KR102145376B1 - Injection Composition Comprising for Local Fat Reduction Including Choline alfoscerate - Google Patents

Abstract

Provided is an injection composition for local fat removal. The injection composition for local fat removal comprises 5-15 wt% of choline alfoscerate, 0.1-0.3 wt% of lidocaine, 5-15 wt% of L-carnitine, and the rest of physiological saline.

Description

Injection Composition Comprising for Local Fat Reduction Including Choline alfoscerate

The present invention relates to an injection composition for removing local fat containing choline alfoscerate, and specifically, in an injection composition containing choline alfoscerate in units of 250 mg to 1000 mg, and containing at least one local anesthetic and lipolysis accelerator. About.

The present invention promotes the reduction of local adipose tissue, improves obesity and maintains weight loss and body shape, and achieves side effects or even removal of fat by the use of drugs.

Recently, due to the increasing obesity population, interest in obesity has increased, the number of obesity clinics has increased day by day, and various social problems caused by obesity are becoming an issue.

In short, obesity is defined as a state in which body fat is over-accumulated, provides the cause of adult diseases such as high blood pressure, diabetes, and hyperlipidemia, and forms an axis of metabolic syndrome.

In particular, women tend to crave a slim and balanced body in appearance, even if they are not obese.

In order to remove local fat such as abdominal fat accumulated by obesity, a surgical operation, liposuction, is used in various ways.

However, these surgical methods may cause serious side effects including wounds, swelling, numbness and burning sensation at the surgical site, risk of infection, other damage to the skin or nerves, or perforation injuries to important organs.

In addition, since liposuction requires a significant treatment period, and surgical procedures such as liposuction require local anesthesia or, in some cases, general anesthesia, there is always a risk associated with serious anesthesia.

For the above reasons, in order to improve the apparent obesity resulting from the accumulation of body fat, a lipolysis accelerator that decomposes various local fats has recently been used.

On the other hand, lipolysis is a process in which triglycerides are broken down into free fatty acid (FFA) and glycerol by the action of hormone sensitive lipase (HSL) accumulated in adipocytes. Say.

Hyaluronidase (HAase), a generic term for an enzyme that reduces hyaluronic acid as a lipolytic agent that promotes lipolysis, was initially known as a diffusion factor by Duran-Reynals, but then hyaluronic acid (HAase). HA) has been observed to exhibit potent activity, so it has been called hyaluronidase.

These hyaluronidases are known to hydrolyze the bond between hyaluronic acid (HA) and chondroitin, and D-glucuronic acid and N-acetyl-D-glucosamine present in chondroitin sulfate.

In addition, it is possible to perform depolymerization of long-chain mucopolysaccharides that can accumulate in the dermis and cause retardation by capillary compression of the diffusion of organic liquids to remove bound water and metabolic wastes.

The depolymerization referred to herein cuts the long chains of mucopolysaccharides into short chains, resulting in the loss of bound water and waste products, and restoration of venous and lymphatic circulation, so that the disappearance of local edema can be achieved.

In recent years, the method of subcutaneous injection of hyaluronidase, as a result of the above-described connective tissue dissolving action, loosens the connective tissue in the abdomen to reduce swelling in the tissue, and helps blood and lymph circulation. It is used as a method of removing local fat by facilitating the decomposition and metabolism of internal fat cells.

As one of the methods for removing local fat using lipolysis by hyaluronidase, the LLD (Lipolytic Lymph Drainage) treatment is widely used (Korean Patent Laid-Open No. 10-2009-0111916, a pharmaceutical formulation for local fat removal).

The LLD treatment destroys some fat cells and rapidly moves the substances related to the accumulated fat to the lymphatic vessels and oxidizes them, thereby correcting the overall body shape.

However, in the above literature, hyaluronidase is used at a high dose (1500 IU), and it is difficult to remove a wide range of fat, resulting in skin dipping, sagging and wrinkles, and continued due to the occurrence of side effects caused by drugs. There is a problem that is difficult to treat.

In addition, Korean Patent Laid-Open No. 10-2013-0003394 (Cellulite Correction Device) discloses pain and allergies by an injection composition in which hyaluronidase, lidocaine, a local anesthetic, and phennylaime, an antihistamine, are mixed by 1 cc each. A composition that prevents the phenomenon is described, but this is also the side effect of causing depression, sagging skin, and wrinkles by injecting the injection solution at 4 to 6 points at 5 cm intervals between the high-dose hyaluronidase and the injection point. There is a problem that cannot be solved.

In order to solve the problems of the above patents, the present inventors developed an injection composition for removing local fat containing a low-dose hyaluronidase, an antihistamine, a local anesthetic, a lipolysis accelerator, and a collagen production accelerator, and patent registration No. 10-1706549 It has been registered as an injectable composition for topical fat removal containing hyaluronidase.

In addition, a microneedle device for decomposing abdominal fat containing a component similar to the registered patent of the present inventor was registered as Patent Registration No. 10-1806074 (composition for fat decomposition).

And the composition for inhibiting obesity containing choline alfoscerate is disclosed in Korean Patent Laid-Open No. 10-2017-0094667 (composition for inhibiting obesity containing choline alfoscerate), alpocholine and alpha lipoic acid, L-carnitine, and choline alfosce. Patent registration No. 10-1865914 (diet injectable composition containing lipolysis and cellulite improvement ingredients), No. 10-1882400 (cellulite improvement ingredient and antioxidant effect) Ingredients, edema reduction and pain relief ingredients containing diet injection composition).

The lipolytic injection compositions described in the above patent documents have some effect of removing fat, but there are still insufficient parts to obtain a satisfactory effect.

On the other hand, phosphatidylcholine, which was typically used to reduce local subcutaneous fat through subcutaneous fat injection in the past, changes the stability of fat cell membranes, resulting in a number of complex enzymatic reactions including the release of Lipase, one of the lipolytic enzymes. It triggers a rapid apoptosis reaction that leads to the death or necrosis of fat cells.

However, when phosphatidylcholine is used, there is excessive edema that lasts for a long time for more than a week, and in most cases itching or bruising due to tissue damage that occurs during the fat removal process, bruises that last several weeks are pigmented in some patients. The sequelae of deposition has been reported, and sometimes it causes serious problems such as necrosis of the skin tissue.

Injectable composition for removing local fat, Registration No. 10-2005752, Registration of Korean Intellectual Property Office Patent Publication B1, July 25, 2019. Injectable composition for removing local fat containing hyaluronidase, Registration No. 10-1706549, Registration of Korean Intellectual Property Office Patent Publication B1, 2017. 02. 08. Pharmaceutical formulation for topical fat removal, Publication No. 10-2009-0111916, Korean Patent Office Publication A1, October 28, 2009 Publication Cellulite Correction Apparatus, Publication No. 10-2013-0003394, Korean Patent Office Publication No. A1, 2013. 01. 09. Publication Injectable composition for removing local fat containing hyaluronidase, Registration No. 10-1706549, Registration of Korean Intellectual Property Office Patent Publication B1, 2017. 02. 08. Composition for fat decomposition, Registration No. 10-1806074, Registration of Patent Publication B1, Korean Intellectual Property Office, November 30, 2017 A composition for suppressing obesity containing choline alfoscerate, Publication No. 10-2017-0094667, Korean Patent Office Publication A1, 2017. 08. 21. Diet injection composition containing lipolysis and cellulite improvement ingredients, Publication No. 10-2017-0101081, Korean Patent Office Publication A1, 2017. 09. 05. Publication Diet injection composition containing cellulite improving ingredients and antioxidant active ingredients, edema reduction and pain relief ingredients, Publication No. 10-2018-0064362, Korean Patent Office Publication A1, 2018. 06. 14.

Under the above-described technical background, it is obvious to a person skilled in the art that it is preferable to perform facial fat reduction procedures only with drugs that have relatively no side effects and are effective among various drugs known to be effective for local fat reduction.

In addition, the reaction after the procedure should be effective, and the duration of general side effects should be short and the recovery period should be quick, and the reaction of the drug should be seen even when a small amount of the drug is injected.

However, Choline alfoscerate, which is suggested as an alternative to phosphatidylcholine, is originally called glycerylphosphorylcholine (GPC), and is a major component of nerve cell membrane phospholipids and a choline precursor. In other words, it plays a role in synthesizing acetylcholine by smoothing the supply of choline, and as a result, it improves the neurotransmitter function and restores the normalization of nerve function, and at the same time, the supply of glycerophosphate is a neuronal cell membrane phospholipid. It plays a role in restoring nerve cell membranes and improving nerve function. Therefore, this neurological effect makes it possible to play a role as a therapeutic agent for dementia patients.

On the other hand, choline (Choline) has a lipolytic effect by activating fat metabolism when administered in a large amount, and a fat reduction injection therapy combining choline alfoscerate and L-carnitine As we have seen in several examples, it can be seen that all the limitations of contour injection can be satisfied because the effect is expected with a small amount of injection, side effects are rare, reaction is immediate, and down time is short.

Accordingly, the problem to be solved by the present invention is to present a new paradigm as contour injection that does not cause bruising, as having the above-mentioned effect, and to present a composition that can expect new results of fat reduction. .

Other objects and technical features of the present invention are presented in more detail by the specific content, claims and drawings for carrying out the following invention.

The present invention is a result of a long clinical trial to minimize side effects and efficient fat decomposition using choline alfoscerate, and by confirming the optimal dosage unit of choline alfoscerate and the composition and composition ratio of additives to prevent side effects of injections. The present invention has been completed.

In order to suppress the occurrence of bruising and swelling caused by dizziness, out of focus, tingling and subcutaneous bleeding that can occur when overdose of choline alfoscerate, the optimal amount of choline alfoscerate was found, and injection pain It has succeeded in manufacturing injection formulations including local anesthetics for palliation and lipolysis accelerators for rapid decomposition of fat.

Therefore, the inventors of the present invention in order to find the optimal dose of choline alfoscerate capable of decomposing fat, unit dose 100mg, 200mg, 300mg, 400mg, 500mg, 600mg, 700mg, 800mg, 900mg, 1000mg, 1100mg, 1200mg, 1300mg, 1400mg, 1500mg , 1600mg, 1700mg, 1800mg, 1900mg, 2000mg, as a result of the experiment, a unit dose of choline alfoscerate from 250mg to 1000mg can sufficiently secure the effect of fat removal while minimizing side effects by clinical trials, and the present invention Was completed.

In addition, in the above dosage range, when the injection solution is injected at a dose of 1 cc, the diffusion range is confirmed by clinical experiment to be about 1 cm in diameter, and the injection solution volume is 0.5 to 2 cc within the unit of 250 mg to 1000 mg of choline alfoscerate, and the injection point By administering at intervals of 0.5 to 1.5 cm, it is possible to administer at a high density and accordingly, lipolysis is evenly performed.

In addition, to provide an injection composition comprising a local anesthetic and a lipolysis accelerator for promoting lipolysis to relieve pain by injection of an injection solution.

More specifically, the injection composition of the present invention is composed of choline alfoscerate 250mg~1000mg, local anesthetic 20~40mg, fatty acidation accelerator 200~400mg, and the remainder of physiological saline based on 10cc injection solution.

The above composition range is determined in consideration of the fact that the daily dosage of each component is 15,000 IU of hyaluronidase, 200 mg of local anesthetic, and 2000 mg of fatty acidation accelerator. If the above range is exceeded, side effects may occur in the human body.

Local anesthetics are substances that can be toxic when used in excessive amounts, and should be used at a minimum.

It was confirmed that up to 40 mg per 10 cc of this injection was preferable.

L-carnitine is a mesotherapy drug and is used in various ways for the effect of lipolysis.

L-carnitine is a decomposing enzyme that acts on the mitochondrial TCA cycle for energy supply, and plays a close role in energy production in the human body. Mitochondria are small organs that affect energy production within cells, and they play a role in decomposing ingested glucose so that it can be used as an energy source that can act.

When L-carnitine is insufficient, fatty acid decomposition cannot be achieved, and energy generated by the decomposition of fatty acids decreases, resulting in fat accumulation and a vicious cycle of worsening obesity. In particular, L-carnitine plays an important role in the treatment for obesity due to irregular eating habits.

This lipolytic effect of L-carnitine is widely used as an additive to various drugs or health foods that aid in diet. In particular, administration of high concentrations of 2g or more L-carnitine plays a role in weight loss. According to Brandsch, L-carnitine does not affect body weight in the case of low calorie intake, so it only affects the case of overweight.

However, L-carnitine may have side effects such as nausea, vomiting, abdominal pain, diarrhea, and body odor, and seizures may occur. In patients with a previous seizure history, the frequency and intensity of seizures increase, promoting fat metabolism and As a result of several studies to find out the dose that can minimize the same side effects, it was confirmed that L-carnitine can be administered up to 400 mg based on 10 cc of the injection composition.

The injection composition of the present invention enables continuous obesity treatment by minimizing side effects under the above-described technical background.

Hereinafter, an injection composition for removing local fat containing choline alfoscerate according to the present invention will be described in detail. At this time, unless there are other definitions in the technical terms and scientific terms used, they have the meanings commonly understood by those of ordinary skill in the technical field to which this invention belongs, and the gist of the present invention is unnecessarily described in the following description. Descriptions of noticeable functions and configurations that may be blurry are omitted.

From now on, the present invention will be described in more detail through specific examples.

Phosphatidylcholine (polyene phosphatidylcholine), a type of glycerophospholipid, a type of glycerol, is a phospholipid component that mainly composes cell membranes and is a precursor of acetylcholine. .

It is a component extracted from a substance called lecithin that is abundantly present in egg yolk, soybean, and other animal and plant tissues, and is abundant in soybeans and tofu. It is an essential phospholipid component containing unsaturated fatty acids. It is an essential phospholipid component that alters the metabolism of cholesterol and triglycerides. Cause

Phosphatidylcholine is also decomposed into lysophosphatidylcholine (LPC) and fatty acids by phospholipase A2 (PLA2), and also into phosphatidic acid and choline by phospholipase D (PLD).

For this reason, it has been used for hyperlipidemia, fat embolism, arteriosclerosis, dementia, etc., but it was first used for beauty in the 80s in Italy and has since been used in various countries such as the United States, Europe, and South America. , It is widely used for treatment of double chin, etc.

It is assumed that the mechanism used for lipolytic injection is'reduction of subcutaneous fat due to necrosis of fat cells due to direct toxicity or surfactant effect'.

Mechanistically, after being administered into the body, ppc binds to the hepatocyte membrane, and then penetrates into the hepatocyte membrane, thereby reducing blood triglycerides and LDL, increasing HDL, and preventing mitochondrial oxidation. Thus, it restores damaged cellular cognitive lipids and promotes hepatocyte regeneration. It prevents liver fibrosis and fat accumulation.

Substances called PPC and deoxycholate destroy fat cell membranes to extract triglycerides and cause fat cells to die. It directly destroys fat cells and naturally excretes them out of the body through veins and lymphatic vessels.

The mechanism by which phosphatidylcholine destroys fat cells and breaks down fat is not clear. Rather, it is more reasonable for now to see that a component called sodium deoxycholate added to PPC injections destroys cells. This ingredient is a fat-dissolving detergent that can cause widespread tissue necrosis if misused or abused as an injection.

As an alternative to phosphatidylcholine, GPC (L-glycerophosphocholine) suggests lipolysis using acetylcholine precursors.

It passes through the blood vessel-brain barrier and enters the brain, where it is separated into choline and glyceryl phosphate dehydrogenase. Choline is a precursor to acetylcholine (ACh), a brain neurotransmitter that plays a central role in memory and learning, and supplements acetylcholine, which is insufficient in patients with brain dysfunction. Acetylcholine normalizes neurotransmitter function, which is degraded by brain nerve damage. In addition, glyceryl dehydrogenase phosphate is metabolized into phospholipids, a component of cell membranes, to normalize damaged neuronal function.

Choline has a lipolytic effect by activating fat metabolism when administered in a large amount.

By administering choline alfoscerate in units of 250 mg to 1000 mg, the present inventor can minimize side effects caused by drug use and remove fat in a large area with a minimum dose.

Choline alfoscerate 250mg ~ 1000mg by administering an injection volume of 0.5 to 2 cc and injection point intervals at 0.5 to 1.5 cm intervals, it is possible to administer at a high density and accordingly, lipolysis is evenly performed.

In addition, local anesthetics for pain relief by administration of injections and lipolysis accelerators for rapidly dissolving and decomposing decomposed fatty fatty acids into the mitochondria have excellent effects in quickly removing fat without side effects.

The local anesthetic agent may be a drug commonly used in an injection solution, but in the present invention, lidocaine was used, and the dose is 20 to 40 mg.

Lipolysis accelerators contain 200-400 mg of L-carnitine.

In addition, the present invention further includes vitamins, Placenta (placenta) components, such as aminophylline and caffeine, which are lipolytic agents generally used in injection solutions, or pentoxifylline components that improve blood circulation. can do.

[Test Example 1] Preparation of injection composition

In the injection administration method of the present invention, the injection volume is 0.5 ㏄ in the choline alfoscerate 500 mg unit, the injection point interval is 20 points at 1 cm intervals, a total of 4 doses at 1 week intervals, and a decrease in abdominal waist circumference after 1 week. After the measurement, the waist circumference of the abdomen was measured again 1 month later, and the average value was recorded in the following [Table 1].

Based on the 0.5㏄ dose, 20 injections can be administered, and the injection site can be used on the whole body area where fat is accumulated, such as the abdomen, buttocks, thighs, calves, chin, forehead, and forearm.

When the injection composition for removing local fat of the present embodiment is expressed in weight %, it may have the following range. Choline alfoscerate of this example may be made of 5 to 15% by weight, 0.1 to 0.3% by weight of lidocaine, 5 to 15% by weight of L-carnitine, and the remainder of physiological saline. Preferably, choline alfoscerate may be composed of 9 to 11% by weight, lidocaine 0.2 to 0.25% by weight, L-carnitine 9 to 11% by weight, and the remainder of physiological saline. More preferably, choline alfoscerate may consist of 10% by weight, lidocaine 0.2133% by weight, L-carnitine 10% by weight, and the rest of physiological saline.

As a specific experimental example for this, choline alfoscerate (1 vial 1g), lidocaine (1 vial 21.33mg), L-carnitine (1 vial 1g), and this was dissolved in physiological saline to prepare 10 cc of an injection solution composition.

The subjects of treatment were 20 adult males and females over the age of 20 years of age, and the circumference of the abdomen was measured one month after abdominal injection to evaluate the lipolysis effect.

division Before treatment After treatment Degree of improvement all 92.5+-2.5 85.6+-2.0 7.5+- Woman 90.8+-1.5 85.2+- 5.6+-1.2 man 94.2+-3.2 86.5+- 9.2+-2.3

According to [Table 1], it was confirmed that after 1 month, the female showed a decrease of -5.6±1.2cm, and the male showed a decrease in the waist circumference of 9.2±2.3cm, and it was confirmed to be maintained without the yo-yo phenomenon. As shown in the above results, It was confirmed that the injection formulation of the present invention has excellent local fat removal effect, significantly reduces side effects, and has no yo-yo phenomenon.

[Test Example 2] BMI evaluation for the injection composition of the present invention

The injection composition of the present invention was administered, and the BMI shown in each patient was evaluated by clinical trials.

division Before treatment After treatment Degree of improvement all 23.5 20.8 2.6 Woman 21.6 19.3 2.3+-1.5 man 26.6 23.4 3.2+-1.8

According to [Table 2], it was confirmed that after 1 month, it was -2.3±1.5 in women, and 3.2±1.8 BMI was decreased in men, and it was confirmed that it was maintained as it was without a yo-yo phenomenon. By controlling the unit dose of serate, it is possible to administer an injection to a wide area, thereby evenly removing fat, and exhibiting BMI reduction and size reduction effects.

Choline alfoscerate is an effective substance that does not have any special side effects in the removal of local fat. It is known to have little effect compared to other drugs, and it is known to have few side effects with other drugs. It seems to be able to maximize the effect of treatment.

The present invention was completed to provide an injection composition for presenting a dose that maximizes the effect while minimizing side effects.

The detailed description and examples of the present invention are merely illustrative of the present invention, which are used only for the purpose of describing the present invention, and those used to limit the meaning or the scope of the present invention described in the claims are no. Therefore, those of ordinary skill in the art will understand that various modifications and equivalent other embodiments are possible therefrom. Therefore, the true technical scope of the present invention should be determined by the technical idea of the appended claims.

The following is a list of examples of the above-described local fat removal injection composition.

Item 1 may provide an injection composition for topical fat removal comprising choline alfoscerate in units of 250 mg to 1000 mg.

Item 2 may provide an injection composition for topical fat removal according to Item 1, further comprising a local anesthetic, a lipolysis accelerator, and a physiological saline solution.

Item 3 may provide an injection composition for topical fat removal according to items 1 and 2, wherein a single injection dose is 0.5 to 2 cc.

Item 4 may provide an injection composition for topical fat removal according to items 1 to 3, wherein the injection point interval is administered at 0.5 to 1.5 tsu.

Item 5 may provide an injection composition for topical fat removal of items 1 to 4, wherein the local anesthetic is 20 to 40 mg based on the total weight of the composition.

Item 6 may provide an injection composition for topical fat removal of items 1 to 5, wherein the lipolysis accelerator is 200 to 400 mg of L-carnitine.

Item 7 may provide an injection composition for topical fat removal according to items 1 to 6, wherein the local anesthetic is lidocaine.

Item 8, Choline alfoscerate is 5 to 15% by weight, lidocaine 0.1 to 0.3% by weight, L-carnitine 5 to 15% by weight, and the remainder is physiological saline and/or aminophylline, caffeine, vitamins, placenta, pentoxifylline. An injection composition for removing local fat may be provided.

Item 9, Choline alfoscerate is 9 to 11% by weight, lidocaine 0.2 to 0.25% by weight, L-carnitine 9 to 11% by weight, and the rest is physiological saline and/or minophylline, caffeine, vitamins, placenta, pentoxifylline An injection composition for removing local fat may be provided.

Item 10, Choline alfoscerate is 10% by weight, lidocaine 0.2133% by weight, L-carnitine 10% by weight, and the remainder is physiological saline and / or aminophylline, caffeine, vitamins, placenta, injection composition for topical fat removal consisting of pentoxifylline Can be provided.

Item 11, Choline alfoscerate is 5 to 15% by weight, lidocaine 0.41% by weight, L-carnitine 5 to 15% by weight, and the remainder is a topical consisting of physiological saline and/or aminophylline, caffeine, vitamins, placenta, pentoxifylline. An injection composition for removing fat may be provided.

Item 12, Choline alfoscerate is 9 to 11% by weight, lidocaine 0.41% by weight, L-carnitine 9 to 11% by weight, and the remainder is physiological saline and / or a topical consisting of minophylline, caffeine, vitamins, placenta, pentoxifylline An injection composition for removing fat may be provided.

Item 13, Choline alfoscerate is 10% by weight, lidocaine 0.41% by weight, L-carnitine 10% by weight, and the remainder is physiological saline and / or aminophylline, caffeine, vitamins, placenta, injection composition for topical fat removal consisting of pentoxifylline Can be provided.

Claims (1)

In the injection composition for removing local fat,
Choline alfoscerate 5 to 15% by weight, lidocaine 0.1 to 0.3% by weight, L-carnitine 5 to 15% by weight, and an injection composition for topical fat removal comprising the remaining physiological saline.