KR101883918B1 - Composition for hypotonic lipolysis and manufacturing method thereof - Google Patents

Abstract

The present invention discloses a storage fat decomposition composition and a process for its preparation. That is, the present invention provides a method for producing a sustained fat composition comprising deoxycholic acid, hyaluronidase and the like in a preservative solution composed of distilled water and sodium chloride, thereby improving the infusion site consolidation phenomenon caused by the use of deoxycholic acid alone And reduces the effects on cells containing other fat components other than adipocytes (including neurons, muscle cells, osteocytes, etc.) compared to deoxycholic acid alone, resulting in nerve palsy, muscle atrophy, (Adverse effect) such as edema, swelling, erythema, and pain, and by using hyaluronidase in combination with a preservative solution, fat cells It is possible to increase the efficiency of disruption and to use as an agent for reducing fat accumulated in the local region by subcutaneous administration.

Description

≪ Desc / Clms Page number 1 > Composition for hypotonic lipolysis and manufacturing method &

The present invention relates to a storage lipid decomposing composition and a method for preparing the same, and more particularly to a storage lipid composition comprising distilled water and sodium chloride, sodium deoxycholate, hyaluronidase, And to a process for preparing the same.

In general, complex preparations using phosphatidylcholine (PPC) and deoxycholate (sodium deoxycholate) have been widely used for local obesity for the purpose of lipoplasty.

However, due to the occurrence of fat necrosis by the combination preparation injection using phosphatidylcholine and deoxycholic acid, a lipolytic composition using a deoxycholic acid single agent other than phosphatidylcholine has been developed, but a deoxycholic acid single agent In the case of the fat-degrading composition, side effects such as edema, erythema, pain, skin tightness and the like frequently occur.

Korean Patent No. 10-0911949 [Name: marine mineral composition inhibiting lipolysis and formation]

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

Another object of the present invention is to provide a storage fat decomposing composition for producing a storage fat decomposing composition comprising deoxycholic acid, hyaluronidase, buffer, additives, etc. in a storage solution composed of distilled water and sodium chloride, and a process for producing the same There is.

The storage lipid decomposing composition according to an embodiment of the present invention is characterized in that in the storage lipid decomposition composition, 0.1 g to 8.9 g of sodium chloride is added to 1000 ml of distilled water and the mixture is stirred to lower the concentration of physiological saline, And sodium deoxycholate for selectively destroying adipocytes expanded by the storage solution and hyaluronidase added to transfer the deoxycholic acid to adipocytes. . ≪ / RTI >

As an example related to the present invention, the deoxycholic acid may be contained in an amount of 0.01% by weight to 9.9% by weight based on the total weight of the composition.

As an example related to the present invention, the storage solution is prepared by applying 0.1 g to 8.9 g of sodium chloride to 1000 ml of distilled water and stirring it to have a lower concentration than physiological saline, thereby simultaneously applying physical and biochemical lipolysis It is possible to increase the fat decomposition effect compared to the application of deoxycholic acid alone, while applying less than 10% by weight of deoxycholic acid.

The method for preparing a storage lipid decomposition composition according to an embodiment of the present invention comprises the steps of adding 0.1 g to 8.9 g of sodium chloride to 1000 ml of distilled water and stirring to obtain a concentration lower than that of physiological saline, ≪ / RTI > producing a shelf-stable solution that induces physical adipocyte degradation; Adding oxycolic acid to the prepared preservative solution to selectively destroy the fat cells expanded by the preservative solution and stirring to prepare a mixed solution; And a step of adding the hyaluronidase to the A mixed solution so that the deoxycholic acid is transferred to adipocytes and stirring the mixture to prepare the storage fat decomposition composition.

The present invention relates to a method for producing a sustained-release lipolytic composition comprising deoxycholic acid, hyaluronidase and the like in a preservative solution composed of distilled water and sodium chloride, thereby causing a consolidation phenomenon at the injection site due to the use of deoxycholic acid alone Compared with deoxycholic acid alone, it reduces the effect on cells containing other fat components other than adipocytes (including neurons, muscle cells, osteocytes, etc.), thereby causing nerve palsy, muscle atrophy, (Adema effect) such as edema, swelling, erythema, and pain, and the use of hyaluronidase based on a storage-stable solution to reduce the adverse effects of adipocyte destruction It is effective to increase the efficiency and to use as an agent for fat reduction which is accumulated in the local region by subcutaneous administration.

The present invention also relates to a method for producing a lipid decomposable composition comprising deoxycholic acid, hyaluronidase, a buffer, an additive and the like in a preservative solution composed of distilled water and sodium chloride, , Deoxycholic acid is effectively transferred to adipocytes, resulting in effective lipolytic effect even with a low concentration of deoxycholic acid. In addition, high concentration of deoxycolinic acid injected, edema, erythema, pain, skin tightness There is an effect of reducing the phenomenon of < RTI ID = 0.0 >

FIG. 1 is a flow chart illustrating a method of manufacturing a storage fat-decomposing composition according to a first embodiment of the present invention.
FIG. 2 is a flow chart illustrating a method of manufacturing a storage lipid decomposing composition according to a second embodiment of the present invention.
FIG. 3 is a graph showing the relative weights between the examples according to the present invention and the comparative examples according to the present invention.

It is noted that the technical terms used in the present invention are used only to describe specific embodiments and are not intended to limit the present invention. In addition, the technical terms used in the present invention should be construed in a sense generally understood by a person having ordinary skill in the art to which the present invention belongs, unless otherwise defined in the present invention, Should not be construed to mean, or be interpreted in an excessively reduced sense. In addition, when a technical term used in the present invention is an erroneous technical term that does not accurately express the concept of the present invention, it should be understood that technical terms that can be understood by a person skilled in the art can be properly understood. In addition, the general terms used in the present invention should be interpreted according to a predefined or prior context, and should not be construed as being excessively reduced.

Furthermore, the singular expressions used in the present invention include plural expressions unless the context clearly dictates otherwise. The term "comprising" or "comprising" or the like in the present invention should not be construed as necessarily including the various elements or steps described in the invention, Or may further include additional components or steps.

Furthermore, terms including ordinals such as first, second, etc. used in the present invention can be used to describe elements, but the elements should not be limited by terms. Terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be referred to as a second component, and similarly, the second component may also be referred to as a first component.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings, wherein like reference numerals refer to like or similar elements throughout the several views, and redundant description thereof will be omitted.

In the following description, well-known functions or constructions are not described in detail since they would obscure the invention in unnecessary detail. It is to be noted that the accompanying drawings are only for the purpose of facilitating understanding of the present invention, and should not be construed as limiting the scope of the present invention with reference to the accompanying drawings.

Hereinafter, a method for producing the storage fat-degrading composition according to the present invention will be described in detail with reference to FIGS. 1 to 3. FIG.

FIG. 1 is a flow chart illustrating a method of manufacturing a storage fat-decomposing 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 shelf stable solution.

The sodium chloride is used to prepare a low osmotic solution (or a hypotonic solution) (or the storage solution).

That is, the sodium chloride has an effect of inducing physical fat cell destruction (or degradation) due to osmotic pressure difference during subcutaneous injection of the storage fat decomposition composition.

Wherein the distilled water is present in an amount of 1 wt% to 99 wt% based on the total weight of the storage fat decomposition composition, and the sodium chloride is present in an amount of 0.01 wt% to 0.89 wt% (generally 0.45 wt% %).

Here, the stirring conditions and time are agitated for 5 to 20 minutes (generally 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 conditions (the stirring conditions and times) in all stirring steps (S110).

Then, sodium deoxycholate is added to the prepared storage solution and stirred to prepare (or prepare) the A mixture.

The deoxycholic acid has the effect of selectively destroying adipocytes and subcutaneously injecting the decomposable lipid decomposing composition, thereby reducing fat volume. Such destroyed adipocytes are unable to accumulate fat again and cause a permanent decrease in fat volume.

The deoxycholic acid may be 0.01 wt% to 9.9 wt% (generally 0.075 wt%) based on the total weight of the storage fat decomposition composition (S120).

Thereafter, the hyaluronidase is added to the mixed solution A and stirred to prepare (or prepare / complete) the storage fat decomposition composition.

The hyaluronidase is a huge family of enzymes that degrade hyaluronic acid. The hyaluronic acid is a key component of the extracellular matrix of the cell and is a major member of the interstitial barrier. The hyaluronidase catalyzes the hydrolysis of the hyaluronic acid to lower the viscosity of the hyaluronic acid, thereby increasing tissue permeability and diffusion. Therefore, the hyaluronidase is used as an electrodeposition agent or a dispersing agent together with other reagents, drugs, proteins and the like to enhance dispersibility and transmission.

That is, the hyaluronidase promotes (or catalyzes) the hydrolysis of the hyaluronic acid to increase the drug penetration ability of the subcutaneous connective tissue, so that the deoxycholic acid contained in the storage fat decomposition composition effectively diffuses ), Delivery, and effect.

In addition, the hyaluronidase may be selected from the group consisting of hyaluronidase (EC 4.2.99.1) of bacteria, hyaluronidase (EC 3.2.1.36) derived from leech, other parasites and crustaceans, mammalian-type hyaluronidase (EC 3.2.1.35).

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

That is, the above-mentioned arbitrary nonhuman hyaluronidase such as rats, dogs, cats, rabbits, birds, cows, sheep, pigs, horses, fishes, frogs, fungi, leeches, other parasites, . ≪ / RTI >

For example, hyaluronidase from nonhuman origin can be used in a variety of ways, including cows, wasps, bees, white face bumble bee, longevity wasp, rat, pig, rat (rabbit), rabbit, sheep, orangutan, Philippine monkey, guinea pig, Streptococci, and hyaluronidase derived from clostridium perfringens.

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

The hyaluronidase includes both positive and minor PH20, soluble human PH20, soluble rHuPH20 and the like.

The hyaluronidase having a biological activity of hyaluronidase at room temperature of 50 IU / ml to 3,000 IU / ml (generally 90 IU / ml) may be added to the A mixture.

As described above, the storage lipid decomposing 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 to 0.89 Deoxycholic acid 0.01 to 9.9 Hyaluronidase 50 to 3,000 IU / ml

In addition, the storage lipid decomposing composition may be composed of the composition ratio (% by weight) as shown in Table 1. In addition, the storage fat decomposition composition may contain the hyaluronidase at a concentration of 50 IU / ml to 3,000 IU / ml And 0.01% by weight to 9.9% by weight of the deoxycholic acid with respect to the total weight of the composition. Herein, the storage solution is intended to induce physical fat cell destruction (or degradation) due to osmotic pressure difference during subcutaneous injection of the storage fat decomposition composition, wherein 0.1 to 8.9 g of sodium chloride 4.5 g) and the remaining distilled water.

In addition, the storage lipolytic composition may be formulated as a solution or administered (or constituted / prepared / prepared) as a lyophilized formulation.

In addition, when the storage fat-decomposing composition is a lyophilized formulation, it may be prepared in a liquid state by a diluent (S130).

Thereafter, the prepared (or prepared) storage fat decomposition composition is packaged in a predetermined container (not shown) by use (or unit). Here, the storage lipid decomposing composition containing the pharmaceutical active compound to be packaged must be sterilized.

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

In addition, the packaged sustained lipolysis composition can be directly injected into the subcutaneous fat layer of the user's body, selectively destroying the adipocytes, thereby reducing fat volume, and reducing and correcting the face and body shape. At this time, the storage lipid decomposing composition may be injected into subcutaneous fat layers such as a double-chin area of the user.

That is, when the storage lipid decomposing composition is injected into the human tissue, the cells of the tissues into which the storage lipid decomposing composition is injected (including fat cells, for example) swell due to the osmotic pressure difference, The cells that are swollen make the destruction of the fat cells more effectively by the deoxycholic acid.

As described above, it is possible to directly inject the storage lipid decomposing composition into a double-chin region of a user having a relatively small amount of motor nerve, thereby maximizing the lipolytic effect and reducing side effects due to the permanent damage of the motor nerve.

The lipid membrane is destroyed by the action of the lipid decomposing composition injected into the subcutaneous fat layer, and the lipid is changed to a water-soluble form. Thereafter, the water-soluble fat may be discharged to the outside of the body through urine or sweat (S140).

Thus, in the examples of the present invention, phosphatidylcholine, which is related to the occurrence of side effects, was not included in the storage lipolytic composition.

On the other hand, the storage lipolytic composition contained deoxycholic acid, which proved the effect of lipolysis.

In addition, the storage lipid decomposing composition maximizes the lipid degradation effect of the deoxycholic acid, including the hyaluronidase based on the storage solution, and can reduce the inconvenience of edema, erythema, pain, skin tightness have.

FIG. 2 is a flow chart illustrating a method of manufacturing a storage lipid decomposing 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 shelf stable solution.

The sodium chloride is used for producing a low osmotic solution (or the above-mentioned storage solution).

That is, the sodium chloride has an effect of inducing physical fat cell destruction (or degradation) due to osmotic pressure difference during subcutaneous injection of the storage fat decomposition composition.

Wherein the distilled water is present in an amount of 1 wt% to 99 wt% based on the total weight of the storage fat decomposition composition, and the sodium chloride is present in an amount of 0.01 wt% to 0.89 wt% (generally 0.45 wt% %).

Here, the stirring conditions and time are agitated for 5 to 20 minutes (generally 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. Further, a mixed solution may be prepared under the stirring conditions (the stirring conditions and times) in all the stirring steps (S210).

Thereafter, deoxycholic acid is added to the prepared storage solution and stirred to prepare (or prepare) the A mixture.

The deoxycholic acid has the effect of selectively destroying adipocytes and subcutaneously injecting the decomposable lipid decomposing composition, thereby reducing fat volume. Such destroyed adipocytes are unable to accumulate fat again and cause a permanent decrease in fat volume.

The deoxycholic acid may be 0.01 wt% to 9.9 wt% (generally 0.075 wt%) based on the total weight of the storage fat decomposition composition (S220).

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

The hyaluronidase having a biological activity of hyaluronidase of 50 IU / ml to 3,000 IU / ml (generally 90 IU / ml) may be added to the mixture A at room temperature (S230).

Thereafter, a buffering agent and other additives are added to the B mixed solution and stirred to prepare (or prepare / complete) the storage fat decomposition composition.

The buffer may be used for controlling the pH of the storage fat decomposition composition and may be selected from the group consisting of lactose hydrate, succinate, acetate, phosphate, citrate, Aconitate, malate, carbonate, and the like.

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

The additive is used for maintaining the effective period of the depot lipid decomposing composition and includes a carrier such as a diluent, an adjuvant, an excipient, and a vehicle.

Here, the pharmaceutical carrier may be an oil containing sterile liquid, water and a carrier of vegetable or synthetic origin such as petroleum, animal, peanut oil, soybean oil, mineral oil and sesame oil.

In addition, saline solution, aqueous dextrose, clecerol 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, topical anesthetics, suspending and dispersing agents, emulsifying agents, Chelating agents, other pharmacologically acceptable substances, and the like.

Such aqueous vehicles include sodium chloride injections, Ringer injections, isotonic dextrose injections, sterile injectable solutions, dextrose and lactate ringer injections, and the like.

The non-aqueous vehicles (or non-aqueous parenteral vehicles) include fixed oils of plant origin, cottonseed oil, corn oil, sesame oil, peanut oil and the like.

The antimicrobial agent in a bacteriostatic or bactericidal concentrate may be selected from the group consisting of phenol or cresol, benzyl alcohol, chlorobutanol, methyl and propyl p-hydroxybenzoic esters ), Thimerosal, benzalkonium chloride, benzethonium chloride, and the like.

Such isotonic agents include sodium chloride, dextrose, and the like.

The antioxidant includes sodium bisulfate and the like.

The topical anesthetic includes lidocaine hydrochloride, procaine hydrochloride, and the like.

The suspending agent and the dispersing agent include sodium carboxymethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrollidone, and the like.

The emulsifying agent includes polysorbate 80 (TWEENs 80) and the like.

The metal sequestering or killing agent of the metal ion includes ethylenediaminetetraacetic acid (EDTA) and the like.

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

The additive may also contain a diluent (e.g., lactose, sucrose, dicalcium phosphate, carboxymethylcellulose and the like), a lubricant (e.g., magnesium stearate ), Calcium stearate, talc, etc.), binders (including starches, natural gums, etc.), and the like.

The additive may also contain minor amounts of wetting or emulsifying agents, pH buffering agents (e.g., acetate, sodium citrate, cyclodextrin derivative, sorbitan monooleate, triethanolamine acetate, Triethanolaminolate, and the like), and the like.

The buffering agent may be added in an amount of 0.01 to 50 wt% based on the total weight of the storage lipolytic composition, the additive (or other additives) may be added in an amount of 0.01 to 50 wt% Lt; / RTI >

Thus, the storage lipid decomposing composition may be prepared by stirring the distilled water, the sodium chloride, the deoxycholic acid, the hyaluronidase, the buffer, the additives, and the like.

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

In addition, the storage lipid decomposing composition may be composed of the composition ratio (% by weight) as shown in Table 2. In addition, the storage fat decomposition composition may contain the hyaluronidase at a concentration of 50 IU / ml to 3,000 IU / ml 0.01 to 9.9% by weight of the deoxycholic acid with respect to the total weight of the storage lipid decomposing composition, 0.01 to 50% by weight of a buffer for controlling the acidity of the storage lipid decomposing composition, 0.01% to 50% by weight of an additive for maintaining the effective period of the composition, and the remaining preservative solution. Herein, the storage solution is intended to induce physical fat cell destruction (or degradation) due to osmotic pressure difference during subcutaneous injection of the storage fat decomposition composition, wherein 0.1 to 8.9 g of sodium chloride 4.5 g) and the remaining distilled water.

In addition, the storage lipolytic composition may be formulated as a solution or administered (or constituted / prepared / prepared) as a lyophilized formulation.

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

Thereafter, the prepared (or prepared) storage fat decomposition composition is packaged in a predetermined container (not shown) by use (or unit). Here, the storage lipid decomposing composition containing the pharmaceutical active compound to be packaged must be sterilized.

That is, the prepared (or prepared) storage fat decomposition composition is packaged in ampoules, vials, syringes with needles, and the like.

In addition, the packaged sustained lipolysis composition can be directly injected into the subcutaneous fat layer of the user's body, selectively destroying the adipocytes, thereby reducing fat volume, and reducing and correcting the face and body shape. At this time, the storage lipid decomposing composition may be injected into subcutaneous fat layers such as a double-chin area of the user.

That is, when the storage lipid decomposing composition is injected into the human tissue, the cells of the tissues into which the storage lipid decomposing composition is injected (including fat cells, for example) swell due to the osmotic pressure difference, The cells that are swollen make the destruction of the fat cells more effectively by the deoxycholic acid.

As described above, it is possible to directly inject the storage lipid decomposing composition into a double-chin region of a user having a relatively small amount of motor nerve, thereby maximizing the lipolytic effect and reducing side effects due to the permanent damage of the motor nerve.

The lipid membrane is destroyed by the action of the lipid decomposing composition injected into the subcutaneous fat layer, and the lipid is changed to a water-soluble form. Thereafter, the water-soluble fat may be discharged to the outside of the body by urine or sweat (S250).

<Examples>

The storage lipolytic composition (or injectable composition) according to an embodiment of the present invention used 9000 IU of hyaluronidase, 75 mg of deoxycholic acid, 450 mg of sodium chloride and the remaining distilled water based on 100 ml of the total solution.

&Lt; Comparative Example 1 &

And physiological saline was used alone.

&Lt; Comparative Example 2 &

A high dose of deoxycholic acid (1000 mg) was used in physiological saline.

&Lt; Comparative Example 3 &

75 mg of deoxycholic acid was used for physiological saline.

&Lt; Comparative Example 4 &

Hyaluronidase 9000I.U was used for physiological saline.

&Lt; Comparative Example 5 &

The storage solution was used alone.

&Lt; Comparative Example 6 >

9000 IU of hyaluronidase and 75 mg of deoxycholic acid were used in physiological saline.

The composition of the injectable composition according to the present invention and the injectable composition according to Comparative Example 1 to Comparative Example 6 can be shown in Table 3 below.

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 75 mg
(0.075%) - 1000 mg
(One%) 75 mg
(0.075%) - - 75 mg
(0.075%) Sodium chloride 450 mg
(0.45%) 900 mg
(0.9%) 900 mg
(0.9%) 900 mg
(0.9%) 900 mg
(0.9%) 450 mg
(0.45%) 900 mg
(0.9%) Distilled water Balance Balance Balance Balance Balance Balance Balance Total amount 100ml 100ml 100ml 100ml 100ml 100ml 100ml

Here, all injectable composition was prepared to 100 ml. At this time, hyaluronic acid (1 vial 1500I.U) of Wooridul Pharmaceutical Co. was used as the hyaluronidase. The composition of the injectable composition was measured with a microbalance according to the content of deoxycholic acid (Sigma-Aldrich), and then physiological saline (Korean Chemical Industries) or physiological saline and distilled water In the case of injectable compositions containing hyaluronidase as in the above Examples, Comparative Example 4 and Comparative Example 6, each of the prepared solutions Was placed in a vial of Hialeaf to dissolve the lyophilized hyaluronidase, and then recovered again to prepare an injectable composition.

<Test Example>

Male Sprague Dawley rats, 5-week-old, were purchased from Orient Bio. The environmental conditions of Rat were set at 22 ℃ ~ 24 ℃ and relative humidity was 30% ~ 50%. Two rats were kept in each box. From 7:00 am to 7:00 pm, it was illuminated from 150 lux to 300 lux, turned on for 12 hours a day and turned off for 12 hours. Diets were fed free using high fat diets (45% fat, 2018, Research Diet Inc, USA). In addition, the animals that induced obesity for 8 weeks in a high fat diet were grouped on the basis of body weight, and injected in the right subcutaneous inguinal region of the animals after injection of the present invention (or Example) and Comparative Examples 1 to 6 The injection was subcutaneously injected once a week for 4 weeks.

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

After administering the injection once a week for 4 weeks, the animal was inhaled with isoflurane 2 weeks after the injection, and the left and right inguinal fat were all extracted and the weight of the fat extracted with the microbalance was measured And the relative weight of the adipose tissue was calculated by dividing the fat weight by the weight of the animal. All the test results obtained by the tests were expressed as mean ± standard error, and were used with SPSS (version 20, IBM SPSS Statistics, USA) Respectively. In addition, Levene's test was performed to compare the variance homogeneity for all data. When the variance was homogeneous, one-way ANOVA was performed. When the significance was observed, Dunnett's T-test was performed to determine the test group with significant differences between the two groups. The number of individuals per group was 8, and statistical significance was determined and marked with an asterisk (* or **). (Significance level *: 5% for both sides, **: 1%)

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

As shown in Fig. 3, the obesity animals were subcutaneously injected once per week for 4 weeks with the injections according to the example of the present invention and the injections of the comparative examples 1 to 6. As a result, 6 and the injection according to the example of the present invention showed a marked difference from the left inguinal fat.

Also, as shown in FIG. 3, the injections of Comparative Example 2, Comparative Example 6, and Examples of the present invention showed significantly lower relative weights than those of the right inguinal fat of the obesity-induced control group.

Particularly, as shown in the following Table 5, the relative weight of the right inguinal fat of the group administered with the injection according to the example of the present invention was 0.0120 ± 0.0019, and the relative weight of the right inguinal fat of the obesity-induced control group was 0.0167 ± 0.0026 And 28.1%, respectively.

Injection
Furtherance group Left inguinal fat relative weight
(Left inguinal fat weight / weight) Right inguinal fat relative weight
(Right inguinal fat weight / weight) Obesity-induced control group
Relative fat reduction rate Comparative Example 1 Normal control group 0.0057 ± 0.0008 0.0055 ± 0.0010 ** - Comparative Example 1 Obesity-induced control group 0.0169 + 0.0030 0.0167 ± 0.0026 - Comparative Example 2 Experiment 1 0.0168 ± 0.0031 0.0128 ± 0.0020 23.3% Comparative Example 3 Experiment 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 Experiment 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 Experiment group 6 0.0172 0.0023 0.0120 ± 0.0019 ** 28.1%

As described above, as compared with the case where deoxycholic acid or hyaluronidase is used alone in a physiological saline solution in a high dose or when deoxycholic acid and hyaluronidase are used in physiological saline, the storage solution according to the embodiment of the present invention In the examples of the present invention, the lipolysis effect of the above-mentioned storage fat decomposition composition was maximized, and the fatigue life of the exercise nerve However, the present invention is not limited to this, and it may be applied to a body part (for example, a clown, a ball, oropharynx, etc.), a body part (For example, abdomen, back, side, upper arm, thigh, calf, etc.) Oxy choline hyaluronic acid to be contained in the water through a stability test such as according to the composition ratio of the kinase is the facepiece, the body part or the like may also be injected into the Storage fat composition.

As described above, the embodiment of the present invention is a method for preparing a storage fat decomposition composition containing deoxycholic acid, hyaluronidase and the like in a storage solution composed of distilled water and sodium chloride, (10% by weight to 95% by weight) of deoxycholinic acid alone is used to reduce the incidence site consolidation phenomenon, and the cells containing other fat components other than adipocyte (Eg, nerve cells, muscle cells, bone cells, etc.), thereby reducing the occurrence of side effects such as nerve palsy, muscle atrophy, and bony atrophy, and reducing edema, swelling, erythema, The adverse effect of the fat is reduced, and the use of the hyaluronidase based on the storage solution increases the efficiency of the fat cell destruction, and by subcutaneous administration, It can be used as a medicine for medicine.

In addition, as described above, the embodiment of the present invention is a method for preparing a storage fat decomposing composition comprising deoxycholic acid, hyaluronidase, buffer, additives and the like in a storage solution composed of distilled water and sodium chloride, Deoxycholinic acid is effectively delivered to adipocytes in the tissue to which the degradative composition is injected, resulting in an effective fat (e. G., From 0.01% to 9.9% by weight of the total weight of the storage lipolytic composition) And it is possible to reduce the phenomenon of injection edema, erythema, pain and skin hardening due to high concentration of deoxycholic acid injection.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or essential characteristics thereof. Therefore, the embodiments disclosed in the present invention are intended to illustrate rather than limit the scope of the present invention, and the scope of the technical idea of the present invention is not limited by these embodiments. The scope of protection of the present invention should be construed according to the following claims, and all technical ideas within the scope of equivalents should be construed as falling within the scope of the present invention.

The present invention relates to a method for producing a sustained-release lipolytic composition comprising deoxycholic acid, hyaluronidase and the like in a preservative solution composed of distilled water and sodium chloride, thereby causing a consolidation phenomenon at the injection site due to the use of deoxycholic acid alone Compared with deoxycholic acid alone, it reduces the effect on cells containing other fat components other than adipocytes (including neurons, muscle cells, osteocytes, etc.), thereby causing nerve palsy, muscle atrophy, (Adema effect) such as edema, swelling, erythema, and pain, and the use of hyaluronidase based on a storage-stable solution to reduce the adverse effects of adipocyte destruction And it can be used as a drug for reducing fat in the local area by subcutaneous administration. It can be widely used in the field of skin care, medical industry, etc. Can be used.

Claims (4)

In a storage lipolytic composition,
0.1 g to 8.9 g of sodium chloride was added to 1000 ml of distilled water and stirred, and the resulting solution was stored at a concentration lower than that of physiological saline,
Sodium deoxycholate to selectively destroy the fat cells expanded by the storage solution,
Wherein the deoxycholic acid is added to deliver to the adipocyte. &Lt; RTI ID = 0.0 &gt; 20. &lt; / RTI &gt; The method according to claim 1,
The deoxycholic acid,
Wherein the composition comprises 0.01% by weight to 9.9% by weight of the total amount of the storage fat decomposition composition. The method according to claim 1,
The above-
0.1 to 8.9 g of sodium chloride is added to 1000 ml of distilled water and stirred to give a concentration lower than that of physiological saline so that deoxycholic acid is applied at less than 10% by weight through simultaneous application of physical and biochemical lipolysis Wherein the fat decomposition effect is enhanced as compared with the case of using deoxycholic acid alone. In a method for preparing a storage lipolytic composition,
0.1 g to 8.9 g of sodium chloride is added to 1000 ml of distilled water and stirred to prepare a storage solution having a concentration lower than that of physiological saline and inducing physical fat cell degradation by osmotic pressure difference;
Adding oxycolic acid to the prepared preservative solution to selectively destroy the fat cells expanded by the preservative solution and stirring to prepare a mixed solution; And
And adding the hyaluronidase to the prepared mixed solution to transfer the deoxycholic acid to adipocytes, followed by stirring to prepare the storage fat-decomposing composition.

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