KR20190117207A - Composition for Adipolysis - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for promoting lipolysis or a slimming cosmetic composition containing bromelain and lipase as active components. A composition for lipolysis containing bromelain and lipase as active components according to the present invention is safe for the human body and can obtain an excellent lipolysis effect by a non-surgical method.

Description

Composition for lipolysis {Composition for Adipolysis}

The present invention relates to a pharmaceutical composition for promoting fat decomposition or a cosmetic composition for slimming containing bromelain and lipase as active ingredients.

Humans store surplus energy in case of lack of energy supply, and fat cells play this role. Fat cells store extra energy in the form of triglycerides and release the stored energy in the form of fatty acids whenever needed. Obesity is an accumulation of excess fat tissue. People who are nutrient-rich, likely to sit predominantly and become genetically obese can cause serious health problems as their fat tissue increases.

Local obesity is an excessive fat deposit in certain areas, such as the abdomen and buttocks, and is more common in women due to endocrine and anatomical factors. Local obesity has a special meaning in that it directly affects health and quality of life and also causes psychological atrophy and social maladjustment in the face of cosmetic surgery. In view of such health and aesthetics, various methods for improving obesity have been attempted.

Until now, many patients have resorted to liposuction, which is a surgical operation to remove local fats such as abdominal fat. These liposuctions can be permanently maintained and have a relatively easy and quick visual effect, but require general and local anesthesia, and can damage muscles, blood vessels and lymphatic vessels during the procedure. This can cause severe concomitance with contour irregularity, serous, hyperpigmentation, asymmetry, hypertrophic scar, skin necrosis, or infection. There was a problem of frequent side effects (Elisa Bellini et al., Annals of Medicine and Surgery 24: 53-60, 2017).

Thus, non-surgical therapies have begun to emerge to supplement the serious side effects of liposuction for fat removal. Non-surgical therapies are common for lipolytic injections of subcutaneous injections of lipolytic substances. However, non-surgical methods are less likely to achieve satisfactory lipolytic effects than shorter periods of time compared to surgical methods (DP Friedmann et al., Dermatologic Surgery . 41 (1): 18). -34, 2015).

In addition, conventionally known methods for resolving obesity include diet, exercise, surgery, and drug therapy for the purpose of inhibiting energy intake and increasing consumption in addition to plastic surgery. However, these methods do not completely solve obesity, and there is no clear guarantee on safety since the yo-yo phenomenon or serious side effects are reported. From aesthetic point of view, eliminating obesity requires fat breakdown and additional skin safety, so the above treatments are inadequate to meet all the necessary conditions (KM Gadde et al., Journal of the American College of Cardiology 71 (1): 69-84, 2018).

Many women are now steadily increasing their demand for slimming and anti-celullite cosmetics, which are relatively safe and inexpensive products due to the psychological burden, cost and side effects of plastic surgery. L-Cartinine and Horse Chestnut, which are used in existing slimming products, are used to break down fatty acids to energize them or to promote the circulation of lymph / blood around fat cells, which improves cellulite. The generated energy is again used for fat accumulation (resynthesis), resulting in a slimming effect.

Conventional lipolytic accelerators include methylxanthine-based substances such as caffeine and theophylline, which promote or promote phosphodiesterase, an adenylate cyclase, an enzyme closely related to lipolysis in adipocytes. It shows the effect of lipolysis through the inhibitory effect of (phosphodiesterase). However, they were reported to be addictive and reported side effects such as bronchial dilatation and exacerbation of premenstrual syndrome, thus ensuring no safety (PJ Barnes et al., Pharmaceuticals 3: 725-747, 2010).

Therefore, the present inventors have made diligent efforts to obtain satisfactory level of lipolysis effect by non-surgical method while improving the problems of the prior art. It confirmed and completed this invention.

An object of the present invention to provide a pharmaceutical composition for promoting lipolysis and slimming cosmetic composition containing bromelain and lipase as an active ingredient that can obtain a satisfactory level of lipolysis effect in a more safe and non-surgical way to the human body. have.

Another object of the present invention to provide a pharmaceutical composition for promoting fat decomposition containing collagenase and hyaluronidase as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for promoting fat decomposition containing bromelain and lipase as an active ingredient.

The present invention also provides a slimming cosmetic composition containing bromelain and lipase as an active ingredient.

The present invention also provides a pharmaceutical composition for promoting fat decomposition containing collagenase and hyaluronidase as active ingredients.

The present invention also provides a method for promoting lipolysis and comprising the step of administering a composition containing the bromelain and lipase as an active ingredient or a composition containing collagenase and hyaluronidase as an active ingredient. For use in promoting lipolysis.

The lipolytic composition containing bromelain and lipase according to the present invention as an active ingredient is safe for the human body and can obtain excellent lipolytic effect by a non-surgical method.

Figure 1 shows the amount of fat dissolved for 11 days after the addition of a single composition of lipolysis solution to 3cc of adipose tissue extracted from the human body, (A) normal saline 6cc (control), (B) lipase 6cc, (C ) Bromelain 6cc, (D) collagenase 6cc, (E) hyaluronidase 6cc were added to adipose tissue. (Left: Day 1, Middle: Day 3, Right: Day 11)
Figure 2 shows the amount of fat dissolved for 11 days after adding the lipolysis solution of the two mixed compositions to 3cc of adipose tissue extracted from the human body, (A) lipase 3cc + bromelain 3cc, (B) lipase 3cc + Collagenase 3cc, (C) Lipase 3cc + Hyaluronidase 3cc, (D) Bromelain 3cc + Collagenase 3cc, (E) Bromelain 3cc + Hyaluronidase 3cc, (F) Collagenana Aze 3cc + hyaluronidase 3cc was added to adipose tissue. (Left: Day 1, Middle: Day 3, Right: Day 11)
Figure 3 is added to the lipolysis solution of the three mixed compositions to the fat tissue 3cc extracted from the human body after 11 days to observe the amount of dissolved fat, (A) lipase 2cc + bromelain 2cc + collagenase 2cc, (B) lipase 2cc + collagenase 2cc + hyaluronidase 2cc, (C) bromelain 2cc + collagenase 2cc + hyaluronidase 2cc, (D) lipase 2cc + bromelain 2cc + hyaluronidase 2cc of aze is added to adipose tissue
4 is added to 3cc of adipose tissue extracted from the human body to add a lipolysis solution (lipase 1.5cc + bromelain 1.5cc + collagenase 1.5cc + hyaluronidase 1.5cc) after 10 days of melting Observed the amount of fat.
Figure 5 was observed three weeks after the injection of the lipolysis composition to the double chin or cheek area of the face, (A) is a lipase 6cc + bromelain 6cc injection, (B) lipase 6cc + collagenase 6cc was injected and (C) was injected with collagenase 6cc + hyaluronidase 6cc. (Top: before injection, bottom: after injection)
Figure 6 was observed three weeks after the lipolysis composition injection to the double chin or cheek area of the face, (A) is a lipase 4cc + bromelain 4cc + collagenase 4cc, (B) is a lipase 4cc + collagenase 4cc + hyaluronidase 4cc was injected, (C) injection of bromelain 4cc + collagenase 4cc + hyaluronidase 4cc. (Top: before injection, bottom: after injection)
Figure 7 shows the left and right face after three weeks after the injection of the lipolysis composition of lipase 3cc + bromelain 3cc + collagenase 3cc + hyaluronidase 3cc in the double chin or cheek area of the face. (Top: before injection, bottom: after injection)

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.

Unlike other tissues, adipose tissue is divided into septa and surrounds a group of fat cells. The septum contains coarse blood vessels and nerves, and is mainly composed of fibrous tissues, and collagen is a main component.

The fat cell group inside the septum is called fat lobule, which is composed of fat cells (adipocytes) and interstitial tissues.

The cell membrane of adipocytes is composed mainly of phospholipids, in which protein clumps are embedded inside the double layer of lipid components. In addition, fat cells have the largest structure of triglyceride, and the cytoplasm and nucleus are skewed to one side.

Interstitial tissue is a connective tissue between cellular components and consists of protein fiber and ground substance. Protein fiber is composed of collagen, reticular, elastic fibers. The filling in between is composed of tissue fluid, glycosaminoglycans, and proteoglycans, and glycosaminoglycans are composed of hyaluronic acid, heparin sulfate, chondroitin sulfate, and dermatan sulfate. and keratin sulfate.

Bromelain of the present invention is a mixture of various compounds of vegetable proteolytic enzymes extracted from the fruit and stem of pineapple and other components not yet identified. It is a substance that breaks down muscle fibers well and is widely used for anticancer, antiplatelet, respiratory inflammation, indigestion, rheumatoid arthritis and mastitis. It is mainly used as an anti-inflammatory and anti-edema agent, and is known to be particularly effective for treating inflammation of soft tissues, traumatic events and post-operative tissue reactions. The inflammation treatment is known to occur by bromelain improves the nutritional supply to the inflammatory site, such as degradation of the fibrous layer of the inflammatory site, anti-edema, pain relief and improved blood circulation, and enhance immune function. Bromelain is a type of protease, a protease, which can help break down proteins in fat cell membranes or interstitial tissues.

Lipase of the present invention is an enzyme belonging to an ester hydrolase which hydrolyzes an ester bond of a higher fatty acid triglyceride as a lipid hydrolase. Usually referred to as triacylglycerol lipase. True substrates are fats, ie esters that are insoluble in water, and because they are insoluble in water, they increase in action with an increase in interfacial area where oil-water interfaces occur. Lipase is a lipid hydrolase, so it can break down phospholipid double layers of fat cell membranes and even triglycerides to break down fat cells.

Collagenase of the present invention is an enzyme that catalyzes the hydrolysis of collagen, and uses various extracellular substrates as substrates. Collagen is a fibrous tissue that gives skin flexibility and is mainly produced in fibroblasts in the dermal layer of the skin and is a major component of about 70% of dermal tissue. The main functions of collagen are known as mechanical firmness of skin, resistance of connective tissue and binding of tissue, support of cell adhesion, induction of cell division and differentiation (in organic growth or wound healing) (Van der Rest et al., 1990). Collagenase helps to dissolve not only the septum of adipose tissue but also the interstitial tissue.

Hyaluronidase of the present invention is a generic term for an enzyme that lowers hyaluronic acid. Hyaluronic acid is a biosynthetic natural substance that is present in many skins such as animals. It is a hydrophilic substance because of many hydroxyl groups (-OH), and plays a role of moisturizing in the skin of animals and the like. It is also present in human skin, and because it is moisturizing, it is contained in many cosmetics. It regulates various physiological actions in response to the CD44 protein expressed in various epithelial cells. Hyaluronidase is known to hydrolyze the binding of hyaluronic acid (HA) with D-glucuronic acid and N-acetyl-D-glucosamine in chondroitin and chondroitin sulfate. Hyaluronidase can break down interstitial tissue around adipocytes when injected into adipose tissue.

In the present invention, it was observed that the fat is decomposed by adding bromelain to the adipose tissue extracted from the human body, and a mixture of bromelain and lipase was injected into the human ear to confirm the lipolysis effect.

Therefore, the present invention relates to a pharmaceutical composition for promoting fat decomposition containing bromelain and lipase as active ingredients in a consistent point.

In the present invention, the lipolysis-promoting pharmaceutical composition preferably further comprises one or more selected from the group consisting of collagenase and hyaluronidase, but is not limited thereto.

In one embodiment of the present invention, but lipolysis solution of 1.5 ~ 6cc bromelain, lipase, collagenase or hyaluronidase, but when used in the human body 1 ~ 16cc, 10 ~ the body part Can be used up to 200cc.

The dosage of bromelain usable to the human body is 0.6-12000 IU / cc (0.0006-12 IU / mg), and the commonly used dose is 0.6-2400 IU / cc (0.0006-2.4 IU / mg). In one embodiment of the present invention used 1.5 ~ 6 cc bromelline, the dose is 90 ~ 200 IU / cc (0.09-0.2 IU / mg).

In the present invention, the bromelain is preferably included in 0.0006-15 IU / mg, more preferably 0.0006-12 IU / mg, but is not limited thereto.

The dose of lipase usable in the human body is 1-60000 IU / cc (0.001-60 IU / mg), and the commonly used dose is 0.001-12 IU / mg. In one embodiment of the present invention used 1.5 ~ 6 cc of lipase, the dose is 120 ~ 1800 IU / cc (0.12-1.8 IU / mg).

In the present invention, the lipase is preferably included in 0.001 ~ 40000 IU / mg, more preferably 0.001 ~ 60 IU / mg, but is not limited thereto.

In addition, the dose of collagenase available to the human body is 0.6-12000 IU / cc (0.0006-12 IU / mg), and the dose generally used is 0.0006-2.4 IU / mg. In one embodiment of the present invention used 1.5 ~ 6 cc collagenase, the dose is 5-120 IU / cc (0.005-0.12 IU / mg).

In the present invention, the collagenase is preferably included in 0.0006 ~ 800 IU / mg, more preferably 0.0006 ~ 12 IU / mg, but is not limited thereto.

The dose of hyaluronidase available to the human body is 0.6-12000 IU / cc (0.0006-12 IU / mg), and the commonly used dose is 0.0006-2.4 IU / mg. In one embodiment of the present invention used 1.5 ~ 6 cc hyaluronidase, the dose is 60-750 IU / cc (0.06-0.75 IU / mg).

In the present invention, the hyaluronidase is preferably included in 0.0006 ~ 15000 IU / mg, more preferably 0.0006 ~ 12 IU / mg, but is not limited thereto.

In the present invention, the composition may be characterized in that the injection for topical fat removal.

In the present invention, "local" means a part of the whole, and means any part of the living body. For example, skin areas, subcutaneous areas may be included, and in more detail, under eyes, under the chin, under the arms, abdomen, thighs, calf, neck, armpits, buttocks, hips, cheeks, forehead, calf, back, thigh It may include, but not limited to, thighs, ankles or abdomen is included in the scope of the invention corresponding to the whole or part of the living body.

In addition, "fat removal" means to remove the fat present in the living body, fat removal in the present invention may be to reduce the fat through the decomposition of fat, reduction of fat or death of fat cells and the like. For example, by treating the injection composition of the present invention with a portion of fat present, the fat after treatment may be reduced compared to the fat before treatment.

The compositions of the present invention can be administered by subcutaneous, intraperitoneal, intramuscular or intravenous injection. In particular, the lipolytic composition may be administered, for example, forearms, abdomen, thighs, face, buttocks for topical fat removal.

In addition, the dosage of the composition of the present invention may vary depending on the condition and weight of the patient, the type and extent of the disease, the route and duration of administration, and may be appropriately selected by those skilled in the art. For example, 0.001 ml to 10 ml per target site may be administered transdermally or subcutaneously, and the target site may be 0.1 cm × 0.1 cm to 5 cm × 5 cm, but is not limited thereto. In addition, the administration may be administered once a day or divided into several times, thereby not limiting the scope of the present invention.

The subject to which the composition of the present invention is administered or treated may be a mammal including a human, but is not limited thereto, and the composition of the present invention may be applied to all living organisms that form fat.

Compositions of the present invention are proteases such as Bromelain (Pepsin, Trypsin, Protease, Chymotrypsin, Chymosin, Ficin, Cathepsin, Papain, Dipeptidase, Actinidin) and carbohydrate degrading enzymes (Amylase, Diastase, Ptyalin, Glycosidase, Dextrinase, Maltase, Sucrase) , Galactase), Caffeine, Nicotine, Fucus Vesiculosus Extract, Cynara Scolymus Artichoke Extract, Peripheral Micro-circulation Enhancer (Ginkgo Biloba Extract, Centella Asiatica Extract, Horse Chestnut Extract, Juglans Regia, Sophora Japonica Flower Extract, Escin), Soy Isoflavone Ferment, It is possible to add or replace Visnadine, L-Carnitine, Capsaicin, Nattokinase, Phosphatidylcholine, Bile Acid type such as Deoxycholic acid or Urosodeoxycholic acid, Methylxanthine type such as Aminophylline, Theophylline, and Steroid type such as Triamcinolone.

In addition, the composition of the present invention may further comprise a pharmaceutically acceptable additive, the additive may be preservatives, stabilizers, preservatives, etc., the kind and amount thereof may be added to the drug commonly used in the art Level is enough. That is, it is included in the scope of the present invention without limitation, so long as it corresponds to an additive that can be added to and used in a conventional drug.

When the composition of the present invention is prepared in the form of a pharmaceutical preparation, the active ingredient is combined with a pharmaceutically acceptable conventional carrier to prepare parenteral administration such as aerosol, sterile injectable solution or sterile powder, etc., depending on the purpose of administration. It can be formulated in the form of. In addition, injections in the form of solutions or suspensions for parenteral administration can be administered parenterally, eg, subcutaneously, intravenously, intramuscularly or intraperitoneally. Generally, injectable solutions or suspensions are effective amounts in pharmaceutically acceptable liquid carriers, such as water, saline, aqueous dextrose and related sugar solutions, nonvolatile oils, glycols such as ethanol, glycerin, polyethylene glycol, propylene glycol, and the like. It can be prepared by homogeneously mixing the active ingredients of.

In addition, if necessary, auxiliary agents such as antibacterial agents, chelating agents, buffers, and preservatives may be included. As the pharmaceutically acceptable carrier, any adjuvant may be used that is pharmaceutically pure, substantially non-toxic, and which does not inhibit the action of the active ingredient.

Injectables are prepared by dissolving the main medicine and other additives in distilled water for injection, filtering the solution with a bacterial filter, aseptically, filling the vial in a sterile state and then sealing it. Water can be used. The water for injection may be distilled water made to dissolve the solid injection or dilute the aqueous injection. Specific examples include glucose injection, xylitol injection, D-mannitol injection, fructose injection, physiological saline, dextran 40 injection, dextran 70 injection, amino acid injection, Ringer's solution, lactic acid-Linger's solution and the like.

Pharmaceutically acceptable carriers may be oils, non-aqueous carriers, diluents, solvents, vehicles used in compositions for parenteral administration, ie injection or bolus injection. Examples of oils or non-aqueous carriers, diluents, solvents or vehicles include propylene glycol, polyethylene glycol, vegetable oils (eg olive oil) and injectable organic esters (eg ethyl oleate), or molded Formulations such as preservatives, wetting agents, emulsifiers or suspending agents, stabilizers and / or dispersants may be included. The lipolytic composition is preferably an injectable formulation, and in one aspect the composition may be an injectable formulation for use mixed with physiological saline immediately before use, or may be a liquid formulation dissolved in water for injection.

As used herein, the term "lipolysis" component refers to a component that performs or promotes lipolysis combustion, and is not limited to performing decomposition or combustion of fat cells and has a significant effect on inhibiting or eliminating the production of cellulite. Includes all substances that represent

In addition, "fat removal" means to remove the fat present in the living body, in the present invention, fat removal may be to reduce fat through the decomposition of fat, reduction of fat or death of fat cells. For example, by treating the injection composition of the present invention with a portion of fat present, the fat after treatment may be reduced compared to the fat before treatment.

In another aspect, the present invention relates to a method for promoting lipolysis comprising administering a composition containing bromelain and lipase as an active ingredient.

In another aspect, the present invention relates to the use of a composition containing bromelain and lipase as an active ingredient to promote fat breakdown.

In still another aspect, the present invention relates to a slimming cosmetic composition containing bromelain and lipase as active ingredients.

In the present invention, the slimming cosmetic composition further comprises one or more selected from the group consisting of collagenase and hyaluronidase, but is not limited thereto.

In the present invention, the bromelain is preferably included in 0.0006-15 IU / mg, more preferably 0.0006-12 IU / mg, but is not limited thereto.

In the present invention, the lipase is preferably included in 0.001 ~ 40000 IU / mg, more preferably 0.001 ~ 60 IU / mg, but is not limited thereto.

In the present invention, the collagenase is preferably included in 0.0006 ~ 800 IU / mg, more preferably 0.0006 ~ 12 IU / mg, but is not limited thereto.

In the present invention, the hyaluronidase is preferably included in 0.0006 ~ 15000 IU / mg, more preferably 0.0006 ~ 12 IU / mg, but is not limited thereto.

As used herein, the term "slimming" refers to making the skin smooth and elastic through the reduction of cellulite from an aesthetic point of view, as well as the prevention and prevention of obesity through the reduction of body fat from a medical point of view.

In the present invention, the composition may be characterized in that it shows an effect of promoting fat decomposition or cellulite reduction.

The cosmetic composition of the present invention can be applied to all formulations applied to the skin. More specifically, such as skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, foundation, essence, nutrition essence, spray, pack In addition to cosmetics, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cream, body oil, body cleaner, shampoo, ointment, patch (hydrogel slimming patch) and the like, but is not limited thereto. . In addition, it can also be produced as a skin contact material in contact with the skin such as makeup, detergent, and fiber.

The cosmetic composition of the present invention can be appropriately selected as desired.

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

If 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, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane / butane Or propellants such as dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as the carrier component, for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol , Fatty acid esters of 1,3-butylglycol oil, glycerol aliphatic esters, polyethyleneglycol or sorbitan.

When the dosage form of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Sung cellulose, aluminum metahydroxy, bentonite, agar or tragacanth and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing, an aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid as carrier components 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.

In addition to the above-mentioned components, the external preparations of the present invention may be formulated with an application amount of various known components to be applied to cosmetics or external medicines and quasi-drugs applied to the skin or mucous membranes.

Specifically, the slimming cosmetic composition of the present invention may be blended with other ingredients usually formulated into cosmetics as needed in each formulation. Examples of the ingredient that can be added include antioxidants (for example, carboxylic acids such as ascorbic acid and citric acid; phenols such as tocopherol and dibutylhydroxytoluene), and humectants (for example, glycerin, propylene glycol, dipropylene glycol Glycols such as 1,3-butylene glycol; organic salts such as hyaluronic acid; amides such as urea), viscous agents (e.g., high molecular compounds such as polyethylene glycol; sodium carboxymethyl cellulose, carboxypropyl cellulose Celluloses), buffers (e.g., organic acids such as citric acid, lactic acid, tartaric acid; inorganic acids such as hydrochloric acid, boric acid; salts such as sodium dihydrogen phosphate, sodium citrate; organic bases such as triethanolamine; sodium hydroxide, hydroxide Inorganic bases such as potassium), adsorbents (e.g. hydrous aluminum silicates such as kaolin, bentonite; Inorganic salts such as magnesium, aluminum hydroxide), bases (e.g., white petrolatum, Tween60, Tween80, liquid paraffin, beeswax, petrolatum, castor oil, silicone oil, hardened castor oil, natural rubber, palm oil fatty acid diethanolamide, Organic materials such as polyoxyethylene hardened castor oil, natural rubber latex, 1,3-pentadiene copolymer resin; polybutene, synthetic rubber SBR, monostearic acid polyethylene glycol, monostearic acid polyoxyethylene glycol, polyoxyethylene setster High molecular compounds such as aryl ether, polyoxyethylene oleylcetyl ether, silicone, starch acrylate 300, sodium polyacrylate, n-butyl copolymer of methacrylic acid and acrylic acid, carboxyvinyl polymer; fatty acids such as stearic acid; Alcohols such as stil alcohol; fats such as myristic acid octadodecyl, myristic acid isopropyl, and cetyl octanoate Esters), solvents (e.g., ethanol, isopropanol, 1,3-butylene glycol, n-octadecyl alcohol, crotamiton, carbohydrates such as tri (caprylic acid / capuron) glycerin), stabilizers (e.g. For example, inorganic salts such as sodium metaphosphate, zinc oxide, titanium oxide; organic salts such as polyoxyethylene lauryl sulfate ether sulfate, sodium lauryl sulfate), pressure-sensitive adhesive (for example, sodium polyacrylate, dipropylene glycol High molecular compounds), emulsifiers (eg, carbohydrates such as monoolefin acid sorbitan, monoolefin acid polyoxyethylene sorbitan, D-sorbitol, monolauric acid polyglycerol, polyoxyethylene lauryl ether sodium sulfate), surfactants (For example, high molecular compounds such as polyglycerol monolauric acid and polyoxyethylene oleyl alcohol ether), perfumes, pigments (dyes, pigments), metal blockers, deodorants, A film former, a ultraviolet absorber, an ultraviolet scattering agent, vitamins, etc. are contained.

The cosmetic composition of the present invention can be applied by applying an appropriate amount to the skin according to the skin area to be applied, it can be used once to several times a day as needed. The amount and frequency of the application may be appropriately increased or decreased as necessary according to the skin condition of the individual, the dosage form, the age, sex, weight, and obesity of the subject to be administered, the responsiveness, and the duration of the application.

One skilled in the art can appropriately select a dosage that is effective for the desired effect, for example, an effective amount will be in the range of 0.1 mg to 5000 mg, preferably 100 mg to 500 mg, per day of skin surface area (cm ² ), It can be applied 1 to 5 times a day. The dosage form of the composition may be a single dose or a repeated dose formulation, and the daily effective amount may be administered in several divided doses.

The pharmaceutical or cosmetic composition of the present invention, for the purpose of enhancing the permeability of the active ingredient, iontophoresis, sonophoresis, electroporation, microelectronic patch, mechanical It can be applied to the skin by pressure, osmotic pressure gradient, occlusive cure or microinfusion, or a combination thereof.

The pharmaceutical or cosmetic composition of the present invention may be used alone, but may be used in combination with exercise therapy, liposuction, hormonal therapy, drug treatment, diet, and the like.

In another aspect, the present invention relates to a pharmaceutical composition for promoting fat decomposition, containing collagenase and hyaluronidase as active ingredients.

In another aspect, the present invention relates to a method for promoting lipolysis including administering a composition containing collagenase and hyaluronidase as an active ingredient.

In another aspect, the present invention relates to the use of a composition containing collagenase and hyaluronidase as an active ingredient to promote lipolysis.

[ Example ]

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.

Example  1: Preparation of Injectable Composition

Bromelain (sigma B4882)> 3 units / mg was diluted in distilled water for injection and used as> 60 IU / cc (> 0.06 IU / mg) and lipase (sigma L3001) 5-15 units / mg in distilled water for injection Diluted to 100-300 IU / cc (0.1-0.3 IU / mg). In addition, collagenase (sigma C0130) 0.25-1.0 units / mg is 5-20 IU / cc (0.005-0.02 IU / mg) and hyaluronidase (sigma H3506) 400-1000 units / mg is 50-125 IU / cc (0.05-0.125 IU / mg) was also used diluted in distilled water for injection.

Table 1 shows the injectable compositions for in vitro experiments, and Table 2 shows the injectable compositions for in vivo experiments. The volume of the injectable composition was used at 6 cc.

Injectable Injection Composition NO. ingredient cc IU One normal saline 6 2 Lipase 6 600-1800 3 Bromelain 6 > 360 4 Collagenase 6 30-120 5 Hyaluronidase 6 300-750 6 Lipase
Bromelain 3
3 300-900
> 180 7 Lipase
Collagenase 3
3 300-900
15-60 8 Lipase
Hyaluronidase 3
3 300-900
150-375 9 Bromelain
Collagenase 3
3 > 180
15-60 10 Bromelain
Hyaluronidase 3
3 > 180
150-375 11 Collagenase
Hyaluronidase 3
3 15-60
150-375 12 Lipase
Bromelain
Collagenase 2
2
2 200-600
> 120
10-40 13 Lipase
Bromelain
Hyaluronidase 2
2
2 200-600
> 120
100-250 14 Lipase
Collagenase
Hyaluronidase 2
2
2 200-600
10-40
100-250 15 Bromelain
Collagenase
Hyaluronidase 2
2
2 > 120
10-40
100-250 16 Lipase
Bromelain
Collagenase
Hyaluronidase 1.5
1.5
1.5
1.5 150-450
> 90
7.5-30
75-187.5

In vivo Injectable Composition NO. ingredient cc IU One Lipase
Bromelain 6
6 600-1800
> 360 2 Lipase
Collagenase 6
6 600-1800
30-120 3 Collagenase
Hyaluronidase 6
6 30-120
300-750 4 Lipase
Bromelain
Collagenase 4
4
4 400-1200
> 240
20-80 5 Lipase
Collagenase
Hyaluronidase 4
4
4 400-1200
20-80
200-500 6 Bromelain
Collagenase
Hyaluronidase 4
4
4 > 240
20-80
200-500 7 Lipase
Bromelain
Collagenase
Hyaluronidase 3
3
3
3 300-900
15-60
15-60
150-375

Example  2: Evaluation of in vitro lipolysis efficacy

6cc of the lipolysis solution of Table 1 was added to 3cc of subcutaneous fat tissue extracted from the abdomen of the human body, and the lipolysis effect was observed for 11 days.

2-1: monolithic lipolysis solution

As a result, there was no change in normal saline, and lipase, bromelain, collagenase, hyaluronidase, respectively, were observed after 11 days of degradation of adipose tissue by a single component (FIG. 1). Lipase was 0.4cc, bromelain 0.4cc, collagenase 0.5cc, hyaluronidase 0.3cc was able to confirm the degraded adipose tissue (Table 3).

2- 2: 2 things  Mixed composition of lipolysis solution

Then, the same experiment was performed with a solution prepared by mixing two lipolytic components (FIG. 2). As a result, lipase / bromelain is 0.5cc, lipase / collagenase is 0.8cc, lipase / hyaluronidase is 0.5cc, bromelain / collagenase is 0.6cc, bromelain / hyaluronidase 0.5cc, collagenase / hyaluronidase was 1.1cc of fat was broken down (Table 3).

That is, it was found that the lipase / bromelain mixed solution had better fat cell decomposition ability than the known lipase and bromelain alone. In addition, the lipase / collagenase mixed solution compared to the conventional lipase and collagenase alone alone, and the collagenase / hyaluronidase mixed solution than the conventional collagenase and hyaluronidase alone are much better in adipocyte degrading ability. It was.

2- 3: 3 things  Mixed composition of lipolysis solution

This time, the same experiment was performed with a solution prepared by mixing three lipolytic components (FIG. 3). As a result, 1.3cc for lipase / bromelain / collagenase, 1.0cc for lipase / bromelain / hyaluronidase, 1.5cc for lipase / collagenase / hyaluronidase, bromelain / collagena Azase / hyaluronidase degraded 1.5cc of fat (Table 3).

Again, the lipase / bromelain / collagenase mixed solution with bromelain added to the lipase / collagenase mixture of Example 2-2 was remarkably superior in the ability to degrade fat cells and collagenase / hyaluronidase. The fat cell lysis capacity of collagenase / bromelain / hyaluronidase with bromelain added was significantly better than that of azeotrope. That is, it was confirmed that bromelain increases the lipolysis capacity.

2- 4: 4 kinds  Mixed composition of lipolysis solution

Finally, the same experiment was performed with a solution prepared by mixing the four lipolytic components of lipase / bromelain / collagenase / hyaluronidase (FIG. 4).

As a result, a mixed solution of four combinations of lipase / bromelain / collagenase / hyaluronidase is more fat than lipase, bromelain, collagenase, hyaluronidase alone or a mixture of two or three of them. It was found that the cell decomposition ability was the best.

The results of degraded fat mass indicating the effects of the lipolytic compositions are shown in Table 3 below.

NO. ingredient Broken down fat (cc) One normal saline 0 2 Lipase 0.4 3 Bromelain 0.4 4 Collagenase 0.5 5 Hyaluronidase 0.3 6 Lipase / Bromelain 0.5 7 Lipase / collagenase 0.8 8 Lipase / hyaluronidase 0.5 9 Bromelain / Collagenase 0.6 10 Bromelain / Hyaluronidase 0.5 11 Collagenase / Haluronidase 1.1 12 Lipase / bromelain / collagenase 1.3 13 Lipase / bromelain / hyaluronidase 1.0 14 Lipase / collagenase / hyaluronidase 1.5 15 Bromelain / Collagenase / Hyaluronidase 1.5 16 Lipase / bromelain / collagenase / hyaluronidase 1.6

Example  3: Clinical Trial Evaluation

12cc of the lipolysis solution of Table 2 was injected into the double chin or cheek area of the face, and the lipolysis effect was observed 3 weeks later (FIGS. 5 to 7).

As a result, the lipase / bromelain mixed solution, the lipase / collagenase mixed solution and the collagenase / hyaluronidase mixed solution were excellent in the resolution of fat cells (FIG. 5). In other words, it was more effective to use lipase / bromelain mixed solution so that lipase breaks down the fat cell membrane and bromelain breaks down the interstitial tissue, and it breaks down the septa and interstitial tissue while breaking the fat cell membrane. Using a lipase / collagenase solution to a higher degree showed a higher effect. In addition, the collagenase / hyaluronidase mixed solution that can further break down the interstitial tissue was also effective.

Next, the lipase / bromelain / collagenase mixed solution, lipase / collagenase / hyaluronidase mixed solution and bromelain / collagenase / hyaluronidase mixed solution were examined. 6). As a result, lipase / bromelain / collagenase was added with bromelain that degrades fat cells and degrades interstitial tissue, rather than lipase / collagenase solution that degrades septa and interstitial tissue while decomposing fat cell membranes. The solution showed a higher effect, and the lipase / collagenase / hyaluro added with lipase or bromelain that could break down the fat cell membrane than the collagenase / hyaluronidase mixed solution that degrades the septum and interstitial tissue. Nidase mixed solution or bromelain / collagenase / hyaluronidase mixed solution showed higher effect.

Finally, observing the effects of the lipase / bromelain / collagenase / hyaluronidase mixed solution, it is possible to decompose all the fat cell membranes, septum and interstitial tissue more than other conventional mixtures. Therefore, the lipolysis effect appeared to be the best (FIG. 7).

As described above in detail specific parts of the present invention, it will be apparent to those skilled in the art that these specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. will be. Therefore, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (12)

A pharmaceutical composition for promoting fat decomposition containing bromelain and lipase as active ingredients.
The pharmaceutical composition of claim 1, further comprising at least one selected from the group consisting of collagenase and hyaluronidase.
The pharmaceutical composition for promoting fat decomposition according to claim 1 or 2, wherein the composition is an injection for local fat removal.
The pharmaceutical composition according to claim 1 or 2, wherein the composition further comprises a pharmaceutically acceptable carrier, excipient or diluent.
Slimming cosmetic composition containing bromelain and lipase as active ingredients.
The slimming cosmetic composition for promoting fat decomposition according to claim 5, further comprising at least one selected from the group consisting of collagenase and hyaluronidase.
According to claim 5 or 6, wherein the composition is a slimming, characterized in that the formulation of the lotion, nutrient lotion, nourishing cream, massage cream, essence, pack, hydrogel slimming patch, bath cleaner, soap, mist or aerosol. Cosmetic composition.
The slimming cosmetic composition according to claim 5 or 6, wherein the composition exhibits an effect of promoting fat decomposition or reducing cellulite.
A pharmaceutical composition for promoting lipolysis containing collagenase and hyaluronidase as active ingredients.
10. The pharmaceutical composition for promoting fat decomposition according to claim 9, further comprising any one or more selected from the group consisting of bromelain and lipase.
The pharmaceutical composition for promoting fat decomposition according to claim 9 or 10, wherein the composition is an injection for local fat removal.
The pharmaceutical composition of claim 9 or 10, wherein the composition further comprises a pharmaceutically acceptable carrier, excipient or diluent.

Images