound 48/80 alone, the released histamine content was lower And less than the released histamine level in the experimental group to which bee venom was administered at a dose of 0.01 mg / kg in the test group administered with 0.1 mg / kg of bee venom.

Histamine is secreted from mammalian mast cells to protect the body when the mammal is exposed to allergens, often causing itching and sneezing.

That is, the highest amount of histamine released from an animal model injected with compound 48/80 alone, which causes skin itch, means that itching is caused to a great extent. On the other hand, the histamine release rate of bee venom treated with 0.01 mg / kg of bee venom was significantly lower than that of the compound 48/80 injected animal model.

This suggests that bee venom can be used as a natural antihistamine agent since it means that the bee venom has a mitigating effect on skin itching.

Especially, histamine content was decreased in proportion to the bee venom concentration, and it was expected that treatment of skin pruritus would be possible in the experimental group treated with bee venom 0.1 mg / kg in a similar degree to the normal group.

<Experimental Example 5> Measurement of decrease effect of TNF-α, IL-4 and IL-1β expression in bee venom

Allergic reactions are caused by the action of cytokines secreted by mast cells or basophils.

These cytokines bind to receptors and induce cell-cell interactions, thus acting to further amplify the allergic response. Examples of such cytokines include TNF-a, IL-4, and IL-1 [beta].

1. Experimental Method

The amount of expression of TNF-α, IL-4 and IL-1β in the skin pruritus-induced animal model prepared in Experimental Example 2 was measured by ELISA (enzyme-linked immunosorbent assay: A test for diagnosing lesion infection by the action of an enzyme causing this color change).

2. Experimental results

6, 7 and 8, on the basis of the content of TNF-α, IL-4 and IL-1β expressed in the animal model (control) injected subcutaneously with compound 48/80 alone, / kg, the levels of TNF-α, IL-4 and IL-1β expressed were lower in the experimental group.

This means that bee venom has an effect of inhibiting the expression of factors causing skin itching. In contrast, bee venom 0.1 mg / kg was associated with bee venom concentration of 0.1 mg / kg, compared with bee venom 0.01 mg / kg. kg, the skin pruritus inducing factor inhibitory effect is similar to that of the normal group.

Based on the above results, it is possible to provide a composition for improving skin pruritus containing bee venom which is excellent in safety to human body and effective in suppressing and alleviating itching, thereby providing a skin pruritus improvement treatment for skin pruritus caused by side effects and tolerance to existing medicines A cosmetic composition and a functional food composition which have excellent skin pruritus improvement and therapeutic effect while overcoming the above problems.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. You can implement the examples. The scope of the present invention is defined by the appended claims, and all differences within the scope of the claims are to be construed as being included in the present invention.

Claims (11)

A tablet bee venom having an effect of suppressing and alleviating itching of the skin as an effective ingredient,
Wherein the tablet bee venom is derived from a beeswax of Apis meliffera L. wyssomes over 15 days of age and has water solubility by removing saccharides and volatile substances, and wherein the tablet bee poisoning is 10 ^-5 to 10 ^-7 wt% . &Lt; / RTI &gt;
A pharmaceutical composition for improving and treating skin pruritus.
delete delete The method according to claim 1,
Wherein said composition further comprises a pharmaceutically acceptable carrier, diluent, or excipient or a combination thereof,
A pharmaceutical composition for improving and treating skin pruritus.
A tablet bee venom having an effect of suppressing and alleviating itching of the skin as an effective ingredient,
Wherein the tablet bee venom is derived from a beeswax of Apis meliffera L. wyssomes over 15 days of age and has water solubility by removing saccharides and volatile substances, and wherein the tablet bee poisoning is 10 ^-5 to 10 ^-7 wt% . &Lt; / RTI &gt;
A cosmetic composition for improving skin pruritus.
delete delete A tablet bee venom having an effect of suppressing and alleviating itching of the skin as an effective ingredient,
Wherein the tablet bee venom is derived from a beeswax of Apis meliffera L. wyssomes over 15 days of age and has water solubility by removing saccharides and volatile substances, and wherein the tablet bee poisoning is 10 ^-5 to 10 ^-7 wt% . &Lt; / RTI &gt;
A functional food composition for improving skin pruritus. delete delete delete

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