KR102517928B1 - Injection composition comprising hyaluronidase for removing local fat - Google Patents

Abstract

The present invention relates to an injection composition for local fat removal which includes hyaluronidase in units of 200 to 300 IU, and includes choline alfoscerate 5 to 15 wt%, lidocaine 0.1 to 0.5 wt%, L-carnitine 5 to 10 wt%, 0.1 to 5 wt% of alpha mangosteen, 0.01 to 1 wt% of vitamin C, 0.01 to 1 wt% of vitamin B6, and physiological saline. By preparing a composition by mixing components in a desired ratio, the injection composition for local fat removal of the present invention has an excellent lipolytic effect while containing a smaller amount of hyaluronidase and choline alfoscerate which are lipolytic agents. Accordingly, satisfactory changes in a contour and a body shape can be achieved while minimizing side effects such as skin depression and bumps. In addition, since no separate anesthesia is required, a procedure is simple and a quick return to daily life is possible. Therefore, the injection composition for local fat removal can be useful not only for beauty but also for preventing or treating local fat-related diseases.

Description

Injectable composition comprising hyaluronidase and choline alfoscerate for removing local fat

The present invention relates to an injectable composition for local fat removal comprising hyaluronidase and choline alfoscerate.

Recently, due to the gradually increasing obese population, interest in obesity has increased, the number of obesity clinics has increased day by day, and various social problems caused by obesity have become an issue. Obesity, simply put, is defined as a state in which body fat is over-accumulated, and it provides the cause of adult diseases such as hypertension, diabetes, and hyperlipidemia, and forms an axis of metabolic syndrome.

In particular, women tend to long for a slim and well-proportioned body even if they are not obese.

Liposuction, which is a surgical operation, is used in various ways to remove local fat such as abdominal fat accumulated by obesity, but this surgical operation has the risk of scarring, swelling, numbness and burning sensation, and infection at the surgical site. However, serious side effects may occur, including perforation injuries to vital organs or other damage to the skin or nerves.

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

For the above reason, lipolysis accelerators that decompose various local fats have recently been used in order to improve the apparent obesity that occurs as a result of accumulation of body fat. Lipolysis refers to a process in which neutral fat is decomposed into free fatty acid (FFA) and glycerol by the action of hormone sensitive lipase (HSL) accumulated in fat cells.

Hyaluronidase, a generic term for enzymes that submolecularize hyaluronic acid as a lipolytic agent, was first known as a diffusion factor by Duran-Reynals, but it was then observed that it exhibits strong activity on hyaluronic acid. HAase).

As one of the local fat removal methods by lipolysis using hyaluronidase, LLD (Lipolytic Lymph Drainage) treatment is widely used (Patent Publication No. 10-2009-0111916). However, in the above document, it is difficult to remove fat evenly over a wide range by using high-dose (1500 IU) of high-dose (1500 IU), resulting in skin dimpling, skin sagging and wrinkles, and continuous There are problems that are difficult to treat.

Therefore, there is a need for research on the composition of local fat removal injections with low side effects and excellent lipolysis effect and research on appropriate injection treatment methods.

Meanwhile, choline alfoscerate is a substance originally called glycerylphosphorylcholine (GPC), which is a major component of nerve cell membrane phospholipids and is also a choline precursor. In other words, it plays a role in synthesizing acetylcholine by facilitating the supply of choline, and as a result, it restores normalization of nerve function by improving nerve transmission function, and at the same time, supply of glycerol-3-phosphate (Glycerophosphate) promotes phospholipids in nerve cell membranes. It plays a role in restoring nerve cell membranes and improving nerve function. Therefore, the effect of such neural function makes it possible to serve as a therapeutic agent for dementia patients.

The inventors of the present invention completed the present invention by developing an injection for local fat removal containing hyaluronidase and choline alfoscerate while studying to solve the above problems, and confirming its fat removal effect.

An object of the present invention is to provide an optimal injectable composition for local fat removal containing hyaluronidase and choline alfoscerate.

The present invention includes hyaluronidase in units of 200 IU to 300 IU, 5 to 15 wt % of choline alfoscerate, 0.1 to 0.5 wt % of lidocaine, 5 to 10 wt % of L-carnitine, 1 to 3 wt % of alpha lipoic acid, Provided is an injectable composition for topical fat removal comprising 0.01 to 1% by weight of vitamin C, 0.01 to 1% by weight of vitamin B6, and physiological saline.

The injectable composition for topical fat removal of the present invention exhibits an excellent lipolysis effect while containing smaller amounts of hyaluronidase and choline alfoscerate, which are lipolytic agents, by preparing the composition by mixing the components in a desired ratio, Satisfactory contour and body shape changes can be obtained while minimizing side effects such as skin depression and bumpy phenomena, and the procedure is simple as it does not require separate anesthesia, allowing quick return to daily life. It can also be usefully used for the prevention or treatment of related diseases.

1 is a view showing the measurement of adipocyte solubility through MTT assay for compositions containing hyaluronidase and choline alfoscerate according to the present invention and compositions having different contents of active ingredients.
Figure 2 is a diagram showing the measurement of adipocyte solubility through MTT assay for compositions containing hyaluronidase, choline alfoscerate and alpha-mangostin according to the present invention and compositions having different contents of active ingredients.

The present invention includes hyaluronidase in units of 200 IU to 300 IU, 5 to 15 wt % of choline alfoscerate, 0.1 to 0.5 wt % of lidocaine, 5 to 10 wt % of L-carnitine, 1 to 3 wt % of alpha lipoic acid, Provided is an injectable composition for topical fat removal comprising 0.01 to 1% by weight of vitamin C, 0.01 to 1% by weight of vitamin B6, and physiological saline.

Hereinafter, the present invention will be described in detail.

Hyaluronidase, which is an active ingredient of the present invention, is an enzyme that converts hyaluronic acid into small molecules as a lipolytic agent, and is composed of D-glucuronic acid and N-acetyl- It is known to hydrolyze the bonds of D-glucosamine.

The hyaluronidase is included in 200 IU to 300 IU units, preferably 250 IU. When hyaluronidase is used in excess, as a high-concentration injection is administered to one part of the skin, the skin curve may become uneven and the skin may turn off.

Choline alfoscerate is a substance called glycerylphosphorylcholine (GPC), which plays a role in synthesizing acetylcholine by facilitating the supply of choline, and as a result, improves nerve transmission function to At the same time as restoring the normalization of functions, the supply of glycerophosphate acts on the phospholipids in the nerve cell membrane to restore the nerve cell membrane and improve nerve function. The choline alfoscerate may be included in 5 to 15% by weight, preferably 10% by weight.

Lidocaine is a local anesthetic and is used for pain relief by injection. Local anesthetics are substances that can be toxic when used in excess and should be used at a minimum, so they are limited to 0.1 to 0.5% by weight.

L-carnitine (L-carnitine) is a lipolysis accelerator, and is used to quickly move fatty acids from decomposed fat to mitochondria for decomposition. Mitochondria are organelles that affect energy production within cells. They break down ingested glucose so that it can be used as an energy source for activities. When L-carnitine is insufficient, fatty acids cannot be decomposed, which leads to a decrease in energy generated by the decomposition of fatty acids, resulting in a vicious cycle in which fat accumulates and obesity worsens. In particular, when obesity occurs due to irregular eating habits, L-carnitine plays an important role in the treatment for this.

However, L-carnitine can cause side effects such as nausea/vomiting, abdominal pain, diarrhea, and body odor, and seizures can occur. In patients with a previous history of seizures, the frequency and intensity of seizures increase, promoting fat metabolism while It is limited to 5 to 10% by weight because it must be administered in a dose that can minimize the same side effects.

Alpha-lipoic acid is a fatty acid produced in small amounts in the human body. It is a medium-length fatty acid that helps mitochondrial respiratory enzymes. there is. The alpha-lipoic acid was limited to 1 to 3% by weight, which is an optimal composition, through experiments.

Vitamin C was used as a collagen production promoting material to prevent skin sagging, which is the most problematic during lipolysis and diet, and to make elastic skin, and was limited to 0.01 to 1% by weight, which is an optimal composition through experiments.

Vitamin B6 belongs to the vitamin B complex, and can be expected to have effects of preventing skin aging and relieving and preventing dermatitis, dry skin, acne, etc., and was limited to the optimal composition of 0.01 to 1% by weight through experiments.

In addition, the present invention may further include alpha mangosteen.

Alpha mangosteen is a material derived from mangosteen and has a structure represented by Chemical Formula 1 below.

[Formula 1]

By activating AMPK, alpha-mangosteen reduces blood sugar, free fatty acid, total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol in obese conditions, reduces body weight, and reduces the accumulation of fat cells and the growth of fat cells. The effect of reducing the size is excellent.

The alpha-mangosteen may preferably be included in an amount of 0.5 to 1.0% by weight.

In addition, the composition of the present invention further includes aminophylline, caffeine, and placenta (placenta) components, which are lipolysis agents commonly used in injection solutions, or pentoxifylline components that improve blood circulation. can do.

The composition of the present invention is a suitable carrier, excipient, penetration enhancer, dispersant, disintegrant, lubricant, wetting agent, emulsifier, suspending agent, diluent, binder, lubricant, preservative, stabilizer, anti-adhesive agent, Additives such as glidants, colorants or preservatives may be further included. Carriers, excipients and diluents that may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate and mineral oil. When the composition is formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

As used herein, the term 'administration' refers to providing a predetermined composition of the present invention to a subject through injection, and the administration method includes subcutaneous injection, intradermal injection, intravenous injection, intramuscular injection, intraperitoneal injection, subcutaneous transplantation, and implantable injection. , It may be by an ointment, or a patch, and preferably, it is a mesotherapy method in which the drug is injected into the skin layer and the subcutaneous layer, and is injected into the body parts where fat is accumulated, such as the abdomen, buttocks, thighs, calves, chin, forehead, and forearms. can do.

The preferred dosage of the injectable composition of the present invention varies depending on the condition and body weight of the subject, the severity of the disease, the route and duration of administration, but can be appropriately selected by those skilled in the art. For desirable effects, the injectable composition of the present invention can be administered in an amount of 1.0 to 2.0 cc once, and can be administered once a day or divided several times.

The injection point is most preferably injected at intervals of 0.5 to 1.5 cm, and the daily dose of hyaluronidase is preferably within 15,000 IU.

Through the administration of the injectable composition of the present invention, it is possible to non-surgically remove localized fat deposits. As a result of measuring the effect on the size of fat cells and inflammatory response through experiments, it was confirmed that the lipolysis effect was excellent without causing tissue necrosis and inflammation.

In addition, the present injectable composition can be used for the prevention or treatment of local fat-related diseases such as eyelid fat prolapse, lipoma, Dercom disease, Madelon's neck, lipoedema, pyosogenic nodule, xanthoma, cellulite and lipodystrophy, For the prevention and treatment of the above diseases, it can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

The injection of the present invention dissolves the main ingredient and other additives in physiological saline, filters the solution through a bacterial filter, sterilizes it, and then fills the vial in an aseptic state and seals it.

Hereinafter, preferred examples, experimental examples, and formulation examples are presented to aid understanding of the present invention. However, the following examples are only provided to more easily understand the present invention, and the content of the present invention is not limited thereby.

Example 1. Preparation of Injectable Composition 1

Hyaluronidase, choline alfoscerate, lidocaine, L-carnitine, alpha lipoic acid, vitamin C and vitamin B6 were evenly mixed in the contents shown in the table below and dissolved in physiological saline to prepare an injectable solution composition.

ingredient Example 1 Comparative Example 1-1 Comparative Example 1-2 Comparative Example 1-3 Comparative Example 1-4 Comparative Example 1-5 hyaluronidase 250 IU 250 IU 150 IU 150 IU 400IU 1000 IU choline alfoscerate 10% (w/v) 5% (w/v) 10% (w/v) 20% (w/v) 2.5% (w/v) 2.5% (w/v) lidocaine 0.3% (w/v) 0.3% (w/v) 0.3% (w/v) - - - L-Carnitine 7% (w/v) 7% (w/v) 7% (w/v) - - - alpha lipoic acid 2% (w/v) 2% (w/v) 2% (w/v) - - - vitamin C 0.1% (w/v) 0.1% (w/v) 0.1% (w/v) - - - vitamin B6 0.1% (w/v) 0.1% (w/v) 0.1% (w/v) - - - saline solution balance balance balance balance balance balance Total weight % 100% (w/v) 100% (w/v) 100% (w/v) 100% (w/v) 100% (w/v) 100% (w/v)

Example 2. Preparation of injectable composition 2

Hyaluronidase, choline alfoscerate, lidocaine, L-carnitine, alpha lipoic acid, vitamin C and vitamin B6, and alpha mangosteen were evenly mixed in the contents shown in the table below, and dissolved in physiological saline to prepare an injectable solution composition.

ingredient Example 2 Comparative Example 2-1 Comparative Example 2-2 Comparative Example 2-3 Comparative Example 2-4 hyaluronidase 250 IU 250 IU 250 IU 400IU 400IU choline alfoscerate 10% (w/v) 10% (w/v) 2.5% (w/v) 2.5% (w/v) 2.5% (w/v) lidocaine 0.3% (w/v) 0.3% (w/v) 0.3% (w/v) 0.3% (w/v) 0.3% (w/v) L-Carnitine 7% (w/v) 7% (w/v) 7% (w/v) 7% (w/v) 7% (w/v) alpha lipoic acid 2% (w/v) 2% (w/v) 2% (w/v) 2% (w/v) 2% (w/v) alpha mangosteen 1% (w/v) - 1% (w/v) - 1% (w/v) vitamin C 0.1% (w/v) 0.1% (w/v) 0.1% (w/v) 0.1% (w/v) 0.1% (w/v) vitamin B6 0.1% (w/v) 0.1% (w/v) 0.1% (w/v) 0.1% (w/v) 0.1% (w/v) saline solution balance balance balance balance balance Total weight % 100% (w/v) 100% (w/v) 100% (w/v) 100% (w/v) 100% (w/v)

Experimental Example 1. Confirmation of fat cell lysis effect

After culturing 3T3-L1 adipocytes, each of the above examples and comparative examples was treated and cultured at room temperature. The cells were washed with PBS, treated with MTT reagent (50 μl), and left for 2 hours. After removing the supernatant, DMSO was treated to dissolve MTT formazan (crystal), and absorbance was measured at 540 nm using a microplate reader. The results of Example 1 and Comparative Examples 1-1 to 1-5 are shown in FIG. 1, and the results of Example 2 and Comparative Examples 2-1 to 2-4 are shown in FIG.

As shown in FIG. 1, the value of Example 1 is 50%, which shows a better effect than Comparative Examples 1-1 to 1-3 containing hyaluronidase and / or choline alfoscerate at different contents. , and showed similar values to Comparative Examples 1-4 containing more 400 IU of hyaluronidase, confirming that excellent effects can be exhibited even with less hyaluronidase.

In addition, as shown in FIG. 2, the value of Example 2 was 43%, showing a better effect than Comparative Examples 2-1 to 2-2 that did not contain alpha-mangosteen, and more 400 IU of hyaluronan. It was confirmed that the results were similar to those of Comparative Examples 2-3 and 2-4, which contained the hyaluronidase, and showed excellent effects even when less hyaluronidase was used.

Through the above experiments, it was confirmed that the injectable composition of the present invention is more stable and economical against side effects because the active ingredients are mixed to generate a synergistic effect and can exhibit a more favorable lipolysis effect while using less hyaluronidase. .

Claims (10)

Contains hyaluronidase in 250 IU units, choline alfoscerate 5 to 15% by weight, lidocaine 0.1 to 0.5% by weight, L-carnitine 5 to 10% by weight, alpha lipoic acid 1 to 3% by weight, alpha mangosteen 0.5 to 10% by weight An injectable composition for topical fat removal comprising 1.0% by weight, 0.01 to 1% by weight of vitamin C, 0.01 to 1% by weight of vitamin B6, and physiological saline. delete The injectable composition for topical fat removal according to claim 1, wherein the choline alfoscerate is contained in an amount of 10% by weight. delete delete According to claim 1, from the group consisting of excipients, penetration enhancers, dispersants, disintegrants, lubricants, wetting agents, emulsifiers, suspending agents, diluents, binders, glidants, preservatives, stabilizers, anti-adhesives, glidants, colorants or preservatives. An injectable composition for removing local fat, characterized in that it further comprises at least one selected additive. The injectable composition according to claim 1, wherein the injectable composition removes localized fat deposits non-surgically. The injectable composition for topical fat removal according to claim 1, wherein the injectable composition has a single injection volume of 1.0 to 2.0 cc. The injectable composition for removing local fat according to claim 6, wherein the injectable composition is administered at an injection point interval of 0.5 to 1.5 cm. The method of claim 1, wherein the injectable composition is used for the treatment of local fat-related diseases selected from the group consisting of eyelid fat prolapse, lipoma, Dercom disease, Madelon's neck, lipoedema, pyosogenic nodule, xanthoma, cellulite, and lipodystrophy. An injectable composition for local fat removal, characterized in that it is used for prevention or treatment.

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