KR102116238B1 - Composition for hypotonic lipolysis and manufacturing method thereof - Google Patents

Abstract

The present invention discloses a hypotonic lipolytic composition and a method of making the same. That is, the present invention is to prepare a hypotonic lipolysis composition containing deoxycholic acid, hyaluronidase, etc. in a hypotonic solution composed of distilled water and sodium chloride, thereby consolidating the injection site due to the use of deoxycholic acid alone. Reduces the incidence and reduces the effects on cells containing fat components other than fat cells (e.g., nerve cells, muscle cells, bone cells, etc.) compared to using deoxycholic acid alone. Reduces side effects such as atrophy, reduces adverse effects such as edema, swelling, erythema, pain, and fat cells by using hyaluronidase in combination with hypotonic solutions It increases the efficiency of destruction and can be used as a drug for reducing fat accumulated in the local area by subcutaneous administration.

Description

Composition of hypotonic lipolysis and its manufacturing method

The present invention relates to a hypotonic lipolysis composition and a method for preparing the same, particularly in a hypotonic solution composed of distilled water and sodium chloride, deoxycholate, hyaluronidase, buffer, additives, etc. It relates to a hypotonic lipolytic composition for preparing the hypotonic lipolytic composition contained therein and a method for manufacturing the same.

In general, in combination with phosphatidylcholine (PPC) and deoxycholic acid (sodium deoxycholate) for the purpose of lipoplasty, injections of complex preparations have been frequently used for local obesity.

However, due to the generation of fat necrosis lumps by injection of a combination preparation using phosphatidylcholine and deoxycholic acid, a lipolysis composition using a deoxycholic acid-only formulation excluding phosphatidylcholine was developed, but a deoxycholic acid-only formulation was used. In the case of a lipolysis composition, there are problems in that side effects such as edema, erythema, pain, and skin induration frequently occur.

Korean Registered Patent No. 10-0911949 [Name: Marine mineral composition that inhibits fat breakdown and production]

An object of the present invention is to provide a hypotonic lipolysis composition for preparing a hypotonic lipolysis composition containing deoxycholic acid, hyaluronidase, and the like in a hypotonic solution composed of distilled water and sodium chloride, and a method for preparing the same.

Another object of the present invention is to provide a hypotonic lipolysis composition for preparing a hypotonic lipolysis composition containing deoxycholic acid, hyaluronidase, a buffer, an additive, etc. in a hypotonic solution composed of distilled water and sodium chloride, and a method for preparing the same Having

The hypotonic lipolytic composition according to an embodiment of the present invention may contain a hypotonic solution and a deoxycholine acid as an active ingredient in the hypotonic lipolytic composition.

As an example related to the present invention, the hypotonic solution is composed of distilled water, or by stirring the distilled water and sodium chloride to have a lower concentration than physiological saline, thereby deoxy through simultaneous application of physical and biochemical lipolysis. While applying cholinic acid to less than 10% by weight, it is possible to increase the fat decomposition effect compared to deoxycholinic acid alone.

As an example related to the present invention, the deoxycholic acid may be included in less than 10% by weight relative to the total weight of the hypotonic lipolytic composition.

A method for preparing a hypotonic lipolysis composition according to an embodiment of the present invention comprises the steps of preparing a hypotonic solution using distilled water or distilled water and sodium chloride; And adding deoxycholic acid to the prepared hypotonic solution and stirring to prepare a hypotonic lipolytic composition.

The present invention, by preparing a hypotonic lipolysis composition containing deoxycholic acid, hyaluronidase, etc. in a hypotonic solution composed of distilled water and sodium chloride, the occurrence of consolidation at the injection site due to the use of deoxycholic acid alone Reduces the effect on cells containing fat components other than fat cells (e.g., nerve cells, muscle cells, bone cells, etc.) compared to using deoxycholic acid alone, thereby reducing nerve paralysis, muscle atrophy, bone atrophy, etc. Reduces side effects of edema, reduces adverse effects such as edema, swelling, erythema, pain, and destroys fat cells by using hyaluronidase in combination with a hypotonic solution. It increases the efficiency and has the effect of being used as a medicament for fat reduction accumulated locally by subcutaneous administration.

In addition, the present invention by preparing a hypotonic lipolysis composition containing deoxycholic acid, hyaluronidase, buffer, additives, etc. in a hypotonic solution composed of distilled water and sodium chloride, the tissue in which the hypotonic lipolysis composition is injected Deoxycholic acid is effectively delivered to the fat cells, so it is possible to obtain effective lipolysis even with low concentrations of deoxycholic acid, and edema, erythema, pain, and skin hardening due to injection of high concentrations of deoxycholic acid. It has the effect of reducing the phenomenon of.

1 is a flow chart showing a method of manufacturing a hypotonic lipolytic composition according to a first embodiment of the present invention.
2 is a flow chart showing a method of manufacturing a hypotonic lipolytic composition according to a second embodiment of the present invention.
Figure 3 is a graph showing the relative weight between the examples and comparative examples according to the hypotonic lipolytic composition according to an embodiment of the present invention.

It should be noted that the technical terms used in the present invention are only used to describe specific embodiments, and are not intended to limit the present invention. In addition, technical terms used in the present invention should be interpreted as meanings generally understood by a person having ordinary knowledge in the technical field to which the present invention belongs, unless otherwise defined in the present invention. It should not be interpreted as a meaning or an excessively reduced meaning. In addition, when the technical term used in the present invention is a wrong technical term that does not accurately represent the spirit of the present invention, it should be understood as being replaced by a technical term that can be correctly understood by those skilled in the art. In addition, the general terms used in the present invention should be interpreted as defined in the dictionary or in context before and after, and should not be interpreted as an excessively reduced meaning.

In addition, the singular expression used in the present invention includes a plural expression unless the context clearly indicates otherwise. In the present invention, terms such as “consisting of” or “comprising” should not be construed as including all of the various components or steps described in the invention, and some of the components or some steps are not included. It may be, or should be construed to further include additional components or steps.

Further, terms including ordinal numbers such as first and second used in the present invention may be used to describe elements, but the elements should not be limited by terms. The terms are used only to distinguish one component from other components. For example, the first component may be referred to as a second component without departing from the scope of the present invention, and similarly, the second component may be referred to as a first component.

Hereinafter, preferred embodiments according to the present invention will be described in detail with reference to the accompanying drawings, but the same or similar elements will be given the same reference numbers regardless of the reference numerals, and redundant descriptions thereof will be omitted.

In addition, in the description of the present invention, when it is determined that detailed descriptions of related known technologies may obscure the subject matter of the present invention, detailed descriptions thereof will be omitted. In addition, it should be noted that the accompanying drawings are only for easy understanding of the spirit of the present invention and should not be interpreted as limiting the spirit of the present invention by the accompanying drawings.

Hereinafter, a method for producing a hypotonic lipolytic composition according to the present invention will be described in detail with reference to FIGS. 1 to 3.

1 is a flow chart showing a method of manufacturing a hypotonic lipolytic composition according to a first embodiment of the present invention.

First, sodium chloride is added to distilled water and stirred to prepare (or prepare) a hypotonic solution.

The sodium chloride is used for preparing a low osmotic pressure solution (or hypotonic solution) (or the hypotonic solution).

That is, the sodium chloride has an effect of inducing physical fat cell destruction (or decomposition) by osmotic pressure difference when subcutaneously injecting the hypotonic lipolysis composition.

In this case, the distilled water is 1% by weight to 99% by weight based on the total weight of the hypotonic lipolysis composition, and the sodium chloride is 0.01% by weight to 0.89% by weight (generally 0.45% by weight) based on the total weight of the hypotonic lipolysis composition. %).

Here, the stirring conditions and time is stirred for 5 minutes to 20 minutes (typically 10 minutes) in a stirrer (not shown) having a rotation speed of 250 rpm to 300 rpm, and the pressure at this time may be atmospheric pressure and the temperature may be room temperature. . The stirring conditions and time may be variously set according to the designer's design. In addition, a mixed solution may be prepared under the stirring environment (the stirring conditions and time) in all the stirring steps below (S110).

Subsequently, deoxycholinic acid (sodium deoxycholate) is added to the prepared hypotonic solution and stirred to prepare (or prepare) a mixed solution A.

The deoxycholic acid has the effect of selectively destroying fat cells when subcutaneously injecting the hypotonic lipolytic composition, thereby reducing fat volume. Fat cells that have been destroyed in this way cannot accumulate fat again and cause a permanent decrease in fat volume.

At this time, the deoxycholic acid may be 0.01% by weight to 9.9% by weight (generally 0.075% by weight) based on the total weight of the hypotonic fat-decomposing composition (S120).

Then, hyaluronidase (hyaluronidase) is added to the prepared A mixture and stirred to prepare (or prepare / complete) the hypotonic lipolytic composition.

The hyaluronidase is a huge family of enzymes that break down hyaluronic acid. The hyaluronic acid is a key component of the cell's extracelluar matrix and is a major member of the interstitial barrier. The hyaluronidase catalyzes the hydrolysis of the hyaluronic acid, thereby lowering the viscosity of the hyaluronic acid, thereby increasing tissue permeability and diffusion. Therefore, the hyaluronidase is used as an electrodeposition agent or dispersant in combination with other reagents, drugs, proteins, and the like to enhance dispersibility and delivery properties.

That is, the hyaluronidase promotes (or catalyzes) the hydrolysis of the hyaluronic acid, thereby increasing the drug permeability of the subcutaneous connective tissue, thereby effectively dispersing deoxycholic acid contained in the hypotonic lipolytic composition into fat cells. ), Delivery (delivery), has the effect of helping to effect (effect).

In addition, the hyaluronidase is a hyaluronidase of bacteria (EC 4.2.99.1), hyaluronidase from leeches, other parasites and crustaceans (EC 3.2.1.36), and mammalian-type hyaluronidase depending on the mechanism of action. (EC 3.2.1.35).

In addition, the hyaluronidase described in the present invention is not limited thereto, and may include hyaluronidase of human origin, hyaluronidase of human origin, and the like.

That is, hyaluronidase of any of the non-human origins such as murines, dogs, cats, rabbits, birds, cows, sheep, pigs, horses, fish, frogs, fungi, leeches, other parasites, crustaceans, etc. It may include.

For example, hyaluronidase of non-human origin includes bovine, wasp, bee, white face amber bee, long-lived wasp, rat, pig, rat (rat), rabbit, sheep, orangutan, Philippine monkey, guinea pig, Staphylococcus aureus, Streptococcus, hyaluronidase from Clostridium perfringens.

In addition, hyaluronidase of human origin includes HYAL1, HYAL2, HYAL3, HYAL4, PH20 and the like.

In addition, the hyaluronidase includes sheep and bovine PH20, soluble human PH20, soluble rHuPH20, and the like.

In addition, the hyaluronidase having a biological activity of 50 I.U / ml to 3,000 I.U / ml (typically 90 I.U / ml) at room temperature may be added to the A mixture.

As such, the hypotonic lipolysis composition may be prepared by stirring the distilled water, the sodium chloride, the deoxycholic acid, the hyaluronidase, and the like.

ingredient Composition ratio (% by weight) Distilled water 1 to 99 Sodium chloride 0.01 ~ 0.89 Deoxycholic acid 0.01 ~ 9.9 Hyaluronidase 50 ~ 3,000 I.U / ml

In addition, the hypotonic lipolysis composition may be composed of a composition ratio (% by weight) as in [Table 1]. In addition, the hypotonic lipolysis composition is 50 IU / ml to 3,000 IU / ml of the hyaluronidase. Included in units, the deoxycholic acid relative to the total weight of the hypotonic lipolytic composition is composed of 0.01 to 9.9% by weight and the remaining hypotonic solution. Here, the hypotonic solution is intended to induce physical fat cell destruction (or degradation) due to the osmotic pressure difference when subcutaneously injecting the hypotonic lipolytic composition, and based on 1000 ml of the hypotonic solution, sodium chloride 0.1g to 8.9g (typically 4.5g) and the rest of the distilled water.

In addition, the hypotonic lipolysis composition is a formulation of a solution or is managed (or constituted / manufactured / prepared) as a lyophilized formulation.

In addition, when the hypotonic lipolytic composition is a lyophilized formulation, it may be prepared in a liquid state by a diluent (S130).

Thereafter, the prepared (or prepared) hypotonic lipolytic composition is packaged by use (or unit) in a preset container (not shown). Here, the hypotonic lipolytic composition containing the pharmaceutically active compound to be packaged should be guaranteed sterility.

That is, the prepared (or prepared) hypotonic lipolysis composition is packaged in an ampoule, a vial, a syringe with a needle, and the like.

In addition, the packaged hypotonic lipolysis composition is injected directly into the subcutaneous fat layer of the user's body, causing fat volume reduction by selectively destroying fat cells, and can reduce and correct facial and body shape. At this time, the hypolipidemic composition may be injected into the subcutaneous fat layer, such as the user's double chin area.

That is, when the hypotonic lipolysis composition is injected into human tissue, cells of the tissue into which the hypotonic lipolysis composition has been injected (including fat cells, etc.) are swollen due to the osmotic pressure difference, due to the osmotic pressure difference. The swollen cells make the destruction of fat cells by the deoxycholic acid more effective.

In this way, the hypotonic composition can be directly injected into the double chin area of a user with relatively few motor nerves, thereby maximizing the effect of fat degradation and reducing side effects due to permanent damage to the motor nerves.

The fat cell membrane is destroyed by the action of the hypotonic fat-decomposing composition injected into the subcutaneous fat layer, and the fat is changed to water-soluble. Subsequently, the fat changed to water solubility may be discharged to the body through urine or sweat (S140).

As such, in the embodiment of the present invention, phosphatidylcholine, which is related to the occurrence of side effects, was not included in the hypolipidemic composition.

On the other hand, the hypotonic lipolytic composition contained deoxycholic acid, which has been proven effective in lipolysis.

In addition, the hypotonic lipolytic composition includes the hyaluronidase on the basis of the hypotonic solution to maximize the lipolysis effect of the deoxycholic acid and reduce discomfort such as edema, erythema, pain, and skin induration. have.

2 is a flow chart showing a method of manufacturing a hypotonic lipolytic composition according to a second embodiment of the present invention.

First, sodium chloride is added to distilled water and stirred to prepare (or prepare) a hypotonic solution.

The sodium chloride is used for preparing a low osmotic pressure solution (or the hypotonic solution).

That is, the sodium chloride has an effect of inducing physical fat cell destruction (or decomposition) by osmotic pressure difference when subcutaneously injecting the hypotonic lipolysis composition.

In this case, the distilled water is 1% by weight to 99% by weight based on the total weight of the hypotonic lipolysis composition, and the sodium chloride is 0.01% by weight to 0.89% by weight (generally 0.45% by weight) based on the total weight of the hypotonic lipolysis composition. %).

Here, the stirring conditions and time is stirred for 5 minutes to 20 minutes (typically 10 minutes) in a stirrer (not shown) having a rotation speed of 250 rpm to 300 rpm, and the pressure at this time may be atmospheric pressure and the temperature may be room temperature. . The stirring conditions and time may be variously set according to the designer's design. In addition, a mixed solution may be prepared under the stirring environment (the stirring conditions and time) in all the stirring steps below (S210).

Subsequently, deoxycholic acid is added to the prepared hypotonic solution and stirred to prepare (or prepare) a mixed solution A.

The deoxycholic acid has the effect of selectively destroying fat cells when subcutaneously injecting the hypotonic lipolytic composition, thereby reducing fat volume. Fat cells that have been destroyed in this way cannot accumulate fat again and cause a permanent decrease in fat volume.

In this case, the deoxycholic acid may be 0.01% by weight to 9.9% by weight (generally 0.075% by weight) based on the total weight of the hypotonic fat-decomposing composition (S220).

Then, hyaluronidase is added to the prepared A mixture solution and stirred to prepare (or prepare) the B mixture solution.

In addition, the hyaluronidase having the biological activity of hyaluronidase at room temperature of 50 I.U / ml to 3,000 I.U / ml (typically 90 I.U / ml) may be added to the A mixture (S230).

Thereafter, a buffer and other additives are added to the prepared B mixture and stirred to prepare (or prepare / complete) the hypotonic lipolysis composition.

The buffer is used for adjusting the acidity (pH) of the hypotonic lipolysis composition, lactose hydrate, succinate, acetate, phosphate, citrate, ah It includes aconitate, malate, carbonate, and the like.

In addition, in addition to the buffers described in the embodiments of the present invention, various buffers that provide acceptable pH stability or satisfy buffer capacity within an indicated (or preset) range may be used.

The additives are used for maintaining the shelf life of the hypotonic lipolytic composition, and include carriers such as diluents, adjuvants, excipients, vehicles, and the like.

In this case, the pharmaceutical carrier may be a sterile liquid, water and petroleum, animal, peanut oil, soybean oil, mineral oil, and oils containing carriers of plant or synthetic origin, such as sesame oil.

In addition, saline solution, aqueous dextrose, cisserol solution and the like can be used as a liquid carrier.

For example, pharmaceutically acceptable carriers used in parenteral formulations include aqueous vehicles, non-aqueous vehicles, antimicrobial agents, tonicity agents, antioxidants, local anesthetics, suspensions and dispersants, emulsifiers, metal blockades Agents or chelating agents, other pharmaceutically acceptable substances, and the like.

The aqueous vehicle includes sodium chloride injection, Ringer injection, isotonic dextrose injection, sterile water injection, dextrose and lactated Ringer injection.

The non-aqueous vehicle (or non-aqueous parenteral vehicle) includes fixed oils of vegetable origin, cottonseed oil, corn oil, sesame oil, peanut oil, and the like.

The antimicrobial agent in bacteriostatic or fungal concentrates is phenol or cresol, benzyl alcohol, chlorobutanol, methyl and propyl p-Hydroxybenzoic esters ), Thimerosal, benzalkonium chloride, benzethonium chloride, and the like.

The isotonic agent includes sodium chloride, dextrose, and the like.

The antioxidant includes sodium bisulfate and the like.

The local anesthetics include lidocaine hydrochloride, procaine hydrochloride, and the like.

The suspending agent and dispersing agent include sodium carboxymethylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and the like.

The emulsifier includes polysorbate 80 (TWEENs 80) and the like.

The metal sequestering agent or chelating agent of the metal ion includes ethylenediaminetertraacetic acid (EDTA).

The pharmaceutical carrier may include ethyl alcohol for water-miscible vehicles, polyethylene glycol, propylene glycol, sodium hydroxide for pH adjustment, hydrochloric acid, citric acid, lactic acid, and the like.

In addition, the additives include diluents (for example, lactose, sucrose, dicalcium phosphate, Carboxymethylcellulose, etc.), lubricants (for example, magnesium stearate ), Calcium stearate (including calcium stearate, talc, etc.), binders (including starch, natural gums, etc.), and the like.

In addition, the additives are trace wetting or emulsifying agents, pH buffering agents (e.g. acetate, sodium citrate, cyclodextrin derivatives, sorbitan monolaurate, triethanolamine sodium acetate, Triethanolaminolate, etc.).

In this case, the buffer is 0.01% to 50% by weight based on the total weight of the hypotonic lipolysis composition, and the additive (or other additive) is 0.01% to 50% by weight based on the total weight of the hypotonic lipolysis composition. Can be

As such, the hypotonic lipolysis composition may be prepared by stirring the distilled water, the sodium chloride, the deoxycholic acid, the hyaluronidase, the buffer, and the additive.

ingredient Composition ratio (% by weight) Distilled water 1 to 99 Sodium chloride 0.01 ~ 0.89 Deoxycholic acid 0.01 ~ 9.9 Hyaluronidase 50 ~ 3,000 I.U / ml Buffer 0.01 ~ 50 additive 0.01 ~ 50

In addition, the hypotonic lipolysis composition may be composed of the composition ratio (% by weight) as in [Table 2]. In addition, the hypotonic lipolysis composition is 50 IU / ml to 3,000 IU / ml of the hyaluronidase. Included as a unit, the deoxycholic acid relative to the total weight of the hypotonic fat-decomposing composition is 0.01% to 9.9% by weight, a buffering agent for adjusting the acidity of the hypotonic fat-decomposing composition, 0.01% to 50% by weight, the hypotonic fat-decomposing It consists of 0.01% to 50% by weight of the additive and the rest of the hypotonic solution to maintain the drug's shelf life. Here, the hypotonic solution is intended to induce physical fat cell destruction (or degradation) due to the osmotic pressure difference when subcutaneously injecting the hypotonic lipolytic composition, and based on 1000 ml of the hypotonic solution, sodium chloride 0.1g to 8.9g (typically 4.5g) and the rest of the distilled water.

In addition, the hypotonic lipolysis composition is a formulation of a solution or is managed (or constituted / manufactured / prepared) as a lyophilized formulation.

In addition, when the hypotonic lipolytic composition is a lyophilized formulation, it may be prepared in a liquid state by a diluent (S240).

Thereafter, the prepared (or prepared) hypotonic lipolytic composition is packaged by use (or unit) in a preset container (not shown). Here, the hypotonic lipolytic composition containing the pharmaceutically active compound to be packaged should be guaranteed sterility.

That is, the prepared (or prepared) hypotonic lipolytic composition is packaged in an ampoule, a vial, a syringe with a needle, and the like.

In addition, the packaged hypotonic lipolysis composition is injected directly into the subcutaneous fat layer of the user's body, thereby causing fat volume reduction by selectively destroying fat cells, and can reduce and correct the face and body shape. At this time, the hypolipidemic composition may be injected into the subcutaneous fat layer, such as the user's double chin area.

That is, when the hypotonic lipolysis composition is injected into human tissue, cells of the tissue into which the hypotonic lipolysis composition has been injected (including fat cells, etc.) are swollen due to the osmotic pressure difference, due to the osmotic pressure difference. The swollen cells make the destruction of fat cells by the deoxycholic acid more effective.

In this way, the hypotonic composition can be directly injected into the double chin area of a user with relatively few motor nerves, thereby maximizing the effect of fat degradation and reducing side effects due to permanent damage to the motor nerves.

The fat cell membrane is destroyed by the action of the hypotonic fat-decomposing composition injected into the subcutaneous fat layer, and the fat is changed to water-soluble. Subsequently, the fat changed to water solubility may be discharged to the body through urine or sweat (S250).

<Example>

The hypotonic lipolysis composition (or injectable composition) according to the embodiment of the present invention was based on 100 ml of total hyaluronidase 9000I.U, 75 mg of deoxycholic acid, 450 mg of sodium chloride, and the remaining distilled water.

<Comparative Example 1>

Physiological saline was used alone.

<Comparative Example 2>

A high dose of deoxycholic acid 1000 mg was used for the saline solution.

<Comparative Example 3>

75 mg of deoxycholic acid was used for the saline solution.

<Comparative Example 4>

Hyaluronidase 9000I.U was used for the saline solution.

<Comparative Example 5>

The hypotonic solution was used alone.

<Comparative Example 6>

Hyaluronidase 9000I.U and deoxycholic acid 75mg were used for physiological saline.

The composition of the injection composition according to the embodiment of the present invention and the comparative example 1 to the comparative example 6 may be represented as shown in [Table 3].

ingredient Example Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Hyaluronidase 9000I.U - - - 9000I.U - 9000I.U Deoxycholic acid 75mg
(0.075%) - 1000mg
(One%) 75mg
(0.075%) - - 75mg
(0.075%) Sodium chloride 450mg
(0.45%) 900mg
(0.9%) 900mg
(0.9%) 900mg
(0.9%) 900mg
(0.9%) 450mg
(0.45%) 900mg
(0.9%) Distilled water Balance Balance Balance Balance Balance Balance Balance Total amount 100ml 100ml 100ml 100ml 100ml 100ml 100ml

Here, all the injection composition was prepared in 100ml. At this time, the hyaluronidase was used hyalup strain (1 vial 1500I.U) of Woori Pharmaceutical Co., Ltd. The composition of the injectable composition is deoxycholic acid (manufacturer: Sigma-Aldrich) measured with a fine balance according to the corresponding content, then physiological saline (manufacturer: Daehan Pharm) or physiological saline and distilled water (manufacturer: Daehan Pharm. ) Was dissolved in a mixed hypotonic solution to prepare each of the corresponding contents. In addition, in the case of the injection composition containing hyaluronidase, as in Examples, Comparative Examples 4 and 6, respectively, the prepared solutions The hyaluronidase was dissolved in a hyaluronic acid vial, and then injected again to prepare an injection composition.

<Test Example>

The male 5 week old Sprague Dawley rat, an experimental animal used in this test, was purchased from Orient Bio. In addition, the environmental conditions of the rats were set at 22 ° C to 24 ° C, relative humidity of 30% to 50%, and two were raised per breeding box. From 7:00 am to 7:00 pm, 150 lux (Lux) to 300 lux was given, and lit 12 hours a day, and turned off 12 hours a day. The feed was freely consumed using a high fat diet (45% fat content, 2018, manufactured by Research Diet Inc, USA). In addition, the animals inducing obesity for 8 weeks with a high-fat diet were grouped on the basis of body weight. The injection was injected subcutaneously once a week for 4 weeks.

Injection composition group feed Dose (ml) Population Comparative Example 1 Normal control General feed 500 8 Comparative Example 1 Obesity Inducing Control High fat feed 500 8 Comparative Example 2 Experiment group 1 High fat feed 500 8 Comparative Example 3 Experiment group 2 High fat feed 500 8 Comparative Example 4 Experiment group 3 High fat feed 500 8 Comparative Example 5 Experimental group 4 High fat feed 500 8 Comparative Example 6 Experiment group 5 High fat feed 500 8 Example Experimental group 6 High fat feed 500 8

After 4 weeks of injection once a week, 2 weeks after the last injection, the animals were sacrificed by inhalation anesthesia with isoflurane, and then the left and right inguinal fats were excised to weigh the fat extracted with a microbalance. Measured, the fat weight was divided by the weight of the animal to calculate the relative weight of adipose tissue. All test results obtained in the test are expressed as mean ± standard error, and use SPSS (version 20, IBM SPSS Statistics, USA). Was tested. In addition, Levene's Test was conducted to compare the homogeneity of variance for all data.If significance is observed by performing a one-way analysis of variance (ANOVA), Dunnett's T-test was performed to find out the test groups with significant differences. The number of individuals in each group was 8, and statistical significance was judged and marked with an asterisk (* or **). (Significance level *: 5% on both sides, **: 1%)

As a result of measuring the extracted inguinal fat, the relative weight of the inguinal fat of the obese-induced control group (or obese control group) was significantly higher than that of the normal control group, and it was observed that the inguinal fat caused by obesity was significantly formed.

As shown in Figure 3, as a result of subcutaneous injection of an injection according to an embodiment of the present invention and the injections of Comparative Examples 1 to 6 once a week for 4 weeks, as shown in FIG. 3, Comparative Example 2, Comparative Example 3, Comparative Example 6 and the injection according to the embodiment of the present invention showed a significant difference from the left inguinal fat.

In addition, as shown in Figure 3, Comparative Example 2, Comparative Example 6 and the injection according to the embodiment of the present invention showed a significantly lower relative weight in contrast to the relative weight of the right inguinal fat of the obese-induced control group.

Particularly, as shown in the following [Table 5], the relative weight of the right inguinal fat of the group to which the injection according to the embodiment of the present invention was administered was 0.0120 ± 0.0019, and the relative weight of the right inguinal fat of the obese-induced control group was 0.0167 ± 0.0026. Compared to 28.1%, it showed the lowest relative weight.

Injection
Furtherance group Left inguinal fat relative weight
(Left groin weight / weight) Relative weight of right inguinal fat
(Right inflation area weight / weight) Obesity-induced control
Contrast fat reduction rate Comparative Example 1 Normal control 0.0057 ± 0.0008 0.0055 ± 0.0010 ** - Comparative Example 1 Obesity Inducing Control 0.0169 ± 0.0030 0.0167 ± 0.0026 - Comparative Example 2 Experiment group 1 0.0168 ± 0.0031 0.0128 ± 0.0020 23.3% Comparative Example 3 Experiment group 2 0.0170 ± 0.0026 0.0139 ± 0.0028 16.7% Comparative Example 4 Experiment group 3 0.0167 ± 0.0044 0.0157 ± 0.0035 5.9% Comparative Example 5 Experimental group 4 0.0165 ± 0.0025 0.0162 ± 0.0025 2.9% Comparative Example 6 Experiment group 5 0.0168 ± 0.0038 0.0130 ± 0.0038 * 22.1% Example Experimental group 6 0.0172 ± 0.0023 0.0120 ± 0.0019 ** 28.1%

Thus, compared to the case of using a high dose of deoxycholic acid or hyaluronidase alone in physiological saline or deoxycholic acid and hyaluronidase in physiological saline, a hypotonic solution according to an embodiment of the present invention When deoxycholic acid and hyaluronidase are used, it can be confirmed that the local fat decomposition effect is better. In the embodiment of the present invention, the fat decomposition effect of the hypotonic fat decomposition composition is maximized, and motor neurons are permanently used. In order to reduce side effects due to damage, it is described to directly inject the hypotonic lipolysis composition into the user's double chin area, but is not limited thereto, including the face (for example, cheeks, cheeks, orbital fat, etc.), body parts (For example, including the abdomen, back, flanks, upper arm, thigh, calf, etc.), and the like through the stability test according to the composition ratio of deoxycholic acid and hyaluronidase contained in the hypotonic lipolysis composition, The hypotonic fat-decomposing composition may also be injected into the body or the like.

In the embodiment of the present invention, as described above, in a hypotonic solution composed of distilled water and sodium chloride, deoxycholic acid, hyaluronidase, etc. are prepared to produce a hypotonic lipolysis composition, and a high concentration (for example, the total weight of the composition). Reduces the occurrence of consolidation at the injection site due to the use of deoxycholic acid alone (10 wt% ~ 95 wt%), and cells containing fat components other than fat cells compared to the use of deoxycholic acid alone (e.g. For example, by reducing the effects on nerve cells, muscle cells, bone cells, etc.), it reduces the occurrence of side effects such as nerve paralysis, muscle atrophy, and bone atrophy. Edema, swelling, erythema, pain, etc. It reduces the adverse effects of, and increases the efficiency of fat cell destruction by using hyaluronidase in combination with a hypotonic solution, and can be used as a drug for reducing fat accumulated locally by subcutaneous administration.

In addition, the embodiment of the present invention, as described above, in a hypotonic solution composed of distilled water and sodium chloride, deoxycholic acid, hyaluronidase, buffer, additives, etc. to prepare a hypotonic lipolysis composition, hypotonic fat Deoxycholic acid is effectively delivered to adipocytes in the tissue injected with the decomposition composition, and thus effective fat with deoxycholic acid at a low concentration (for example, 0.01 wt% to 9.9 wt% of the total weight of the hypotonic decomposition composition). The effect of decomposition can be obtained, and edema, erythema, pain, and skin stiffness caused by injection of high concentration of deoxycholic acid can be reduced.

The above-described contents may be modified and modified without departing from the essential characteristics of the present invention by those skilled in the art to which the present invention pertains. Therefore, the embodiments disclosed in the present invention are not intended to limit the technical spirit of the present invention, but to explain, and the scope of the technical spirit of the present invention is not limited by these embodiments. The scope of protection of the present invention should be interpreted by the claims below, and all technical spirits within the equivalent range should be interpreted as being included in the scope of the present invention.

The present invention, by preparing a hypotonic lipolysis composition containing deoxycholic acid, hyaluronidase, etc. in a hypotonic solution composed of distilled water and sodium chloride, the occurrence of consolidation at the injection site due to the use of deoxycholic acid alone Reduces the effect on cells containing fat components other than fat cells (e.g., nerve cells, muscle cells, bone cells, etc.) compared to using deoxycholic acid alone, thereby reducing nerve paralysis, muscle atrophy, bone atrophy, etc. Reduces side effects of edema, reduces adverse effects such as edema, swelling, erythema, pain, and destroys fat cells by using hyaluronidase in combination with a hypotonic solution. It increases the efficiency and can be used as a medicament for reducing fat accumulated in a local area by subcutaneous administration, and can be widely used in the field of skin beauty, medical industry, and the like.

Claims (9)

A pharmaceutical composition for lipolysis injection containing hypotonic solution, sodium deoxycholate and hyaluronidase, which is an aqueous solution of 0.01% to 0.89% by weight sodium chloride. delete According to claim 1, wherein the deoxycholic acid is a pharmaceutical composition for lipolysis injection containing from 0.01% to 9.9% by weight based on the total weight of the lipolysis composition. According to claim 1, wherein the hyaluronidase is 50 I.U / ml to 3,000 I.U / ml is a pharmaceutical composition for lipolysis injection. According to claim 1,
The hypotonic solution is a 0.01% to 0.89% by weight aqueous sodium chloride solution,
The deoxycholic acid is included in an amount of 0.01% to 9.9% by weight based on the total weight of the lipolysis composition,
The hyaluronidase is a pharmaceutical composition for lipolysis injection to which 50 IU / ml to 3,000 IU / ml is added. The pharmaceutical composition for lipolysis injection according to claim 1, wherein the hypotonic solution has a lower concentration than physiological saline. The pharmaceutical composition for lipolysis injection according to claim 1, further comprising a buffer. The pharmaceutical composition for lipolysis injection according to claim 1, further comprising at least one additive selected from diluents, adjuvants, excipients, and vehicles. The pharmaceutical composition for lipolysis injection according to claim 1, further comprising lidocaine hydrochloride or procaine hydrochloride as the local anesthetic.

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