KR20190092822A - A composition for improving and treating skin disease comprising aptamin C as effective component - Google Patents

Abstract

The present invention relates to a composition for alleviating and treating skin diseases containing vitamin C and a complex of an aptamer binding to vitamin C as active components. When the composition of the present invention is treated to patients with atopic dermatitis, psoriasis, acne, and eczema, all of them show an alleviation and treatment effect, thereby having an effect of being used as medicines and cosmetics for patients with such diseases.

Description

A composition for improving and treating skin disease comprising aptamin C as effective component

The present invention relates to a composition for improving and treating skin diseases comprising a complex of vitamin C and an aptamer binding to vitamin C as an active ingredient.

Inflammatory skin diseases include atopic dermatitis, contact dermatitis, seborrhoic dermatitis and acne. Atopic dermatitis is generally used in the same sense as eczema, which is an eczema-like skin lesion that occurs in atopic dermatitis.

The cause of atopic dermatitis has not been identified to date and is known to have a genetic tendency, and now it is persuaded that it is a kind of autoimmune disease. Unlike normal eczema or dermatitis, it shows unusual symptoms and course, and 70-80% of pediatric eczema is present, and it occurs in adults recently.

Antihistamines, vitamin ointments, and corticosteroids have been used mainly for the treatment of inflammatory skin diseases. However, these drugs are often temporary and often have severe side effects. In particular, in the case of atopic dermatitis, various 5-lipokishgenase inhibitors have been proposed as candidate compounds for anti-allergic agents, and chromoline alleviates the reaction of allergens with tissue mast cells. It is known that the above substances also have the disadvantage that the clinical effect is not obvious.

Acne has been used to treat acne by using an antibiotic such as erythromycin or a method of controlling sebum using estrogen, a female hormone, but there are problems associated with side effects. Vitamin A derivatives, benzoyl peroxide, salicylic acid, triclosan, etc. have been used in cosmetics for acne treatment, but these substances have some antibacterial effects, but have side effects such as skin redness, skin sensitization, or photosensitivity. .

Therefore, there is an urgent need for external preparations that combine the prevention, improvement and treatment of skin diseases that can solve the above problems.

[Previous Patent Document]

Republic of Korea Patent Publication No. 10-2010-0016450

The present invention has been made by the above necessity, the object of the present invention is to provide a novel composition for improving skin diseases.

Another object of the present invention to provide a composition for treating a novel skin disease.

In order to achieve the above object, the present invention provides a composition for improving and treating skin diseases comprising a complex of vitamin C and an aptamer binding to vitamin C as an active ingredient.

In one embodiment of the present invention, the skin disease is preferably one or more diseases selected from the group consisting of atopic dermatitis, contact dermatitis, seborrheic dermatitis, psoriasis, acne and eczema, but is not limited thereto.

In another embodiment of the present invention, the aptamer preferably consists of the nucleotide sequence of SEQ ID NO: 1 or 2, but is not limited thereto.

In another embodiment of the present invention, the mixing ratio of vitamin C and aptamer of the composition is preferably 1: 1 to 200: 1 by weight, the mixing ratio of vitamin C and aptamer of the composition is 100: 1 to 200: More preferably, the weight ratio is not limited thereto.

In some embodiments, the concentration of the aptamer in the pharmaceutically acceptable composition is 0.001% to 2% (eg, 0.001% to 1.5%, 0.001% to 1.0%, 0.001% to 0.5%, 0.001% to 0.2% , 0.01% to 1.0%, 0.01% to 0.5%, or 0.01% to 0.2%), and the concentration of vitamin C is 0.1% to 20% (eg, 0.1% to 15%, 0.1% to 10%, 0.1). % To 5%, 0.1% to 2%, 1.0% to 20%, 1.0% to 10%, 1.0% to 5%, or 1.0% to 2%).

In some embodiments, the pharmaceutically acceptable composition comprises a spray (eg, aerosol), liquid, ointment, cream, lotion, solution (eg, aqueous solution), suspension, emulsion, paste, gel, powder, foam, It is administered as slow release nanoparticles, slow release microparticles, bioadhesives, patches, bandages, semi-solid dosage forms or wound dressings.

In some embodiments, the pharmaceutically acceptable composition is administered as an aqueous solution.

In some embodiments, the pharmaceutically acceptable composition is administered as a semi-solid dosage form.

In some embodiments, the pharmaceutically acceptable composition is administered as a cream.

In some embodiments, the pharmaceutically acceptable composition is administered 1-2 times a day.

Formulations of suitable cosmetics of the present invention may be provided in the form of, for example, creams, skins, lotions, powders, ointments, sprays or conceal sticks in the form of solutions, gels, semisolids or solids. It may also be prepared in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

In addition, the cosmetic compositions of the present invention may further comprise fatty substances, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionics. Type emulsifiers, fillers, metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or auxiliaries commonly used in the field of cosmetics or dermatology. It may contain. In addition, the above components may be introduced in an amount generally used in the dermatology field.

Examples of products to which the cosmetic composition of the present invention can be added include, for example, lotion, essence, lotion, cream, pack, gel, ointment, patch, or spray.

The cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, and specific formulations thereof include skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream It may include formulations such as nutrition cream, moisturizing cream, hand cream, essence, nutrition essence, pack, soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser and the like.

Hereinafter, the present invention will be described.

Eczema (eczema) is clinically itching, erythema, edema and ulcers. Histologically, eczema shows spongiosis of the epidermis, inflammatory cell infiltration and vascular growth and expansion of the dermis, and inflammatory cell infiltration around the blood vessels. Skin disease is characterized in that. Eczema is generally used as a synonym for dermatitis. However, if dermatitis is a histological term, eczema is a clinical term, and eczema is referred to in cases of clinical manifestations such as erythema, edema, and erythema.

However, most doctors, including dermatologists, do not distinguish eczema from dermatitis and use a mixture of atopic dermatitis, atopic eczema, contact dermatitis and contact eczema. Eczema can be classified into acute, subacute and chronic eczema depending on the extent and timing of dermatitis. Acute eczema is characterized by severe edema, erythema and rash. Chronic eczema is characterized by thickening of the skin and keratin, and subacute eczema is acute and chronic. As mentioned earlier, eczema is a term used to refer to skin diseases that show clinical histological characteristics. There are various detailed diseases, and the clinical manifestations such as the cause, exacerbation factor, and the site of lesion are different, and each treatment and prognosis are different.

Eczema is named based on its cause, such as contact dermatitis, atopic dermatitis, and autosensitized dermatitis, and may be named according to the shape or area of occurrence of the eczema, such as coin eczema and seborrheic dermatitis. Eczema can be largely divided into endogenous and exogenous. In general, eczema is said to be exogenous when the main cause of the disease is in the surrounding environment, and it is difficult to distinguish clearly between the two.

Exemplary exogenous eczema is contact dermatitis, and endogenous eczema is atopic dermatitis. There are many types of eczema, but here we will discuss only the most common contact dermatitis, atopic dermatitis, seborrheic dermatitis, coin eczema and dry dermatitis.

Contact dermatitis

Contact dermatitis is a dermatitis caused by contact with foreign substances. It is classified into stimulating contact dermatitis and allergic contact dermatitis.

Irritation contact dermatitis

Irritant contact dermatitis is a dermatitis caused by exposure to chemicals or physical irritants that are irritating to the skin at a certain concentration and over time. Severe irritants can cause severe reactions with short exposures, but most irritant dermatitis results from repeated prolonged exposure to one or several irritants.

In addition to dermatitis, exposure to irritants may cause burns, acne rashes, hypopigmentation or hyperpigmentation and granulomatous reactions. Irritant contact dermatitis is more common than allergic contact dermatitis, but the symptoms are relatively mild and transient, and patients do not visit the hospital because they know the cause and can easily avoid it. Irritant contact dermatitis can occur to anyone who is exposed to irritants, but it is often caused occupationally, accounting for 80% of occupational skin diseases.

In people with atopic diseases, irritant contact dermatitis occurs well, and even if the barrier function of the stratum corneum falls, the irritant penetrates well and dermatitis occurs well. If the temperature is low, dry, high temperature and high humidity, if the irritant is exposed in a closed state, irritated contact dermatitis can easily occur even if exposed after skin damage.

The most common and common irritant contact dermatitis is housewife eczema, and diaper rash is also a form of irritant contact dermatitis.

2) allergic contact dermatitis

While irritant contact dermatitis is a dermatitis that can occur to anyone exposed to irritants, allergic contact dermatitis is a dermatitis that occurs when a person who is sensitized to a specific contact antigen contacts the contact allergen (a substance that causes an allergic reaction) again. to be. Contact antigen, sensitization process and induction process are required for allergic contact dermatitis.

(1) contact antigen

It is often a lipophilic chemical with a molecular weight of 400 or less and there are more than 4,000 contact antigens.

(2) sensitization

The contact antigen is absorbed through the skin and then moved to the peripheral lymph nodes by antigen presenting cells present in the skin, and it is a process of remembering the antigen in T cells.

(3) induction

When a person who is sensitized to a specific antigen contacts the antigen again, the T cell that remembers the antigen is activated and dermatitis occurs. This process is called a provoking process and clinically shows erythema, edema and a rash.

Metals such as nickel, chromium, and cobalt that cause allergic contact dermatitis are well known, and are mainly included in women's precious metals and jewelry, and also included in watches and glasses, which can cause allergic contact dermatitis. Recently, eczema is repeatedly generated around the abdomen due to metal buttons of jeans, or dermatitis caused by metal contained in a mobile phone has been reported.

In addition, when dermatitis occurs on the face or neck area in people who use cosmetics because there are a lot of allergic contact dermatitis due to the ingredients contained in cosmetics, a patch test should be performed with the cosmetics and cosmetic ingredients used by the patient to find the causative antigen. do.

In order to diagnose allergic contact dermatitis, the patient's medical history is the most important, so it is correlated with the substance contacted with the site where the dermatitis has occurred, the relationship between when the suspected substance is contacted and when the dermatitis has occurred, and the patient's allergic contact dermatitis Differentiate between atopic dermatitis or seborrheic dermatitis in consideration of past medical history and the presence of a person with similar lesions.

Atopic dermatitis

Atopic dermatitis is a representative eczema that begins in infancy. In many patients, atopic dermatitis has a family history of atopic dermatitis, and eczema develops chronically at specific sites according to age. In recent years, the prevalence of atopic dermatitis has increased, with a prevalence of more than 20% in Northern Europe, which has a high incidence of atopic dermatitis, and a 19.1% prevalence in a 2008 survey of children in Seoul.

The causes of atopic dermatitis are thought to be a combination of factors. First of all, the fact that 70 ~ 80% of patients have family history, genetic factors are important, and in many patients with atopic dermatitis, allergic reactions to food or inhaled antigens are environmental factors. Until now, it has been thought that atopic dermatitis can occur due to abnormal immune response to this substance when exposed to food or inhaled antigen in people with genetic predisposition to atopy. Recently, there is an abnormality in the barrier function of the skin of atopic dermatitis patients, so that there is a report that the absorption of various harmful substances through the skin, thereby causing an abnormal immune response. Patients with atopic dermatitis may have allergic asthma, allergic rhinitis or allergic conjunctivitis as they age.

Symptoms of atopic dermatitis include severe itching and scratches. It is also an important feature that chronic lesions occur in certain areas of the skin, such as elephant skin. Depending on the time of occurrence, it can be divided into infancy, childhood, and adulthood. In infancy, it appears as a form of acute eczema, and in childhood, it appears as acute or chronic eczema in the folding part of the arm and leg, and in adulthood, the folding of arms and legs Along with the area, lesions appear on the face, neck and scalp. The principle of treatment of atopic dermatitis, along with general eczema treatment, it is important to identify the cause or worsening factors to avoid as much as possible.

In addition, proper skin moisturization should be maintained to compensate for impairment of skin barrier function. In general, topical steroids and antihistamines are most commonly used for treatment. Recently, the application of continuous or intermittent topical immunomodulators has been widely used for the purpose of reducing side effects of long-term use of steroids and preventing exacerbation of dermatitis. If symptoms are severe, professional treatment such as systemic immunosuppressive agents or ultraviolet light treatment is required.

Seborrheic dermatitis

Seborrheic dermatitis is a dermatitis that occurs recurrently in a region rich in sebaceous glands. Seborrheic dermatitis is more common in the age range between three months and between 40 and 70 years of age when sebaceous glands develop. The cause is still unclear, but it is thought to be related to sebum, fungi called Pyrosporum ovale, abnormalities in neurotransmitters, physical factors, epidermal growth abnormalities, and drug or nutritional disorders. Symptoms of seborrheic dermatitis are itching, but they are generally not as severe as atopic dermatitis or contact dermatitis, and eczema is confined to areas around the nose, forehead, head, eyebrows, and ear sebum, which are rich in sebaceous glands. It is characteristic. As the lesion progresses, it can appear all over the face, and can also occur between the breast and inguinal and hips. In addition to general eczema, immunomodulators used in the treatment of atopic dermatitis have recently been reported to be effective. In some cases, local or systemic antifungal agents may be used.

Coin-shaped eczema

Coin-shaped eczema is a relatively well-shaped coin-shaped eczema, with small blisters scattered on the lesion along with the papules. Beginning with small blisters and papules on the extensor side of the back of the hand, instep and limbs, they merge into a characteristic coin-shaped lesion. Sometimes accompanied by atopic dermatitis or dry dermatitis. Mainly acute eczema, complains of severe itching.

Dry eczema

Dry eczema is eczema associated with decreased lipids on the surface of the skin. It is characterized by erythema, dryness, cracks on the surface of the skin and fine dead skin cells, and occurs when exposed to dry, cold air. Symptoms begin with fine keratin in the limbs, especially the shin area, accompanied by itching, and as the disease progresses, cracks develop on the surface of the skin.

As can be seen through the present invention, in the case of treating atopic dermatitis, psoriasis, acne and eczema patients comprising a composition comprising the complex of vitamin C of the present invention and the aptamer binding to vitamin C as an active ingredient All of them show an improvement and therapeutic effect, and thus can be used as medicines and cosmetics for patients with such diseases.

1 to 10 is a figure showing the effect on atopic dermatitis,
11 to 13 is a diagram showing the effect on psoriasis,
14 to 23 is a figure showing the effect on acne,
24 to 29 is a picture showing the effect on eczema,
In this figure, aptamers that bind to vitamin C (ascorbic acid) were named aptamine C.

Hereinafter, the present invention will be described in more detail with reference to non-limiting examples. However, the following examples are intended to illustrate the present invention and the scope of the present invention is not to be construed as limited by the following examples.

Example  1: Effect on Atopic Dermatitis

10 ml of distilled water is mixed with 0.25% (w / v) of ascorbic acid and 0.0025% (w / v) of aptamer binding to the vitamin C (FIGS. 1 to 2 and 7 to 10), or 0.5% of ascorbic acid (w / v). v) and 0.0025% (w / v) of the aptamer binding to the vitamin C is mixed (Fig. 3) or ascorbic acid 0.5% (w / v) and 0.005% (w / v) of the aptamer binding to the vitamin C ) Or mixed with ascorbic acid 0.2% (w / v) and aptamer 0.002% (w / v) binding to the vitamin C (Fig. 5), or ascorbic acid 0.15% (w / v) ) And 0.0015% (w / v) of aptamer binding to vitamin C were mixed (FIG. 6) to prepare a composition of the present invention.

The prepared composition was applied to the affected area of 45 patients with atopic dermatitis once or twice a day, and all of them were slightly different depending on the severity of symptoms of patients as shown in FIGS. 1 to 10. After treatment to the affected area of all patients, improvement of the visually discernible symptom was observed between 5 and 10 days. No adverse effects were observed in them.

Example  2: On psoriasis  For effect

10 ml of distilled water is mixed with 0.5% (w / v) of ascorbic acid and 0.0025% (w / v) of the aptamer binding to the vitamin C (FIG. 11), or 0.25% (w / v) of ascorbic acid and the vitamin C. The composition of the present invention was prepared by mixing 0.0025% (w / v) of aptamer to bind (FIGS. 12 to 13).

The prepared composition was applied to the affected area of 7 psoriasis patients once to twice a day.

As can be seen in Figures 11 to 13, there is a slight difference depending on the severity of the symptoms of the patient, but the improvement of the symptoms that can be visually distinguished between about 15 to 20 days after treatment on the affected area of all patients Could confirm. No adverse effects were observed in them.

Example  3: effects on acne

0.1% (w / v) of ascorbic acid and 0.001% (w / v) of aptamer binding to vitamin C were mixed (10 and 17) in 10 ml of distilled water, or 0.25% (w / v) of ascorbic acid and The aptamer 0.0025% (w / v) that binds to vitamin C is mixed (Figures 15 to 16), or ascorbic acid 0.2% (w / v) and the aptamer 0.002% (w / v) that binds to the vitamin C The compositions of the present invention were prepared by mixing (FIGS. 18-23).

The prepared composition was applied to the affected area of 19 acne patients once to twice a day.

As can be seen in Figures 14 to 23, although there is a slight difference depending on the severity of the symptoms of the patient, the improvement of the symptoms that can be visually distinguished between about 1 week and 2 weeks after treatment on the affected area of all patients Could confirm. No adverse effects were observed in them.

Example  4: effects on eczema

10 ml of distilled water is mixed with 0.2% (w / v) of ascorbic acid and 0.002% (w / v) of aptamer binding to the vitamin C (FIG. 24), or 0.15% (w / v) of ascorbic acid and the vitamin C. Combined aptamer 0.0015% (w / v) is mixed (Fig. 25), or ascorbic acid 0.25% (w / v) and the aptamer 0.0025% (w / v) is bound to the vitamin C (Fig. 26 to 29) to prepare a composition of the present invention.

The prepared composition was applied to the affected area of 11 eczema patients once to twice a day.

As can be seen from Figures 24 to 29 there is a slight difference depending on the severity of the symptoms of the patient, but the improvement of the symptoms that can be visually distinguished between about 2 days to 2 weeks after treatment on the affected area of all patients Could confirm. No adverse effects were observed in them.

<110> NEXMOS CO., LTD. <120> A composition for improving and treating skin disease comprising          aptamin C as effective component <130> P18-0010HS <160> 2 <170> KopatentIn 2.0 <210> 1 <211> 32 <212> DNA <213> Artificial Sequence <220> <223> Aptamer <400> 1 agagctcgcg ccggagttct caatgcaaga gc 32 <210> 2 <211> 32 <212> DNA <213> Artificial Sequence <220> <223> Aptamer <400> 2 gtggaggcgg tggccagtct catacgcggc ag 32

Claims (5)

Composition for improving and treating skin diseases comprising a complex of vitamin C and aptamer binding to the vitamin C as an active ingredient. According to claim 1, wherein the skin disease is atopic dermatitis, contact dermatitis, seborrheic dermatitis, psoriasis, acne and eczema composition for improving and treating skin diseases, characterized in that at least one disease selected from the group consisting of. According to claim 1, wherein the aptamer is a composition for improving and treating skin diseases, characterized in that consisting of the nucleotide sequence of SEQ ID NO: 1 or 2. According to claim 1, wherein the mixing ratio of vitamin C and aptamer of the composition is a skin disease improvement and treatment composition, characterized in that 1: 1 to 200: 1 by weight. According to claim 1, wherein the mixing ratio of vitamin C and aptamer of the composition is a composition for improving and treating skin diseases, characterized in that the weight ratio of 100: 1 to 200: 1.

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