KR20170031494A - Bee venom composition for enhanced degradation of intradermal bee venom - Google Patents

Abstract

The present invention relates to a bee venom composition for promoting intradermal degradation of bee venom. The bee venom composition for promoting intradermal degradation of bee venom according to the present invention comprises 5-10 wt% of lanolin, 3-5 wt% of petrolatum, 6-7 wt% of stearic acid, 0.03-0.06 wt% of propyl parahydroxybenzoate and the balance of purified water, and further comprises 0.5-1.5 wt% of bee venom and 1-4 wt% of triethanolamine. According to the present invention, it is possible to provide a bee venom composition having an effect of preventing and treating skin diseases by promoting intradermal degradation of bee venom.

Description

[0001] The present invention relates to a bee venom composition for enhancing the degradation of bee venom in the skin,

The present invention relates to a bee venom composition for accelerating the degradation of bee venom in the skin, and more particularly, to a bee venom composition for promoting the degradation of bee venom so that bee venom is decomposed in the central part of the skin horny layer, ≪ / RTI >

Skin disorders refer to all abnormalities that appear in the skin of animals, including humans. Since the skin covers the surface of the body, there are many opportunities for external stimuli such as ultraviolet rays, direct contact with various pathogens, and strong influence from the body.

In addition, diseases are caused by various causes because they are affected by pathological changes such as genetic, inflammatory, benign and malignant tumors, hormones, trauma, degenerative degeneration. Inflammatory skin disease refers to a disease that causes a series of clinical signs and symptoms within the skin epithelium. Inflammatory skin diseases include atopic dermatitis, contact dermatitis, seborrhoic dermatitis, and acne.

In particular, steroids, antihistamines, vitamin ointments, and adrenocortical hormones have been mainly used for the treatment of inflammatory skin diseases such as atopic dermatitis.

However, these medicines are excellent for clinical efficacy and exhibit various side effects. Therefore, there is a desperate need to develop a medicament that can be safely used with less side effects and high safety.

Accordingly, the inventors of the present invention have developed a cosmetic or external preparation that exhibits the preventive and therapeutic effects of skin diseases using bee venom among various natural substances.

Bee venom is an animal natural physiologically active substance that is stored in the venom endotracheal tube (poison 囊) and is linked to the needle and is secreted during stimulation. It is used to separate and purify the bee venom component and use it for treatment of dementia or cancer. Physiological studies and analysis of the components of bee venom have already been reported.

Such bee venom has been used for a long time as a therapeutic agent for inflammatory diseases in oriental medicine, and is studying anti-inflammatory effect and anti-cancer effect, and various development studies using bee venom have already been carried out in many research institutes.

Korean Priority No. 10-1424105 (composition for improving skin pruritus including bee venom) and Korean Registration No. 10-1165510 (composition for treating skin diseases containing bee venom as an active ingredient) have been disclosed as related prior arts .

However, there is no known method for accelerating the decomposition of bee venom so that the bee venom ingredient decomposes to the center of the skin stratum corneum.

Accordingly, the inventors of the present invention have completed the present invention by developing a bee venom composition capable of absorbing and decomposing bee venom containing peptides and enzymes as a main component into the skin to produce a desired effect.

It is an object of the present invention to provide a bee keeping composition for accelerating the decomposition of bee venom in the skin.

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 achieve the above object, the present invention provides a bee-toad composition for accelerating the decomposition of bee venom in the skin, comprising 5-10 wt% of lanolin, 3-5 wt% of Petrolatum, ), 6-7 wt% propyl parahydroxybenzoate, 0.03-0.06 wt% propyl parahydroxybenzoate, and the remainder being purified water, 0.5-1.5 wt% bee venom and triethanolamine 1-4 wt%, and the bee venom is characterized by being tablet bee venom.

The composition may further contain 0.05 to 0.1 wt% of methyl parahydroxybenzoate or 0.03 to 1.5 wt% of disodium edetate, or may contain propylene glycol 3 To 7% by weight.

The composition is characterized by having the effect of preventing or treating skin diseases.

The present invention is further characterized in that the external preparation for skin disease or cosmetic for skin disease prevention comprises the above composition.

According to the present invention, there is provided a beebin composition having an effect of preventing and treating skin diseases through promotion of decomposition of bee venom in the skin.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail, and a detailed description of known functions and configurations that may unnecessarily obscure the gist of the present invention will be omitted.

The present invention provides a bee keeping composition for accelerating the decomposition of bee venom in the skin.

Bee venom is generally absorbed from the upper part of the stratum corneum during application of the skin, and it is difficult to penetrate into the skin and to produce its effect. It was confirmed that, in the case of a composition containing bee venom, no remnants of bee venom remained from the upper part of the skin stratum corneum, as supported by the following experimental examples.

Therefore, the effect of the bee venom application on skin diseases such as atopy is less than expected and it is difficult to use it as an alternative agent for antihistamines or steroids, which is a conventional chemical agent.

Accordingly, the inventor of the present invention has studied several times to solve such problems. As a result, the inventors of the present invention have found that bee venom efficacies infiltrate into the skin to promote decomposition of bee venom in the middle of the skin horny layer, The present invention has been made to develop a bee venom composition. In the bee venom composition developed in the present invention, melitin content was confirmed in the upper part of the stratum corneum, but not in the stratum corneum.

Hereinafter, the method for producing the bee keeping composition of the present invention will be described in detail.

1. Stage 1: Ready to Read

In this step, bee venom, which is one of the constituents of the following composition, is first prepared, preferably purified bee venom is prepared.

In the present invention, purified bee venom isolated from any species may be used, but it is preferable to use purified bee venom isolated from a Western bee ( Apis mellifera L.), more preferably, It is necessary to use purified pure bee venom, which is obtained by removing the saccharides and volatile substances which cause bacterial contamination through the simple purification method after separating from the worker bees over 15 days old, , Cosmetics, and functional foods, it is preferable to use them because they are made in a safe state for human body.

2. The second step; Preparation of bee venom composition

Lanolin, Petrolatum, Stearic Acid, Propyl Parahydroxybenzoate, which is a component generally used for prevention and treatment of skin diseases, And the remainder are prepared to include purified water.

At this time, it is preferable that 5-10 wt% of the lanolin, 3-5 wt% of the Petrolatum, 6-7 wt% of the stearic acid and the propyl parahydroxybenzonate (Propyl Parahydroxybenzoate) is prepared to contain 0.03-0.06 wt%.

Then, bee venom and triethanolamine are included in the bee venom composition of the present invention.

In this case, the bee venom is contained in an amount of 0.5 to 1.5 wt%, and the triethanolamine used for neutralization is contained in an amount of 1-4 wt%.

If the content of the bee venom is less than 0.5 wt%, it is difficult to obtain the preventive and therapeutic effect of the skin disease of the present invention. If the bee venom is contained in an amount exceeding 1.5 wt%, the bee venom is toxic, This is because it becomes difficult to use.

When the content of triethanolamine is less than 1 wt%, the neutralization is not performed well and the bee venom is difficult to penetrate into the skin. When the content exceeds 4 wt%, the toxicity of triethanolamine Which makes it difficult to use it as a material for external preparations or cosmetics.

The bee keeping composition may further contain 0.05 to 0.1 wt% of methyl parahydroxybenzoate or 0.03 to 1.5 wt% of disodium edetate, or may contain propylene glycol Glycol) 3 to 7% by weight,

Methyl Parahydroxybenzoate improves the softness of the skin. When it is contained in an amount of less than 0.05 wt%, it is difficult to spread the skin evenly on the skin surface due to low spreadability of the skin, If it is more than 0.1 wt%, it is likely that the bee venom will be decomposed in the upper part of the skin stratum corneum due to overaging.

Disodium edetate and Propylene Glycol are excellent in dissolving power, prevent fungi growth, and do not ferment, so that the composition of the present invention can be stored for a long time.

If the content of the disodium edetate is less than 0.03 wt% or the content of the propyl glycol is less than 3 wt%, it is difficult to commercialize the external preparation or cosmetics because the effect is insufficient as described above. When the content of Disodium Edetate exceeds 1.5 wt% or the content of the above-mentioned propyl glycol exceeds 7 wt%, the excess amount of Disodium Edetate or Propylene Glycol There is a possibility that the bee venom will be decomposed in the upper part of the skin stratum corneum.

As described above, the bee keeping composition prepared as described above has excellent prophylactic and therapeutic activities against inflammatory skin diseases or allergic skin diseases, especially allergic skin diseases, more preferably atopic dermatitis.

The bee venom is advantageous in that it can be taken for a long period of time because it is safe, toxic and has no side effects because it is based on a natural ingredient, not an artificially synthesized compound. In addition, the composition may be used not only in humans but also in animals such as cattle, dogs, etc., which may cause inflammatory skin diseases or allergic skin diseases.

Accordingly, the bee keeping composition of the present invention can be usefully used for external preparations or cosmetics showing preventive or therapeutic effects against skin diseases, and the composition can be treated to prevent or treat inflammatory skin diseases or allergic skin diseases.

The inflammatory skin diseases or allergic skin diseases include diseases such as acute chronic eczema, contact dermatitis, atopic dermatitis, dermatitis dermatitis, chronic simplex poisoning, but are not limited to, diseases induced by inflammatory reaction and allergic reaction , And more preferably, atopic dermatitis.

As used herein, the term "prevention" refers to any act that inhibits or delays the onset of the disease by treatment of the bee venom composition according to the present invention.

As used herein, the term "treatment" refers to any action that improves or alters the condition of the disease by treatment of the bee venom composition according to the present invention.

The present invention may also be provided as an external preparation containing a bee keeping composition.

That is, the composition of the present invention can be added to an external preparation for the treatment of inflammatory skin diseases or allergic skin diseases. When the composition of the present invention is used as a external preparation, the composition may be directly added or used in combination with other quasi-drugs or quasi-drugs, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment).

Preferably, the quasi-drug composition can be used for the production of shampoo, rinse, hair tonic, hair lotion, hair cream, disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, mask, ointment and coating agent.

The present invention also provides a cosmetic comprising the bee keeping composition.

The cosmetic of the present invention may be prepared by mixing with the external preparation for skin such as water, physiological saline, glycerol, a surfactant, a moisturizer, a thickener, a chelating agent, , It can be manufactured in various forms. For example, the cosmetic may contain ointment, cream, softening water (skin), convergent lotion (lotion), emulsion, astringent, massage cream, nutritional cream, essence, pack, powder , Suspension, spray, or serum, and the like.

In addition, the cosmetic compositions of the present invention may contain customary adjuvants such as stabilizers, solubilizers, vitamins, pigments, and flavorings commonly used in the art of composition. In the composition, the content of the bee keeping composition may be an amount effective to achieve an antioxidative effect, for example, 0.001 to 10% by weight, preferably about 0.01 to 5% by weight, based on the total weight of the composition. But is not limited thereto.

Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples. However, these Examples and Experimental Examples are for illustrative purposes only and are not intended to limit the scope of protection of the present invention.

≪ Examples 1 and 2 and Comparative Examples 1 and 2 > Preparation of bee keeping composition

The bee keeping compositions of Examples 1, 2 and Comparative Examples 1 and 2 were prepared according to the compositions shown in Table 1 below.

At this time, as a basic base, 8.5% w / v of lanolin, 4.2% w / v of Petrolatum, 6.8% w / v of stearic acid, ) 0.05% w / v.

Example 1 Example 2 Comparative Example 1 Comparative Example 2 Beijing
(Bee venom) 1% w / v 1% w / v 1% w / v 1% w / v Methyl Parahydroxybenzoate < RTI ID = 0.0 > 0.1% w / v 0.05% w / v 1% w / v 0.01% w / v Disodium Edetate < RTI ID = 0.0 > 0.05% w / v 1.5% w / v 2% w / v 0.001% w / v Propylene Glycol 5% w / v 7% w / v 10% w / v 1% w / v Triethanolamine
(Triethanolamine) 1% w / v 4% w / v 0% w / v 0.5% w / v Purified water Remainder Remainder Remainder Remainder

EXPERIMENTAL EXAMPLE 1 Skin penetration test of bee venom composition

1. Experimental Method

1) Lette skin extraction

Sprague-Dawley rats (male, body weight 230 ± 20 g) were used to test skin.

The rats were sacrificed with diethyl ether 12 hours before the test, and the dorsal hair was removed using an electric epilator to prevent damage to the horny layer and then removed.

The area of the excised site was extracted with 5 × 5 cm ² , and the subcutaneous fat was removed and stored at -20 ° C. until the experiment.

2) Measurement of skin permeability of melitin, an index component of bee venom according to the base

(1) The physiological saline solution with sufficient solubility was used as a receptor phase to maintain a sink condition during permeation of melitin.

② During the experiment, the temperature of the receptor phase was maintained at 32 ± 0.5 with constant temperature circulation pump while stirring at 600 rpm.

③ The skin area in contact with the receptor phase was about 1.766 cm ² , and the receptor phase had a capacity of 12 ml.

④ The cryopreserved lette skin before the test was hydrated in physiological saline and slowly thawed. After 0.2, 1, 2, 3, 4, 5, 6, 8, 10, Of the receptor phase and immediately supplemented with the same amount of physiological saline.

⑤ Immediately after collecting the final sample, skin was separated from Franz diffusion cell (PemeGear), washed with distilled water, and skin and skin layers were separated by tape stripping method.

⑥ The skin with the stratum corneum removed was separated into epidermis and dermis.

⑦ Concentration of melittin in bee venom which was transferred to each skin layer and receptor phase was quantified by LC-MS / MS method. Melitin in each sample was sufficiently extracted in distilled water before analysis.

3) MRM chromatography measurement method

Melatonin, a major component of bee venom, was quantitatively analyzed by high-performance liquid chromatography tandem mass spectrometry (LC / MS / MS). The analytical conditions were as follows.

 end. Used equipment

- LC / MS / MS: API 2000 triple quadrupole mass spectrometer equipped with a tubo ion spay ionization (ESI) source coupled with Waters 2690 HPLC separation module

- Integrator: Analyst 1.4

Analytical column: Halo (R) C18 column (2.1 x 50 mm, 2.7 m)

- Guard coumn: SecurityGuard Guard Catridge

I. Condition

- Mobile phase: Binary solvent gradient of 0.1% formic acid in acetonitrile and D.W

Time (min) Composition
(ACN; DW, both containing 0.1% formic acid) 0 - 0.5 5: 95 1 - 3.5 70: 30 4 - 10 5: 95

- Flow rate: 0.3 ml / min

- Column temperature: 30 ° C

- Injection volume: 5 μl

All. MS / MS conditions

Parameter Melittin Internal standard (felodipine) Polarity Positive [M + 5H] Positive [M + H] Mass transition (m / z) 570.1 -> 86.2 384.0 - > 337.9 Dwell time (ms) 300 300 DP (V) 31 21 EP (V) 370 370 EP (V) 3.5 12 CE (V) 61 23 CXP (V) 2 12 Curtain gas (psi) 25 25 Collision gas (psi) 4 4 Turbo gas temperature (℃) 320 320

2. Experimental results

The results of the experiment are shown in Table 4 below.

Time (h) Example 1 Example 2 Comparative Example 1 Comparative Example 2 One N.D. N.D. N.D. N.D. 2 N.D. N.D. N.D. N.D. 3 N.D. N.D. N.D. N.D. 4 N.D. N.D. N.D. N.D. 5 N.D. N.D. N.D. N.D. 6 N.D. N.D. N.D. N.D. 8 N.D. N.D. N.D. N.D. 10 N.D. N.D. N.D. N.D. 12 N.D. N.D. N.D. N.D. 24 N.D. N.D. N.D. N.D. 36 N.D. N.D. N.D. N.D.

As shown in Table 4, analysis of receptor phase samples revealed that melitin was not detected in the receptor phase at all time points.

In addition, the final amount of melitin in the skin of the skin surface and the stratum corneum and of the skin layer melittin was determined by measuring the amount of melittin remaining in the receptor phase (Table 4), the amount measured in the donor phase And the amount remaining in the skin, respectively, and then the recovery rate was measured from the sum of these.

The results are shown in Table 5 below.

Matrices Example 1 Example 2 Comparative Example 1 Comparative Example 2 Wash N.D. N.D. N.D. N.D. Tape 0 ≪ 0.05% ≪ 0.05% ≪ 0.05% ≪ 0.05% Tape 1
(Top of stratum corneum) ≪ 0.05% ≪ 0.05% N.D. N.D. Tape 2
(Central portion of stratum corneum) N.D. N.D. N.D. N.D. Tape 3
(Lower part of stratum corneum) N.D. N.D. N.D. N.D. Viable epidermis N.D. N.D. N.D. N.D. Dermis N.D. N.D. N.D. N.D.

As shown in Table 5, in the bee venom compositions of Comparative Examples 1 and 2, since melitin was not detected from the upper part of the stratum corneum, it was not penetrated into the inside of the skin from the upper part of the skin, .

On the other hand, in Examples 1 and 2, melittin was detected in the upper part of the stratum corneum but not in the middle part of the stratum corneum, and the bee venom was permeated to the upper part of the skin layer by the composition of the present invention. That is, it was confirmed that the bee venom composition of the present invention has an effect of penetrating bee venom to the upper part of the skin layer.

In addition, the measured recovery was very low, less than 0.05%, indicating that melitin was not detected in the receptor because it was not metabolized by the enzyme in the skin, not through the skin at all.

Therefore, bee venom is effective in the skin and does not remain, so it can be known that it is safer than the conventional chemical.

Formulation Example 1: Preparation of cosmetics >

Using the bee keeping composition prepared in Example 1 as an active ingredient, the essence was prepared in the following composition.

[Furtherance]

10 mg of the active ingredient, 3.0 mg of glycerin, 0.05 mg of EDTA, 0.04 mg of benzophenone-9, 0.2 mg of carboxyvinyl polymer, 0.6 mg of oxydoteth-25, 1.0 mg of glyceryl monostearate, 0.01 mg of preservative, Perfume 0.01 mg, purified water balance

≪ Preparation Example 2: Preparation of Ointment Agent >

Using the bee keeping composition prepared in Example 2 as an active ingredient, ointments were prepared in the following composition.

[Furtherance]

60% by weight of hydrogenated castor oil, 0.5% by weight of sorbitan sesquioleate, 5.0% by weight of petroleum jelly, 5.0% by weight of liquid paraffin, 10.0 wt%

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the inventions. 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 (8)

5-10 wt% of lanolin, 3-5 wt% of petrolatum, 6-7 wt% of stearic acid, 0.03-0.06 wt% of propylparahydroxybenzoate, And the remainder being purified water,
Characterized in that it comprises from 0.5 to 1.5 wt% of bee venom and from 1 to 4 wt% of triethanolamine.
A bee venom composition for accelerating the degradation of bee venom in the skin.
The method according to claim 1,
Characterized in that the bee venom is a tablet bee venom.
A bee venom composition for accelerating the degradation of bee venom in the skin.
The method according to claim 1,
Characterized in that said composition further comprises 0.05 to 0.1 wt% of methyl parahydroxybenzoate.
A bee venom composition for accelerating the degradation of bee venom in the skin.
The method according to claim 1,
Characterized in that the composition further comprises 0.03 to 1.5 wt% disodium edetate.
A bee venom composition for accelerating the degradation of bee venom in the skin.
The method according to claim 1,
Characterized in that the composition further comprises 3 to 7 wt% propylene glycol.
A bee venom composition for accelerating the degradation of bee venom in the skin.
A composition according to any one of claims 1 to 5, which is characterized by having a preventive or therapeutic effect on skin diseases,
A bee venom composition for accelerating the degradation of bee venom in the skin.
An external preparation for the treatment of skin diseases comprising the composition according to any one of claims 1 to 5.
A cosmetic for preventing skin diseases, which comprises the composition according to any one of claims 1 to 5.