KR20110131699A - Intravenous infusion solution for preventing or treating side effects induced by nutrition supply - Google Patents

Abstract

PURPOSE: A fluid composition of intravenous injection containing bile acid and derivative thereof, GABA and derivative thereof, thiotic acid or derivative, thioctic acid, or derivative thereof is provided to prevent or treat side effect. CONSTITUTION: A fluid composition of intravenous infection contains bile acid of chemical formula 1 and derivative thereof, GABA of chemical formula 2 and derivative thereof, thiotic acid or derivative, thioctic acid, or derivative thereof. The bile acid or derivative thereof is ursodeoxycholic acid, glyco ursodeoxycholic acid, tauroursodeoxycholic acid, chenodeoxy-cholic acid, acid, glycocholic acid, taurocholic acid, deoxycholic acid or lithocholic acid. The GABA derivative is gabapentin, pregabalin, baclofen, vigabatrin, 3-methylgaba, or 3,3-dimehtylgaba. The composition additionally contains amino acids, sugar, vitamin, pH adjusting agent, stabilizing agent, or solubilizer.

Description

Intravenous fluid solution for the prevention or treatment of side effects of nutritional supply {INTRAVENOUS INFUSION SOLUTION FOR PREVENTING OR TREATING SIDE EFFECTS INDUCED BY NUTRITION SUPPLY}

The present invention relates to an intravenous infusion solution composition for preventing or treating side effects of the nutritional supply of a patient receiving parenteral nutrition through intravenous injection, and a fluid containing the same.

In general, intravenous infusions are administered to patients who cannot orally eat food due to surgery or trauma, or who need additional nutritional supplementation due to nutritional deficiency or dehydration. Such fluids include glucose fluids, amino acid fluids, lipid fluids, and the like, which can supplement three major nutrients of carbohydrates, proteins, and fats. The supply of glucose is administered by supplementing the basic calorie. Patients who have undergone surgery or trauma are in a pathology that promotes catabolic catabolism. Therefore, amino acids other than glucose should be additionally supplied to prevent the consumption of constituent proteins. In addition, if the patient is nourished parenterally for a long time, deficiency of essential fatty acids may be shown, and lipid sap is provided to prevent this.

However, in the case of parenteral nutrition through intravenous injection, bile acid secretion is reduced because there is no irritation of food contents in the gastrointestinal tract, and fatty acid cannot be absorbed, thus reducing the absorption of fatty acid and the production of bile acid. In bile salts, cholesterol in bile is dissolved in the form of a mixture of leukin and vesicles and vesicles. Cholesterol gallstones can develop due to bile deficiency and consequently decreased cholesterol dissolution. Stagnation of bile acid secretion can block bile ducts, decrease liver function, and increase enzyme levels such as AST and ALT. In addition, patients who are unable to eat and are nourished with fluids temporarily increase blood sugar and develop symptoms of diabetes. This increase in blood glucose also occurs in patients who did not have diabetes before hospitalization, which causes a problem of additional administration of diabetes treatment after hospitalization. In addition, patients receiving parenteral nutrition through intravenous injection show increased metabolism in the body, which leads to increased protein consumption. At this time, oxidative stress increases and the body's antioxidant system is depleted. Deterioration leads to various complications. There is an urgent need for an infusion system that can improve these problems.

It is an object of the present invention to provide an intravenous infusion solution composition useful for the prevention and treatment of side effects caused by nutrient supply and an intravenous infusion solution comprising the same.

In order to achieve the above object, the present invention is an intravenous infusion solution containing at least one component selected from the group consisting of bile acid and its derivatives of formula (1), Gaba and its derivatives of formula (2), chioctic acid and salts thereof To provide a composition.

[Formula 1]

[Formula 2]

Where

R ₁ is a hydroxy group, glycine group or taurine group,

R ₂ and R ₃ are each independently hydrogen or a hydroxyl group,

R ₄ and R ₅ are each independently hydrogen, methyl group, isobutyl group, phenyl or cyclohexyl group substituted with halogen;

R ₆ is hydrogen or a vinyl group.

The present invention also includes one or more chamber bags, each chamber bag independently of one or more components selected from the group consisting of bile acids and derivatives thereof, Gaba and derivatives thereof, chioctic acid and salts thereof Provided is an intravenous infusion solution comprising an intravenous infusion composition.

The intravenous infusion solution composition according to the present invention comprises at least one component selected from the group consisting of bile acids and their derivatives of formula (1), gaba and derivatives thereof of formula (2), chioctic acid and salts thereof.

The intravenous infusion solution composition of the present invention may include bile acids, derivatives thereof, or salts thereof as one of the components useful for shortening the recovery period of a patient. As described above, bile acids, derivatives thereof, or salts thereof may be useful for the prevention or treatment of cholestasis since cholesterol gallstones or cholestasis may occur as a side effect of the supply of the fluid. Commercially available bile acid products are used for the treatment of gallstones, primary biliary cirrhosis, etc., and most of the internal solids are not used in fluids.

In one embodiment, ursodeoxychoic acid, glycourrsodeoxycholic acid, tauroursodeoxycholic acid, kenodeoxycholic acid, chenodeoxycholic acid, as bile acids or derivatives thereof Cholic acid, glycolic acid (glycocholic acid), taurocholic acid (taurocholic acid), deoxycholic acid (deoxycholic acid), lithocholic acid (lithocholic acid) and the like can be used. In the present invention, the derivative of bile acid includes all derivatives of bile acids exhibiting the same or similar efficacy as well as the compounds specifically exemplified above.

The bile acids or derivatives thereof are useful as immunomodulators and prevent cell death by induction of deoxycholic acid by regulating mitochondrial transmembrane potential and production of reactive oxygen species. In addition, it prevents the induction of nitric oxide synthase in the visceral epithelial cells of the human body and in vivo, and has a cytoprotective function against liver necrosis inflammation disease by the hydrophilicity of bile acids. In addition, it significantly improves the cholestatic enzyme index of liver damage in aminotransferase and chronic hepatitis, and bile acids substantially interfere with the growth of H. pylori. Secondary bile acids are the most potent pepsin inhibitors of bile acids, and high levels of bile acids significantly inhibit the growth of hepatitis C virus. In addition, secondary bile acids stabilize the cell membrane, reduce alcoholic fatty liver, show vasodilating effect, but do not alter pulmonary vascular function and heart function. Therefore, the intravenous infusion solution composition of the present invention containing the bile acid or derivatives thereof can prevent or treat side effects caused by parenteral nutrition such as cholestasis, hepatic deterioration, and antioxidant function deterioration. The period can be shortened.

In the intravenous infusion solution composition of the present invention, the bile acid, bile acid derivatives or salts thereof may be included in 0.002 to 0.05 wt / v%. In order to reduce the risk of precipitation in the infusion solution while imparting the above functionality to the intravenous infusion solution, it is preferably used within the above range. The bile acid, bile acid derivatives or salts thereof may be administered, for example, in an amount of 10 to 1500 mg, based on the bile acid, and preferably in an amount of 30 to 200 mg per day.

In addition, the infusion composition of the present invention may include Gaba, its derivatives or salts thereof as another ingredient useful for shortening the recovery period of a patient.

GABA (γ-aminobutyric acid) is an endogenous neurotransmitter present in the central nervous system and is known to have various effects. Has antidepressant action and suppresses insomnia and seizures. Neuralgia, muscle pain, pain caused by inflammation, etc. It is known that it suppresses inflammation and also inhibits vomiting (US Patent Nos. 5025035, 6306910, 5563175, 6242488, 6887902, and 5719185). ). Gaba derivatives, gabapentin, are approved by the US Food and Drug Administration to treat epilepsy or suppress neuralgia.Pregabalin is used in patients with type 1 or 2 diabetes with diabetic neuralgia. A large-scale clinical trial of the study confirmed that it could suppress diabetic neuralgia, and was approved by the US Food and Drug Administration for fibromyalgia. Baclofen can also be used to treat spastic movement disorders, especially spinal cord injuries, spastic bilateral palsy, multiple sclerosis, amyotrophic lateral sclerosis, and tertiary Yeti neuralgia. vigabatrin) can be used to treat epilepsy, alcoholism, stimulant dependence, nicotine dependence and obsessive-compulsive disorder, which are not fully controlled by other epileptics.

Gaba functions through Gaba A and Gaba B receptors in the central nervous system and pancreas. The Gaba A receptor is a receptor present in α cells, and is involved in the Cl- ion channel. Gaba hyperpolarizes α cells through the Gaba A receptor to inhibit glucagon secretion. Chronic diabetic patients often lose glucagon control and excessive glucagon can cause failure of blood sugar control. Glucagon is weaker than insulin, so even if it is continuously suppressed, hypoglycemia does not come. Thus, inhibition of glucagon may be a safer guideline for glycemic control (Rorsman, P., Berggren, PO., Bokvist, K., Ericson, H., Mohler, H., Ostenson, CG. And Smith, PA, 45-5 Glucose-inhibition of glucagon secretion involves activation of GABAA receptor chloride channels.Nature 341 233-236 (1989)). The Gaba B receptor is a receptor present in β cells and G protein is involved in its function. Gaba acts on the Gaba B receptor to produce ATP in β cells, thereby increasing the concentration of calcium ions and increasing insulin secretion. Gaba can also induce the growth of pancreatic cells. Gaba administration stimulates the growth of cells, including the pancreas, the central nervous system, kidneys, and the spleen, thereby increasing intracellular DNA synthesis. Administered Gaba acts through the Gaba B receptor and can effectively increase pancreatic islet cells in insulin-dependent diabetes. Thus, this may be an effective treatment for the prevention and treatment of type 1 diabetes (Kaupmann, K., Huggel, K., Heid, J., Flor, PJ, Bischoff, S., Mickel, SJ, McMaster, G., Angst, C., Bittiger, H., Froestl, W., and Bettler, B. Expression cloning of GABA B receptors uncovers similarity to metabotropic glutamate receptors.Nature 386, 239-246 (1997)).

Gaba and Gaba derivatives also inhibit diabetic neuralgia that can occur in diabetic patients. Gava and Gaba derivatives have a large affinity for the α2δ portion of the GavaA receptor with respect to calcium channels. As a result, the secretion of pain-related neurotransmitters may be inhibited to inhibit peripheral neuralgia and spasms in diabetic neuralgia patients (Diabetes Obes Metab. 2008 Feb; 10 (2): 99-108. Epub 2007 Jun 26. Diabetic neuropathy: new strategies for treatment. Vakonyi T, Kempler P.).

Therefore, by including Gaba, its derivatives, or salts thereof in the intravenous infusion composition of the present invention, various problems described above, such as temporary diabetes symptoms caused by parenteral nutrition, can be improved.

In one embodiment, the gaba or derivative thereof included in the infusion composition of the present invention may be gabapentin, pregabalin, baclofen, bigatrine, 3-methylgava, or 3,3-dimethylgaba.

In the present invention, 'a derivative of Gaba' includes all of Gaba's derivatives exhibiting the same or similar efficacy in addition to the compounds specifically exemplified above.

In the intravenous infusion composition of the present invention, the Gaba, Gaba derivatives or salts thereof may be included in a total of 0.01 to 0.6 wt / v%. In order to impart the above functionality to the formulation while having stability when formulated, it is preferably included within the above range. The Gaba or its derivatives may be administered, for example, in an amount of 10 to 4500 mg, based on Gaba, and preferably in an amount of 200 to 1500 mg per day.

The present invention may also include chioctic acid or a salt thereof as another component useful for shortening the recovery period of a patient.

Thioctic acid (alpha-lipoic acid) acts as an essential coenzyme of many complex enzymes and, in particular, as a coenzyme during aerobic metabolism of the pyruvate dehydrogenase complex. It has one enantiomer and the chioctic acid molecule has a structure having two sulfur groups in a carboxyl group and a pentagonal ring. Only the enantiomers of the R-form are physiologically useful, small amounts are produced in the body, and they also convert sugar into energy. Small molecules of chioctic acid can easily pass through the blood brain barrier, inside and outside the cell, and also form metal ions and chelate compounds.

Chioctic acid has a very effective antioxidant effect, which can reduce oxidized Vit C, Vit E and GSH (glutathione) in vitro, and also serves as a free radical scavenger.

As such, the chioctic acid may act as an antioxidant, but is used only for the treatment of multiple neuritis and is not yet supplied to patients as an antioxidant.

In the infusion composition of the present invention, chioctic acid or a salt thereof may be included in a total amount of 0.01 to 0.08 wt / v%. In order to reduce the risk of precipitation in the infusion solution while imparting the above functionality to the intravenous infusion solution, it is preferably used within the above range. The chioctic acid or salt thereof may be administered, for example, in an amount of 10 to 6000 mg per day, and preferably in an amount of 20 to 300 mg.

In the infusion composition of the present invention, bile acids and their derivatives, Gaba and its derivatives, and chioctic acid, which are exemplified as components useful for shortening the recovery period of a patient, may be included independently in the form of salts. Salts of the above components can be any pharmaceutically acceptable salt. For example, sodium salt, lithium salt, potassium salt, hydrochloride, acetate, sulfate, etc. can be used.

In addition to the above components, the infusion composition according to the present invention may include pharmaceutical components included in a general intravenous infusion solution composition. For example, the intravenous infusion composition may further comprise one or more components selected from the group consisting of amino acids, sugars, lipids, vitamins, electrolytes, pH adjusters, stabilizers, osmotic pressure adjusters and dissolution aids. Depending on the type of component such as amino acids, sugars or lipids, the infusion composition of the present invention can be utilized as a preparation for intravenous injection of various compositions.

Pharmaceutical components included in the infusion composition may vary depending on the condition of the patient. Taking the amino acid as an example, the ratio of essential and non-essential amino acids, the ratio of branched amino acids and aromatic amino acids to be used according to the symptoms of the patient is different, the type of electrolyte is also different. In case of general amino acid solution, the daily amino acid requirement of the patient is 1g / kg for mild, 1.5g / kg for moderate, 2g / kg for severe, and 4 ~ 4.6% of amino acid solution for mild. 6-8% of patients with liver disease, 6% of patients with kidney disease, and 10-13% of patients with severe disease are given an amino acid solution. For example, in patients with liver disease, when the liver is normal, the ratio of essential amino acids to non-essential amino acids is similar to 50:50, whereas abnormal patients use more essential amino acids than non-essential amino acids. This is because the concentration of branched amino acids in the blood of patients with liver disease decreases and the concentration of aromatic amino acids increases, so that when the Fischer ratio (a ratio of branched amino acids / aromatic amino acids) is 3 or less, a relatively high concentration of aromatic amino acids occurs. This can be caused by severe blood flow through the Blood Brain Barrier. In addition, patients with liver disease should use a small amount of amino acetate, serine, threonine, and lysine, which have various metabolisms in the liver, and contain a large amount of arginine, which detoxifies the ammonia produced in the liver. In addition, the dosage of the infusion composition to the human body may vary depending on the patient's age, sex, weight, nationality, health condition and degree of disease, and may be dividedly administered according to the prescription of the prescriber.

As can be seen in the following examples, the infusion composition of the present invention is not only excellent in the stability of the formulation, but also prevents side effects such as cholestasis, diabetes, hepatic function or antioxidant activity caused by the supply of the fluid or It is useful for treatment, and as a result, liver function improvement and antioxidant effect can shorten the recovery period of patients.

The intravenous infusion solution composition of the present invention may be commercialized as a 'intravenous infusion solution' in the form of a final product enclosed in a plastic or glass container.

Accordingly, the present invention also includes one or more chamber bags, each chamber bag independently comprising one or more components selected from the group consisting of bile acids and derivatives thereof, gaba and derivatives thereof, chioctic acid and salts thereof Provided is an intravenous infusion containing a fluid composition.

The intravenous infusion solution means a final product form in which the intravenous infusion solution composition of the present invention described above is contained in a plastic or glass container.

Chamber bags comprising the intravenous infusion composition of the present invention may be, but are not limited to, amino acid chamber bags, sugar chamber bags or lipid chamber bags.

The intravenous infusion solution comprising the intravenous infusion composition of the present invention may have the form of a product with one chamber or alternatively may have the form of a product with two or more chambers.

The intravenous infusion solution may include, but is not limited to, one or more of an amino acid chamber bag, a sugar chamber bag, and a lipid chamber bag. In addition, the intravenous infusion may include additional chambers, such as vitamin chambers, in addition to amino acid chamber bags, sugar chamber bags, or lipid chamber bags.

The amino acid chamber bag is composed of isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, arginine, histidine, alanine, aminoacetic acid, boglutamic acid, proline, cysteine, serine, tyrosine, aspartic acid or salts thereof as amino acid components. It may contain. It also contains sodium acetate, potassium dihydrogen phosphate, sodium glycerophosphate, potassium chloride, magnesium chloride, etc. as electrolyte components, and sodium bisulfite, sodium hyposulfite, etc. as a stabilizer, and a suitable amount of sodium hydroxide or glacial acetic acid It may contain. Generally, amino acid chambers are composed of isoleucine 0.06-1.0 w / v% leucine 0.1-1.5 w / v% as amino acid components. As lysine 0.05-1.5 w / v%, methionine 0.05-0.5 w / v%, phenylalanine 0.06-1.0 w / v%, threonine 0.05-0.7 w / v%, tryptophan 0.01-0.3 w / v%, valine 0.06-0.7 w / v%, arginine 0.2-1.5 w / v%, histidine 0.05-0.6 w / v%, alanine 0.3-1.7 w / v%, amino acetate 0.2-1.4 w / v%, boglutamic acid 0.5-0.7 w / v% , Proline 0.07-1.2 w / v%, cysteine 0.02-0.1 w / v%, serine 0.05-0.5 w / v%, tyrosine 0.004-0.05 w / v%, aspartic acid 0.3-1.1 w / v%, electrolyte Ingredients include sodium acetate 0.6-1.0 w / v%, potassium dihydrogen phosphate 0.07-0.5 w / v%, sodium glycophosphate 0.1-0.6 w / v%, potassium chloride 0.06-0.5 w / v%, and magnesium chloride 0.02 0.1 to w / v%, 0.01 to 0.05 w / v% sodium bisulfite or 0.06 w / v% sodium hyposulfite as a stabilizer, and may contain an appropriate amount of sodium hydroxide or glacial acetic acid as a pH adjuster.

The sugar chamber contains 5 to 50 w / v% of glucose as a sugar component and sodium chloride, potassium chloride, magnesium chloride, calcium chloride, potassium acetate, potassium dihydrogen phosphate, magnesium sulfate, calcium gluconate, zinc sulfate, etc. as electrolyte components. And citric acid or the like as the pH adjuster. In general, the sugar chamber is composed of 0.02 to 0.08 w / v% sodium chloride, 0.2 to 0.4 w / v% potassium chloride, 0.02 to 0.15 w / v% magnesium chloride, 0.06 to 0.09 w / v% calcium chloride, and 0.2 to potassium acetate. 0.3 w / v%, potassium dihydrogen phosphate 0.01-0.015 w / v%, magnesium sulfate 0.09-0.1 w / v%, calcium gluconate 0.2-0.3 w / v%, zinc sulfate 0.7-0.75 w / v% And citric acid or sodium hydroxide as the pH adjuster.

Soybean oil, olive oil, middle chain triglyceride (MCT) as a lipid component, refined egg yolk lecithin as emulsifier, sodium oleate as stabilizer, glycerin as osmotic pressure regulator, propylene glycol, glycerin as dissolution aid and sodium hydroxide as the pH adjuster. Specifically, 0.5 to 2.5 w / v% of purified yolk lecithin as an emulsifier, 0.01 to 0.05 w / v% of sodium oleate as a stabilizer, 1.0 to 4.0 w / v% of glycerin as an osmotic pressure regulator and sodium hydroxide as a pH regulator. It may contain.

The infusion composition of the above-described configuration preferably contains 20 to 100 g / L as total amino acid, 10 to 400 g / L as glucose and 32 to 125 g / L as lipid.

An exemplary process for preparing an intravenous infusion formulation according to the present invention is as follows.

A) Preparation of the Infusion Composition in Sugar Chamber Bag

1. Dissolution and pH Control Process: After injecting water for injection into an appropriate volume tank, dissolve sugar, bile acid or its derivatives or its salts, Gaba or its derivatives, and optionally additives such as vitamins and electrolytes. Cool to room temperature to adjust the pH from weakly acidic to neutral.

2. Filtration Process: The solution is passed through a mediator layer with a 0.2 to 1.2 micrometer pore to filter the microorganisms and particulates.

3. Filling and nitrogen replacement process: Fill the filtrate to the indicated amount using a charger, replacing nitrogen as necessary.

4. Sealing process: When filling is complete, seal with rubber stopper.

5. Sterilization process: Kill the bacteria in the filling solution by autoclaving or hydrothermal sterilization at about 115 to 121 ° C. for 15 to 50 minutes.

B) Preparation of a Fluid Composition Contained in an Amino Acid Chamber Bag

1. Dissolution and pH Control Process: After injecting water for injection into an appropriate volume tank, active ingredients such as amino acids, bile acids or derivatives thereof or salts thereof, Gaba or derivatives thereof, and optionally additives such as vitamins and electrolytes are dissolved. After cooling to room temperature, the pH is adjusted from weakly acidic to neutral.

2. Filtration Process: The solution is passed through a mediator layer with a 0.2 to 1.2 micrometer pore to filter the microorganisms and particulates.

3. Filling and nitrogen replacement process: Fill the filtrate to the indicated amount using a charger, replacing nitrogen as necessary.

4. Sealing process: When filling is complete, seal with rubber stopper.

5. Sterilization process: Kill the bacteria in the filling solution by autoclaving or hydrothermal sterilization at about 115 to 121 ° C. for 15 to 50 minutes.

C) Preparation of Infusion Compositions Contained in Lipid Chamber Bags

C-1) Preparation of Lipid Layer Using Bile Acids

1. Main ingredient mixing and dissolution process: Soybean oil, olive oil, MCT mixed solution and active substances such as bile acid and chioctic acid are dissolved by heating to about 110 to 125 ℃ and cooled to about 70 to 80 ℃. Thereafter, optionally, an additive such as vitamin yolk lecithin is added and then dissolved by running a high speed stirrer.

2. Suspension process: After putting the water for injection in a separate container, add Gabba, vitamins, glycerin, etc., mix and stir, and then mix the mixture of 1 again, stir to form a suspension, and then add a pH adjuster Adjust the pH to about 8.0 to 9.5

3. Emulsification Process: The solution is homogenized several times using a high pressure homogenizer at a pressure of about 500 to 1000 bar and then passed through a medium having a pore size of 0.2 to 1.2 micrometers to filter foreign matter.

4. Filling and nitrogen replacement process: Fill the filtrate to the indicated amount using a charger, replacing nitrogen as necessary.

5. Sealing process: When filling is complete, seal with rubber stopper.

6. Sterilization process: Kill the bacteria in the filling solution by autoclaving or hydrothermal sterilization at about 115 to 121 ° C. for 15 to 50 minutes.

C-2) Preparation of Lipid Layer Using Bile Salts

1. Main ingredient mixing and dissolving process: Warm the mixed solution of soybean oil, olive oil and MCT to about 70 to 80 ℃, add active ingredients such as chioctic acid, and optional additives such as vitamin and egg yolk lecithin, and then operate a high speed stirrer Dissolve.

2. Suspension process: After the water for injection in a separate container, add bile salt, vitamins, glycerin and stir to mix, and then the mixture of 1 again is mixed and stirred to form a suspension, and then the pH adjuster is added to the pH of about 8.0 To 9.5

3. Emulsification Process: The solution is homogenized several times using a high pressure homogenizer at a pressure of about 500 to 600 bar and then passed through a medium having a pore size of 0.2 to 1.2 micrometers to filter foreign matter.

4. Filling and nitrogen replacement process: Fill the filtrate to the indicated amount using a charger, replacing nitrogen as necessary.

5. Sealing process: When filling is complete, seal with rubber stopper.

6. Sterilization process: Kill the bacteria in the filling solution by autoclaving or hydrothermal sterilization at about 115 to 121 ° C. for 15 to 50 minutes.

Advantages and features of the present invention and methods for achieving them will be apparent with reference to the embodiments described below in detail. However, the present invention is not limited to the embodiments disclosed below, but will be implemented in various forms, and only the embodiments are intended to complete the disclosure of the present invention, and the general knowledge in the technical field to which the present invention pertains. It is provided to fully convey the scope of the invention to those skilled in the art, and the present invention is defined only by the scope of the claims.

The infusion composition of the present invention can be usefully used to prevent or treat side effects such as cholestasis, diabetes mellitus, hepatic function or antioxidative function, which occur according to the supply of the fluid, and consequently shorten the recovery period of the patient. have.

[Example]

Example 1 Preparation of Amino Acid Sap Containing Bile Salts

0.5L water for injection at 80-90 ° C. was placed in a tank of an appropriate capacity, and then L-isoleucine, L-leucine, acetate-L-lysine, L-methionine, and L- as shown in Table 1 below. Phenylalanine, L-threonine, L-tryptophan, L-valine, L-alanine, L-arginine, L-aspartic acid, L-cysteine, L-glutamic acid, L-histidine, L-proline, L-serine, L-tyrosine, After dissolving aminoacetic acid, sodium hydroxide, sodium pyrosulfite, sodium edetate, and UDCA Na, the mixture was cooled to room temperature and adjusted from mildly acidic to neutral with hydrochloric acid or sodium hydroxide as a pH adjuster. The solution was passed through a media layer with a 0.2 micrometer pore to filter the microorganisms and particulates. The filtrate was filled in the infusion bottle or chamber bag to the indicated amount using a charger, replacing nitrogen as needed. After the filling was completed, the mixture was sealed with a rubber stopper, and autoclaved or hydrothermal sterilized at about 121 ° C. for 15 minutes to kill the bacteria in the filling solution to prepare an amino acid sap containing bile salts.

Example 2 Preparation of Amino Acid Sap Containing Bile Salt and Gaba

0.5L water for injection at 80-90 ° C. was placed in a tank of an appropriate capacity, and then L-isoleucine, L-leucine, acetate-L-lysine, L-methionine, and L- as shown in Table 1 below. Phenylalanine, L-threonine, L-tryptophan, L-valine, L-alanine, L-arginine, L-aspartic acid, L-cysteine, L-glutamic acid, L-histidine, L-proline, L-serine, L-tyrosine, Amino acetic acid, sodium hydroxide, sodium pyrosulfite, sodium edetate, UDCA Na and Gabba were dissolved, cooled to room temperature, and adjusted slightly to neutral using hydrochloric acid or sodium hydroxide as a pH adjuster. The solution was passed through a media layer with a 0.2 micrometer pore to filter the microorganisms and particulates. The filtrate was filled in the infusion bottle or chamber bag to the indicated amount using a charger, replacing nitrogen as needed. After the filling was completed, it was sealed with a rubber stopper, and the bacteria in the filling solution were killed by autoclaving or hot water sterilization at about 121 ° C. for 15 minutes to prepare an amino acid sap containing bile salts and gaba.

Example 3: Preparation of Amino Acid Sap Containing TUDCA

It was prepared in the same manner as in Preparation Example 1, except that TUDCA was added instead of UDCA Na in each component and content of Table 1 below.

Example 4 Preparation of Amino Acid Sap Containing CDCA Na and Gaba

It was prepared in the same manner as in Preparation Example 2, except that CDCA Na was added instead of UDCA Na as the ingredients and the contents of Table 1 below.

Example 5 Preparation of Amino Acid Sap Containing Gava

0.5L water for injection at 80-90 ° C. was placed in a tank of an appropriate capacity, and then L-isoleucine, L-leucine, acetate-L-lysine, L-methionine, and L- as shown in Table 1 below. Phenylalanine, L-threonine, L-tryptophan, L-valine, L-alanine, L-arginine, L-aspartic acid, L-cysteine, L-glutamic acid, L-histidine, L-proline, L-serine, L-tyrosine, After dissolving aminoacetic acid, sodium hydroxide, sodium pyrosulfite, sodium edetate, and gaba, the mixture was cooled to room temperature, and adjusted from weakly acidic to neutral using hydrochloric acid or sodium hydroxide as a pH adjuster. The solution was passed through a media layer with a 0.2 micrometer pore to filter the microorganisms and particulates. The filtrate was filled in the infusion bottle or chamber bag to the indicated amount using a charger, replacing nitrogen as needed. After the filling was completed, it was sealed with a rubber stopper, and an amino acid sap containing Gabba was prepared by killing bacteria in the filling solution by autoclaving or hot water sterilization at about 121 ° C. for 15 minutes.

Example 6: Preparation of Glucose Sap Containing Bile Salts

0.5L of water for injection at 80 to 90 ° C is placed in a tank of an appropriate capacity, and then glucose, UDCA Na, calcium chloride, magnesium chloride, potassium dihydrogen phosphate and sodium chloride are dissolved at room temperature as shown in Table 1 below. The mixture was cooled to and adjusted to weakly acidic to neutral using citric acid or sodium hydroxide as a pH adjuster. The solution was passed through a media layer with a 0.2 micrometer pore to filter the microorganisms and particulates. The filtrate was filled in the infusion bottle or chamber bag to the indicated amount using a charger, replacing nitrogen as needed. After the filling was completed, it was sealed with a rubber stopper, and the bacteria in the filling solution were killed by autoclaving or hydrothermal sterilization at about 121 ° C. for 15 minutes to prepare a glucose sap containing UDCA Na.

Example 7 Preparation of Glucose Sap Containing Bile Salt and Gaba

0.5L water for injection at 80 to 90 ° C was put in a tank of an appropriate capacity, and then glucose, UDCA Na, Gaba, calcium chloride, magnesium chloride, potassium hydrogen phosphate, and sodium chloride were dissolved as shown in Table 1 below. It was then cooled to room temperature and adjusted from mildly acidic to neutral with citric acid or sodium hydroxide as the pH adjuster. The solution was passed through a media layer with a 0.2 micrometer pore to filter the microorganisms and particulates. The filtrate was filled in the infusion bottle or chamber bag to the indicated amount using a charger, replacing nitrogen as needed. After the filling was completed, it was sealed with a rubber stopper, and the bacteria in the filling solution were killed by autoclaving or hot water sterilization at about 121 ° C. for 15 minutes to prepare a glucose sap containing UDCA Na and Gabba.

Example 8 Preparation of Glucose Sap Containing UDCA Na and Gabapentin

It was prepared in the same manner as in Preparation Example 7, except that gabapentin was added instead of Gaba in each component and content of Table 1 below.

Example 9 Preparation of Gaba Containing Glucose Sap

0.5L water for injection at 80-90 ° C is placed in a tank of a suitable capacity, and then glucose, GABA, calcium chloride, magnesium chloride, potassium hydrogen phosphate and sodium chloride are dissolved at room temperature as shown in Table 1 below. Cool and adjust from mild to neutral using citric acid or sodium hydroxide as pH adjuster. The solution was passed through a media layer with a 0.2 micrometer pore to filter the microorganisms and particulates. The filtrate was filled in the infusion bottle or chamber bag to the indicated amount using a charger, replacing nitrogen as needed. After the filling was completed, the mixture was sealed with a rubber stopper, and the bacteria inside the filling solution were killed by autoclaving or hydrothermal sterilization at about 121 ° C. for 15 minutes to prepare a glucose sap containing Gabba.

Example 10 Preparation of Lipid Sap Containing Bile Acids

After mixing soybean oil, olive oil, MCT in a suitable container as described in each component and content according to Table 1, UDCA was added and dissolved by heating to about 120 ℃ and cooled to about 80 ℃. Egg yolk lecithin was added and dissolved by running a high speed stirrer.

After putting about 0.2L of water for injection in a separate container, glycerol was added and stirred, and the mixture was mixed and stirred again to prepare a suspension. A pH adjuster was added to the prepared suspension to pH about 9.0. The pH-adjusted suspension was homogenized several times using a high pressure homogenizer at a pressure of about 500 to 600 bar and then passed through a medium with a 1.0 micrometer pore to filter foreign matter. While replacing nitrogen, the filtrate was filled into the infusion bottle or chamber bag to the indicated amount using a charger. After the filling was completed, it was sealed with a rubber stopper, and the bacteria in the filling solution were killed by autoclaving or hydrothermal sterilization at about 121 ° C. for 15 minutes to prepare a lipid sap containing UDCA.

Example 11: Preparation of Lipid Sap Containing Bile Salts

Soybean oil, olive oil, MCT in a suitable container as shown in each component and content according to Table 1, and then dissolved by heating to about 120 ℃ and then cooled to about 80 ℃. Egg yolk lecithin was added and dissolved by running a high speed stirrer.

After putting about 0.2L of water for injection in a separate container, UDCA Na and glycerol were added and stirred, and the mixture was mixed again and stirred to prepare a suspension. A pH adjuster was added to the prepared suspension to pH about 9.0. The pH-adjusted suspension was homogenized several times using a high pressure homogenizer at a pressure of about 500-600 bar and then passed through a medium having a 1.0 micrometer pore to filter foreign matter. The filtrate was filled in the infusion bottle or chamber bag to the indicated amount using a charger, replacing nitrogen as needed. After the filling was completed, it was sealed with a rubber stopper, and the bacteria in the filling solution were killed by autoclaving or hydrothermal sterilization at about 121 ° C. for 15 minutes to prepare a lipid sap containing UDCA Na.

Example 12 Preparation of Lipid Sap Containing CDCA

It was prepared in the same manner as in Example 10 except that CDCA was added instead of UDCA in each ingredient and content of Table 1 below.

Example 13: Preparation of Lipid Sap Containing Chioctic Acid

To prepare according to the components and contents according to Table 1 below, except that it contains chioctic acid instead of UDCA, it was carried out in the same manner as in Example 10 to prepare a lipid sap containing chioctic acid.

Example 14 Preparation of Lipid Sap Containing Gava

Prepared according to the ingredients and contents according to Table 1 below, except that it contains Gaba instead of UDCA Na, was carried out in the same manner as in Example 11 to prepare a lipid sap containing Gaba.

Example 15 Preparation of Lipid Sap Containing Chioctic Acid and Gava

After mixing soybean oil, olive oil, MCT in a suitable container as shown in each component and content according to Table 1, the chioctic acid was added and warmed to about 120 ℃ dissolved and cooled to about 80 ℃. Egg yolk lecithin was added and dissolved by running a high speed stirrer.

After putting about 0.2L of water for injection into a separate container, Gaba and glycerol were added and stirred, and the mixture was mixed and stirred again to prepare a suspension. A pH adjuster was added to the prepared suspension to pH about 9.0. The pH-adjusted suspension was homogenized several times using a high pressure homogenizer at a pressure of about 500 to 600 bar and then passed through a medium with a 1.0 micrometer pore to filter foreign matter. While replacing nitrogen, the filtrate was filled into the infusion bottle or chamber bag to the indicated amount using a charger. After filling is complete, seal it with a rubber stopper and kill the bacteria inside the filling solution by autoclaving or hot water sterilization at about 121 ℃ for 15 minutes.

Lipid sap containing chioctic acid and gaba was prepared.

Example 16: Preparation of Lipid Sap Containing Bile Acid, Chioctic Acid, and Gava

After mixing soybean oil, olive oil, and MCT in a suitable container as described in each component and content according to Table 1 below, UDCA and chioctic acid were added, dissolved by heating to about 120 ℃ and cooled to about 80 ℃. Egg yolk lecithin was added and dissolved by running a high speed stirrer.

After putting 0.2L of water for injection in a separate container, Gaba and glycerol were added and stirred, and the mixture was mixed and stirred again to prepare a suspension. A pH adjuster was added to the prepared suspension to adjust the pH to about 9.0. The pH-adjusted suspension was homogenized several times using a high pressure homogenizer at a pressure of about 500-600 bar and then passed through a medium with a 1.0 micrometer pore to filter foreign matter. While replacing nitrogen, the filtrate was filled into the infusion bottle or chamber bag to the indicated amount using a charger. After the filling was completed, it was sealed with a rubber stopper, and the bacteria inside the filling solution were killed by autoclaving or hydrothermal sterilization at about 121 ° C. for 15 minutes to prepare a lipid sap containing UDCA, chioctic acid, and gaba.

Example 17 Preparation of Lipid Sap Containing Bile Salts, Chioctic Acid, and Gava

Soybean oil, olive oil, MCT and chioctic acid were mixed in a suitable container as shown in Table 1 below, and then dissolved by heating to about 120 ° C and then cooling to about 80 ° C. After adding egg yolk lecithin, it was dissolved by operating a high speed stirrer.

0.2L water for injection in a separate container, UDCA Na, Gaba and glycerol were added and stirred, mixed, and then the mixture was mixed again and stirred to form a suspension, and then adjusted to pH 9.0 by adding a pH adjuster. . The pH-adjusted suspension was homogenized several times using a high pressure homogenizer at a pressure of about 500-600 bar and then passed through a mediator with a 1.0 micrometer pore to filter foreign matter. The filtrate was filled in the infusion bottle or chamber bag to the indicated amount using a charger, replacing nitrogen as needed. After the filling was completed, sealed with a rubber stopper, and killed the bacteria in the filling solution by autoclaving or hot water sterilization at about 121 ℃, 15 minutes to prepare a lipid sap containing UDCA Na, chioctic acid and Gaba.

Example 18 Preparation of Triple Chamber Bags Containing Bile Acids, Chioctic Acid, and Gava

1) Preparation of Amino Acid Layer

To prepare according to the components and contents according to Table 1 below, except that it does not contain bile salts in the same manner as in the preparation method of Example 1 to prepare an amino acid sap, and to form an amino acid layer.

2) Preparation of Glucose Layer

To prepare according to each component and content according to Table 1, except that it does not contain bile salts in the same manner as in the preparation method of Example 6 to prepare a glucose sap, and to form a glucose layer.

3) Preparation of Geological Layer

The lipid sap was prepared by the same method as the preparation method of Example 16 according to each component and the content according to Table 1 to form a lipid layer.

Example 19 Preparation of Triple Chamber Bags Containing Bile Salts, Chioctic Acid, and Gava

1) Preparation of Amino Acid Layer

To prepare according to the components and contents according to Table 1 below, except that it does not contain bile salts in the same manner as in the preparation method of Example 1 to prepare an amino acid sap, and to form an amino acid layer.

2) Preparation of Glucose Layer

To prepare according to each component and content according to Table 1, except that it does not contain bile salts in the same manner as in the preparation method of Example 6 to prepare a glucose sap, and to form a glucose layer.

3) Preparation of Geological Layer

The lipid sap was prepared by the same method as the preparation method of Example 17 according to each component and the content according to Table 1 to form a lipid layer.

Example 20 Preparation of Triple Chamber Bags Containing Bile Salts, Chioctic Acid, and Gava

1) Preparation of Amino Acid Layer

To prepare according to each component and content according to Table 1, except that the filling in the chamber bag was carried out in the same manner as in the manufacturing method of Example 2 to prepare an amino acid sap, and to form an amino acid layer.

2) Preparation of Glucose Layer

To prepare according to each component and content according to Table 1, except that it does not contain bile salts in the same manner as in the preparation method of Example 6 to prepare a glucose sap, and to form a glucose layer.

3) Preparation of Geological Layer

The lipid sap was prepared by the same method as the preparation method of Example 13 according to each component and the content according to Table 1 to form a lipid layer.

Example 21 Preparation of Triple Chamber Bags Containing Bile Salts, Chioctic Acid, and Gava

1) Preparation of Amino Acid Layer

To prepare according to the components and contents according to Table 1 below, except that it does not contain bile salts in the same manner as in the preparation method of Example 1 to prepare an amino acid sap, and to form an amino acid layer.

2) Preparation of Glucose Layer

To prepare according to each component and content according to Table 1, except that the filling in the chamber bag was carried out in the same manner as in the manufacturing method of Example 7 to prepare a glucose sap, to form a glucose layer.

3) Preparation of Geological Layer

The lipid sap was prepared by the same method as the preparation method of Example 13 according to each component and the content according to Table 1 to form a lipid layer.

Example 22 Preparation of Triple Chamber Bags Containing Bile Salts, Chioctic Acid, and Gava

1) Preparation of Amino Acid Layer

0.4L of water for injection was put in a tank of an appropriate capacity, and then L-isoleucine, L-leucine, acetate-L-lysine, L-methionine, L-phenylalanine, and L-threonine as shown in Table 1 below. , L-Tryptophan, L-valine, L-alanine, L-arginine, L-aspartic acid, L-cysteine, L-histidine, L-proline, L-serine, L-tyrosine, aminoacetic acid, Gaba and UDCA Na After cooling to room temperature, the pH was adjusted to slightly acidic to neutral using hydrochloric acid or sodium hydroxide. The solution was passed through a media layer with a 0.2 micrometer pore to filter the microorganisms and particulates. While replacing nitrogen, the filtrate was filled into the infusion bottle or chamber bag to the indicated amount using a charger. After the filling was completed, it was sealed with a rubber stopper, and the bacteria in the filling solution were killed by autoclaving or hot water sterilization at about 121 ° C. for 15 minutes to prepare an amino acid sap to form an amino acid layer.

2) Preparation of Glucose Layer

0.4L of water for injection was put in a tank of an appropriate capacity, and then dissolved in glucose, calcium chloride, magnesium chloride, potassium dihydrogen phosphate, and sodium chloride as shown in Table 1 below and then cooled to room temperature, and citric acid as a pH adjuster. Or it was adjusted to mildly acidic to neutral with sodium hydroxide. The solution was passed through a media layer with a 0.2 micrometer pore to filter the microorganisms and particulates. The filtrate was filled in the infusion bottle or chamber bag to the indicated amount using a charger, replacing nitrogen as needed. After the filling was completed, it was sealed with a rubber stopper, and the bacteria in the filling solution were killed by autoclaving or hydrothermal sterilization at about 121 ° C. for 15 minutes to prepare a glucose sap.

3) Preparation of Geological Layer

Soybean oil, olive oil, MCT in a suitable container as shown in each component and content according to the following Table 1 was added to the chioctic acid was dissolved by heating to about 120 ℃ and cooled to about 80 ℃. Egg yolk lecithin was added and dissolved by running a high speed stirrer.

After putting about 0.2L of water for injection in a separate container, glycerol was added and stirred, and the mixture was mixed and stirred again to prepare a suspension. A pH adjuster was added to the prepared suspension to pH about 9.0. The pH-adjusted suspension was homogenized several times using a high pressure homogenizer at a pressure of about 500 to 600 bar and then passed through a medium with a 1.0 micrometer pore to filter foreign matter. While replacing nitrogen, the filtrate was filled into the infusion bottle or chamber bag to the indicated amount using a charger. After the filling was completed, it was sealed with a rubber stopper, and the bacteria in the filling solution were killed by autoclaving or hot water sterilization at about 121 ° C. for 15 minutes to prepare a lipid sap containing chioctic acid.

In order to compare the effect of the fluid composition was tested with Example 22, Comparative Example 1 and Comparative Example 2. As Comparative Examples 1 and 2, commercial nutrient solutions Oli-Clinomel ^® N4 and N7 (manufactured by baxter) were used.

Composition Comparative Example 1
Peripheral
Oli-clinomel
N4 1000ml) Comparative Example 2
(Central
Oli-Climomel
N7 1000ml) Example 22 Lipid (g) 200 ml 200 ml 200 ml olive oil 16 32 7.5 Soybean oil 4 8 11.5 MCT - - One Chioctic acid - - 0.2 Amino acid (g) 400ml 400ml 400ml L-alanine 4.56 8.28 3.36 L-arginine 2.53 4.6 6.148 Glycine 2.27 4.12 2.16 L-histidine 1.06 1.92 1.24 L-isoleucine 1.32 2.4 3.68 L-Leucine 1.61 2.92 3.78 L-lysine HCl 1.6 2.9 - Acetic L-Lysine - - 1.58 L-Methionine 0.88 1.6 0.18 L-phenylalanine 1.23 2.24 0.12 L-proline 1.5 2.72 2.12 L-serine 1.1 2 1.04 L-threonine 0.92 1.68 0.856 L-Tryptophan 0.4 0.72 0.28 L-tyrosine 0.09 0.16 0.16 L-valine 1.28 2.32 3.56 L-cysteine - - 0.1 L-aspartic acid - - 0.08 GABA - - 0.75 UDCA Na (50 mg as UDCA) - - 0.053 Glucose (g) 400ml 400ml 400ml Glucose monohydrate 88 166 - Glucose anhydride 100 Electrolyte (mmol) salt 21 32 25 potassium 16 24 24 calcium 2 2 3.2 magnesium 2.2 2.2 2.4 Goat 33 48 40 Phosphate 8.5 10 6.4 acetate 30 57 27.2 sum Nitrogen (g) 3.6 6.6 4.88 Total Amino Acid (TAA) (g) 22 40 30 Branched amino acid (BCAA) (g) 4.21 7.64 11.02 BCAA / TAA (%) 19.1 19.1 36.7 Aromatic amino acid (AAA) (g) 1.72 3.12 0.56 Essential Amino Acids (EAA) (g) 8.92 16.20 13.58 Non-Essential Amino Acids (NEAA) (g) 13.11 23.80 16.23 EAA / NEAA (%) 68.04 68.07 83.66 Fisher ratio (M) 4.2 4.2 54.2 Total calories (kcal) 610 1,200 855 Non-protein calorie (NPC) (kcal) 520 1,040 735 Glucose (kcal) 320 640 240 Lipid (kcal) 200 400 495 NPC / N 144 158 149 pH 6 6 6 mOsm / L 750 1,450 909

Experimental Example 1: Stability Test

Stability experiments were carried out for the Examples and Comparative Examples prepared above. As shown in Table 3 below, the long-term and accelerated stability tests were performed for each test item for 6 months, and the sap compositions of the examples satisfied the criteria in all the test items. On the other hand, the comparative examples did not meet the criteria in most test items.

Test Items Comparative Example 1 Comparative Example 2 Example 22 Example 2 Example 8 Example 17 Example 18 Example 21 Appearance fitness fitness fitness fitness fitness fitness fitness fitness Test fitness fitness fitness fitness fitness fitness fitness fitness Purity Test incongruity incongruity fitness fitness fitness fitness fitness fitness content amino acid incongruity incongruity fitness fitness - - fitness fitness glucose incongruity incongruity fitness - fitness fitness fitness fitness Geology incongruity incongruity fitness - - - fitness fitness Electrolyte fitness incongruity fitness fitness fitness - fitness fitness GABA - - fitness fitness fitness fitness fitness fitness UDCA Na - - fitness - fitness fitness - fitness UDCA - - - - - - fitness - Chioctic acid - - fitness - - fitness fitness fitness

Experimental Example 2: Confirmation of improvement effect on cholestasis, hepatic value, elevated blood sugar in liver injury model rat

For the sap of Example 22 and Comparative Examples 1 and 2, hepatic damage model rats were used to evaluate the effect of improving the bile ducts and liver levels, and normal rats were used to evaluate the effect of improving blood glucose levels. Hepatic injury was induced by i.p administration of 400 mg / kg galactosamine to 7-week-old male SD rats.

(1) Evaluation of liver damage inhibitory effect

The control and test materials were pretreated for 4 days once a day. Hepatic damage was induced after 18 hours and one additional dose of control and test substance was added after 6 hours. After 18 hours of additional administration, blood samples were collected from the abdominal vein and centrifuged (1000 rpm, 5 min). Hepatic damage inhibitory effects were evaluated by comparing liver enzyme (ALT, AST, g-GTP) levels of the control and test groups.

As a result of comparison between normal and negative control group, AST and ALT were significantly increased, indicating liver damage caused by galactosamine. In the group administered with Example 22 compared to the negative control group, it was confirmed that the ALT item was significantly reduced compared to the negative control group, and in the group administered Comparative Example 1 and Comparative Example 2, there was no significant decrease in the numerical value compared to the negative control group. .

Test group AST (IU / L) ALT (IU / L) Normal 103.42 ± 14.34 * 58.07 ± 5.20 * Vehicle 204.12 ± 86.95 99.77 ± 41.28 Comparative Example 1 140.58 ± 52.18 53.76 ± 9.43 Comparative Example 2 150.22 ± 54.05 78.12 ± 36.54 Example 22 125.32 ± 26.43 52.28 ± 2.60 *

(*, p <0.05 vs Vehicle)

(2) antioxidant effect evaluation

The control and test materials were pretreated for 4 days once a day. Hepatic damage was induced after 18 hours and one additional dose of control and test substance was added after 6 hours. Eighteen hours after the additional administration, blood samples were collected from the abdominal vein and centrifuged (13,000 rpm, 5 min), and plasma MDA (Malondialdehyde) levels were analyzed using an ELISA kit. The antioxidant effects of the test substances were evaluated by comparing the MDA values of the control and test groups.

Negative control group induced oxidative stress through liver damage was significantly elevated in blood MDA compared to normal group. Comparative Example 1 and Comparative Example 2 did not significantly reduce the MDA value compared to the negative control group, while Comparative Example 22 was confirmed to significantly reduce the MDA value compared to the negative control group.

Test group Malondialdehyde (MDA) Normal 4.957 ± 0.913 * Vehicle 20.367 ± 11.462 Comparative Example 1 9.097 ± 2.538 Comparative Example 2 5.526 ± 0.516 *- Example 22 4.072 ± 1.501 *

(*, p <0.05 vs Vehicle)

(4) Evaluation of blood sugar improvement effect

1) Blood glucose measurement: After administration of the test substance for 4 days, 16 g of fasting and 2 g / kg of glucose were orally administered to each experimental animal. Thereafter, changes in blood glucose over 2 or 4 hours were observed.

2) Insulin measurement: At the end of the final blood glucose observation, blood collection was performed in the abdominal vein and the blood insulin concentration was quantified using the ELISA kit.

The sap of Example 22 was converted to energy instead of sugar in the muscle compared to Comparative Examples 1 and 2, and the aromatic amino acid excess because of the high content of branched amino acids used to make muscle protein and enzymes, and very high Fischer ratio. It can be expected that consciousness, confusion, and lethargy can be prevented. In addition, the sap of Example 22 had a high proportion of essential fatty acids and a low proportion of non-essential amino acids that were broken down in the liver, kidney, and uterus to produce ammonia, thereby making the liver and kidneys tired.

Olive oil and soybean oil also contain saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids, respectively. According to the British Pharmacopoeia, the lipid composition of olive oil consists of 8 ~ 22% saturated fatty acids, 56 ~ 89% monounsaturated fatty acids, and 3.5 ~ 21% polyunsaturated fatty acids, and 3.5 ~ 20% omega 6 in polyunsaturated fatty acids. Omega 3 is less than 1.2%. Soybean oil has a lipid composition of 12 ~ 20% saturated fatty acid, 17 ~ 31% monounsaturated fatty acid, and 53 ~ 69% polyunsaturated fatty acid. It contains 48 ~ 58% omega 6 and 5% omega 3 in polyunsaturated fatty acid. ~ 11%. In addition, medium chain fatty acids (MCT) almost all belong to saturated fatty acids. In view of such a composition, it can be seen that in the lipid layers, the ratios of omega 6: omega 3 are 8: 1 and sap of Example 22 is 7: 1 in Comparative Examples 1 and 2. As described above, the sap of Example 22 has a higher ratio of omega 3 compared to Comparative Examples 1 and 2, indicating that the burden on the cardiovascular system is less.

Claims (10)

An intravenous infusion solution composition comprising at least one component selected from the group consisting of bile acids of formula (1) and derivatives thereof, gaba and derivatives of formula (2), chioctic acid and salts thereof:
[Formula 1]

(2)

Where
R ₁ is a hydroxy group, glycine group or taurine group,
R ₂ and R ₃ are each independently hydrogen or a hydroxyl group,
R ₄ and R ₅ are each independently hydrogen, methyl group, isobutyl group, phenyl or cyclohexyl group substituted with halogen;
R ₆ is hydrogen or a vinyl group.
The method of claim 1,
The intravenous infusion solution composition wherein the bile acid or a derivative thereof is ursodeoxycholic acid, glycoursodeoxycholic acid, taurusodeoxycholic acid, kenodeoxycholic acid, cholic acid, glycocolic acid, taurocholic acid, deoxycholic acid or lithopholic acid.
The method of claim 1,
A bile acid, a bile acid derivative or a salt thereof is an intravenous infusion composition comprising 0.002 to 0.05 wt / v%.
The method of claim 1,
The intravenous infusion solution composition wherein the derivative of Gaba is gabapentin, pregabalin, baclofen, vigabatrin, 3-methylgava, or 3,3-dimethylgava.
The method of claim 1,
The gaba, gaba derivatives or salts thereof are included in a total of 0.01 to 0.6 wt / v% intravenous infusion composition.
The method of claim 1,
The chioctic acid or a salt thereof is an intravenous infusion composition comprising a total of 0.01 to 0.08 wt / v%.
The method of claim 1,
The composition is an intravenous infusion solution composition further comprises one or more components selected from the group consisting of amino acids, sugars, vitamins, electrolytes, pH adjusting agents, stabilizers, osmotic pressure adjusting agents and dissolution aids.
The method of claim 1,
The composition is an intravenous infusion solution composition for preventing or treating side effects due to the supply of fluids selected from cholestasis, diabetes, reduced liver function or antioxidant function.
One or more chamber bags,
Each chamber bag is a vein comprising an intravenous infusion solution composition independently comprising at least one component selected from the group consisting of bile acids and their derivatives of Formula 1, Gaba and its derivatives of Formula 2, chioctic acid and salts thereof Injectable Infusions:
[Formula 1]

(2)

Where
R ₁ is a hydroxy group, glycine group or taurine group,
R ₂ and R ₃ are each independently hydrogen or a hydroxyl group,
R ₄ and R ₅ are each independently hydrogen, methyl group, isobutyl group, phenyl or cyclohexyl group substituted with halogen;
R ₆ is hydrogen or a vinyl group.
10. The method of claim 9,
The intravenous infusion solution includes one or more chamber bags selected from the group consisting of an amino acid chamber bag, a sugar chamber bag and a lipid chamber bag.