INJECTABLE COMPOSITION FOR INDUCING LIPOLYSIS AND METHOD USING THE SAME

Abstract

Provided is an injectable composition for inducing lipolysis with less pain when injected. Since the composition has an osmolarity within an appropriate range and has a neutral pH, pain at the time of injection of the composition is very small. Also, as a large amount of drug is injected during one treatment, the lipolytic effect is excellent, and local fat removal is possible in a short period of time. The composition may be used safely without side effects. Therefore, the composition may be used in a method for inducing lipolysis.

Claims

1. An injectable composition for inducing lipolysis, the composition comprising: based on a total weight of the composition, about 1.5 to 2.0 weight % of an amino acid formulation; about 2.0 to 4.0 weight % of choline alfoscerate; about 0.5 to 1.5 weight % of aminophylline; about 1.0 to 2.5 weight % of lipoic acid; about 0.3 to 2.0 weight % of L-carnitine; about 0.26 to 0.43 weight % of a multivitamin formulation; about 0.5 to 1.0 weight % of hycomin; about 0.4 to 1.5 weight % of sodium bicarbonate; about 1300 IU to 1700 IU of hyaluronidase; about 1.0 to 2.5 weight % of lidocaine; about 0.2 to 0.6 weight % of peniramin; and about 0.06 to 0.10 weight % of epinephrine; with the remainder being half saline, wherein the amino acid formulation comprises aminoacetic acid, L-alanine, L-arginine, L-histidine, L-isoleucine, L-leucine, L-lysine acetate, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-valine, N-acetyl-L-cysteine, and L-tryptophan, the multivitamin formulation comprises nicotinic acid amide, dexpanthenol, riboflavin sodium phosphate, cyanocobalamin, thiamine hydrochloride, and pyridoxine hydrochloride, and an osmolarity of the composition is in a range of about 180 to 230 mOsm/L.

2. The composition of claim 1, wherein an amount of the half saline in the composition is in a range of about 400 to 500 ml.

3. The composition of claim 1, wherein a pH of the composition is in a range of about 7.0 to 8.0.

4. A method of inducing lipolysis, the method comprising administering an effective amount of the composition of claim 1 to a subject in need thereof.

5. The method of claim 4, wherein the total amount of the composition administered is in a range of about 450 to 600 ml.

6. The method of claim 5, wherein the total amount of the composition is administered once in a single dose or in 2 to 6 divided doses.

7. The method of claim 4, wherein the administering of the composition is an injection using an infusion pump.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0067] The above and other aspects, features, and advantages of certain embodiments of the disclosure will be more apparent from the following description taken in conjunction with the accompanying drawings, in which:

[0068] FIG. 1 shows the results of measuring circumferences of neck, chest, abdomen, and hips after injecting a composition for lipolysis injection prepared in Example 1 each week;

[0069] FIGS. 2A to 2D show the results of measuring changes in body weight (2A), changes in body fat (2B), and changes in size of legs (2C) and abdomen (2D) after injecting the composition for lipolysis injection prepared in Example 1 each week;

[0070] FIGS. 3A to 3C show the results of measuring changes in body weight (3A), changes in body fat (3B), and changes in size of legs (3C) after injecting the composition for lipolysis injection prepared in Example 1 each week;

[0071] FIGS. 4A to 4D show the results of measuring changes in body weight (4A), changes in body fat (4B), changes in size of abdomen (4C), and changes in visceral fat mass (4D) after injecting the composition for lipolysis injection prepared in Example 1 each week;

[0072] FIG. 5 shows the results of measuring changes in body weight after injecting the composition for lipolysis injection prepared in Example 1 each week;

[0073] FIG. 6 shows the results of measuring changes in body fat after injecting the composition for lipolysis injection prepared in Example 1 each week; and

[0074] FIGS. 7A to 7B show images of before (7A) and after (7B) 4 injections of the composition for lipolysis injection prepared in Example 1 over 4 weeks.

DETAILED DESCRIPTION

[0075] Reference will now be made in detail to embodiments, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to like elements throughout. In this regard, the present embodiments may have different forms and should not be construed as being limited to the descriptions set forth herein. Accordingly, the embodiments are merely described below, by referring to the figures, to explain aspects of the present description. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items. Expressions such as “at least one of,” when preceding a list of elements, modify the entire list of elements and do not modify the individual elements of the list.

[0076] Hereinafter, the present invention will be described in further detail with reference to the following Examples. However, the following Examples are for illustrative purposes and are not intended to limit the scope of the present invention.

Example 1. Preparation of Composition for Lipolysis Injection

[0077] A composition for lipolysis injection was prepared with ingredients and amounts shown in Table 1. In particular, the remaining ingredients were mixed in 0.45% of physiological saline. The amounts were calculated based on the total weight of the composition.

TABLE-US-00001 TABLE 1 Category Ingredient Amount Content Solvent 0.45 % of Physiological saline (Half saline; 500 ml including 0.45 % of NaCl) Amino acid 250 ml of Saeronamin Injection (available 1 g (10 cc) 1.75 formulation from Dai Han Pharm) weight % Adipocyte Choline alfoscerate 16 g (16 cc) 2.8 decomposer weight % Adipocyte Aminophylline 125 mg (5 cc) 0.88 decomposer weight % Increase in Lipoic acid or Thioctic acid 100 mg (10 cc) 1.75 energy weight % consumption, antioxidant Increase in L-carnitine 1 g (5 cc) 0.88 protein weight % synthesis in muscle, increase in use of glucose Multivitamin Beecomhexa Injection (available from 20 mg (2 cc) 0.35 formulation Yuhan Corporation) weight % Anti- Hycomin Injection (available from Huons) 20 mg (4 cc) 0.7 inflammatory weight % analgesic pH adjusting Sodium Bicarbonate 105 mg (5 cc) 0.88 agent weight % Lymphedema Hyaluronidase 1500 IU (1 cc) 0.18 treatment weight % agent Local Lidocaine 40 mg (10 cc) 1.75 anesthetic weight % Antihistamine Peniramin Injection (available from Yuhan 4 mg (2 cc) 0.35 Corporation) weight % Vasoconstrictor Epinephrine Injection 0.5 mg (0.5 cc) 0.08 weight %

[0078] In Table 1, ingredients of Saeronamin Injection are 0.582 g/100 ml of aminoacetic acid, 0.464 g/100 ml of L-alanine, 1.072 g/100 ml of L-arginine, 0.28 g/100 ml L-histidine, 1.04 g/100 ml of L-isoleucine, 1.309 g/100 ml of L-leucine, 0.971 g/100 ml of L-lysine acetate, 0.11 g/100 ml of L-methionine, 0.088 g/100 ml of L-phenylalanine, 0.573 g/100 ml of L-proline, 0.224 g/100 ml of L-serine, 0.44 g/100 ml of L-threonine, 1.008 g/100 ml of L-valine, 0.07 g/100 ml of N-acetyl-L-cystein, and 0.07 g/100 ml of L-tryptophan.

[0079] Ingredients of Beecomhexa Injection are 40 mg/2 mL of nicotinic acid amide, 5.17 mg/2 mL of dexpanthenol, 5.47 mg/2 mL of riboflavin phosphate sodium, 10 μg/2 mL of cyanocobalamin, 10 mg/2 mL of thiamine hydrochloride, and 5 mg/2 mL of pyridoxine hydrochloride.

[0080] An ingredient of Hycomin Injection is 5 mg/2 ml of hydroxocobalamin.

[0081] An ingredient of Peniramin Injection is 4 mg/2 ml of chlorpheniramine maleate.

Experimental Example 1: Calculation of Osmolarity

[0082] An osmolarity of the composition for lipolysis injection prepared in Example 1 was calculated. Calculation of osmolarity usually matters whether the material is ionizable in an infusion solution. In Table 1, the half saline, vitamin, sodium bicarbonate, and amino acid correspond to ingredients capable of changing the osmolarity of the composition. The rest of the ingredients may slightly raise or lower the osmolarity, but the effect is mostly considered insignificant, and medically these drugs are not included in calculation of an osmolarity of an infusion solution.

[0083] 1) Half saline is a solution including 77 mOsm of NaCl in pure water.

[0084] 2) A 5 mEq (milliequivalent) osmolarity of sodium bicarbonate (8.4%) is 10 mOsm.

[0085] 3) An osmolarity of 6 cc of multivitamin formulation is 24.7 mOsm.

[0086] 4) An osmolarity of 10 cc of amino acid formulation is 10 mOsm.

[0087] 5) The total amount of the composition of Example 1 is 570.5 mL.

[0088] Therefore, an osmolarity (mOsm/L) of the composition of Example 1 is (77+10+24.7+10) mOsm/570.5 mL=213 mOsm/L.

[0089] Experimental Example 2: Confirmation of lipolytic effect

[0090] (1) Case 1

[0091] The composition for lipolysis injection of Example 1 was injected into the thigh of a woman in early 40s once a week for a total of 6 injections in 6 weeks. For each injection, the total amount of the composition for lipolysis injection of Example 1 was all injected using an infusion pump. After 6 weeks, the body weight of the woman decreased from 54.7 kg (25.5% of body fat percentage) to 51.7 kg (20.2% of body fat percentage), and the circumference size of the upper thigh decreased from 54 cm to 49 cm. Thereafter, the shape of the convex area of the thigh did not return even when the weight increased again.

[0092] (2) Case 2

[0093] The composition for lipolysis injection of Example 1 was injected into the buttocks of a woman in early 30s once a week for a total of 5 injections in 5 weeks. For each injection, the total amount of the composition for lipolysis injection of Example 1 was all injected using an infusion pump. Body composition was analyzed using InBody. InBody is an excellent device that shows where the measurer's statuses such as muscle mass, fat mass, and the size of a particular part of the body are at compared to the average based on the body data such as heights and weights of Koreans.

[0094] FIG. 1 shows the results of measuring circumferences of neck, chest, abdomen, and hip after injecting the composition for lipolysis injection of Example 1 each week.

[0095] As shown in FIG. 1, the patient did not lose weight for 5 weeks due to the lack of diet control, but the size of the hip circumference after the injection of the composition for lipolysis injection was reduced by 6 cm. No particular side effects were found, and satisfaction of the patient was high as the injections were effective in relieving fatigue.

[0096] (3) Case 3

[0097] The patient was a 33-year-old female with a central obesity type with long and thin legs and arms and a lot of fat in the abdomen. The patient wanted to reduce the size of the abdomen without changing the size of the legs. The composition for lipolysis injection of Example 1 was injected into the abdomen of the patient once a week for a total of 5 injections in 5 weeks. For each injection, the total amount of the composition for lipolysis injection of Example 1 was all injected using an infusion pump.

[0098] FIGS. 2A to 2D show the results of measuring changes in body weight (2A), changes in body fat (2B), and changes in size of legs (2C) and abdomen (2D) after injecting the composition for lipolysis injection prepared in Example 1 each week.

[0099] As shown in FIGS. 2A to 2D, the graphs related to the size of legs and abdomen have a baseline, which refers to the average size of legs and abdomen of Koreans having the same height and weight. That is, the patient had a body type of a Westerner having a thicker abdominal circumference and slender leg circumferences as compared with other Koreans of the same height and weight. However, the sizes of legs and other sites where the fat was not desired to be removed without injection of the composition for lipolysis injection for 5 weeks were almost unchanged, and only the size of abdomen, the desired site, significantly decreased. The weight loss for 5 weeks was 4.4 kg, of which fat mass decreased by 4 kg, and there was almost no muscle loss.

[0100] Therefore, it was confirmed that the composition for lipolysis injection of Example 1 has an excellent effect as a local lipolysis injection and overall lipolysis effects.

[0101] (4) Case 4

[0102] The patient was a 20-year-old female who did not lose her leg size while losing more than 13 kg of weight through diet management and thus wanted to reduce the size of her legs. The composition of lipolysis injection of Example 1 was injected into the thighs of the patient once a week for a total of 6 injections in 6 weeks. For each injection, the total amount of the composition for lipolysis injection of Example 1 was all injected using an infusion pump.

[0103] FIGS. 3A to 3C show the results of measuring changes in body weight (3A), changes in body fat (3B), and changes in size of legs (3C) after injecting the composition for lipolysis injection prepared in Example 1 each week.

[0104] As shown in FIGS. 3A to 3C, the size of thighs was reduced by 6 cm and the abdominal size by 1.5 cm for 6 weeks as a result of injecting the composition for lipolysis injection.

[0105] (5) Case 5

[0106] The patient was a 42-year-old male who wanted to lose abdominal visceral fat and abdominal fat after being diagnosed with hypertension and diabetes. The composition for lipolysis injection of Example 1 was injected into the abdomen of the patient once a week for a total of 6 injections in 6 weeks. For each injection, the total amount of the composition for lipolysis injection of Example 1 was all injected using an infusion pump.

[0107] FIGS. 4A to 4D show the results of measuring changes in body weight (4A), changes in body fat (4B), changes in size of abdomen (4C), and changes in visceral fat mass (4D) after injecting the composition for lipolysis injection prepared in Example 1 each week.

[0108] As shown in FIGS. 4A to 4D, the abdominal size was reduced by 13.6 cm in 6 weeks, and the body weight and body fat mass were also decreased significantly. Meanwhile, diabetes, hyperlipidemia, and hypertension of the patient have been normalized. The body weight was almost maintained, and the abdominal size was also maintained within 1 cm almost without change even after 6 months.

[0109] (6) Case 6

[0110] The patient was a 49-year-old female who had been taking obesity drugs for 3 years, and she had the diabetes, hyperlipidemia, and hypertension which had been worsened for 5 years. Thus, the patient wanted health care and abdominal fat reduction. The composition for lipolysis injection of Example 1 was injected into the abdomen of the patient once a week for a total of 17 injections in 17 weeks. For each injection, the total amount of the composition for lipolysis injection of Example 1 was all injected using an infusion pump.

[0111] FIG. 5 shows the results of measuring changes in body weight after injecting the composition for lipolysis injection of Example 1 each week.

[0112] FIG. 6 shows the results of measuring changes in body fat after injecting the composition for lipolysis injection of Example 1 each week.

[0113] As shown in FIGS. 5 and 6, the body weight and body fat steadily decreased without a single stagnation period in 17 weeks. Also, 3 months after the start of the procedure, the levels of diabetes and hyperlipidemia were almost normalized, and thus the drug for hyperlipidemia was discontinued. After 2 months from then on, hypertension, hyperlipidemia, and diabetes of the patient were completely within the normal range, and thus the patient stopped all the drugs and started exercise and maintenance therapy.

[0114] (7) Case 7

[0115] The patient was a woman in late 50s who wanted to lose abdominal fat. The composition for lipolysis injection of Example 1 was injected into the abdomen of the patient once a week for a total of 4 injections in 4 weeks. For each injection, the total amount of the composition for lipolysis injection of Example 1 was all injected using an infusion pump.

[0116] FIGS. 7A to 7B show images of before (7A) and after (7B) 4 injections of the composition for lipolysis injection prepared in Example 1 over 4 weeks.

[0117] As shown in FIGS. 7A to 7B, the waist line became slim due to the reduced abdominal fat, and the weight was also reduced by about 5 kg.

[0118] In addition to the above cases, dozens of patients of various ages and sexes, from 18-year-old female students to 75-year-old men, were treated with the composition for lipolysis injection of Example 1, and there were no side effects.

[0119] Therefore, it was confirmed that the composition for lipolysis injection according to an embodiment safely exhibits a local lipolysis effect of only a desired area without side effects.

[0120] According to an embodiment, an injectable composition for inducing lipolysis has an osmolarity within an appropriate range and a neutral pH, and thus injection of the composition is less painful. Also, since an amount of the drug being injected in a single procedure is a lot, the lipolytic effect of the composition is excellent, which makes local fat loss possible in a short period of time. The composition may be used safely without side effects. Therefore, the composition may be used in a method of inducing lipolysis.

[0121] It should be understood that embodiments described herein should be considered in a descriptive sense only and not for purposes of limitation. Descriptions of features or aspects within each embodiment should typically be considered as available for other similar features or aspects in other embodiments. While one or more embodiments have been described with reference to the figures, it will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the disclosure as defined by the following claims.