KR20120115780A - A pharmaceutical composition for prevention or treatment of pruritus, acne and atopic dermatitis comprising organometallic compound containing zinc and iron as an effective component and a functional cosmetic composition - Google Patents

Abstract

PURPOSE: A pharmaceutical composition and a functional cosmetics composition for preventing or treating pimples, atopic dermatitis and pruritus and a manufacturing method thereof are provided to alleviate or treat pimples, atopic dermatitis and pruritus without side effects in short time. CONSTITUTION: A manufacturing method of pharmaceutical composition for preventing or treating pimples, atopic dermatitis and pruritus comprises the following steps: dissolving 1-3 parts by weight of organic acid based on 100 parts by weight of water; respectively putting zinc and iron at 1000-3000ppm concentration; reacting at 50-60 deg. Celsius for 48-72 hours; and refining after obtaining supernatant. The organic acid of the first step is citric acid. The functional cosmetics composition includes the organometallic compound as an active ingredient. The functional cosmetics composition is effective on pimples, atopic dermatitis and pruritus improvement.

Description

Pharmaceutical composition and functional cosmetic composition for the prevention or treatment of itching, acne and atopic dermatitis, and functional cosmetic composition comprising an organometallic compound containing zinc and iron COMPOUND CONTAINING ZINC AND IRON AS AN EFFECTIVE COMPONENT AND A FUNCTIONAL COSMETIC COMPOSITION}

The present invention is a pharmaceutical composition and functional for the prevention or treatment of pruritus, acne and atopic dermatitis comprising an organometallic compound containing zinc and iron as an active ingredient. It relates to a cosmetic composition.

Skin is the largest organ in the body and is exposed to the outside, so it is an immune organ that is sensitive to various external stimuli. For this reason, various diseases accompanied by itching occur frequently on the skin. Representative skin diseases accompanied by itching are contact dermatitis including atopic dermatitis and febrile pruritus, urticaria, psoriasis and the like. These itching-related diseases are often scratched and scratched, which is accompanied by skin infections caused by bacterial infection and secondary infections caused by external allergens. As a result, immune cells such as T-cells and macrophages are activated to secrete various cytokines and neuropeptides, including IL-1, causing itching. Scratching again causes the symptoms of dermatitis to amplify and develop into a more serious condition.

It is estimated that 10-20% of the world's population suffers from itching, and the incidence rate is continuously increasing due to factors such as the increase of airborne allergens caused by recent environmental pollution. It is a social problem. In addition, skin itching (senile pruritus) in the elderly is also a symptom that occurs in most elderly people. In addition, it is estimated that at least 20-30% of the population will suffer from itching, including other diseases that cause skin itching. Itching is therefore the most common and important symptom of bothering humans. However, no drug has been developed so far to free itching. The only drug is antihistamine, which causes skin itch due to the involvement of histamine, IL-1 and other cytokines, neuropeptides (serotonin, acethycholine, substance P) and various inflammatory substances (leukotrines, prostaglandins). (J. Clin. Invest. 2006, 116 (5): 1174-1185).

Conventionally, in order to ameliorate the itch, a lipid complex of ceramide for moisturizing and restoring the skin barrier is applied (Korean Patent Publication No. 2001-0044622), oral administration of an antihistamine to treat the itch, a steroid for anti-inflammatory Methods such as application of agents have been generally used, and methods of applying oligosaccharides to improve skin immune status (Korean Patent Publication No. 2000-0029754) have been proposed, but topical and systemic drugs such as steroids, There are problems such as drowsiness due to oral administration of antihistamines, immunosuppressants, and the like, lowered immunity and safety to the skin according to topical administration, stability when formulating the composition for external application of the skin, and its use is also limited and its effects are insignificant.

Therefore, there is no side effect on the human body, and there is an urgent need for the development of substances that can alleviate or heal skin itching, which is one of the important challenges that humanity must solve.

Next, the cause of acne is not known exactly, but a combination of causes rather than one cause. The excess of male hormones during puberty stimulates the secretion of sebaceous glands and the epithelium of the hair follicles causes dyskerosis (abnormal keratinization with incomplete and immature keratinization), clogging the hair follicles and causing them to stiffen in the follicles (comedone). Sebum) is formed. Among the bacteria residing in hair follicles, propionibacterium acnes, in particular, secrete lipolytic enzymes, which break down triglycerides in sebum to form free fatty acids and stimulate hair follicles. In addition, the immunological response to Propionibacterium acnes contributes to the inflammatory response of acne.

It is well known that there is a family history of acne outbreaks. However, its exact genetic form is not yet clear. It is well known that many components of cosmetics can cause acne. In addition, the use of oily substances, excessive detergents and soaps contained in pomade can also cause acne. Acne usually begins in puberty, with men usually between 15 and 19 years old and women between 14 and 16 years old. About 80% of them disappear until the middle of 20 years old, but sometimes even after 30-40 years.

The primary symptom of acne is scalp (stiffened sebum in the hair follicles). There are two types of scalp: open scalp with open inlet and closed scalp with open inlet, which is black due to melanin deposition. White color If the scalp is old, inflammation occurs around it. Depending on the degree of inflammation, red acne (papulesy), pimples (purulent), nodules, cysts, etc. are formed. It is characterized by a mixture of rashes.

When acne becomes inflamed, it first turns red and then turns brown over time. If acne is left to inflame, or squeeze out, the sebum will burst into the skin, causing bumpy skin or concave scars (convex and concave scars). Acne scars are very sharp and deeply cut at the edges of other scars, and in practice, the scar bottom is often connected to the fat layer. The damage to the skin is widespread and scars are often connected to each other.

Acne treatment can be divided into two categories: medication, eating medicine and surgical treatment. Topical medications are direct antiseptics for acne bacteria, modified from topical antibiotics (Klymycin and erythromycin) and vitamin A to prevent the production of free fatty acids. Skin regeneration ointment (tretinoin, adapalene) that exfoliates keratin and releases sebum well, and strong antibacterial agent reduces bacterial populations and acne ointment (benzoyl peroxide) that has a slight anti-inflammatory and lytic effect. . There are two main types of medicine to take: antibiotics that help to kill acne and reduce inflammation, and retinoids made from modified vitamin A, commonly known as locutan. Retinoids are well known as sebum control agents because they reduce sebum secretion, but this drug is not only sebum control but also causes other acne, such as abnormal keratinization (abnormal keratinization with incomplete and immature keratinization), inflammatory reactions, bacterial growth, etc. It helps block all the paths of acne outbreaks. However, pregnancy can cause fetal malformation, so contraception is necessary from one month before the start of the drug to one month after the discontinuation. Surgical treatments include injection therapy, symptom extrusion, and dermabrasion. Large acne is scary to look at, but it is more likely to remain scars, so treatment with injection therapy will reduce scarring. If your acne is very hard and your skin is hardened, you can inject the diluted triamcinolone directly into the area so that the acne disappears quickly and no scars remain. As a side effect, the skin may shrink, but after 6 to 12 months, you do not have to worry too much. Too much squeezing acne often leaves a scar after the treatment. The reason for this is that the inflammation is weakened by excessively squeezing and destroying the oil glands walls weakened by the inflammation. However, extruded treatments performed by dermatologists do not cause these side effects because they clean the pores and clean the pores with hot steam and then squeeze acne with a special device.

Finally, atopic dermatitis is a common skin disorder with unexplained strong pruritus and a combination of dry skin, erythema and inflammation (Lancet. 1998; 351: 1715-1715). Atopic dermatitis is a chronic disease that causes great discomfort in long-term life, mainly in infants and young children. It occurs in 10 to 15% of all infants and infants, with the incidence in the atopy group being 60% in infants less than 1 year and 85% in infants less than 5 years (Lancet. 1998; 351: 1715-1721). 40% of children with atopic dermatitis gradually improved with growth, but the incidence rate of adults was about 1 to 3% of all adults due to pollution and environmental pollution caused by rapid industrialization (Immunol. Allergy. Cli. North Am. 2002; 22: 1 ~ 24), and the incidence rate has been increased two to three times as before the industrialization (Lancet. 2003; 361: 151 ~ 160). For this reason, many researchers are interested in reducing the clinical symptoms of atopic dermatitis.

Although clinical symptoms of atopic dermatitis may vary from person to person, the most common symptoms are first, severe itching, second, the patient's skin remains dry, and third, dry skin. Loss of the protective function of the skin surface makes it easier to invade the skin of irritants from outside, and this invasion causes the skin to reject and cause an inflammatory reaction (Lancet. 1998; 351: 1715 ~ 1721, J. Pediatr. Health Care. 2002; 16; 143--145).

Many studies have been conducted on the cause and treatment of atopic dermatitis until recently, but due to the complexity of the disease itself and conflicting research data, no clear theory has yet been established on the exact etiology and effective treatment. Therefore, therapeutic agents for atopic dermatitis, which have been developed to date, include topical anti-inflammatory agents such as steroids, tacrolimus, pimecrolimus, immunosuppressive agents such as antihistamines and cyclosporin. In addition, the use of hypo-allergenic moisturizers and photochemistry using ultraviolet rays as an adjuvant therapy are also being carried out in the clinic. However, these therapies or therapies help to control the symptoms to an appropriate level rather than the underlying treatment, and so far do not fully meet the needs of patients with atopic dermatitis.

The present invention has been made to solve the problems of the prior art, the problem to be solved in the present invention is a pharmaceutical composition and a functional cosmetic composition effective in the prevention and treatment of itching, acne and atopic dermatitis without side effects It is to provide.

In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention or treatment of itching, acne and atopic dermatitis containing an organometallic compound prepared as an active ingredient comprising the following steps:

(1) dissolving 1-3 parts by weight of an organic acid based on 100 parts by weight of water;

(2) adding zinc and iron at concentrations of 1000 to 3000 ppm and 10000 to 30000 ppm, respectively;

(3) reacting at 50 to 60 ° C. for 48 to 72 hours; And

(4) purifying after obtaining a supernatant.

The organic acid of step (1) is preferably citric acid (citric acid).

In addition, the present invention provides a functional cosmetic composition containing the organometallic compound prepared by including each of the above steps as an active ingredient.

The functional cosmetic composition is preferably effective for the improvement of itching, acne and atopic dermatitis.

When the pharmaceutical composition and the functional cosmetic composition of the present invention is applied to itching, acne and atopic dermatitis, it has an effect of alleviating or healing the above symptoms without side effects in a short time.

1 is a graph showing a mass spectrum of an organometallic compound containing zinc and iron of the present invention.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

The inventors of the present invention have been researched on the development of substances to alleviate or treat the symptoms of itching, acne and atopic dermatitis. As a result, organometallic compounds containing a certain amount of zinc and iron do not have side effects, and within a short time, It has been confirmed that it is effective in alleviating or treating acne and atopic dermatitis.

Accordingly, the present invention provides a pharmaceutical composition for the prevention or treatment of itching, acne and atopic dermatitis, comprising an organometallic compound prepared as an active ingredient comprising the following steps:

(1) dissolving 1-3 parts by weight of an organic acid based on 100 parts by weight of water;

(2) adding zinc and iron at concentrations of 1000 to 3000 ppm and 10000 to 30000 ppm, respectively;

(3) reacting at 50 to 60 ° C. for 48 to 72 hours; And

(4) purifying after obtaining a supernatant.

The organic acid of step (1) is preferably citric acid (citric acid). If the amount of the organic acid added to the water is less than 1 part by weight, there is a problem that the reactant is too small to sufficiently obtain an organometallic compound serving as an active ingredient. If the content is more than 3 parts by weight, the solubility is low, and the reaction time is reduced. There is a problem that becomes too long.

Zinc and iron in step (2) react with the organic acid molecules dissolved in water to form a zinc, iron and organic acid complex. In this case, the content of zinc and iron to be added is preferably in a concentration of 1000 ~ 3000ppm and 10000 ~ 30000ppm, respectively, the composition containing the organometallic compound prepared in the above concentration range is the most effective for itching, acne and atopic dermatitis Confirmed.

Under the reaction conditions of step (3), the reaction of the composition comprising the organometallic compound of the present invention is completed. Specifically, the reaction temperature is carried out at 50 ~ 60 ℃, the reaction time is too long when the reaction is carried out at a temperature of less than 50 ℃, the reaction rate is faster if the reaction is carried out at a temperature exceeding 60 ℃ but side reactions There is little improvement in the resulting itching, acne and atopic dermatitis. The reaction time is 48 to 72 hours, and when the reaction is performed for less than 48 hours, the metal and the organic acid cannot react sufficiently, and when the reaction time exceeds 72 hours, a side reaction proceeds to be a problem.

Step (4) is a step of purifying the reaction product completed in step (3), after separating the supernatant from the precipitate to purify the supernatant containing the organometallic compound of the present invention by filtration, chromatography, etc. Can be.

The results of the mass spectra (Mass Spectrum) for the result of the step (1) to step (4) is shown in Figure 1, it can be seen that the molecular weight of the organometallic compound of the present invention is 472.

In addition, the components of the organometallic compound of the present invention are shown in Table 1 below.

Name of circle Component Content (%) Atomic mass C 15.72 111 O 66.91 154 H 3.37 168 N - - S - - Fe 11 11 Zn 3 3

The composition containing the organometallic compound obtained according to the production method of the present invention comprises 1 to 14% by weight based on the total weight of the pharmaceutical composition.

For the prevention and treatment of itching, acne and atopic dermatitis containing the composition containing the organometallic compound of the present invention as an active ingredient The pharmaceutical composition may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions. The pharmaceutical composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, granules, fine granules, powders, hard capsules, soft capsules, syrups, emulsions, suspensions or solutions, and the like. May be administered as a pharmaceutical composition for oral administration of oral injection, intravenous, intramuscular or subcutaneous injection, mucus, suppository, transdermal absorbent, transmucosal absorbent, nasal drops, ear drops, eye drops, inhalants, creams It is also possible to administer it as a pharmaceutical composition for parenteral administration, such as ointment and pape. The formulation prepared as a pharmaceutical composition in powder form may be dissolved at the time of use and used as an injection or a mucus. In particular, the pharmaceutical compositions of the present invention may preferably be in the form of paste ointments, creams, milks, powders, powders, penetration pads, solutions, gels, sprays, lotions or suspensions.

For the preparation of pharmaceutical compositions, additives for the preparation of solids or liquids may be used. The additive for preparation may be either organic or inorganic.

When preparing oral solid preparations, excipients, additional binders, disintegrants, lubricants, colorants, and the like are added to the main medicine, and then tablets, coated tablets, granules, powders, capsules are prepared by conventional methods. Formulations in the form of can be prepared. Examples of excipients to be used include lactose, sucrose, white sugar, glucose, corn starch, starch, talc, sorbet, crystalline cellulose, dextrin, kaolin, calcium carbonate, silicon dioxide and the like. Examples of the binder include polyvinyl alcohol, polyvinyl ether, ethyl cellulose, methyl cellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, calcium citrate, Dextrin, pectin, and the like. Examples of the lubricant include magnesium stearate, talc, polyethylene glycol, silica, and hydrogenated vegetable oil. As a coloring agent, if it is normally permitted to add to a pharmaceutical, all can be used. These tablets and granules can be appropriately coated according to sugar, gelatin coating and other needs. Moreover, preservatives, antioxidants, etc. can be added as needed.

Inert diluents commonly used in the preparation of liquid preparations for oral administration, for example emulsions, syrups, suspensions, solutions, may be used, for example water or vegetable oils. In addition to the inert diluent, this preparation may be formulated with an adjuvant such as a wetting agent, suspending aid, sweetener, fragrance, colorant or preservative. After the liquid formulation is prepared, it may be filled into a capsule of absorbable material such as gelatin.

As a solvent or suspending agent used for preparation of a parenteral administration agent, for example, an injection or a suppository, water, propylene glycol, polyethylene glycol, benzyl alcohol, ethyl oleate, lecithin are mentioned, for example. As a base used for manufacture of a suppository, a cacao butter, an emulsified cacao butter, a laurin butter, and a witezol are mentioned, for example. The preparation method of the formulation is not particularly limited, and any method commonly used in the art can be used.

In the case of injections, diluents such as water, ethyl alcohol, macrogol, propylene glycol, citric acid, acetic acid, phosphoric acid, lactic acid, sodium lactate and sulfuric acid, sodium citrate, PH adjusting agents and buffers such as sodium and sodium phosphate, and stabilizers such as sodium pyrosulfite, ethylenediamine acetic acid, thioglycolic acid and thio lactic acid. In this case, in order to prepare an isotonic solution, a sufficient amount of salt, glucose, mannitol, or glycerin may be blended in the formulation, or a conventional dissolution aid, analgesic agent, or local anesthetic may be used.

In the case of ointments such as pastes, creams, and gels, bases, stabilizers, wetting agents, preservatives, and the like, which are commonly used, may be blended as necessary, and the components may be mixed and formulated by conventional methods. . As the base, for example, white petrolatum, polyethylene, paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicone, bentonite and the like can be used. Methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoic acid, etc. can be used as a preservative. When it is set as the form of a patch, the said ointment, cream, gel, paste, etc. can be apply | coated to a normal support body by a conventional method. As the support, a film or foam sheet such as a woven or nonwoven fabric made of cotton, staple fibers and chemical fibers, soft vinyl chloride, polyethylene, and polyurethane can be suitably used.

The dosage of the pharmaceutical composition of the present invention is not particularly limited, but in the case of oral administration, it is usually 0.1 to 500 mg / kg, preferably 1 to 100 mg / kg per kg, as the weight of the substance as an active ingredient per adult. have. It is preferable to appropriately increase or decrease this dosage depending on the age, condition and symptoms of the patient. The daily dose may be administered once or in two or three times a day at appropriate intervals or may be administered intermittently at intervals of several days. When used as an injection, the weight of the substance as an active ingredient per adult may be usually 0.01 to 10 mg / kg, preferably 0.1 to 1 mg / kg per kg. However, since the dosage of the pharmaceutical composition of the present invention is determined in view of various related factors such as the route of administration, the age, sex, weight of the patient, the severity of the patient, the dosage limits the scope of the present invention in any aspect. It should not be understood to be.

In addition, the present invention provides a functional cosmetic composition containing the organometallic compound prepared by including each of the above steps as an active ingredient.

The functional cosmetic composition is effective in improving itching, acne and atopic dermatitis.

The cosmetic composition according to the present invention may be formulated as an external preparation for skin or cosmetics.

The external preparation for the skin may include an ointment, a warning agent, a spray, a suspension, an emulsion, a cream, a gel, and the like.

The cosmetics may include basic cosmetics, makeup cosmetics, body cosmetics, shaving cosmetics, and the like. Examples of the basic cosmetics include creams, lotions, packs, massage creams, emulsions, etc. Examples of the makeup cosmetics include foundations, makeup bases, lipsticks, eyeshadows, eyeliners, mascara, eyebrow pencils, and the like. Examples of cosmetics include soaps, liquid detergents, baths, sunscreen creams, sun oils, and the like. Examples of shaving cosmetics include aftershave and shaving creams, but are not limited thereto.

Components included in the cosmetic composition of the present invention may include components commonly used in cosmetic compositions in addition to the composition comprising the organometallic compound of the present invention as an active ingredient, for example, antioxidants, stabilizers, solubilizers, vitamins Conventional adjuvants such as pigments and perfumes, and carriers. In addition, the cosmetic composition may further include a skin absorption promoting substance to enhance the effect.

When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

In the case where the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. Especially, in the case of a spray, a mixture of chlorofluorohydrocarbons, propane / Propane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.

In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is a surfactant-containing cleansing, as a carrier component, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

The composition containing the organometallic compound contained in the cosmetic composition of the present invention is preferably contained in 1 to 14% by weight based on the total dry composition weight.

[ Example ]

Hereinafter, the examples are only for illustrating the present invention in more detail, and the scope of the present invention is not limited by these examples according to the gist of the present invention, and modifications, substitutions, and insertions commonly known by those skilled in the art It will be apparent to those skilled in the art that the present invention may be included in the scope of the present invention.

1. Preparation of a composition comprising an organometallic compound

1000 ml of water was added to a 5 L reactor, followed by dissolving 20 g of citric acid. Zinc and iron were added to the final concentration of 2000 ppm and 20000 ppm, respectively, into the aqueous citric acid solution, and stirred at 50 ° C. for 72 hours. After the precipitate was removed through the filter paper and the supernatant was purified by chromatography, a cream formulation was prepared such that the composition of the present invention was at a concentration of 10% by weight.

2. Experimental  Screening and Application

Ten patients each had itching, acne, millet spots, erosion, and pigmentation. After applying the cream prepared in Example 1 to the lesion site once a day, the number and duration of patients whose symptoms were observed were examined, and the results are shown in Table 2.

Symptom ＼ Treatment Period 1 day 3 days 1 week 2 weeks 3 weeks Itching 9 people 1 person acne 2 people 8 people Millet 1 person 7 people 2 people Erosion 1 person 6 people 3 people Pigmentation 2 people 8 people

As shown in Table 2, the composition containing the organometallic compound of the present invention showed a remarkable improvement by only one administration in the case of itching, 3 days for acne and millet spots, 1 week for erosion In the case of pigmentation, it can be seen that a three-week administration shows a therapeutic effect.

Claims (4)

A pharmaceutical composition for the prevention or treatment of itching, acne and atopic dermatitis, comprising an organometallic compound prepared as an active ingredient comprising the following steps:
(1) dissolving 1-3 parts by weight of an organic acid based on 100 parts by weight of water;
(2) adding zinc and iron at concentrations of 1000 to 3000 ppm and 10000 to 30000 ppm, respectively;
(3) reacting at 50 to 60 ° C. for 48 to 72 hours; And
(4) purifying after obtaining a supernatant. The pharmaceutical composition of claim 1, wherein the organic acid of step (1) is citric acid. A functional cosmetic composition containing an organometallic compound prepared as an active ingredient, comprising the steps of claim 1. The functional cosmetic composition according to claim 4, which is effective in improving itching, acne and atopic dermatitis.

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