KR20050021689A - Cholesterol in blood-lowering composition and its complex and methods for preparing them - Google Patents

Abstract

PURPOSE: A method for producing a cholesterol-lowering composition and the cholesterol-lowering composition therefrom are provided, which composition is stable to human, and is useful for treatment of hypercholesterolemia and prevention of heart disease and hypertension. CONSTITUTION: The method for producing the cholesterol-lowering composition comprises the steps of: (a) drying phytosterol/tannin and flavonoid-based hesperidin at room temperature; (b) dissolving the dried phytosterol/tannin and flavonoid-based hesperidin in solvent in a ratio of 10:1 to 1:10 and stirring the mixture to prepare a solution; (c) heating the solution of step (b) at 60 to 100 deg. C for 3 to 100 minutes and cooling the solution to the room temperature; (d) adding a weak acid solution into the solution, stirring the solution, and heating the solution at 60 to 100 deg. C for 3 to 100 minutes; and (e) removing the solvent from the solution, and drying the solution, wherein the solvent is water, ethanol or a mixture thereof; and the weak acid solution is fruit vinegar.

Description

Preparation method of composite composition for lowering blood cholesterol and composite composition produced by the same {CHOLESTEROL IN BLOOD-LOWERING COMPOSITION AND ITS COMPLEX AND METHODS FOR PREPARING THEM}

       The present invention relates to a method for producing a composite composition for lowering blood cholesterol and a composite composition prepared thereby.

      In general, cholesterol is known as a very important substance in the human body, such as the formation of cell membranes and steroid hormones.

      However, maintaining too high levels of LDL cholesterol or lipids in blood, especially LDL cholesterol and blood lipids, can increase the likelihood of disease or atherosclerosis and eventually lead to death or disability.

      As one of the methods to lower blood cholesterol, it is recommended to suppress the intake of foods high in cholesterol or saturated fatty acids, reduce weight and increase exercise.

      In many cases, however, this method is not effective and not easy to implement.

       Therefore, a more specific method has been exemplified. Among them, a method of inhibiting the absorption of cholesterol in the intestine has been proposed, and several therapeutic and food supplements have been developed and used for this purpose, but have side effects and are excellent in terms of efficacy. Can't.

      However, several studies have reported that phytosterol has little side effects and reduces blood cholesterol (see, eg, J. Nutr., 107, 2011 (1977)).

      In particular, beta-sitosterol can be easily obtained from soybeans or rice, and it has been confirmed that it has a similar structure to cholesterol except for an ethyl group of 24 carbon atoms, which is a competitive reaction that prevents the absorption of cholesterol in the human body. Atherosclerosis, 28,326 (1977).

       Natural phytosterols have the same basic skeleton in structure and slightly different branching chains.

        Most of the vegetable sterols consumed by food are beta-sitosterol and campesterol, and some of them are absorbed by the intestine and then released out of the body. There are no side effects.

      Therefore, in addition to vegetable sterols themselves, substances that lower blood cholesterol have been developed by using hydrogenated compounds such as ethanol and fatty acid esters thereof (see J. Lipid Res., 20, 646, ( 1979); J. Nutr., 107, 1139 (1977).

       Recently, it has been reported that margarine added with an ester compound of beta-cytostanol lowers blood cholesterol (see WO / 19640).

      However, despite the fact that such an effect, in fact, vegetable sterols have the disadvantage that only a small amount of absorption in the micelle (microcell) state of the small intestine, there is a difficulty in that excessive intake to obtain the actual effect.

      Therefore, while overcoming the above problems, the development of new substances of more effective cholesterol lowering agent is urgently required.

      In particular, coronary heart disease causes more than 30% of all deaths, which is a serious problem in developed countries such as the United States and Europe.In developing countries, heart disease is increased due to lack of eating habits and lack of exercise. The trend is.

      These coronary cardiovascular diseases are generally caused by excessive blood cholesterol levels. When the amount of cholesterol in the blood is high, macrophage and foam cells are formed and deposited on the walls of blood vessels. Atherosclerosis is known to be easy to form by inhibiting blood circulation. Ross, R., Nature, 362, 801-809 (1993).

      To reduce the amount of cholesterol in the blood, cholesterol ester delivery that inhibits the activity of acyl CoA (cholesterol-o-acyltransferase (ACAT) in the liver or mediates cholesterol transfer between lipoproteins Inhibits the action of the cholesterol (cholesterol ester transfer protein, CETP), or inhibits the action of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is involved in cholesterol biosynthesis in the liver. have.

     The ACAT is an enzyme that converts cholesterol esters into human tissues. Foam cells that are deposited on the walls of blood vessels during atherosclerosis are formed by the action of ACAT. These foam cells contain cholesterol esters carried by LDL in the blood. It contains a lot.

      In other words, foam cells in the arterial vessel wall are often found with increased ACAT activity, and inhibiting ACAT activity in the liver can lower the level of LDL-cholesterol in the blood (Witiak, DT and DRFeller (eds)). , Anti lipidemic Drags: Medicinal, Chemical, and Biochemical Aspects, Elsevier, pp 159-195 (1991)).

      In addition, HMG-CoA reductase is an enzyme that mediates the synthesis of mevalonic acid, an intermediate step in the biosynthesis pathway of sterols or isoprenoid compounds, and slows down the rate of cholesterol biosynthesis if the enzyme is reduced in activity. Inhibitors of this enzyme can be effectively used to treat hypercholesterolemia (William, WP, Cardiovascular Pharmacologe, Kanu Chatterjee (ed). Wolfe Pullishing, 8.6.-8.7 (1994)).

      Inhibitors of HMG-CoA reductase currently in use include lovastatin and simbastatin, derived from Penicillium or Aspergillus, developed by Merck, USA, and pravastatin, developed by Sankyo, Japan. (pravastatin).

       However, statins can cause side effects in the central nervous system (Saheki, AT et al., Pharm, Res., 11, 304-311 (1994)), and lovastatin and simvastatin may inhibit the activity of LDL receptors in the liver. Increasing the amount of LDL-cholesterol in the blood, however, has been reported to cause side effects such as increased levels of other enzymes, increased creatine kinase, and rhabdomyolysis (Farmer, JA et al. , Baillers-clin.Endocrinol. Metab., 9, 825-847 (1995).

      Therefore, the development of a new HMG-CoA reductase activity inhibitors that are cheap and have no side effects is in progress.

      On the other hand, excessively ingested foods or alcohol containing a lot of fat components, or infected with hepatitis B or C virus, such as hepatitis, hepatic lesions, liver cancer, if the liver function is reduced and worsened.

      In particular, ingesting excess fat through food becomes fatty liver, and lipids accumulate in liver tissue, and excessive alcohol intake can also cause fatty liver.

      Fatty liver increases GOT (glutamate-oxaloacetate transaminase), GPT (glutamate-pyruvate transaminase), and gamma-GPT (gamma-glutamyl transpeptidase) in serum (T. Banciu, et al., The Hepatic Component in Alcoholic). Encephalopath ', Med. Lnterne., 20, 69-71 (1982): and A. Par, et al.,' Serum Gamma-Glutamy Transpeptidase: 1ts Cliniccal Significanse ', Acta. Med. Acad. Sci. Hung., 33 , 309-319 (1976).

        Hayashi et al. Concluded that the administration of green tea extract to rats prevented the increase of serum GOT and GPT, which could be seen as an effect of green tea on liver function in rats (M. Hayaya, et al. , Nippon Yakuri.Gaku Zasshi, 100, 391-399 (1992).

 In order to reduce blood cholesterol, especially LDL (LOW-DENSITY LIPOPROTEIN) cholesterol and to help treat hypercholesterolemia and some heart diseases, the main component is phytosterol, a natural plant sterol, and hesperidin, a tannin and flavonoid strain. It is to provide a composite composition comprising a medicinal preparation, liquid injection, food additives and the like.

In order to achieve this object, in the present invention, the complex composition for lowering blood cholesterol is characterized by including hesperidin, a natural vegetable sterol and tannin and flavonoid strains in a weight ratio of 10: 1 to 1:10. .

In other words, in the present invention, the phytosterol / tannin and flavonoid-based hesperidin complex composition prepared by mixing phytosterol, a natural vegetable sterol, which can be used safely without harming the human body, and hesperidin, a tannin and flavonoid strain, have no expectation of lowering blood cholesterol. After confirming that the synergistic effect has not been completed, the present invention has been completed.

Representative examples of the phytosterols described above are beta-stosterol, campy sterol, stigma sterol, foco sterol, brassica sterol and the like.

In the present invention, one or a mixture of two or more thereof may be used as the main component of the aforementioned vegetable sterols.

The tannin is generally contained in stems, leaves, roots, etc. of plants, or may be used in fruits and vegetables, immature fruits and vegetables, seeds of plants, and the like.

It has recently been found that tannin compounds have various physiological activities. For example, they have been shown to exhibit various physiologically active functions in addition to improving blood circulation and antioxidant effects.

Looking at these tannins by category,

(Iii) catechins and their derivatives,

(Ii) leucoanthocyanins,

(Iii) anthocyanidins,

(Iii) Acids with phenolic groups, such as chlorogenic acid, that is, polyphenolic acids.

As one component of the composite composition in the present invention, one or a mixture of two or more of the above-described tannin compounds may be used.

A typical example of the catechins is catechin, which has a C6-C3-C6 carbon skeleton, which is a structural feature common to flavonoids and anthocyanins. .

Tannins belonging to this category include catechins (catechin, trans-form), epicatechin (epi-catechin, cis-form), 3-galloyl epi-catechin, 3-galloylgallocatechin (3- galloyl gallocatechin).

Representative examples of the leucoansocyanins include leucoanthocyanidins and leucoolinidine.

Ansocyanidins of the ansocyanidins have a basic structure of 3,5,7-trihydroxy flavylium chloride (3,5,7-trihydroxy flavylium cholride).

The content ratio of phytosterol, a main component of the composite composition of the present invention, and hesperidin, a tannin and flavonoid strain, is 10: 1 to 1:10 by weight as described above, and more preferably 4: 6 to 6: 4.

If necessary, other known compounds may be included in addition to the main components, which may further enhance the effects of the present invention.

Synergistic effects have been demonstrated with simple mixed compositions, not in the form of a complex of picosterol, tannin and hesperidin, a flavonoid family.

Accordingly, it can be seen that the present invention also provides a complex composition for lowering blood cholesterol comprising phytosterol in a weight ratio of 10: 1 to 1:10 and hesperidin, a tannin and flavonoid lineage, as its main components.

However, the composite composition obtained by dissolving phytosterol, tannin, and flavonoid-based hesperidin together in a solvent and heat treatment under certain conditions further enhances the synergistic effect by mixing the two components.

Accordingly, the present invention provides a method for preparing the hesperidin complex composition of the phytosterol / tannin and flavonoid lineage.

In the present invention, a method for preparing a complex composition for lowering blood cholesterol requires drying of phytosterol, tannin, and flavonoid-based hesperidin in an acidic solvent, and then reacting at 20 to 100 ° C to remove and dry the solvent from the product. Include.

More specifically, the manufacturing method

(A) drying the phytosterol and the tannin and flavonoid line hesperidin at or near the room temperature, respectively;

(B) dissolving the dried phytosterol, tannins and flavonoid-based hesperidin in a solvent in a weight ratio of 10: 1 to 1:10, followed by stirring to prepare a uniform solution;

(C) heating the solution at 60 to 90 ° C. for 3 to 100 minutes, and then cooling the solution to room temperature or near its temperature before and after;

(D) adding a weakly acidic solution, stirring the solution in an acidified state, and then heating at 60-90 ° C. for 3-100 minutes; And

(E) removing the solvent and drying the resulting material.

More preferably, the heating temperature of the step (C) and (D) is about 70 ° C and the heating time is about 5 to 30 minutes.

As the solvent used in step (B), water, ethanol, a mixture of water and ethanol may be used.

As the weakly acidic solution used in the step (D), preferably an edible acidic solution, fruit vinegar, etc. may be used as a representative example.

The composite composition of the present invention can be used in various forms such as medicinal preparations for lowering blood cholesterol, medicinal injectables, food additives, etc. by directly or adding other necessary ingredients.

For example, in the case of medicinal preparations, the complex composition may be used as an active ingredient, but other excipients may be mixed in the form of a preparation. In the case of medicinal injectables, the complex composition may be used as an active ingredient, but a solvent such as distilled water or saline solution may be used. It can be dissolved in and used.

In particular, when used as a food additive can be used in the form of adding to foods with high cholesterol, the complex composition of the powder can be used simply by adding to the food raw materials or food finished products.

Even if a large amount of the composite composition is not particularly harmful to the human body, there is no limit to the daily dose.

However, it is particularly preferable that the daily dose of 10g or less based on the adult (60kg).

Therefore, the present invention is a blood cholesterol lowering agent, a blood cholesterol injection comprising the complex composition as an active ingredient. Food additives for lowering cholesterol in the blood, and various foods including the composite material can be used.

The preparation method of the preparations, injections and food additives will not be described separately since the general preparations and preparations of the injections can be used as they are.

In addition, the method for preparing a food containing the composite composition of the present invention may be added in various ways under the condition that the activity of the present ingredient is not impaired.

In other words, when the food is subjected to excessive heat in the manufacturing process may be added in the final state of the food, if the excessive heat in the manufacturing process may be added together in the raw material state and processed together.

The food is not particularly limited in form.

That is, the concept includes both liquid foods such as drinks and solid foods such as meat for hamburgers.

Therefore, the composite composition of the present invention can be used as a medicinal agent, a medicinal injectable, a food additive, or the like to lower blood cholesterol or inhibit absorption of cholesterol, thereby treating hypercholesterolemia and treating some heart diseases.

The following examples illustrate the content of the present invention in more detail, but the following examples are only illustrative and do not limit the scope of the present invention.

Example 1 Preparation of a Complex Composition of Beta-Sito Sterol and Hecateridine, a Catechin and Flavonoid Lineage

A mixture of 200 mg of kena-sitosterol, a type of phytosterol, and 280 mg of hesperidin, a type of tannin, a catechin and a flavonoid family, was dried at room temperature for 30 minutes.

50 mg of ethanol aqueous solution was added to the mixture to make a uniform solution with stirring for 1 hour.

This solution was heated at 70 ° C. for about 20 minutes.

The material is cooled to room temperature for 30 minutes, and then acidified by adding 10 ml of fruit vinegar.

The acidified solution is again stirred at room temperature for 15 minutes and then heated at 70 ° C. for about 5 minutes.

The excess solvent was removed and the formed material was dried and then filtered through a 20 mesh sieve to obtain a uniform product.

Example 2: Animal test for the composite composition prepared in Example 1

Thirty four week-old Sprauque-Dawley rats were normalized under laboratory conditions for one week, and then divided into four groups. Cholesterol and cholic acid were fed into the feed by 1% and 0.5%, respectively. After addition, it was fed for a week to raise blood cholesterol level.

Subsequently, the total cholesterol level, LDL-cholesterol level and HDL-cholesterol level over time were measured with the addition of 0.5%, 1% and 3% of the composite composition at different concentrations.

The results are shown in Table 1 below.

Table 1

group

Condition

Total Cholesterol Level (Decrease Rate)

LDL-

cholesterol

HDL-

cholesterol

Group 1

(Control)

1% cholesterol + 0.5% cholic acid

254

172

79

Group 2

1% cholesterol + 0.5% cholic acid

+ 0.5% composite material

209 (18%)

135

72

Group 3

1% cholesterol + 0.5% cholic acid

+ 1% composite material

186 (27%)

119

70

Group 4

1% cholesterol + 0.5% cholic acid

+ 3% composite material

169 (34%)

91

71

Unit: mg / dl

At this time, group 2 and 3 are the results after 2 weeks, and group 4 is the result after 5 days.

As shown in Table 1, the effect of lowering blood cholesterol by the composite composition of the present invention was very excellent.

Groups 2 and 3 showed a decrease in total cholesterol levels to 18% and 27%, respectively, two weeks after the effect was slowly due to the low concentration of the composites. As a result, blood cholesterol levels of 34% were reduced in just 5 days.

Therefore, it was confirmed that the composite composition of the present invention lowered the total cholesterol level in blood and decreased LDL-cholesterol, but did not affect the absorption of useful HDL-cholesterol, thereby obtaining satisfactory results.

As described above and the composite composition of the present invention is a phytosterol / tannin and flavonoid-based hesperidin complex composition prepared by mixing phytosterol which is a natural plant sterol which can be used safely without harming the human body, and hesperidin which is a tannin and flavonoid strain. It is effective in the treatment of hypercholesterolemia or prevention of heart disease and high blood pressure by providing blood cholesterol cholesterol, thereby reducing the blood cholesterol, and thus can be used for the preparation of health functional foods in medicinal preparations, medicinal injectables as well as other foods and beverages. .

Claims (12)

(A) drying the phytosterol and the tannin and flavonoid line hesperidin at room temperature or above and below the temperature respectively; (B) dissolving the dried phytosterol and tannin and flavonoid-based hesperidin in a solvent in a weight ratio of 10: 1 to 1:10, followed by stirring to prepare a uniform solution; (C) heating the solution at 60 to 100 ° C. for 3 to 100 minutes and then cooling to or near room temperature before or after the temperature; (D) adding a weakly acidic solution and stirring the solution in an acidified state, followed by heating at 60 to 100 ° C. for 3 to 100 minutes; (E) removing the solvent and drying the resulting material to produce a complex composition for lowering cholesterol in the blood, the method for producing a complex composition for lowering cholesterol in the blood. The method according to claim 1, The dried phytosterol and tannin and flavonoid-based hesperidin dissolved in a solvent in an acidic state and then removed the solvent from the product reacted at 20 ~ 100 ° C, blood cholesterol lowering complex, characterized in that it comprises a step of drying Method of Preparation of the Composition. The method according to claim 1 or 2, Method for producing a composite composition for lowering blood cholesterol, characterized in that the solvent used in the water. The method according to claim 1 or 2, Method for producing a composite composition for lowering blood cholesterol, characterized in that the solvent used in the above is ethanol. The method according to claim 1 or 2, Method for producing a composite composition for lowering blood cholesterol, characterized in that the solvent used in the above is a mixture of water and ethanol. The method according to claim 1, Method for producing a complex composition for lowering blood cholesterol, characterized in that the weakly acidic solution used in the step (D) is fruit vinegar. A composite composition for lowering blood cholesterol, comprising a natural plant sterol phytosterol and tannin and flavonoid-based hesperidin in a weight ratio of 10: 1 to 1:10 by the method of claim 1. The method according to claim 7, Complex composition for lowering blood cholesterol, characterized in that the phytocholesterol is one of beta-sitosterol, campy sterol, stigma sterol, fuco sterol, brassica sterol. The method according to claim 7, The phytocholesterol is a complex composition for lowering blood cholesterol, characterized in that using a mixture of two or more selected from beta-sitosterol, campy sterol, stigma sterol, fuco sterol, brassica sterol. The method according to claim 7, The tannin is one of catechins (catechins) and their derivatives, leucoanthocyanins, leucoanthocyanins, anthocyanidins, and phenolic acids such as chlorogenic acid. Complex composition for lowering cholesterol in the blood. The method according to claim 10 or 11, Complex composition for lowering blood cholesterol, characterized in that the acid having a phenol group, such as chlorogenic acid (polygenic acid) is polyphenolic acids. The method according to claim 10 or 11, The leuco ansocyanins are leuco ansocyanidins (leucoantho cyanidins), leuco olininidine (luteolinidin), characterized in that the complex composition for lowering blood cholesterol.