KR20190004087A - Injection Composition For Fat Reduction and method of manufacturing the same - Google Patents

Abstract

The present invention relates to an injectable composition for the removal of fat and a method for producing the same, in which choline alfoscerate, which is one of the natural choline compounds, is used without adverse effects on the human body and more specifically, choline alfoscerate ); L-carnitine; Deoxycholic acid salt is mixed in a desirable ratio to prepare a composition to increase the energy metabolism rate in the body to improve basic metabolism and activate fat metabolism to help burn fat, It can help control. In addition, since each of the active ingredients is mixed in a desirable amount, synergistic effects can be expected to result in more fat burning or weight loss than when they are used singly, and in addition, blood cholesterol and triglyceride It can be expected to play a role in reducing the content.

Description

TECHNICAL FIELD The present invention relates to an injectable composition for removing fat and a method for manufacturing the same,

The present invention relates to an injectable composition for removing fat and a method for producing the same, without adverse effects on the human body by using choline alfoscerate, which is one of natural choline compounds.

Recent economic growth and changes in lifestyle have resulted in a decrease in the individual 's momentum due to the improvement of living standards due to economic growth and the increase in the obese population as the traditional fiber - centered eating culture changes into high protein and fast food oriented eating culture And the resulting obesity-related diseases are increasing.

Obesity occurs when excessive energy accumulation occurs due to metabolic imbalance when supply is much higher than that of energy, and it is clinically involved in the occurrence of various diseases or worsens disease. Specifically, diabetes, hypertension, arteriosclerosis, hyperlipidemia , Cardiovascular disease, fatty liver and other various diseases and metabolic disorders are known to cause. In addition, because the abdominal fat is pressurized by fatty tissue caused by obesity, constipation, indigestion and gastrointestinal disorders are often caused by the World Health Organization has warned that obesity is a disease that requires treatment.

Examples of the methods of treating obesity include exercise for increasing the amount of calories, diet for reducing caloric absorption, and drug therapy. However, it is difficult for busy modern people to expect appropriate effects with exercise therapy and diet therapy alone.

In particular, when exercising or dieting for the treatment of obesity, there are various side effects such as a yo-yo phenomenon in which the weight is increased again when the exercise is stopped, nutritional imbalance due to dietary restriction, have.

Therefore, in recent years, it is recommended to use a safe medication therapy properly, and as a part thereof, a lipase inhibitor, an appetite suppressant, and a lipid releasing agent are mainly used.

Patent Publication No. 2017-0043657 (published on April 21, 2017)

The present invention relates to choline alfoscerate, one of the natural choline compounds capable of producing acetylcholine, which can activate lipid metabolism and help break down fat tissue accumulated in the body, It is intended to provide an injectable composition for the removal of fat and a method for producing the same, even if there is no adverse effect on the human body by including L-carnitine.

In order to achieve the above object, one embodiment of the present invention is a choline alfoscerate; L-carnitine; Deoxycholic acid salt; A group consisting of polysorbate, hydoxystearate, polyoxyl-15-hydroxystearate and polyoxyl-35-castor oil. A surfactant comprising at least one selected from the group consisting of surfactants; A preservative comprising at least one selected from the group consisting of phenoxyethanol, methylparaben, ethylparaben and propylparaben; A preservative comprising at least one selected from the group consisting of benzyl alcohol, lidocaine, procaine, ethanol and chlorobutanol; And purified water; Or water for injections.

The composition may further comprise at least one surfactant selected from the group consisting of 3-13% w / v choline alfoscerate, 0.01-2% w / v L-carnitine, 0.1-1% w / v deoxycholate, 0.001-0.003% (w / v) preservatives, 0.25-0.4% (w / v) preservatives, 0.7-1.2% (w / v) preservatives and balance of purified water or water for injection.

Preferably, the composition may further comprise one or a mixture of two or more selected from the group consisting of aminophylline, sodium deoxycholate, L-arginine and nicotinic acid amide, More preferably, the amide mixture solution in which the aminophylline and nicotinic acid amide are mixed in the ratio of 1: 1 in the composition may further comprise 7 to 11% (w / w) of the content of L-carnitine.

According to another embodiment of the present invention, there is provided a method for preparing an injectable composition for removing fat, comprising: a first step of adding deoxycholic acid salt and a preservative and stirring until completely dissolved without a precipitate; A second step in which choline alfoscerate, L-carnitine and a surfactant are sequentially added to the mixture prepared in the first step and stirred until solubilization; And a third step of uniformly mixing the mixture prepared through the second step with a preservative, a total volume of purified water or water for injection, and mixing the mixture.

The first step is to add 0.1 to 1% (w / v) of deoxycholate and 0.7 to 1.2% (w / v) of a preservative on the basis of the whole composition and dissolve the deoxycholate sufficiently to form a clear It is preferable to stir the solution until the solution becomes transparent, and further add 0.05 to 0.15% (w / v) isotactic agent based on the whole composition until transparency is obtained.

Also, the second step may comprise the steps of: 3 to 13% (w / v) choline alfoscerate, 0.01 to 2% w / v L-carnitine, 0.001 to 0.003% w / v L-arginine and nicotinic acid amide are added to the reaction mixture in the presence of at least one of aminophylline, sodium deoxycholate, L-arginine and nicotinic acid amide, Carnitine is further added to the mixture passed through the second step in an amount of 7 to 11% (w / w) based on the amount of L-carnitine, and the mixture is stirred until the mixture becomes transparent .

In the third step, the pH of the mixture may be adjusted to 7.8 to 9.6 by adding a preservative and a pH adjusting agent, and then the total volume may be adjusted with purified water or injection water and mixed homogeneously.

Yet another embodiment of the present invention relates to the fat removing injectable composition; Or a fat removing injectable composition prepared by the above-mentioned production method is a composition that helps injectable body into a body through a syringe.

The present invention relates to choline alfoscerate; L-carnitine; Deoxycholic acid salt is mixed in a desirable ratio to prepare a composition to increase the energy metabolism rate in the body to improve basic metabolism and activate fat metabolism to help burn fat, It can help control.

In addition, since each of the active ingredients is mixed in a desirable amount, synergistic effects can be expected to result in more fat burning or weight loss than when they are used singly, and in addition, blood cholesterol and triglyceride It can be expected to play a role in reducing the content.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings. Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. As well as the fact that

Throughout this specification, when a section is referred to as "including " an element, it may include other elements, not excluding other elements, unless specifically stated otherwise.

Hereinafter, the fat removal injectable composition of the present invention and a method for producing the same will be described in detail.

First, the injectable fat removing composition of the present invention can increase the energy metabolism in the body to improve the basic metabolism, activate the fat metabolism to help the fat burning, and help the fat tissue to decompose And each of the active ingredients contained in the composition is mixed in a desired amount. Therefore, it is possible to expect more fat burning or weight loss effect than the case of using them alone due to the synergistic effect at the time of use, and also the blood cholesterol It can be expected that the content of triglycerides can be reduced.

Specifically, the fat removing injectable composition may be choline alfoscerate; L-carnitine; Deoxycholic acid salt; A group consisting of polysorbate, hydoxystearate, polyoxyl-15-hydroxystearate and polyoxyl-35-castor oil. A surfactant comprising at least one selected from the group consisting of surfactants; A preservative comprising at least one selected from the group consisting of phenoxyethanol, methylparaben, ethylparaben and propylparaben; A preservative comprising at least one selected from the group consisting of benzyl alcohol, lidocaine, procaine, ethanol and chlorobutanol; And purified water or water for injection.

The choline alfoscerate is a natural choline compound found in the brain of L-alpha-glycerylphosphorylcholine (alpha-GPC), which is one of brain neurotransmitters, acetylcholine Precursor. Specifically, choline alfoscerate introduced into the body is metabolized and acts as acetylcholine, which is capable of degrading lipid tissues accumulated in the body by reducing the size of lipocytes by stimulating lipase activity , Preferably 3 to 13% (w / v) in the composition, as a main component of the fat removing injectable composition of the present invention.

When the content of choline alfoscerate is less than 3% (w / v), the fat tissue degradation and weight control effects are insignificant due to insignificant content, and the content of choline alfoscerate is more than 13% (w / v) , The chemical stability is lowered due to the deliquescence of choline alfoscerate. As a result, phase separation of the composition or precipitation of some components may occur.

L-carnitine is a component known to be contained in red meat, which is synthesized in the liver and kidney of a normal person, and is known to be an important component for generating energy by oxidizing fat. Carnitine plays a role in promoting lipid oxidation, and is a substance essential for promoting beta oxidation by transferring a fatty acid to the inner mitochondrial membrane, and is known to play a pivotal role in the utilization of a substrate for energy generation. In addition, L-carnitine is a substance essential for promoting beta oxidation by fatty acids to mitochondrial inner membrane. Specifically, carnitine palmitoyl transferase I, II and acylcarnitine transporter are involved in the action of L-carnitine. In a recent study, carnitine palmitoyl transferase-I is an important rate-limiting enzyme for fatty oxidation, It is known to play a pivotal role in substrate utilization.

In addition, L-carnitine regulates the function of the cortical hormone receptor and promotes the degradation of adipose tissue by playing a role similar to that of the cortical hormone.

Therefore, in order to improve the body fat reduction effect and to improve the metabolic disease, the L-carnitine deficiency causes the body fat burning rate to be lowered and the metabolic rate to drop, 2% (w / v).

When the content of L-carnitine is out of the above range, the expected effect of promoting the metabolism of fat is insignificant, or excessive use of L-carnitine may cause side effects such as nausea, vomiting, abdominal pain, diarrhea and body odor, Seizures may occur.

In order to further improve the fat dissolving effect in the injectable fat removing composition of the present invention, aminophylline or sodium deoxycholate, which is known as fat releasing, and glucagon secretion which directly accelerates decomposition of fatty tissue L-arginine, and nicotinic acid amide, which promote the function of beta cells. The aminophylline and nicotinic acid amide may be mixed in a ratio of 1: 1 to 7 to 11% (w / w) of the amount of L-carnitine in the whole composition, the fat dissolving effect can be further improved.

In addition, the deoxycholic acid salt, which directly plays a role of degrading adipocytes by destroying the adipocyte membrane, is included in order to increase the fat dissolving effect in the injectable adipose composition of the present invention. Preferably, 0.1 to 1.0% (w / v) in the whole composition may be included. If the concentration is outside the above range, it may be difficult to expect a desired fat cell decomposition effect due to a small amount of the fat. Excessive incorporation of oxycholines can cause inflammation in the body.

In particular, deoxycolinic acid may cause an immune response in the body because it damages and destroys the fat cell membrane and decomposes adipose tissue. Depending on the sensitivity of the individual's immune response, side effects may occur. However, Carnitine and choline alfoscerate, which are one of the natural choline compounds contained in the injectable composition, are used in combination to reduce the side effects of the immune reaction, thereby remarkably reducing side effects and generating a synergistic effect, It is possible to remarkably improve the weight control effect through the decomposition. Accordingly, it is preferable that the deoxycholate is contained in the injectable fat removing composition of the present invention according to the aforementioned numerical range.

The surfactant is a polysorbate, hydoxystearate, polyoxyl-15-hydroxystearate, or the like for imparting chemical stability to the injectable fat removing composition. ) And polyoxyl-35-castor oil, preferably a polyoxyethylene higher aliphatic alcohol having a sorbitan fatty acid ester and ethylene oxide bound thereto, It is preferable to use polysorbate which is a nonionic surfactant and polysorbate 20 (monolauric acid), polysorbate 40 (monopalmitic acid), polysorbate 60 (monostearic acid), polysorbate It is most preferable to use polysorbate 60 among 65 (tristearic acid) and polysorbate 80 (monooleic acid).

The surfactant may be contained in an amount of 0.001 to 0.003% (w / v) in the composition for removing fat, and if the content of the surfactant deviates from the above-mentioned content, phase separation may occur during storage of the composition, There is a problem that it is difficult to obtain a desired effect.

The preservative is used for improving the shelf life of the composition. The preservative is not limited as long as it is a component having anti-decay properties generally used in pharmacy, but it is preferably phenoxyethanol, methylparaben, (ethylparaben), and propylparaben (propylparaben).

The preservative may contain 0.25-0.4% (w / v) in the composition for removing fat. If the preservative content is out of the above-mentioned range, it may be difficult to improve the shelf life due to insufficient content, So that side effects may occur.

The preservative of the present invention is included in the composition for inhibiting the growth of microorganisms. Examples of the preservative include benzyl alcohol, lidocaine, procaine, ethanol, and chlorobutanol ), And benzyl alcohol or ethanol may be preferably used.

The preservative may be contained in an amount of 0.7 to 1.2% (w / v) in the total composition. If the preservative content is out of the above-mentioned range, it is difficult to expect the microbial growth inhibition effect due to insufficient content, Side effects can occur.

The remainder of the composition of the present invention may further contain purified water or water for injection. The injection water used in the pharmaceutical composition is not particularly limited and may be glucose water for injections, Xylitol injection water, D-mannitol injection water, fructose injection water, physiological saline, dextran 40 injection water, dextran 70 injection water, amino acid injection water, Ringer's solution, lactic acid-Ringer solution can be used.

It may further comprise an isotonic agent or a pH adjusting agent in the composition. The isotonic agent may be used to properly maintain the osmotic pressure when the injectable fat removing composition of the present invention is administered into the body, and the injectable fat removing composition may be chemically stabilized during storage or distribution.

Such isotonizing agents may be pharmaceutically acceptable sugars, salts or any combination or mixture thereof, and examples thereof may be selected from the group consisting of glucose, sodium chloride, calcium chloride and sodium sulfate, or a combination of two or more thereof. The isotonic agent may be contained in an amount of 0.05 to 0.15% (w / v) in the total composition. Depending on the kinds, amounts, etc. of components contained in the injectable fat removing composition, Can be adjusted to the content.

The pH adjusting agent plays a role of adjusting the pH of the composition. The pH adjusting agent is not limited as long as it is acidic or basic, but preferably a basic substance can be used. This is because the active ingredients contained in the fat removal injectable composition are mostly acidic.

Examples of inorganic bases which can be used as the basic substance include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, magnesium carbonate, calcium carbonate, magnesium oxide, ammonia and synthetic hydrotalcite. , Arginine, meglumine, and the like. Preferably 0.001 to 0.12% (w / v) in the injectable composition for removing fat, and the amount of the pH adjusting agent to be added may be appropriately adjusted depending on the kind and amount of constituent components.

The injectable fat removing composition of the present invention may be prepared in the form of a food or a pharmaceutical preparation and may be ingested or injected into the body. As mentioned above, as long as the effective effect of the active ingredients contained in the composition is not reduced, May be provided in various forms including food or medicine, and pharmaceutically acceptable ingredients. For example, in general, a carrier used in pharmaceuticals and an injectable fat removing composition may be blended together to form tablets, hard or soft capsules, granules, chewing tablets, pills, powders, elixirs, suspensions , Emulsions, liquid forms, syrups, or parenteral dosage forms such as aerosols, syringes, sterile injectable solutions or sterile powders, and the like.

On the other hand, another embodiment of the present invention includes a first step of adding deoxycholic acid salt and a preservative on the basis of the whole composition and stirring until completely dissolved without a precipitate; A second step in which choline alfoscerate, L-carnitine and a surfactant are sequentially added to the mixture prepared in the first step and stirred until solubilization; And a third step of uniformly mixing the mixture prepared through the second step with a preservative, a total volume of purified water or water for injection, and mixing the mixture.

The detailed description of each component contained in the injectable fat removing composition has been previously described and will not be described here.

Specifically, the first step is a step of dissolving deoxycholate and preservative, preferably 0.1 to 1% (w / v) of deoxycholate and 0.7 to 1.2% (w / v) is added and stirred until the deoxycholate is sufficiently dissolved to form a clear solution without a precipitate. At this time, it may further include an isotonic agent, wherein the amount of the isotonic agent may be 0.05 to 0.15% (w / v) based on the total composition.

The second step in which choline alfoscerate, L-carnitine and a surfactant are sequentially added to the mixture prepared through the first step and stirred until solubilization is carried out, (W / v) of choline alfoscerate, 0.01 to 2% (w / v) of L-carnitine and 0.001 to 0.003% (w / v) of a surfactant on the basis of the composition is solubilized Lt; / RTI >

Generally, solubilization means that a poorly soluble substance is dissolved by solubilizing agent more than its solubility, and until it is solubilized in the present invention, it means that the choline alfoselate and L-carnitine are sufficiently dissolved, It means until it becomes transparent without doing.

After the second step, aminophylline, sodium deoxycholate, L-ascorbic acid and the like are added to the mixture prepared through the second step, before the third step of adjusting the total volume through the preservative and the purified water or the injection water. Further adding a mixture of one or more selected from the group consisting of arginine (L-arginine) and nicotinic acid amide, and stirring the mixture. Preferably, the mixture of aminophylline and nicotinamide is mixed at a ratio of 1: 1 One amide mixed solution may be further added in an amount of 7 to 11% (w / w) of the amount of L-carnitine to be stirred until the mixture becomes transparent. The mixture containing the amide mixture solution may be prepared through the third step by preparing the injectable fat removing composition of the present invention.

Specifically, in the third step, a preservative and a pH adjuster are added to the mixture prepared through the second step to adjust the pH of the injectable composition for liposuction of the present invention to 7.8 to 9.6, and then the total volume And homogeneously mixed with each other.

On the other hand, the fat removal injectable composition of the present invention and the fat removal injectable composition prepared by the aforementioned manufacturing method may exist in various forms including, but not limited to, liquid, semi-solid and solid tablet forms. Examples include liquid solutions (e. G., Injection and infusion solutions), dispersions, suspensions, powders, lyophilized powders, or liposomes, or transdermal ointments or patches, It depends on the application.

Preferably, the fat removing injectable composition may be in the form of a solution which is injected into the body, and is preferably a spraying solution.

In one embodiment, the dosage of the injectable fat removing composition of the present invention can be adjusted according to different parameters. These parameters include, but are not limited to, the type of subject being administered, the body weight of the subject being administered, and the local fat thickness and area of the subject being administered. The composition of the present invention may be administered once, several times or continuously within 24 hours at a dose of 50 cc, and may be administered several times or continuously on a weekly or monthly basis. The method of administration may be by subcutaneous injection, intradermal injection, intravenous injection, intramuscular injection, intraperitoneal injection, subcutaneous implantation, implantation injection, ointment, or patch, preferably a mesotherapy method for injecting the drug into the skin layer and subcutaneous layer It can be injected into the body part where fat such as abdomen, buttocks, thighs, calves, chin, forehead and upper arms are accumulated.

Hereinafter, an embodiment of the present invention will be described. However, the scope of the present invention is not limited to the following preferred embodiments, and a person skilled in the art can carry out various modifications of the contents described in the present invention within the scope of the present invention.

[Manufacturing Example]

Preparation of injectable fat composition for fat removal

First, deoxycholate, a preservative and an isotonic agent were added to a beaker in the same ratios as in Table 1, and the mixture was stirred at room temperature until the solution was completely dissolved and no precipitate was formed, Choline alfoscerate, L-carnitine, and a surfactant were sequentially added and stirred. The mixture was agitated until the mixture became completely transparent. Then, an amide mixture solution of aminophylline and nicotinic acid amide in a ratio of 1: 1 was added and stirred for 20 minutes so as to be homogeneously mixed. Then, a preservative and a pH adjuster were added thereto Minute, followed by adding purified water to prepare Examples and Comparative Examples.

Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example
4 Comparative Example
5 Example 1 Example 2 Example 3 Deoxycholate 0.7 0.7 - 0.7 0.7 0.7 0.7 0.7 Preservative
(Benzyl alcohol) 0.9 0.9 0.9 0.9 0.9 0.9 0.9 0.9 An emerging topic
(Sodium chloride) 0.07 0.07 0.07 0.07 0.07 0.07 0.07 0.07 Choline
Alfoscerate 2 15 8 8 8 3 8 13 L-carnitine 1.1 1.1 - 1.1 1.1 1.1 1.1 1.1 Surfactants
(Polysorbate 60) 0.002 0.002 0.002 0.002 0.002 0.002 0.002 0.002 Amide mixture solution 0.1 0.1 - 0.05 0.14 0.1 0.1 0.1 antiseptic
(Propyl paraben) 0.33 0.33 0.33 0.33 0.33 0.33 0.33 0.33 pH adjusting agent
(Magnesium carbonate) 0.003 0.003 0.003 0.003 0.003 0.003 0.003 0.003 Purified water Remainder Remainder Remainder Remainder Remainder Remainder Remainder Remainder total 100 100 100 100 100 100 100 100

^{(unit : total; ml  / The rest; g )}

[Experimental Example 1]

Storage stability test of composition

A control group prepared by mixing 2 g of deoxycholate salt, 0.7 g of choline alfoscerate and 1.1 g of L-carnitine well mixed with purified water was allowed to stand at room temperature for 1 hour, 12 hours and 24 hours , And the properties thereof were observed. The results are shown in Table 2 below.

Control group Example 2 Leave for 1 hour Clear liquid Clear liquid Leave for 12 hours Opaque liquid Clear liquid Leave for 24 hours A liquid phase in which fine precipitates and some suspended particles are observed Clear liquid

As shown in Table 2, when the control and the control were mixed with the same deoxycholate, choline alfoscerate, and L-carnitine, both the control and the Example 2 were observed as a transparent liquid for the first hour, In the control group, the liquid phase became cloudy after 12 hours and the opaque state was observed. After 24 hours, fine precipitate and suspended particles were observed.

It was found that the active ingredients contained in the composition of the present invention were mixed in a desirable amount to exhibit chemical stability and excellent storage stability.

[Experimental Example 2]

Measuring weight control effect

In Examples 1 to 3 and Comparative Examples 1 to 3 prepared in the above Preparation Example, and the control group were administered through the injection system for four months at a total of two times for a total of 2 months. Injection method was performed in the abdomen between the ribs and the pubis 10 cc at 10 points, 1 cm apart.

The control group used a transparent agent before phase separation occurred.

The subjects were 30 adult obese patients with BMI of 25 or more among 20- to 40-year-old adults, and the results were averaged.

Statistical analysis and validation methods were obtained by using the SPSS statistical package. Paired t-test was used to confirm the effect of waist circumference reduction on each test, and the confidence interval was determined to be within 95% And corrected for weight change.

weight Abdomen waist circumference Two months later Two months later Control group 0.5 ± 1.4 kg reduction 3.2 ± 0.8 cm reduction Comparative Example 1 1.1 ± 1.1 kg reduction Reduced by 3.5 ± 1.2 cm Comparative Example 2 2.7 ± 2.0 kg reduction Reduced by 3.8 ± 2.1 cm Comparative Example 3 0.6 ± 0.8 kg reduction 2.7 ± 0.8 cm reduction Comparative Example 4 1.7 ± 0.8 kg reduction 3.7 ± 1.8 cm reduction Comparative Example 5 3.1 ± 1.7 kg reduction 6.7 ± 2.8 cm reduction Example 1 2.9 ± 2.2 kg reduction 7.8 ± 2.1 cm reduction Example 2 3.3 ± 2.1 kg reduction 8.5 ± 1.2 cm reduction Example 3 3.5 ± 1.8 kg reduction 8.4 ± 2.7 cm reduction

In the results of Table 3, it was confirmed that the weight reduction effect of about 3 kg and the waist circumference of the abdomen were reduced by about 8 cm in Examples 1 to 3, but in the case of the control group and Comparative Examples 1 and 3, It was confirmed that the effect of reducing the waist circumference of the abdomen was reduced.

In the case of Comparative Example 2, excessive amounts of choline alfoscerate were contained as compared with Examples 1 to 3. However, as the content of L-carnitine, deoxycholinate, and amide mixture, which helps lipolysis, And the abdominal waist circumference reduction effect was not as good as in Examples 1 to 3, and the experiment was stopped as edema was found in some treatment subjects.

Comparing Comparative Examples 4 and 5 and Example 2 in which the content of the amide mixture solution was different from each other, it was confirmed that the effect of reducing the body weight and the waist circumference of the abdomen was significantly lower than that of the Example in the case of Comparative Example 4 in which the content of the amide mixture solution was insignificant As a result, it was confirmed that the effect of decreasing the body weight and the waist circumference of the abdomen was reduced by the reduction of the content ratio of the other components as the content of the amide mixed solution was increased.

It was anticipated that synergistic effects would be imparted through the desirable ratio between the respective active ingredients contained in the injectable fat removing composition of the present invention, thereby achieving remarkable weight reduction and abdominal girth reducing effect.

[Experimental Example 3]

Adverse Event Evaluation

The above Examples 1 to 3 and Comparative Examples 1 to 3 were administered in the same manner as Experimental Example 2 and the adverse effects observed in the patients were observed.

Flare bookkeeping itch Biceps Skin depression
(dimpling) Skin rash Skin elasticity Comparative Example 1 One One 2 0 0 One 2 Comparative Example 2 0 2 3 0 0 One 2 Comparative Example 3 4 10 4 10 15 0 4 Example 1 One 0 0 0 One 0 3 Example 2 One One 0 One 0 0 3 Example 3 One 2 0 One 0 0 5

 (Skin elasticity was measured by the 5-point scale method by touch, 1: very poor, 2: poor, 3: moderate, 4: slightly good, 5: good Remark shows the number of patients with each side effect)

As a result, in the case of Comparative Example 3, it was confirmed that the number of patients suffering from side effects such as swelling, itching, phlebotomy and skin depression due to excessive choline alfoscerate was higher than those of other experimenters. The adverse events that occurred during the course of the experiment were disappeared within one month after discontinuation of the drug.

Therefore, based on Experimental Examples 2 and 3 described above, the injectable composition for removing fat according to the present invention has a favorable mixing ratio of choline alfoscerate, L-carnitine, and deoxycholate, It was expected to be possible.

Claims (10)

Choline alfoscerate;
L-carnitine;
Deoxycholic acid salt;
A group consisting of polysorbate, hydoxystearate, polyoxyl-15-hydroxystearate and polyoxyl-35-castor oil. A surfactant comprising at least one selected from the group consisting of surfactants;
A preservative comprising at least one selected from the group consisting of phenoxyethanol, methylparaben, ethylparaben and propylparaben;
A preservative comprising at least one selected from the group consisting of benzyl alcohol, lidocaine, procaine, ethanol and chlorobutanol; And
Purified water; Or water for injection. The method according to claim 1,
The composition may comprise,
(W / v) of choline alfoscerate, 0.1 to 1% (w / v) of deoxycholate, 0.001 to 0.003% (w / v) of surfactant, 0.25 to 0.4% (w / v) of a preservative, 0.7 to 1.2% (w / v) of a preservative, and a balance of purified water or water for injection. The method according to claim 1,
In the composition
Characterized in that it further comprises one or a mixture of two or more selected from the group consisting of aminophylline, sodium deoxycholate, L-arginine and nicotinic acid amide. Composition. The method of claim 3,
Characterized in that an amide mixture solution in which the aminophylline and nicotinic acid amide are mixed in a ratio of 1: 1 in the composition further comprises 7 to 11% (w / w) of the amount of L-carnitine. . A deoxycholic acid salt and a preservative, and stirring until the solution is completely dissolved without a precipitate;
A second step in which choline alfoscerate, L-carnitine and a surfactant are sequentially added to the mixture prepared in the first step and stirred until solubilization; And
And a third step of uniformly mixing the mixture prepared through the second step with a preservative, a total volume of purified water or water for injection, and mixing the mixture. 6. The method of claim 5,
In the first step,
0.1 to 1% (w / v) of deoxycholate and 0.7 to 1.2% (w / v) of a preservative were added based on the whole composition and stirred until the deoxycholate was sufficiently dissolved and the solution became clear However,
And further adding 0.05 to 0.15% (w / v) of an isotonic agent based on the whole composition until stirring to obtain a transparent property. 6. The method of claim 5,
The second step comprises:
(W / v) of choline alfoscerate, 0.01 to 2% (w / v) of L-carnitine and 0.001 to 0.003% (w / v) of surfactant, By weight of the composition, and stirring the mixture until the mixture is stirred. 8. The method of claim 7,
After the second step,
A mixture of one or more selected from the group consisting of aminophylline, sodium deoxycholate, L-arginine and nicotinic acid amide is dissolved in an amount of 7 to 11 further comprising the step of further adding% (w / w) to the mixture which has passed through the second step so as to stir until the mixture becomes transparent. 6. The method of claim 5,
In the third step,
Wherein the pH of the mixture is adjusted to 7.8 to 9.6 by adding a preservative and a pH adjusting agent, and then the total volume is adjusted with purified water or injection water and mixed homogeneously. The fat removal injectable composition of any one of claims 1 to 4; or
9. A composition for injecting fat removal, which is prepared by the method of any one of claims 5 to 9, which can be injected into the body through a syringe.