KR101746099B1 - Liver function improved composition and method of manufacturing the liver function improving agent using the same - Google Patents
Liver function improved composition and method of manufacturing the liver function improving agent using the same Download PDFInfo
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- KR101746099B1 KR101746099B1 KR1020150075988A KR20150075988A KR101746099B1 KR 101746099 B1 KR101746099 B1 KR 101746099B1 KR 1020150075988 A KR1020150075988 A KR 1020150075988A KR 20150075988 A KR20150075988 A KR 20150075988A KR 101746099 B1 KR101746099 B1 KR 101746099B1
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Abstract
The present invention relates to a composition for improving liver function and a method for preparing a liver function improving agent using the composition. More particularly, the present invention relates to a composition for improving liver function and a method for preparing liver function improving agent using arginine aspartate (ATC), an arginine tydiacinate As an active ingredient, and a method for producing a liver function improving agent using the same.
The present invention relates to an arginine thiadiacate (ATC) which increases the activity of an alcohol dehydrogenase (ADH) and restores damaged hepatocytes; An amino acid complex comprising arginine aspartate to increase the resilience of degraded liver function due to damaged hepatocytes; A pharmaceutically acceptable excipient,
The amino acid complex further includes arginine glutamate, IMP, Inosine monophosphate, GMP, Guanosine monophosphate, Betaine and L-cysteine. And a method for producing a liver function improving agent using the same.
Description
The present invention relates to a composition for improving liver function and a method for preparing a liver function improving agent using the composition. More particularly, the present invention relates to a composition for improving liver function and a method for preparing liver function improving agent using arginine aspartate (ATC), an arginine tydiacinate As an active ingredient, and a method for producing a liver function improving agent using the same.
Currently, the market for aquaculture feedstuffs is about 500,000 tons, and the feed additive market that supports these feedstuffs is estimated to be about 8,000 tons, which is about 1-2% of the total feed market.
For example, it can be estimated that the liver function improver (soy sauce), food stimulant, and mineral preparation, which are traded in the feed additive market, are consumed by aquaculturists, including feed manufacturers, to a market size of 1.6 million tons . If this amount is converted into 16 billion won, replacing 30% of the total feed market can secure 4.8 billion won market.
In terms of amount, the average price of the liver-improving agent currently marketed among the feed additives is 20,000 ~ 25,000 won / kg. Considering that the minimum use amount for improving hepatic function is 1kg per 1 ton of the fish, About 18,000 kg should be used when breeding fish for 6 months. If we convert this into the amount of money, we can see that it is about 45 million won. This amount has been a big burden for the farmers.
In particular, glutathione, which is generally used in the case of liver function improving agents, is a main component, but since glutathione is composed of three amino acids composed of glutamine, glycine and cysteine and has a very large molecular weight, After being degraded by pepsin secreted from the liver, it is absorbed in the small intestine and used as a raw material for glutathione re - synthesis in the liver. However, the main effect of glutathione is a cytoprotective substance that performs antioxidant function in cells, and the mechanism that acts specifically in the liver has not been confirmed.
In addition, since glutathione is produced by artificially synthesizing a natural substance, its manufacturing method is difficult and its cost is increased, so that it is burdensome for general farmers to use. In addition, since glutathione is decomposed in the body and not used to improve liver function, there is a problem that a relatively large amount of glutathione should be used.
Therefore, by studying amino acid complexes that help restore liver function in animals such as fish, it is urgently required to develop a new technology for improving liver function, which can minimize the burden on end users.
The present invention has been made to solve the above problems and provides a composition for improving liver function which can be used as a high-efficiency feed additive by improving the liver function of an animal such as fish to improve activity, and a method for producing a liver function improving agent using the same It has its purpose.
In order to accomplish the above object, the present invention provides a composition for improving liver function, comprising: Arginine Tidiacicate (ATC) which increases the activity of alcohol dehydrogenase (ADH) and restores damaged hepatocytes; An amino acid complex comprising arginine aspartate to increase the resilience of degraded liver function due to damaged hepatocytes; And a pharmaceutically acceptable excipient, wherein the amino acid complex is selected from the group consisting of Arginine Glutamate, Inosine Monophosphate (IMP), Guanosine Monophosphate (GMP), Betaine Betaine) and L-cysteine (hereinafter, referred to as " L-cysteine ").
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More preferably, the composition for improving liver function comprises 2.5 to 10 wt% of the arginine tidiacicate (ATC), 2.5 to 10 wt% of the amino acid complex, and 80 to 95 wt% of the excipient Wherein the amino acid complex comprises 20 to 90 parts by weight of the arginine aspartate, 2 to 10 parts by weight of the arginine glutamate, 0.3 to 2 parts by weight of the inosine monophosphate (IMP) 0.3 to 2 parts by weight of the guanosine monophosphate (GMP), 0.3 to 2 parts by weight of betaine and 0.3 to 2 parts by weight of L-cysteine .
In order to accomplish the above object, the present invention also provides an ATC pretreatment step of pulverizing arginine tidiacicate (ATC); An amino acid complex pretreatment step of preparing an amino acid complex comprising arginine aspartate; And 2.5 to 10 wt% of the above arginine thiadiacate (ATC), 2.5 to 10 wt% of the amino acid complex and 80 to 95 wt% of the excipient to obtain a composition for improving liver function Wherein the amino acid complex in the amino acid composite pretreatment step is selected from the group consisting of arginine aspartate, arginine glutamate, inosine monophosphate (IMP), guanosine monophosphate (GMP , Guanosine Monophosphate, Betaine and L-cysteine are pulverized, and then 20 to 90 parts by weight of arginine aspartate, 2 to 10 parts by weight of arginine glutamate, 0.3 to 2 parts by weight of inosine monophosphate (IMP), 0.3 to 2 parts by weight of guanosine monophosphate (GMP), 0.3 to 2 parts by weight of betaine And a method for producing the agent for improving liver function using for improving the liver function, characterized in that formed by mixing the L- Cysteine (L-Cysteine) 0.3 ~ 2 parts by weight of the composition of a technical base.
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The composition for improving liver function according to the present invention and the method for producing a liver function improving agent using the same according to the present invention are characterized in that a composition for improving liver function comprises an amino acid complex comprising arginine aspartate and an arginine thiadiacate ) As an active ingredient, it has an effect of restoring damaged hepatocytes and increasing the resilience of liver function deteriorated due to damaged hepatocytes.
BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a graph showing the experimental feed-through rate according to a preferred experimental example of the present invention.
FIG. 2 is a graph showing the experimental weight gain ratio according to a preferred experimental example of the present invention.
FIG. 3 is a graph showing the daily growth rate of an experiment according to a preferred experimental example of the present invention.
FIG. 4 is a graph showing feed efficiency according to the experimental example of the present invention.
FIG. 5 is a graph showing the functional activity and the intracellular immunity increase according to the experimental example of the present invention.
FIG. 6 is a graph showing experimental discrimination stress responses according to a preferred experimental example of the present invention. FIG.
Hereinafter, preferred embodiments of the present invention will be described in detail.
The composition for improving liver function according to a preferred embodiment of the present invention may be composed of an amino acid complex including arginine tidiacetate (hereinafter referred to as ATC), arginine aspartate, and an excipient.
First, arginine thiadiate (ATC) is used to increase the activity of alcohol dehydrogenase (hereinafter referred to as ADH) to restore damaged hepatocytes, and is a raw material used as a bile acid secretion promoter and liver protecting agent can do.
That is, arginine thiadiacate (ATC) is an active ingredient of the present invention. It enhances the activity of alcohol dehydrogenase (ADH) to promote alcohol metabolism, restore damaged hepatocytes, activate various liver enzymes, It is a substance that supplies energy to a living body by promoting metabolism of the body.
And arginine thiadiate (ATC) reduces the concentration of triglyceride and cholesterol accumulated in the hepatocytes, inhibits the occurrence of fatty liver, and activates the ornithine circuit, thereby lowering the concentration of toxic ammonia in the body to protect the liver.
Such arginine thiadiacate (ATC) has the effect of preventing alcoholic fatty liver disease, alcoholic hepatitis and liver cirrhosis by defending the accumulation process of liver fat.
If arginine thiodiacate (ATC) is added in an amount of less than 2.5 wt% in the composition for improving liver function, it may be insufficient to promote the activity of alcohol dehydrogenase (ADH). If it exceeds 10 wt% Arginine thiadiate (ATC) is added in an amount in the range of 2.5 to 10 wt% because the content of other constituents other than diacetate (ATC) is small and it may be difficult for the liver function improving effect to be manifested .
Secondly, the amino acid complex is an effective ingredient of the present invention. It contains arginine aspartate which increases the ability of recovering liver function, which is deteriorated due to damaged hepatocytes, and is produced as a complex salt using sulfurous amino acid derivatives, acidic amino acids and basic amino acids This is an important constituent of high-efficiency feed additives for enhancing activity through improvement of liver function of animals such as fish.
In other words, it has been found that basic amino acids (Asp 0.42 g / 100 ml-H2O, Glu 0.72 g / 100 ml-H2O) with extremely low solubility in water and basic amino acids which have a good pharmacological action in vivo, , And water-soluble high-neutral-type amino acid complex salt, thereby minimizing side effects and enhancing feed efficiency and pharmacological effect.
In other words, arginine, a kind of basic amino acid that plays various roles and functions such as ammonia removal, antioxidative action, immunoregulation, wound healing and growth hormone releasing action in vivo, and both metabolism of TCA circuit and ornithine circuit Asparagine, which is an important acidic amino acid involved, and amino acid complex salt can be obtained by utilizing a cysteine derivative, which is a kind of sulfurous amino acid as a constituent of glutathione and has an action to regenerate liver function in an animal.
In other words, the amino acid complex is composed of arginine aspartate, arginine glutamate, inosine monophosphate (IMP), guanosine monophosphate (GMP), betaine and L-cysteine (L-cysteine). The thus formed amino acid complex improves the liver function of arginine thiadiate (ATC) by enhancing the recovery and regeneration ability of a living body with reduced hepatic function, thereby achieving the object of the present invention.
The arginine aspartate (L-arginine-L-aspartate) of the present invention has an effect of enhancing the vitality of an animal and plays a role in supporting symptoms of mental and physical dysfunction. When the amount of the arginine aspartate is less than 20 parts by weight, the effect of improving the vitality of the animal is not exhibited. When the amount of the arginine aspartate is more than 90 parts by weight, stability of the composition for improving liver function may not be proved. 90 parts by weight.
The arginine glutamate of the present invention means a mixture composed of arginine and glutamic acid, which are two amino acids used for improving liver function, and arginine glutamate also plays a role in promoting vitality enhancement effect of animals. Based on the results of repeated experiments, it can be seen that when the amount of arginine glutamate is less than 2 parts by weight, the activity of arginine glutamate can be reduced. When the amount of arginine glutamate is less than 10 parts by weight, It can be seen that arginine glutamate is preferably added in an amount of 2 to 10 parts by weight because the amount of arginine glutamate is not increased and the consumption of ingredients may be accelerated by adding a lot of ingredients.
Inosine monophosphate (IMP) of the present invention is a substance that increases immunity and induces growth. If it is less than 0.3 part by weight, it can not sufficiently perform an auxiliary role in increasing immunity, and if it does not exceed 2 parts by weight, It is preferable that the inosine monophosphate is added in the range of 0.3 to 2 parts by weight since it is possible to perform an auxiliary function sufficiently to improve the function.
The guanosine monophosphate (GMP) of the present invention is also referred to as 5'-guanidylic acid or guanylic acid, and may be a nucleotide used as a monomer of RNA. It is preferable that the above-mentioned guanosine monophosphate is contained in an amount of 0.3 to 2 parts by weight. If the amount is less than 0.3 part by weight, absorption of the body may be insignificant. If the amount exceeds 2 parts by weight, There is a fear that the action may be deteriorated.
The betaine of the present invention is a substance that increases immunity and induces growth, and is rich in methionine (a kind of sulfur-containing? -Amino acid) and an essential amino acid, thereby protecting the liver. In addition, Betain also plays a role in facilitating detoxification by eliminating blood, blood vessels, organs, wastes, and toxins. When the amount of betaine added is less than 0.3 part by weight, it may be insufficient to protect the liver. When the amount of betaine is more than 2 parts by weight, a more excellent effect is not obtained compared with the case where the amount of betaine is less than 0.3 part by weight. .
The L-cysteine of the present invention is a sulfur amino acid, and plays a role in detoxification action in the liver to enhance the function of the liver. It is also known that acetaldehyde, a carcinogenic substance, is degraded by L-cysteine, and its role is attracting attention. This means that L-cysteine neutralizes acetaldehyde when its concentration in the body is high. Furthermore, as L-cysteine is absorbed into the body, it rapidly activates in the improvement of liver function, so that the chemical structure is stable. When L-cysteine is added in an amount of less than 0.3 part by weight, the above-mentioned effect may not be sufficiently exhibited. When the amount of L-cysteine is more than 2 parts by weight, 2 parts by weight.
The inventors of the present invention have conducted myriad experiments. As a result, when the amount of the amino acid complex is less than 2.5 wt%, the inventors of the present invention have found that when the amount of the amino acid complex is less than 2.5 wt% (ATC), which increases the activity of the alcohol dehydrogenase (ADH) by excessively increasing the amount of the amino acid complex, if the concentration exceeds 10 wt%, the action of increasing the activity of the alcohol dehydrogenase (ADH) It is preferable that the amino acid composite is added in the range of 2.5 to 10 wt%.
As a result, it is possible to improve the liver function and activity of animals such as aquaculture fishes which have improved water solubility due to the amino acid complexes maintained in the range of 2.5 to 10 wt%, to improve the survival rate of the aquaculture fish through health management of fishes, It is possible to prepare a liver function improving agent which can contribute to the increase of the liver function.
Thirdly, the excipient is added to form a composition for improving liver function in an appropriate thickness or shape so that the liver function-improving agent can be easily handled and ingested. The excipient is added to a pharmaceutical composition such as glucose, calcium carbonate, soybean meal, sesame- Can be selected and used.
If the amount of the excipient is less than 80 wt%, the desired thickness or shape of the liver function improving agent may not be produced properly. If the amount of the excipient is more than 95 wt%, the content of arginine thiadiateate (ATC) , It is preferable that the excipient is contained in the range of 80 to 95 wt% in the composition for improving liver function.
Therefore, due to the excipient, it can be formulated into a conventional pharmaceutical preparation, for example, a liquid preparation such as a drink, a syrup, a capsule or the like.
Meanwhile, a method for preparing a liver function improving agent using the composition for improving liver function according to the present invention having the above-described constitution will be described as follows.
However, the thidiacicate (ATC), the amino acid complex and the excipient proposed in the method for producing a liver function improving agent using the composition for improving liver function are the same as those described above, and further explanation will be omitted here.
First, the ATC pretreatment step is a step of pulverizing arginine thiadiate (ATC).
That is, the ATC pretreatment step is a step of pulverizing arginine thiodiacate (ATC) using a pulverizer. When arginine thiadiate (ATC) is pulverized to less than 20 mesh, the efficacy is degraded due to nonuniform mixing of the sample, It is difficult to swallow animals such as fish due to foreign body sensation when ingestion of liver function improver. When crushed to above 50 mesh, arsenic thiodiacate (ATC) To 50 mesh.
Next, the amino acid composite pretreatment step is a step of preparing an amino acid complex containing arginine aspartate.
Specifically, arginine aspartate, arginine glutamate, inosine monophosphate, guanosine monophosphate, betaine and L-cysteine are respectively pulverized. Similar to arginine thyadacyate (ATC), when the amino acid complex is pulverized to less than 20 mesh, it may be difficult for the animal such as fish to swallow due to the deterioration of the effect due to the uneven mixing of the sample and the foreign body feeling when the completed liver function improving agent is ingested , And when it is crushed to more than 50 mesh, the amount of sample loss increases, which may be a disadvantage in the process. Therefore, each of the components constituting the amino acid composite is preferably pulverized to 20 to 50 mesh.
Thereafter, 20 to 90 parts by weight of arginine aspartate, 2 to 10 parts by weight of arginine glutamate, 0.3 to 2 parts by weight of inosine monophosphate, 0.3 to 2 parts by weight of guanosine monophosphate, 0.3 to 2 parts by weight of betaine And 0.3 to 2 parts by weight of L-cysteine are mixed to prepare an amino acid complex.
Finally, the step of forming a composition for improving liver function is a step of obtaining a composition for improving liver function by mixing arginine thiadiacate (ATC), amino acid complex and excipient.
Herein, compositions for improving liver function can be obtained by mixing 2.5-10 wt% of arginine thiadiate (ATC), 2.5-10 wt% of amino acid complex, and 80-95 wt% of excipient.
The composition for improving liver function thus obtained can be used indefinitely as a liver function improver, which is a feed additive. For example, 1 kg of a liver function improving agent composed of a composition for improving liver function per ton of feed for fish can be added and used.
Hereinafter, an experimental example for verifying the efficacy and stability of the liver function-improving agent, which is a feed additive of the present invention, will be described as follows.
<Experimental Example>
Experimental fishes were adapted for two weeks on the breeding experiment and fed commercial commercial feeds during the adaptation period. The size of the rockfish used in the experiment was 20g per paddy and about 2,000 paddies were housed in seven 4 × 4m water tanks. The volume of water was 80 L / min and sufficient oxygen was supplied during the experiment. Feeding the feed twice a day (08:00, 17:00) gave enough food to be 1.5-2.0% of the body weight. The mean temperature of the rearing water during the experiment was 13.6 ± 2.79 ℃, and the light followed the natural light cycle. The breeding experiment was a total of 8 weeks. The diets used in the experiment were fed with commercial diets (20 mg (A20), 40 mg (A40), 60 mg (A60), 80 mg (A80), 100 mg ) Was adsorbed and used. After completion of the experiment, the results of 70 percent of Korean rockfish were sampled to determine the growth rate, growth rate, feed efficiency, liver function, cell immunity and changes in cortisol levels.
1) The results of the growth rate, daily growth rate and feed rate are shown in Table 1 as follows.
(g / fish)
(g / fish)
(kg)
(g / fish)
Growth rate
(%)
FIG. 1 is a graph showing the experimental feed-through rate according to the preferred experimental example of the present invention, FIG. 2 is a graph showing the experimentally-measured weight gain according to the preferred experimental example of the present invention, FIG. 4 is a graph showing the experimental dietary efficiency according to a preferred experimental example of the present invention. Referring to FIGS. 1, 2, 3 and 4, it can be seen that the results shown in Table 1 are graphical.
2) Results of liver function activity and intracellular immunity increase are shown in Table 2 as follows.
(micromole / g)
(micromole / (minute x mg protein))
FIG. 5 is a graph showing the functional activity and intracellular immunity increase according to the experimental example of the present invention. Referring to FIG. 5, it can be seen that the results shown in Table 2 are graphical.
3) Results for the stress response are shown in Table 3 as follows.
(ng / ml)
(hr)
FIG. 6 is a graph showing an experimental discrimination stress response according to a preferred experimental example of the present invention. FIG. Referring to FIG. 6, it can be seen that the results shown in Table 3 are graphical.
4) Final conclusion
Eight weeks of experimental group showed the effect of feeding rate, weight gain, daily growth rate, feed efficiency, liver function and cell immunity in the experimental group supplemented with amino acid compound (amino acid). Although there was a difference in the degree of improvement of each growth and liver function according to the concentration of the amino acid complex, it was confirmed that the addition of the minimum amount of 20 mg or more resulted in the improvement effect.
Among the experiments of the present invention, experiments on a commercially available hepatic function-improving agent (hepatic system) were performed in parallel, and the effect was confirmed. However, it was found that the effect of increasing the feed rate was not observed in the glutathione supplement which is used as a general liver function improver.
Generally, glutathione is synthesized mainly in the liver and plays a role of preventing antioxidative action of whole cells. Since it exists in the form of a polymer having three amino acids bonded thereto, it is absorbed into the living body in a state in which the bond is released for digestion and absorption. Are synthesized.
In view of this, it is judged that the product sold as a conventional hepatic agent does not help to increase the absorption rate, the body weight gain rate and the hepatic functional activity by activating the liver function. The amino acid complex used in the experiment of the present invention, And it is considered that it can improve the efficiency of feed and improve the liver function.
As described above, the composition for improving liver function and the method for preparing liver function improving agent using the same according to the present invention are characterized by comprising an amino acid complex containing arginine aspartate and a liver function improving agent containing arginine thiadiateate (ATC) , It is possible to restore damaged hepatocytes and increase the resilience of degraded liver function due to damaged hepatocytes.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention may be embodied otherwise without departing from the spirit and scope of the invention. Therefore, the embodiments disclosed in the present invention are not intended to limit the technical spirit of the present invention, but are for the purpose of explanation, and the scope of technical spirit of the present invention is not limited by these embodiments. The scope of protection of the present invention should be construed according to the following claims, and all technical ideas within the scope of the claims should be construed as being included in the scope of the present invention.
Claims (5)
Arginine Tidiacicate (ATC), which increases the activity of alcohol dehydrogenase (ADH) and restores damaged hepatocytes;
An amino acid complex comprising arginine aspartate to increase the resilience of degraded liver function due to damaged hepatocytes; And
A pharmaceutically acceptable excipient,
In the amino acid complex,
Characterized in that it further comprises Arginine Glutamate, IMP, Inosine Monophosphate, GMP, Guanosine Monophosphate, Betaine and L-Cysteine. Or a pharmaceutically acceptable salt thereof.
The composition for improving liver function,
2.5 to 10 wt% of the arginine tidiacicate (ATC), 2.5 to 10 wt% of the amino acid complex, and 80 to 95 wt% of the excipient,
Wherein the amino acid complex comprises
20 to 90 parts by weight of the arginine aspartate, 2 to 10 parts by weight of the arginine glutamate, 0.3 to 2 parts by weight of the inosine monophosphate (IMP), the guanosine monophosphate 0.3 to 2 parts by weight of betaine, 0.3 to 2 parts by weight of L-cysteine, and 0.3 to 2 parts by weight of L-cysteine (GMP, Guanosine Monophosphate).
An amino acid complex pretreatment step of preparing an amino acid complex comprising arginine aspartate; And
Composition for improving liver function is obtained by mixing 2.5-10 wt% of arginine tidiacicate (ATC), 2.5-10 wt% of the amino acid complex and 80-95 wt% of excipient to obtain a composition for improving liver function Comprising:
Amino acid complex The amino acid complex in the pre-
Arginine aspartate, arginine glutamate, IMP, inosine monophosphate, guanosine monophosphate, betaine and L-cysteine. ) Were pulverized,
20 to 90 parts by weight of the arginine aspartate, 2 to 10 parts by weight of the arginine glutamate, 0.3 to 2 parts by weight of the inosine monophosphate (IMP), the guanosine monophosphate 0.3 to 2 parts by weight of betaine, and 0.3 to 2 parts by weight of L-cysteine are mixed with 0.3 to 2 parts by weight of a mixture of L-cysteine, GMP and guanosine monophosphate. ≪ / RTI >
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| KR20230054303A (en) | 2021-10-14 | 2023-04-24 | 주식회사 케어사이드 | Composition for prevention of pulmonary hypertension, prevention of liver disease caused by pulmonary hypertension, and improvement of liver function and Functional food comprising the same |
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| KR20230054303A (en) | 2021-10-14 | 2023-04-24 | 주식회사 케어사이드 | Composition for prevention of pulmonary hypertension, prevention of liver disease caused by pulmonary hypertension, and improvement of liver function and Functional food comprising the same |
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