KR102470029B1 - Pharmaceutical compositions for preventing or treating cholesterol gallstone comprising ursodeoxycholic acid(UDCA) and omega-3 and process for producing the same - Google Patents

Abstract

The present invention relates to ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof, which induces a process in which cholesterol gallstones are not formed or dissolved; omega-3 fatty acids; And it relates to a gallstone dissolving agent containing an excipient, a pharmaceutical composition containing the same, and a health functional food composition containing the same.
The pharmaceutical composition prepared with the optimal content of omega-3 fatty acids and UDCA allows cholesterol to remain dissolved without forming crystals, leading to a process in which cholesterol gallstones are not formed or dissolved, preventing or dissolving cholesterol gallstones. treatment effect increases.

Description

Pharmaceutical composition for preventing or treating cholesterol gallstones containing omega-3 fatty acids and ursodeoxycholic acid (UDCA) and method for preparing the same producing the same}

The present invention relates to ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof, which induces a process in which cholesterol gallstones are not formed or dissolved; omega-3 fatty acids; And it relates to a gallstone dissolving agent containing an excipient, a pharmaceutical composition containing the same, and a health functional food composition containing the same.

In the West, 10 to 15% of the population has gallbladder stones, and in the United States, among benign digestive diseases, gallbladder gallstones are one of the top medical expenditures for medical expenses. In particular, the prevalence of cholesterol gallbladder gallstones is very high, with 20 million people receiving treatment for this disease each year. As Korea's economic level improves and dietary life becomes westernized, the number of patients with cholesterol or mixed gallstones is rapidly increasing. According to data released by the National Health Insurance Corporation as of February 2014, between 2007 and 2012, patients with cholelithiasis are increasing at an average annual rate of 7.3%.

Surgical treatment such as cholecystectomy through laparotomy is the basic treatment, and medical treatment has a low success rate and is limited, but there are methods to dissolve gallstones, crush gallstones, and a combination of the two. Methods for dissolving gallstones include a method of dissolving gallstones by injecting oral gallstone dissolvers and drugs into the gallbladder, and methods for crushing gallstones include extracorporeal shock wave lithotripsy. There is a way to remove gallstones from the gallbladder.

With the introduction of Chenodeoxycholid acid (CDCA) in the 1970s and Ursodeoxycholic acid (UDCA) in the 1980s, medical treatment using an oral solubilizing agent was widely used as an alternative to high-risk open surgery. With the introduction of laparoscopic cholecystectomy in the late 1980s, laparoscopic cholecystectomy was suggested as the main treatment rather than medical treatment using oral dissolving agents because of the low success rate of dissolving gallstones (30-40%) and high recurrence rate of gallstones. Skepticism about oral lysis therapy has increased. However, although laparoscopic cholecystectomy is safer than open method, problems related to the operation are still raised. The prevalence of laparoscopic surgery is 1.6-12%, and complications reach 2%. Although the surgical results vary greatly depending on the experience and skill of the operator, even skilled practitioners experience surgical complications of 0.1-0.5%. In addition, although cholecystectomy cures 100% of gallstones in the gallbladder, there is also a report that up to 20% of patients after surgery continue to complain of pain, which was an indication for surgery. For this reason, there is an urgent need to develop preventive and therapeutic methods for this.

Accordingly, the present inventors tested the effects of omega-3, ursodeoxycholic acid (UDCA), or omega-3 and ursodeoxycholic acid (UDCA) in terms of prevention of cholelithiasis. As a result, as a result of administering the omega-3, ursodeoxycholic acid (UDCA), and omega-3 and ursodeoxycholic acid (UDCA) together with the feed for gallstone formation, the omega-3 administered group was administered with ursodeoxycholic acid showed lower gallstone formation than the group. In addition, when omega-3 and ursodeoxycholic acid were administered together, gallstone formation was inhibited compared to the group administered with omega-3 or ursodeoxycholic acid (UDCA) alone, but there was no synergistic effect and statistically significant difference. Furthermore, as a result of examining the degree of hypertrophy of the gallbladder wall and the expression of genes related thereto, omega-3 suppressed the hypertrophy of the gallbladder wall and the expression of genes related thereto, regardless of the presence or absence of ursodeoxycholic acid. Therefore, the present inventors found that omega-3 increases the level of bile phospholipids and inhibits bile mucin formation to attenuate gallstone formation in mice (Journal of Gastroenterology and hepatology; 27 (2012) 1745-1751). However, this is an experiment in which gallstone formation food and omega-3, ursodeoxycholic acid (UDCA), or omega-3 and ursodeoxycholic acid (UDCA) are administered together, and the omega-3, ursodeoxycholic acid (UDCA), or Since the prophylactic effect of omega-3 and ursodeoxycholic acid (UDCA) has been observed, treatment of omega-3, ursodeoxycholic acid (UDCA), or omega-3 and ursodeoxycholic acid (UDCA) with the above description The effect was unknown. In addition, although the effect of omega-3 was confirmed in the previous experiment, the combined effect of omega-3 and ursodeoxycholic acid (UDCA) was similar to that of omega-3, so the combination of omega-3 and ursodeoxycholic acid (UDCA) There was a limitation that the effect could not be confirmed.

Therefore, the present inventors found the therapeutic effect of cholelithiasis of capsules containing omega-3 and ursodeoxycholic acid (UDCA) with excipients added and capsules containing omega-3 and ursodeoxycholic acid (UDCA) with excipients added at a specific ratio. showed the treatment effect of cholelithiasis.

An object of the present invention is ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof, which induces a process in which cholesterol gallstones are not formed or dissolved; omega-3 fatty acids; And to provide a gallstone dissolving agent containing an excipient, a pharmaceutical composition containing the same, and a health functional food composition containing the same.

In order to solve the above-mentioned problems, the present invention is ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; omega-3 fatty acids; and an excipient.

The excipient of the present invention is at least one selected from the group consisting of beeswax, wax mixture, paraffin wax, refined palm oil, hydrogenated coconut oil, hydrogenated soybean oil, hard pet and polyethylene glycol can

The weight ratio of ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof and omega-3 fatty acids in the solubilizing agent of the present invention is 1 (w/v%): 2 (w/v%) to 1 (w/v %): 8.16 (w/v%).

The gallstones of the present invention may be cholesterol gallstones.

The composition of the present invention can induce dissolution of cholesterol gallstones or interfere with the formation of cholesterol gallstone crystals.

Another embodiment of the present invention is ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; omega-3 fatty acids; And it can provide a pharmaceutical composition for preventing or treating cholelithiasis containing an excipient.

The excipient of the present invention is any one or more selected from the group consisting of beeswax, wax mixture, paraffin wax, refined palm oil, hydrogenated coconut oil, hydrogenated soybean oil, hard pet and polyethylene glycol can be

The weight ratio of ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof and omega-3 fatty acids in the composition of the present invention is 1 (w/v%): 2 (w/v%) to 1 (w/v %): 8.16 (w/v%).

The gallstones of the present invention may be cholesterol gallstones.

The composition of the present invention can dissolve cholesterol gallstones or inhibit the formation of cholesterol gallstone crystals.

Another embodiment of the present invention is ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; omega-3 fatty acids; And it provides a health functional food composition for inhibiting the formation of gallstone dissolution or gallstone crystals containing an excipient.

The excipient of the present invention is any one or more selected from the group consisting of beeswax, wax mixture, paraffin wax, refined palm oil, hydrogenated coconut oil, hydrogenated soybean oil, hard pet and polyethylene glycol can be

The composition of the present invention can induce cholesterol gallstones to dissolve or interfere with the formation of cholesterol gallstone crystals.

The weight ratio of ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof and omega-3 fatty acids in the complex of the present invention is 1 (w/v%): 2 (w/v%) to 1 (w/v) %): 8.16 (w/v%).

The gallstones of the present invention may be cholesterol gallstones.

The pharmaceutical composition prepared with the optimal content of omega-3 fatty acids and UDCA allows cholesterol to remain dissolved without forming crystals, leading to a process in which cholesterol gallstones are not formed or dissolved, preventing or dissolving cholesterol gallstones. treatment effect increases.

1 is a schematic diagram of animal studies.
Figure 2, A is a table showing the body weight and weight change according to the diet and treatment administration, B is a schematic diagram.
3 is an anatomical change of the gallbladder and gallstones before and after drug administration.
4 is a classification diagram for gallstone size (Ref: Takashi A et al. cholesterol gallstone in alloxan-diabetic mice, Journal of Lipid Research, 1986).
5 is a result of measuring the size (base) of each group after a high-cholesterol diet and the size after administration of a therapeutic agent.
Figure 6 shows the change in gallstone size by group.
7 is a quantitative change of gallstones before and after administration of a therapeutic agent.
8A is the change in gallstone weight between pre-treatment and post-treatment, and B is a result of comparing the difference before and after treatment.

Hereinafter, the present invention will be described in more detail.

Hereinafter, the present invention will be described in more detail.

As described above, the prevalence of cholelithiasis, especially cholesterol gallstone gallstones, has increased as the diet in Korea has been westernized and changed to a high-protein, high-fat, high-calorie diet. , the development of a treatment for this is an urgent need.

Accordingly, the inventors of the present invention, ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof in an optimal amount; omega-3 fatty acids; and an excipient to dissolve gallstones. The gallstone dissolving agent prepared in the optimal content allows cholesterol to remain dissolved without forming crystals, leading to a process in which cholesterol gallstones are not formed or dissolved, and has a synergistic effect of preventing or treating cholesterol gallstones. .

The present invention relates to ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; omega-3 fatty acids; and an excipient.

Ursodeoxycholic acid (3?, 7β-dihydroxy-5β-cholanoic acid, hereinafter referred to as 'UDCA') is a so-called main component of the so-called male bile, which has been used for liver and biliary tract diseases in Korea, China, and Japan for a long time. It is a type of bile acid found in , has a molecular weight of 392.58 and has the molecular formula C ₂₄ H ₄₀ O ₄ . These UDCAs have the action of cleaning the microscopic bile ducts in the body, which discharges waste products and toxic bile acids in the microbiliary tract, stabilizes liver cell membranes and protects hepatocellular cells, increases hepatic blood flow, and inhibits cholesterol absorption and biosynthesis. , It has the action of dissolving gallstones and inhibiting their formation, and has pharmacological activity that normalizes immune activity, so it is used with major clinical indications for gallstones and biliary tract diseases, chronic liver disease and liver function improvement, indigestion and fatty liver after small bowel resection. to be. In particular, the mechanism of UDCA's cholesterol gallstone-dissolving effect is to lower the activity of HMG CoA reductase, an enzyme necessary for cholesterol synthesis in the liver, to decrease cholesterol secretion into bile, to increase 7?-hydroxylase activity, and to reduce cholesterol in the intestine. It is known to act to reduce absorption. In addition, administration of UDCA changes cholesterol-supersaturated bile into unsaturated bile. The desaturation of bile caused by UDCA administration improves the ability to transport cholesterol and produces multilamellar liposomes with high solubility in bile. (multilamellar liposome (mesophase)) is formed to form a liquid crystal even in bile saturated with cholesterol. Therefore, gallstones dissolve even in bile supersaturated with cholesterol after using UDCA for the reason of forming liquid crystals. Furthermore, it is widely used as a treatment for cholesterol gallstones.

Omega-3 fatty acids are a family of polyunsaturated fatty acids, generally characterized by the location of the final double bond on the third C-C bond starting at the final methyl group of the fatty acid. Omega-3 fatty acids are essential fatty acids, that is, since such fatty acids cannot be produced inside the human body, it is necessary to consume them through food or through a composition. Because of their polyunsaturated nature, omega-3 fatty acids have very special physicochemical functions in the human body (i.e., very low melting points) and have therefore been extensively studied. Today, there are up to 10 omega-3 fatty acids (e.g., stearic acid), which are present in the human body in very small amounts, and with the exception of DHA and/or EPA, their physiological activity is known to be very low or non-existent. . The omega-3 fatty acid used in the present invention may be omega-3-acid ethyl ester 90 containing 400 mg or more of EPA and 340 mg or more of DHA.

The excipient of the present invention is any one selected from the group consisting of beeswax, wax mixture, paraffin wax, refined palm oil, hydrogenated coconut oil, hydrogenated soybean oil, hard pet and polyethylene glycol It may be one or more, and most preferably beeswax or hydrogenated coconut oil.

The weight ratio of ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof and omega-3 fatty acids of the solubilizing agent is 1 (w/v%): 2 (w/v%) to 1 (w/v%): It may be 8.16 (w / v%), preferably 1 (w / v%): 3.06 (w / v%) to 1 (w / v%): 6.12 (w / v%), and the most Preferably, it may be 1 (w/v%): 4.08 (w/v%).

The gallstones may be cholesterol gallstones.

The dissolving agent can dissolve cholesterol gallstones or inhibit the formation of cholesterol gallstone crystals.

The present invention also relates to ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; omega-3 fatty acids; And it can provide a pharmaceutical composition for preventing or treating cholelithiasis containing an excipient.

The excipient of the present invention is any one selected from the group consisting of beeswax, wax mixture, paraffin wax, refined palm oil, hydrogenated coconut oil, hydrogenated soybean oil, hard pet and polyethylene glycol can be more than

The pharmaceutical composition may further include a pharmaceutically acceptable carrier. As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not stimulate organisms and does not inhibit the biological activity and properties of the administered compound. Acceptable pharmaceutical carriers for compositions formulated as liquid solutions are sterile and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added if necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare formulations for injections such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets.

The pharmaceutical composition is any one selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. It can have one formulation. Most preferably, it may be a capsule.

The suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration method, patient's age, weight, sex, medical condition, food, administration time, administration route, excretion rate and reaction sensitivity, A ordinarily skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention is 0.001 to 100 mg/kg.

The weight ratio of ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof and omega-3 fatty acids in the composition of the present invention is 1 (w/v%): 2 (w/v%) to 1 (w/v %): 8.16 (w/v%), preferably 1 (w/v%): 3.06 (w/v%) to 1 (w/v%): 6.12 (w/v%) Yes, and most preferably 1 (w / v%): 4.08 (w / v%).

The gallstones of the present invention may be cholesterol gallstones.

The composition of the present invention can induce dissolution of cholesterol gallstones or interfere with the formation of cholesterol gallstone crystals. Administration of Omega-3 fatty acids raises phospholipids in bile, and administration of UDCA raises bile salts in bile to balance the increased cholesterol in bile, so that cholesterol does not form crystals and remains dissolved, resulting in cholesterol gallstones. may lead to the process of not forming or dissolving.

Another embodiment of the present invention is ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; omega-3 fatty acids; And it is possible to provide a health functional food composition for inhibiting the formation of gallstone dissolution or gallstone crystals containing an excipient.

The excipient of the present invention is any one selected from the group consisting of beeswax, wax mixture, paraffin wax, refined palm oil, hydrogenated coconut oil, hydrogenated soybean oil, hard pet and polyethylene glycol can be more than

The weight ratio of ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof and omega-3 fatty acids in the composition is 1 (w/v%): 2 (w/v%) to 1 (w/v%): It may be 8.16 (w / v%), preferably 1 (w / v%): 3.06 (w / v%) to 1 (w / v%): 6.12 (w / v%), and the most Preferably, it may be 1 (w/v%): 4.08 (w/v%).

The gallstones may be cholesterol gallstones.

Hereinafter, the present invention will be described in more detail through examples. The following examples are only one preferred embodiment of the present invention, and the scope of the present invention is not limited to the scope of the following examples.

Example 1. Creation of a mouse model for confirming cholesterol gallstone formation treatment

The overall schematic diagram of the animal experiment is shown in FIG. 1. In the following, it is explained in more detail. C57BL/6J male mouse was purchased from Central Experimental Animal Co., Ltd. Mice were acclimatized for 4 weeks under controlled light (12 h light and 12 h dark cycle, dark 6:30 pm - 6:30 am), temperature (22 ± 4 °C) and humidity (50% ± 20%) conditions. had Mice had ad libitum access to water (autoclaved distilled water) and were fed ad libitum with a commercial diet (manufacturer and diet name) containing ~kcal% fat, ~kcal% protein and ~kcal% carbohydrates. A lithogenic diet containing cholesterol (10 g/kg) and cholic acid (10 g/kg) (DYET#102136, Dyets, Bethlehem, PA, USA) was administered for 8 weeks to prepare mice in which gallstones were formed on a high-cholesterol diet.

The mice in which gallstones were formed by the high-cholesterol diet were divided into groups as follows and the experiment was conducted for 12 weeks.

① General diet

② General diet + UDCA administration (12.5mg/kg/day)

③ General diet + omega-3 fatty acid administration (51mg/kg/day)

④ General diet + UDCA (12.5mg/kg/day) + Omega-3 fatty acid (51mg/kg/day) administration

⑤ General diet + 0.5 times the complex (UDCA 12.5mg/kg/day + Omega-3 fatty acid 25.5mg/kg/day)

⑥ General diet + 1.0 times the complex (UDCA 12.5mg/kg/day + Omega-3 fatty acids 51mg/kg/day)

⑦ General diet + 1.5 times the complex (UDCA 12.5mg/kg/day + Omega-3 fatty acid 102mg/kg/day)

The mice of group ①, the control group, were mixed with 0.75% Tween80 and distilled water, and 0.3 ml each was administered as a sonde. The UDCA was purchased from Daewoong Pharmaceutical, diluted in 0.75% Tween80 at 12.5 mg/kg/day, and administered as a sonde at 0.3 ml each. The omega-3 fatty acid was diluted in 0.75% Tween80 at each dose (25.5 mg/kg/day, 51 mg/kg/day, and 102 mg/kg/day) by purchasing Omacor® purchased from Youngjin Pharmaceutical. After administering the drug for 12 weeks, animals were sacrificed to obtain Dangnam tissues for experiments. Body weight and liver weight were measured after a high-cholesterol diet, and body weight and liver weight were measured after administering a general diet and treatment (FIG. 2). There was no statistically significant change in body weight or liver weight for each group according to diet or treatment administration by time, and there was no change in liver weight to body weight. Through this result, it was found that the treatment did not cause systemic complications or life-threatening problems in the experimental group.

Example 2. Changes in dangnam and gallstones before and after drug administration

As shown in Figure 3, the mice of the group ① did not change much in the size and amount of gallstones after switching to the normal diet after the co-cholesterol diet. In group ②, the size of gallstones slightly decreased after UDCA administration, but the quantitative decrease was insufficient. In the mice of the ③ group, the size of gallstones decreased slightly after omega-3 administration, and a quantitative decrease was also observed. In the mice of group ④, the size of gallstones decreased slightly after administration of UDCA (12.5mg/kg/day) + omega-3 fatty acid (51mg/kg/day), and the quantity was also reduced. After administering 0.5 times the complex (UDCA 12.5mg/kg/day + omega-3 fatty acid 25.5mg/kg/day) to the mice in group ⑤, the size of gallstones decreased slightly and the quantity decreased as well. After administration of 1.0 times the complex (UDCA 12.5mg/kg/day + omega-3 fatty acid 51mg/kg/day) in the mice of group ⑥, the size of gallstones decreased slightly and a clear quantitative decrease was also observed. After administering 1.5 times the complex (UDCA 12.5mg/kg/day + omega-3 fatty acid 102mg/kg/day) to mice in the ⑦ group, the size of gallstones decreased slightly and quantitatively decreased, but the complex was doubled compared to the ⑥ group. Compared to administration, the effect did not decrease in magnitude in a concentration-dependent manner. That is, when UDCA and omega-3 fatty acids were administered together, the size and quantity of gallstones were reduced, but insignificant. In addition, the size and quantity of omega-3 fatty acids were not decreased in a concentration-dependent manner. Unusually, a clear quantitative decrease was also seen in the mice of group ⑥. As a result of the above, it was found that the concentration-dependent effect of omega-3 fatty acids was not shown, but the effect was increased within a specific range of UDCA and omega-3 fatty acids.

Example 3. Analysis of gallstone size before and after treatment

Gallstones of the gallbladder tissue obtained in Example 1 were analyzed for size based on FIG. 4 (FIG. 5). As a result, the size of gallstones was significantly reduced in the ⑥ group of complex 1-fold, and was not observed when other drugs were administered.

Example 4. Change in gallstone weight before and after treatment

Changes in the weight of gallstones in gallbladder tissues after the high-cholesterol diet (base) and after administration of the therapeutic agent of Example 1 were analyzed (FIGS. 6, 7, and 8). As can be seen in Figure 7, as a result of measuring the change in gallstone weight between pre-treatment and post-treatment, the amount of gallstones decreased after treatment in all groups, but ⑥ of 1.0 times the complex It decreased the most in the group. Surprisingly, doubling the amount of the complex did not increase the change in gallstone weight in a concentration-dependent manner, but rather decreased it. This, it was found that there is a synergistic effect of reducing the weight of gallstones, not by simply increasing the amount of the complex, but by administering a specific content of UDCA and omega-3 fatty acids. In addition, as can be seen in Figure 8, only the ⑥ group of the complex 1.0 times showed a significant gallstone reduction effect with the control group ① group (p-value: 0.041). The ④ and ⑦ groups showed a trend of gallstone reduction compared to the control group ① (p-value: 0.085, 0.075), but there was no statistical significance. In the group that showed a significant trend with the control group, only the ⑥ group showed a significant difference from the ④ group in the comparison between the ④ group and the complex groups ⑤, ⑥ and ⑦ groups (p-value: 0.037).

Claims (14)

ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; omega-3 fatty acids; And as a gallstone dissolving agent comprising an excipient,
The ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; And the weight ratio of omega-3 fatty acids is 1 (w / v%): 4.08 (w / v%) that will, gallstone dissolving agent. The method of claim 1, wherein the excipient is selected from the group consisting of beeswax, wax mixture, paraffin wax, refined palm oil, hydrogenated coconut oil, hydrogenated soybean oil, hard pet, and polyethylene glycol. Any one or more, gallstone dissolving agent. delete According to claim 1, wherein the gallstones are cholesterol gallstones, gallstone dissolving agent. The gallstone dissolving agent according to claim 1, wherein the dissolving agent inhibits the formation of cholesterol gallstone crystals or dissolves cholesterol gallstones. ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; omega-3 fatty acids; And a pharmaceutical composition for preventing or treating cholelithiasis comprising an excipient,
The ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; And the weight ratio of omega-3 fatty acids is 1 (w/v%): 4.08 (w/v%), which is, a pharmaceutical composition for preventing or treating cholelithiasis. The method of claim 6, wherein the excipient is selected from the group consisting of beeswax, wax mixture, paraffin wax, refined palm oil, hydrogenated coconut oil, hydrogenated soybean oil, hard pet and polyethylene glycol Any one or more, a pharmaceutical composition for preventing or treating cholelithiasis. delete According to claim 6, wherein the gallstones are cholesterol gallstones, a pharmaceutical composition for preventing or treating cholelithiasis. According to claim 6, wherein the composition inhibits the production of cholesterol gallstone crystals or dissolving cholesterol gallstones, preventing or treating cholelithiasis pharmaceutical composition. ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; omega-3 fatty acids; And a health functional food composition for inhibiting the formation of gallstone dissolution or gallstone crystals containing an excipient,
The ursodeoxycholic acid (UDCA) or a pharmaceutically acceptable salt thereof; And the weight ratio of omega-3 fatty acids is 1 (w / v%): 4.08 (w / v%) of that, gallstone dissolution or inhibiting the production of gallstone crystals health functional food composition. The method of claim 11, wherein the excipient is selected from the group consisting of beeswax, wax mixture, paraffin wax, refined palm oil, hydrogenated coconut oil, hydrogenated soybean oil, hard pet, and polyethylene glycol. Any one or more, health functional food composition. delete According to claim 11, wherein the gallstones are cholesterol gallstones, health functional food composition.

Images