KR102172439B1 - Composition for lipolysis and injection composition comprising the same - Google Patents

Abstract

The present invention relates to a composition for decomposing fat and an injection composition comprising the same, wherein the composition for decomposing fat according to the present invention comprises at least one plant-derived extract in a salt of deoxycholic acid having excellent lipolysis performance, While maintaining the performance, it is possible to realize the effect of alleviating side effects such as pain and inflammation that occurred when injected under the skin.

Description

Composition for lipolysis and injection composition comprising the same {Composition for lipolysis and injection composition comprising the same}

The present invention relates to a composition for decomposing fat and an injection composition comprising the same, and specifically, a fat that relieves pain and reduces inflammation caused by injection by including a salt of deoxycholic acid and at least one plant-derived extract. It relates to a composition for decomposition and an injection composition.

Recently, through diet and exercise, fat is very slowly lost or cellulite is formed under the skin, making it difficult to lose fat.

The cellulite is a subcutaneous fat that clumps under the skin and makes the skin look thick.It refers to a change in the skin shape of orange peel that mainly occurs on the thighs, buttocks, and abdomen.When viewed or touched, the skin surface is uneven and the nodules are touched deep in the skin. The skin is not elastic and may feel colder than the skin of other areas. Unlike general obesity, it is characterized by structural changes throughout the dermis, fat layer and microcirculation system.

Cellulite causes exudate and swelling between adipocytes due to changes in capillaries and microarteries, and the network structure of the skin tissue is irregularly hyperformed and thickened by the edema, and collagen fibers are formed in the surrounding adipocyte group. After making micro nodules by combining them together, the micro nodules are combined with each other to create a giant nodule. Excess body fluids and fat penetrate into the subcutaneous area due to disorders in micro-blood circulation or lymph circulation, resulting in fat and connective tissue. It is caused by fine change.

Since cellulite is viewed as a normal skin condition rather than a disease, it does not require special treatment, but efforts to remove cellulite in various ways such as massage, treatment, and surgery for cosmetic purposes to modern people are continuing.

As one of them, lipolysis injection, which is an injection method in which a drug is injected into a region where fat loss is hardly achieved, to promote fat loss in the region, has been developed. In addition, since the demand of the body contouring market is wide and continues to grow every year, various methods of lipolysis are being developed.

As an injection widely known and used as lipolytic injection, there is PPC injection. PPC injection is an abbreviation of phosphatidylcholine (PPC), and is an injection containing a fat-soluble substance extracted from soybeans. Phosphatidylcholine extracted from soybeans is well known as an effective ingredient in breaking down fat. When PPC, extracted from soybean lecithin, penetrates the subcutaneous fat with a lipolytic enzyme, it causes deformation of the fat cell membrane and has the effect of decomposing triglycerides in fat cells. In addition, when fat is decomposed after the injection procedure, it is discharged as urine or sweat.

However, according to a paper published in the “International Journal of Immunopathology and Pharmacology” in 2010, there is not only experimental data that sodium deoxycholate has better lipolytic effect compared to phosphatidylcholine, a PPC injection component, but also sodium Deoxycholate has been proven to be an active ingredient that dissolves cell membranes and induces adipocyte degradation (P Palumbo et al. Effects of phosphatidylcholine and sodium deoxycholate on human primary adipocytes and fresh human adipose tissue.:INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY. (2): 481-490, ISSN 0394-6320,2010).

In addition, PPC injection, which has been widely used as a treatment for obesity, was revoked in 2014 due to side effects, and various manufacturers have recently developed lipolytic injections using sodium deoxycholate. However, even when the sodium deoxycholate lipolysis composition is injected subcutaneously, it is still very painful due to pain, and there is a problem in that inflammation (edema) occurs.

Referring to Korean Patent Registration No. 10-1751585, an injection composition using sodium deoxycholate, comprising 1% w/v sodium deoxycholate, 0.9% w/v benzyl alcohol, and 1% w/v sodium chloride The composition is disclosed, and by maintaining the pH of the composition at 8.3, it can be confirmed that it is effective in dissolving fat and is stable in precipitation.

However, the Korean Patent Registration No. 10-1751585 contains benzyl alcohol, which is a chemically synthesized substance, which is harmful to the human body and has a poor pain relief effect, so there is a problem in that a separate local anesthetic such as lidocaine must be applied to the skin and treated. .

Korean Patent Registration No. 10-1751585

P Palumbo et al., “Effects of phosphatidylcholine and sodium deoxycholate on human primary adipocytes and fresh human adipose tissue”, International Journal of Immunopathology and Pharmacology, 23(2), 481-490, ISSN 0394-6320, 2010.

The present invention is to solve the above problems, by including a salt of deoxycholic acid and one or more plant-derived extracts, a composition for decomposing fat capable of reducing pain and inflammation that occurs when injected subcutaneously, and comprising the same An object thereof is to provide an injection composition.

The technical problems of the present invention are not limited to the technical problems mentioned above, and other technical problems that are not mentioned will be clearly understood by those skilled in the art from the following description.

The present invention is a means for solving the above problems, the salt of deoxycholic acid; And it can provide a composition for fat decomposition comprising at least one plant-derived extract.

The present invention is another means for solving the above problems, the fat decomposition composition, pH adjuster, tonicity agent, surfactant, stabilizer, preservative, one or more additives selected from the group consisting of a chelating agent and a buffering agent; And it can provide an injection composition for fat decomposition comprising water for injection.

The composition for decomposing fat according to the present invention includes a salt of deoxycholic acid and one or more plant-derived extracts, so that the fat decomposition performance is maintained, and pain that occurs during injection under the existing subcutaneous can be reduced, and inflammation, etc. There is also an effect that can alleviate the side effects of.

In addition, as an anesthetic for pain relief, natural extracts are used instead of chemically synthesized substances such as benzyl alcohol.

Brief description of each drawing is provided in order to more fully understand the drawings cited in the detailed description of the present invention.
1 to 5 are photographs of results of a pig fat decomposition experiment conducted in an experimental example, respectively.

In the present invention, various modifications may be made and various embodiments may be provided, and specific embodiments will be illustrated in the drawings and described in detail in the detailed description.

However, this is not intended to limit the present invention to a specific embodiment, it is to be understood to include all changes, equivalents, and substitutes included in the spirit and scope of the present invention.

In the present invention, terms such as "comprises" or "have" are intended to designate the presence of features, numbers, steps, actions, components, parts, or a combination thereof described in the specification, but one or more other features. It is to be understood that the presence or addition of elements or numbers, steps, actions, components, parts, or combinations thereof, does not preclude in advance.

In addition, the accompanying drawings in the present invention should be understood as being enlarged or reduced for convenience of description.

Hereinafter, the present invention will be described in detail.

As described above, the demand for decomposing or removing subcutaneous fat using medical techniques has recently increased, and accordingly, interest and development for fat decomposition are actively progressing.

However, the PPC injection containing phosphatidylcholine, which was widely used in the past, was canceled due to side effects, and the composition for decomposing fat containing sodium deoxycholate developed afterwards also had excellent lipolysis capacity, but pain occurred when injected subcutaneously. , There was a problem that inflammation occurs at the injection site.

Accordingly, the present invention provides a composition for decomposing fat comprising a salt of deoxycholic acid and at least one plant-derived extract, and an injection composition comprising the same, so that the lipolysis effect is excellent and at the same time, pain that occurs when injected subcutaneously And to alleviate inflammation.

The composition for decomposing fat according to the present invention includes a salt of deoxycholic acid; And one or more plant-derived extracts.

The deoxycholic acid is a substance mainly extracted from the intestine of livestock, and is one of the bile acids, and makes various organic and molecular compounds. In addition, the deoxycholic acid has properties of removing fat accumulated in the body by acting to destroy the granular structure in cells.

The salt of deoxycholic acid according to the present invention is not particularly limited, but (4R)-4-((3R,5R,10S,12S,13R,17R)-3,12 having an alkali metal or ammonium ion as a cation. -Dihydroxy-10,13-dimethylhexadecahydro-1H-ringpenta[a]phenanthren-17-yl) may mean pharmaceutically acceptable salts of pentanoate. Among them, alkali metal salts are preferred, and sodium salts are more preferred.

Specifically, the salt of deoxycholic acid in the present invention may be sodium deoxycholate having a structure represented by the following formula (1).

[Formula 1]

Sodium deoxycholate, as described above, was widely used in the past, through “Effects of phosphatidylcholine and sodium deoxycholate on human primary adipocytes and fresh human adipose tissue”, a paper published in the 2010 International Journal of Immunopathology and Pharmacology. Compared to the PPC injection containing phosphatidylcholine, the lipolytic effect is more excellent, and sodium deoxycholate is a proven substance that dissolves cell membranes and induces fat cell degradation.

However, since the sodium deoxycholate-containing composition for fat decomposition still has side effects such as pain and inflammation when injected subcutaneously, local anesthetics such as benzyl alcohol and lidocaine are used to relieve pain. There was a problem in that it must be mixed with or applied to the skin and treated.

In contrast, in the present invention, a salt of deoxycholic acid having excellent fat resolution and at least one plant-derived extract that is harmless to the human body are mixed to alleviate the side effects of pain and inflammation that occur when injected subcutaneously.

For example, the plant-derived extract is not particularly limited, but arnica, yarrow, calendula, witch hazel, amaryllis, real beom, chamomile, comfrey, daisy, echinacea, red pepper sprouts, perilla, sarubia, centella, serrata , Western peppermint, bitter grass, parsley, tomentil, jujube, angelica, sandalwood, budcher's brom, safflower, phoenix, peony, broccoli, and grapes. It may be an extract derived from at least one plant selected from the group consisting of.

As such, the present application may replace the local anesthetic agent used to prevent the occurrence of pain and inflammation during subcutaneous injection of the existing composition for decomposing fat with a plant-derived extract.

Specifically, local anesthetics are drugs that inhibit the conduction of excitement by acting on nerve fibers, and are intended to produce local anesthesia (pain), and conduction of not only perceptual nerves but also autonomic nerves and motor nerves is suppressed. Synthetic local anesthetics (procaine, lidocaine, mepivacaine, difcaine, etc.), cold anesthetics (chlorethyl), pain anesthetics (corrosive drugs such as phenol, menthol, ammonia, etc.) synthesized to remove cocaine and side effects from natural resources Etc.

Local anesthesia is divided into 5 types: superficial, infiltrating, conduction epidural, and subarachnoid (spinal cord) anesthesia, depending on the form, and cocaine, oikaine, and tetracaine as surface anesthesia. Ethyl aminobenzoate, hexylkine, cyclomethicine, orthocaine, lidocaine, propitocaine, dimethysokin, phenakaine, benzyl alcohol, sarizenine, and other topical forms are synthetic ones that are well soluble in water (pro Caine, lidocaine, etc) are used.

Side effects of these local anesthetics include cardiovascular system, central nervous system, respiratory system, immune system and musculoskeletal system side effects.

Specifically, cardiovascular side effects occur when a large amount of local anesthetic is accidentally injected into the blood. The effect of local anesthetics on the cardiovascular system depends on the dose administered, and inhibits myocardial suppression, vasodilation, and cardiac conduction, causing hypertension, tachycardia, and myocardial suppression in the early stage, and in the middle period, decreased cardiac output, hypotension, peripheral vascular relaxation, bradycardia. Appears, and in the terminal stage, ventricular arrhythmia, severe circulatory disruption, can also occur.

In addition, side effects of the central nervous system may include headache, dizziness, metallic taste, numbness of the tongue or lips, poor speech, tinnitus, anxiety, convulsions, and coma.

In addition, side effects of the respiratory system may occur when the diaphragm nerve block or the ribs interstitial nerve block is performed, or when a local anesthetic is directly exposed to the respiratory center of the breathing brain (soft water).

In addition, side effects of the immune system may cause an allergic reaction with a solution preservative added rather than the local anesthetic itself. From weak symptoms such as erythema, hives, and swelling, to severe symptoms such as systemic reactive erythema, swelling, organ contraction, and hypotension.

In addition, musculoskeletal side effects, when a local anesthetic is directly injected into the skeletal muscle, may cause muscle fiber overconstriction, and regeneration takes 3 to 4 weeks.

On the other hand, the present invention provides an injection for fat decomposition that does not require a local anesthetic, so that it is safe for the human body and can minimize side effects that may occur due to the existing local anesthetic.

Specifically, the plant-derived extract contained in the composition for decomposing fat according to the present invention may be one or more plant-derived extracts selected from the group consisting of arnica, yarrow, chamomile, daisy, echinacea, and pepper sprouts.

More specifically, the plant-derived extract contained in the composition for decomposing fat according to the present invention may be used by mixing a total of six plant-derived extracts of arnica, yarrow, chamomile, daisy, echinacea, and pepper sprouts.

In addition, the effects known so far for the arnica, yarrow, chamomile, daisy, echinacea, and red pepper sprouts are as follows.

The arnica extract is known in Europe as a plant obtained from essential oils used to treat various traumas, particularly bruises, falls, bruises or fractures as a folk remedy. In particular, it is known to be very effective in suppressing edema, anti-inflammatory action, promoting blood circulation, and healing wounds, and has a good effect on muscle pain, gout, bruises, and degenerative rheumatoid arthritis. In addition, Arnica is known to have various effects on stimulating the nervous system, digestive, respiratory, and circulatory organs. In addition, Arnica is listed as Floraes arnicae in the 7th edition of the German pharmacy room and Flos arnicae in the Swiss pharmacy room VI.Referring to the magazine Complementary Therapies in Medicine in June 2005, there is a description that arnica is helpful in reducing postpartum bleeding. .

The yarrow extract is named as yarrow because its leaves look like sawtooth, and it is a perennial herb native to Europe, and it is widely cultivated for ornamental or medicinal purposes and grows wild in the field or grass. These yarrows are known to brighten the eyes and have a great effect on gangrene, and are useful as an antidote when bitten by snakes or insects. In addition, it contains azulene active ingredient and is known to have analgesic effect. In addition, Western yarrow contains several active ingredients such as Caffeic acid, Luteolin, rutin, and Bisabolol through a paper published in 2017, and has been proved (Sofi). Imtiyaz Ali et al. Pharmacognosy, Phytochemistry and Pharmacological Properties of Achillea millefolium L.: A Review. Phytother. Res. 31: 1140-1161 (2017))

The chamomile flower extract is a representative herb used as a household medicine in Europe until the early 20th century when there was no cold medicine that turned into a famous medicinal herb. Drinking tea is effective for insomnia, and it is effective for cold sweating, antipyretic action, neuralgia, rheumatism, pain relief and soothing action, and coldness in women. In particular, Vikas Gupta et al., “Pharmacological Potential of Matricaria recutita-A Review”, International Journal of Pharmaceutical Sciences and Drug Research 2010; 2(1): Referring to 12-16, it can also be confirmed that chamomile has anti-inflammatory activity.

The daisy extract has excellent efficacy in living organisms so as to be called phytomedicine, and has been traditionally used as a medicinal plant. The ointment made from leaves can be used for trauma or bruise, and the decoction of the root can cure eczema. It is also excellent in detoxification, astringent, and whitening effects, and has antifungal properties, so it is used by spraying to repel insects with the juice brewed from leaves. In addition, phenolic, flavonoid, and terpenoid, among the components of daisy flowers extracted with methanol, have anti-inflammatory action. In addition, FP Karakas et al., “In vitro cytotoxic, antibacterial, anti-inflammatory and antioxidant activities and phenolic content in sild-grown flowers of common daisy-A medicinal plant”, Journal of Herbal Medicine 8 (2017) 31-39 Referring to, daisy extract has been proven to be a traditional medicinal plant as a treatment for inflammatory diseases such as rheumatism, eczema, eye disease and tonsillitis.

The Echinacea extract is a perennial plant of the Asteraceae family that grows wild in the plains of Canada and the United States, and was an important medicinal plant for early settlers and natives of North America. It has been used as a folk remedy for centuries to treat colds, bronchitis, upper respiratory infections, and inflammation. Currently, echinacea is best known as an immune booster and is used for respiratory infections, skin diseases and many other inflammatory diseases. In addition, Tragni E et al. “Anti-inflammatory activity of Echinacea angustifolia fractions separated on the basis of molecular weight”, Pharmacol Res Commun. Referring to 1988 Dec;20 Suppl 5:87-90, there is also experimental data that the degree of anti-inflammatory activity of echinacea extract varies according to molecular weight.

The red pepper sprout flower/leaf/stem extract is known to be helpful in improving many physical conditions such as depression and stress, menstrual syndrome, chronic fatigue, and chronic pain. In addition, it is effective in preventing skin aging and maintaining healthy skin as it has anti-bacterial and anti-inflammatory effects as well as skin antioxidant effects.

The present inventors have confirmed that the six plant-derived extracts, when mixed with sodium deoxycholate, have excellent effects such as fat resolution, solution stability, pain and inflammation relief, etc., through continuous research for a long period of time, and completed the present invention.

The plant-derived extract may be extracted with one or more extraction solvents selected from the group consisting of water, alcohol having 1 to 4 carbon atoms, ethyl acetate, ethylene glycol, propylene glycol, butylene glycol, and glycerin.

Specifically, the plant-derived extract may be extracted using a mixed solution of ethanol as an extraction solvent. By using a mixed solution of ethanol as the extraction solvent, it was possible to extract desired active ingredients from each of arnica, yarrow, chamomile, daisy, echinacea, and red pepper sprouts with high efficiency.

In addition, in some cases, in order to prevent evaporation of the solvent, the active ingredient is extracted by heating extraction at 30 to 100°C for 3 to 48 hours with an extractor equipped with a cooling condenser or immersion at 5 to 30°C for 1 to 5 days. , Obtained by concentrating the extraction solvent with a vacuum concentrator.

As a result, the present invention does not specifically limit the composition through this, but the composition for fat decomposition includes sodium deoxycholate as a salt of deoxycholic acid, and as one or more plant-derived extracts, arnica, yarrow, It may include a mixture of extracts from chamomile, daisy, echinacea and peppercorns.

The composition for decomposing fat according to the present invention may have a pH in the range of 8.1 to 8.5. For example, the pH of the composition for decomposing fat may range from 8.1 to 8.4, 8.1 to 8.3, 8.1 to 8.2, 8.2 to 8.5, or 8.2 to 8.4. By adjusting the pH of the composition for decomposing fat within the above range, an acceptable pH range for injection into the body is implemented, and when stored for a long time, the formation of precipitates is low, so that the solution stability may be excellent.

In the composition for decomposing fat according to the present invention, the salt of deoxycholic acid may be contained in an amount of 0.1% to 3% w/v. For example, in the composition for decomposing fat of the present invention, the salt of deoxycholic acid is 0.1% to 2.8% w/v, 0.1% to 2.5% w/v, 0.1% to 2.3% w/v, 0.1% To 2.0% w/v, 0.3% to 3% w/v, 0.5% to 3% w/v, 0.5% to 2.5% w/v, 0.5% to 2% w/v or 0.8% to 1.2% w/ v Can be included in the range.

For example, in the composition for decomposing fat, when the salt of deoxycholic acid is contained in an amount of less than 0.1% w/v, a problem of lowering the ability to decompose fat occurs, and the salt of deoxycholic acid is 3.0% w/v. If it contains more than v, side effects increase when injected subcutaneously, and if stored for a long time, sediment may occur and use may not be possible.

In addition, in the composition for decomposing fat according to the present invention, the one or more plant-derived extracts may be included in an amount of 0.001% to 1% w/v. For example, in the composition for decomposing fat of the present invention, one or more plant-derived extracts may be included in the range of 0.02% to 0.1% w/v. When two or more plant-derived extracts are included, each extract may be included in the range of 0.001% to 1% w/v.

In the composition for decomposing fat, when the amount of one or more plant-derived extracts is less than 0.001% w/v, there is a problem that the effect of preventing pain and inflammation occurring during subcutaneous injection is reduced, and the plant-derived extract is In the case of containing more than 1% w/v, sediment may occur and solution stability may deteriorate, making long-term storage and use impossible.

According to the present invention, by controlling the content of the salt of deoxycholic acid and the plant-derived extract within the above range, it is possible to provide a composition for decomposing fat with excellent fat decomposition ability and minimized side effects.

The present invention can provide an injection composition for fat decomposition comprising the composition for fat decomposition described above.

Specifically, the composition for lipolysis injection according to the present invention includes the above-described composition for fat breakdown; at least one additive selected from the group consisting of a pH adjusting agent, an isotonic agent, a surfactant, a stabilizer, a preservative, a chelating agent, and a buffering agent; And water for injection.

Specifically, the specific content of the composition for decomposing fat may be the same as the above.

Next, the additive is described in detail as follows.

The pH adjuster serves to adjust the pH of the injection and may include both acidic and basic substances. Specifically, it may contain a pH adjusting agent commonly used in the composition for injection, for example, sodium hydroxide, citric acid, acetic acid, phosphoric acid, gluconic acid, ascorbic acid, and one or more from the group consisting of succinic acid. , But is not limited thereto.

The tonicity agent includes sugar, sugar alcohol, salts, etc., for example, glucose, glycerin, sodium chloride, calcium chloride, sodium sulfate, glycerin, propylene glycol, polyethylene glycol (e.g., polyethylene glycol having a molecular weight of 1000 or less), dextrose Ose, hydroxypropyl betadex, mannitol, potassium chloride, dextran, ficoll, gelatin, hydroxyethyl starch, and the like, but are not limited thereto. As an example, the tonicity agent may be glycerin to sodium chloride, and in particular, glycerin may help to increase the stability of the formulation. The tonicity agent may be used in an amount suitable to provide the osmotic pressure.

Such surfactants include ionic, nonionic, and/or amphoteric surfactants. In one embodiment, the surfactant may be a nonionic surfactant. The non-ionic surfactant may include, for example, a polyoxyethylene sorbitan fatty acid ester and a polyoxyethylene-polyoxypropylene block copolymer, but is not limited thereto.

The stabilizer includes, for example, cholesterol, β-cholesterol, cystosterol, ergosterol, stigmasterol, stigmasterol acetate, lanosterol, and combinations thereof, but is not limited thereto.

The preservative includes antimicrobial agents commonly used in the field of pharmaceuticals. The preservatives are glycerin, m-cresol, phenol, benzalkonium chloride, benzethonium chloride, acacia, albumin, alcohol, alginic acid, ascorbyl palmitate, aspartame, boric acid, citric acid, glycerin, pentetic acid, sodium acetate, sorbic acid , Chlorobutanol, o-cresol, ρ-cresol, chlorocresol, benzalkonium chloride, phenylmercuric acid nitrate, thimerosal, benzoic acid, cholesterol, and the like, but are not limited thereto.

The chelating agent is ethylenediaminetetraacetic acid (EDTA), butylenediaminetetraacetic acid, cyclohexane-1,2-diaminetetraacetic acid (CyDTA; cyclohexane-1,2-diaminetetraacetic acid), diethylene Triaminepentaacetic acid (DETPA), ethylenediaminetetrapropionic acid, (hydroxyethyl)ethylenediaminetriacetic acid (HEDTA; hydroxyethyl)ethylenediaminetriacetic acid), N,N,N',N'-ethylenediaminetetra(methylenephosphonic acid) (EDTMP; ethylenediaminetetra (methylenephosphonic acid), triethylenetetraminehexaacetic acid (TTHA; triethylenetetraminehexaacetic acid;), 1,3-diamino-2-hydroxypropane-N,N,N',N'-tetraacetic acid (DHPTA) ; 1,3-diamino-2-hydroxypropane-N,N,N',N'-tetracetic acid), methyliminodiacetic acid, propylenediaminetetracetic acid, 1,5,9-tri Azacyclododecane-N,N',N''-tris(methylenephosphonic acid) (DOTRP; 1,5,9-triazacyclodecane-N,N',N''-tris(methylenephosphonic acid), 1,4, 7,10-tetraazacyclododecane-N,N',N'',N'''-tetrakis(methylenephosphonic acid) (DOTP; 1,4,7,10-tetraazacyclodecane-N,N',N '',N'''-tetrakis (methylenephosphonic acid), nitrilotris (methylene) triphosphonic acid, diethylenetriamine penta (methylenephosphonic acid) (DETAP; diethylenetriaminephenta (methylenep) hosphonic acid)), aminotri(methylenephosphonic acid), 1-hydroxyethylene-1,1-diphosphonic acid, bis(hexamethylene) Triaminephosphonic acid (bis(hexamethylene)triaminephosphonic acid), 1,4,7-triazacyclononane-N,N',N"-tris(methylenephosphonic acid) (NOTP; 1,4,7-triazacyclononan-N,N',N''-tris(methylenephosphonic acid)), 2-phosphonobutane-1,2,4-tricarbonyl acid (2-phophonobuthan-1,2,4- tricarboxylic acid), nitrilotriacetic acid (NTA), citric acid, fumaric acid, malic acid, maltol, tartaric acid, gluconic acid, Glyceric acid, oxalic acid, phthalic acid, maleic acid, mandelic acid, malonic acid, lactic acid, salicylic acid acid), methyl salicylate, 5-sulfosalicylic acid, galic acid, propylgallate, pyrogallol, 8-hydroxyquinoline Cysteine and the like are included, but are not limited thereto.

The buffer is dibasic sodium phosphate, citric acid, sodium citrate hydrate, potassium citrate, acetic acid, sodium acetate, sodium carbonate, calcium carbonate, tricalcium phosphate, calcium lactate, glycine, maleic acid, malic acid, sodium glutamate, glutamic acid Monosodium, sodium lactate, sodium phosphate and mixtures thereof, and the like, but are not limited thereto.

The water for injection is distilled water prepared to dissolve solid injections or dilute water-soluble injections. Examples include, but are not limited to, amino acid injection, physiological saline, xylitol injection, Ringer's solution, and the like.

The lipolysis composition of the present invention is dissolved in distilled water for injection together with the above-described additives, and the solution is sterilized, filtered, filled into a vial in a sterile state, sealed, and then sterilized with an autoclave. The composition can be prepared.

The method of injecting the injectable composition of the present invention is not limited, but may be injected by a method suitable for a patient in terms of the severity of the disease, and the age, sex, and other conditions of the patient. This route is not particularly limited in its method, but can be injected by subcutaneous injection, intradermal injection, intravenous injection, intramuscular injection, and intraperitoneal injection.

Specifically, the injection composition for decomposing fat according to the present invention may be intended to be injected subcutaneously.

Hereinafter, the present invention will be described in more detail by examples and experimental examples. However, the following examples and experimental examples are merely illustrative of the present invention, and the contents of the present invention are not limited to the following examples and experimental examples.

Preparation Example: Preparation of an injection composition for lipolysis

After dissolving 100 mg of sodium deoxycholate in 6 ml of water for injection at room temperature, 2 mg of arnica extract, 2 mg of yarrow extract, 2 mg of chamomile extract, 2 mg of daisy extract, 2 mg of echinacea extract, and 2 mg of red pepper sprout flower/leaf/stem extract were also at room temperature. Dissolved in to prepare a mixed solution.

Then, 10 mg of disodium hydrogen phosphate was added and dissolved in the mixed solution at 40°C. At this time, the pH was found to be 9.09. Then, sodium dihydrogen phosphate was added to adjust the pH to 8.3. Then, after stirring for about 20 minutes at a stirring speed of 200 rpm, the remaining amount was filled with water for injection, and the total volume was adjusted to 10 ml. Then, 0.45μm and 0.2μm membrane filtration was performed, and then 2ml and 4ml were respectively filled into the vial bottle, sealed, and sterilized for 15 minutes at a temperature of 121°C in an autoclave to decompose fat according to the present invention. A composition for injection was prepared.

Examples 1 to 7: Preparation of injection composition for fat decomposition

It was prepared in the same manner as in Preparation Example, but the concentration of sodium deoxycholate and each plant-derived extract was controlled as shown in Table 1 below to prepare an injection composition for fat decomposition.

Sodium deoxycholate
(% w/v) arnica
(% w/v) milfoil
(% w/v) Chamomile
(% w/v) daisy
(% w/v) Echinacea
(% w/v) Red pepper sprouts
(% w/v) Example 1 0.5 0.05 0.05 0.05 0.05 0.05 0.05 Example 2 One 0.05 0.05 0.05 0.05 0.05 0.05 Example 3 2 0.05 0.05 0.05 0.05 0.05 0.05 Example 4 One 0.01 0.01 0.01 0.01 0.01 0.01 Example 5 One 0.02 0.02 0.02 0.02 0.02 0.02 Example 6 One 0.1 0.1 0.1 0.1 0.1 0.1 Example 7 One 0.2 0.2 0.2 0.2 0.2 0.2

Comparative Example: Preparation of an injection composition for fat decomposition that does not contain plant-derived extracts

In order to compare the effects, an injection composition containing water, benzyl alcohol and sodium deoxycholate was prepared with reference to Example 1 described in Korean Patent Registration No. 10-1751585. The injection composition is a mixture of 0.9% w/v of benzyl alcohol instead of a plant-derived extract, and sodium deoxycholate is contained at 1% w/v/.

Experimental Example 1: Fat resolution experiment

Pig fat decomposition experiment was conducted using the injection composition for fat decomposition according to the present invention prepared in the above example.

Specifically, in this experiment, 3 vial bottles were prepared, and then, only 1 g of pork fat was added to the first bottle, and 4 ml of water was added to 1 g of pork fat in the second bottle (water), and the third bottle ( SDC 1% w/v) was put into 1 g of pork fat and 4 ml of the fat-decomposing injection composition prepared in Example 5. Then, the state of pig fat was observed after about 24 hours, 48 hours and 120 hours. The results can be confirmed through FIGS. 1 to 5 below.

Referring to FIG. 1 below, a picture immediately after starting the experiment can be seen.

In addition, referring to FIG. 2, a picture can be confirmed after 24 hours have elapsed since the start of the experiment.

In addition, referring to FIG. 3, a picture can be confirmed after 48 hours have elapsed since the start of the experiment.

In addition, referring to FIG. 4, a picture can be confirmed after 120 hours have elapsed since the start of the experiment.

As a result, referring to FIGS. 1 to 4 below, it can be seen that the solution in the third bottle became cloudy compared to the other bottles even after 24 hours. In addition, after 48 hours, the shape of the fat also differs greatly, and after 120 hours, the third bottle is significantly different in terms of turbidity of the solution or change in the shape of fat compared to other bottles. .

In more detail, referring to FIG. 5, photos taken from the front and the bottom of the second and third bottles can be enlarged.

As a result of repeating the same experiment for the compositions of Examples other than Example 5, the degree of fat decomposition slightly changed depending on the amount of sodium deoxycholate, but a similar degree of fat decomposition effect as in Example 5 was observed. .

Through this, it was confirmed that the lipolytic injection composition according to the present invention has excellent lipolysis effect.

Experimental Example 2: Solution stability experiment

Solution stability was confirmed through the degree of occurrence of precipitates of the fat-decomposing injection composition prepared in Examples 1 to 7. The results of the degree of precipitate formation are shown in Table 2 below.

pH Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 7.75 10 10 10 10 10 10 10 7.93 7 7 7 7 7 7 10 8.07 2 2 2 2 2 2 7 8.3 One One One One One One 2

In Table 2, the degree of sedimentation is when the composition for lipolysis injection is visually confirmed after storage for one week, "0" means a transparent solution, and "10" represents a substantial precipitation that can be seen with the naked eye. Specifically, it means that the solution becomes cloudy due to the precipitate as it goes from 0 to 10.

As a result of the experiment, it was confirmed that no precipitate was formed when the pH of the solution was adjusted to about 8.3. It can be seen that the pH control of the injection composition for fat decomposition according to the present invention acts as an important factor in solution stability, and the stability of the solution is most excellent when the pH is adjusted to about 8.1 to about 8.5.

On the other hand, when the content of each plant-derived extract was 0.2% w/v (Example 7), a precipitate was formed even when the pH was adjusted to 8.3. Through this, it can be seen that it is preferable to control the respective content of the plant-derived extract according to the present invention to less than 0.2% w/v. As described above, in the injection composition for fat decomposition according to the present invention, the stability of the solution can be optimally adjusted through the content of each component and the pH of the composition.

Experimental Example 3: Pain Relief Effect Experiment

A pain relief effect test was conducted on the fat-decomposing injection composition and the comparative example composition prepared in Examples 1 to 6 above.

Specifically, the test subject was injected subcutaneously in the abdomen in 20 adult women aged 20 to 40 years, and the degree of pain was confirmed. The degree of pain was evaluated in steps of 1 to 5 with respect to the degree of pain felt in the process of injecting the injection composition for lipolysis under the skin. It means that the pain was felt more severely from step 1 to step 5. The experimental results are shown in Table 3 below.

Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Comparative example Degree of pain One One One 2 One One 5

The degree of pain in Table 3 was obtained by obtaining an average value for the evaluation of 20 adult women aged 20 to 40 years old who subcutaneously injected the composition for lipolysis according to Examples 1 to 7.

Referring to Table 3, the subjects who inject the injection composition for lipolysis according to Examples 1 to 3 and 5 to 7 subcutaneously did not generally feel pain other than the pain felt when the injection needle penetrates the skin. Evaluated. However, in the case where the concentration of sodium deoxycholate is the same, and the injection composition for fat decomposition according to Example 4 in which the concentration of each plant-derived extract is 0.01% is injected subcutaneously, in Examples 1 to 3 and 5 to 7 It was evaluated that a slight pain was felt compared to the case of subcutaneous injection of the following lipolysis injection composition. Therefore, it can be seen that the injection composition for fat decomposition according to the present invention has excellent pain reduction effect when the content of each plant-derived extract is in the range of 0.02% to 0.1% w/v.

On the other hand, in the case of the composition of Comparative Example not containing the plant-derived extract, it was confirmed that extreme pain was induced when injected subcutaneously.

Through this, it can be seen that when the injection composition for lipolysis of the present invention is injected subcutaneously without using a local anesthetic, pain occurs at a level that can be said to be substantially painless.

Experimental Example 4: Inflammation reduction effect experiment

In the injectable composition for fat decomposition prepared in Examples 1 to 6 and the composition of Comparative Example were subjected to an experiment on the effect of reducing inflammation.

Specifically, in order to evaluate the degree of edema, the compositions according to Examples 1 to 6 were injected into the feet of rats. Specifically, male Sprague Dolly rats (6 weeks old) were purchased and used after 1 week adaptation. Rats (weight: 170-200g) were randomly selected, and the thickness of the rat foot was measured with a caliper before administration of the experimental drug. In order to observe the edema, PBS and various experimental drugs were administered to the feet of the rats by 0.1 ml. The measurement of the foot volume was performed with a caliper immediately before injection, immediately after injection, and 1 or 2 hours elapsed. In addition, when measuring the thickness, a photo of the sole of the foot (using a 4×4 cm scale) was taken to observe the skin lesion at the injection site.

The degree of edema was evaluated on a scale of 0 to 4. There was no edema immediately after 1 or 2 hours compared to before administration [-, (swelling degree 0% compared to before administration)], mild edema [+, (swelling degree 1 to 20% or less compared to before administration)], Moderate swelling [++, (swelling degree less than 20 to 40% compared to before administration)], severe edema [+++, (swelling degree less than 40 to 60% compared to administration)], severe edema[+++] It was evaluated as +, (60% or more swelling compared to before administration)].

The results are shown in Table 4 below.

Immediately after administration 1 hour after administration 2 hours after administration Example 1 + + + Example 2 + + + Example 3 + + + Example 4 ++ ++ ++ Example 5 + + + Example 6 + + + Comparative example +++ ++++ ++++

Referring to Table 4, it was confirmed that there was a slight difference in the foot of the rat that received the injection of the injection composition for lipolysis according to Examples 1 to 3 and 5 to 6, but no noticeable edema of grade 2 or higher did not occur. . However, when the concentration of sodium deoxycholate was the same and the concentration of each plant-derived extract was 0.01%, the degree of swelling compared to the pre-administration was as low as 20%, which was confirmed as grade 2 edema. Through this, it can be seen that the effect of reducing inflammation is excellent when each concentration of the plant-derived extract is in the range of 0.02% to 0.1% w/v.

On the other hand, in the case of the composition of Comparative Example not containing the plant-derived extract, 3 to 4 marked edema was observed.

Through this, it was confirmed that the injection composition of the present invention has an effect of reducing inflammation as well as pain relief when injected subcutaneously without using a local anesthetic.

Claims (10)

Salts of deoxycholic acid; And
As a composition for fat decomposition comprising at least one plant-derived extract
The salt of deoxycholic acid is sodium deoxycholate,
The one or more plant-derived extracts are extracts derived from at least one plant selected from the group consisting of arnica, yarrow, chamomile, daisy, echinacea, and peppercorns,
The salt of deoxycholic acid is contained in an amount of 0.1% to 3% w/v,
The one or more plant-derived extracts, characterized in that contained in 0.001% to 1% w / v, fat decomposition composition. delete delete The method of claim 1,
The plant-derived extract,
Arnica, yarrow, chamomile, daisy, echinacea and a mixture of plant-derived extracts of red pepper sprouts. The method of claim 1,
The plant-derived extract,
Water, alcohol having 1 to 4 carbon atoms, ethyl acetate, ethylene glycol, propylene glycol, butylene glycol, characterized in that extracted with at least one extraction solvent selected from the group consisting of glycerin, fat decomposition composition. The method of claim 1,
The composition for decomposing fat is characterized in that the pH is 8.1 to 8.5, the composition for decomposing fat. delete delete The composition for decomposing fat according to claim 1;
at least one additive selected from the group consisting of a pH adjusting agent, an isotonic agent, a surfactant, a stabilizer, a preservative, a chelating agent, and a buffering agent; And
Injectable composition for lipolysis containing water for injection. The method of claim 9,
The injection composition is characterized in that for the purpose of subcutaneous injection, lipolysis injection composition.

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