Rutin composition as well as preparation method and application thereof

Abstract

The invention relates to the field of medicines, discloses a composition as well as a preparation method and application thereof, and particularly relates to a solid composition containing rutin and amino acid compounds, which can be used for preparing a rutin supersaturated solution which is high in concentration, is kept stable for a long time and cannot separate out crystals on the premise of not changing the chemical structure of rutin. The rutin supersaturated solution can keep a high-concentration solution state in a digestive tract without separating out crystals, so that the bioavailability of rutin is improved.

Description

Technical Field

[0001] The invention relates to the field of medicines, in particular to a composition containing rutin, a preparation method and an application thereof. Background Art

[0002] Rutin, also known as rutin, is a flavonoid compound widely found in many plants, mainly from plants such as Sophora japonica, Fagopyrum truncatum, and Rutaecarpa. It has a wide range of physiological activities, such as treating cardiovascular and cerebrovascular diseases, antibacterial and anti-inflammatory, antiviral, antihypertensive, antihyperglycemic, and antihyperlipidemic effects.

[0003] Although rutin is effective in treating many diseases, its clinical effect is not significant. The reason is as stated in the standard of rutin tablets. This product (i.e. rutin) is almost insoluble in water and is almost not absorbed in the body, so its oral efficacy is uncertain (see reference 1 Compound Rutin Tablets, Rutin Tablets Standard Description). Since the chemical structure of rutin is a conjugated system, the molecules present a planar structure, and the molecules are tightly stacked in the crystalline form, making it difficult for solvent molecules to penetrate, so that the solubility of rutin in many solvents is very low, or even insoluble (see reference 2, "Natural Medicinal Chemistry", 4th edition, Wu Lijun, p173, flavonoids). In particular, at room temperature, the solubility of rutin in water is only 0.125g / L (about 1g: 10000ml), which makes it impossible for rutin to reach a sufficiently high drug concentration in the digestive tract. Even if rutin enters the digestive tract in the form of an aqueous solution, after it encounters gastric acid, H + The charge state of rutin molecules will be changed, rutin will be converted into pseudo salts and crystallized, which will further reduce the dissolution and absorption of rutin in the body, limiting the performance of its biological activity. However, even at such a low concentration in the body, rutin can still show certain biological activity, which shows that its potential drug effect strength may be very large, but it is limited by its water solubility at room temperature and in gastric acid. Therefore, if the solubility concentration in aqueous solution and gastric acid at room temperature can be increased without changing the chemical structure of rutin, it is expected to significantly enhance the therapeutic activity of rutin, thereby playing a greater role in clinical treatment.

[0004] One of the existing methods to change the solubility of rutin is to change the chemical structure of rutin, that is, to introduce appropriate groups into the chemical structure of rutin to change the rutin molecule from a planar structure to a three-dimensional structure. For example, troxerutin introduces a hydroxyethyl group into the rutin structure. Troxerutin is easily soluble in water, but the change in chemical structure reduces the compatibility of rutin with receptors, and the efficacy and efficacy strength will change.

[0005] Another existing method to change the solubility of rutin is to use the acidity of the phenolic hydroxyl group in the rutin structure to react with a base to form a salt that dissolves in water. However, after the compound is salted, it is identified as a Class II new drug in the new drug approval process, that is, it is a new active substance.

[0006] In addition, CN1153174A discloses a new process for refining rutin called molecular morphology transformation method. This method forms an association complex between rutin molecules and water molecules and solvent methanol molecules at natural temperature to change the molecular morphology of rutin, that is, from a two-dimensional planar structure to a three-dimensional structure, thereby increasing the molecular gap and improving the solubility of rutin.

[0007] Although there are some methods to improve the solubility of rutin in water at room temperature, these methods still have some limitations. For example, they may require complex processes or change the chemical structure of rutin. Therefore, it remains a challenge to develop new, cost-effective and easy-to-scale methods to improve the solubility of rutin. Summary of the invention

[0008] One of the purposes of the present invention is to provide a rutin solid composition, which can prepare a high-concentration rutin supersaturated solution that remains stable for a long time without changing the chemical structure of rutin.

[0009] Another object of the present invention is to provide a supersaturated solution of rutin which can maintain high concentration and stability for a long time at room temperature without precipitation of crystals, and the supersaturated solution of rutin can maintain a high concentration solution state in the digestive tract without precipitation of crystals, thereby improving the bioavailability of rutin.

[0010] The present invention provides a composition comprising rutin and an amino acid compound, wherein, by molar ratio, 1 part of rutin corresponds to more than 0.5 parts of the amino acid compound. In one embodiment, the composition is solid, wherein the rutin and the amino acid compound are a physical mixture. In another embodiment, the composition is liquid, which is a rutin solution obtained by adding rutin and the amino acid compound to hot water for dissolution, or adding rutin and the amino acid compound to water and then heating to dissolve.

[0011] In one embodiment, the composition consists of rutin and an amino acid compound.

[0012] In one embodiment, after the rutin solution is allowed to stand at room temperature, the concentration of rutin in water is greater than 37.5 mg / 300 ml, preferably in the range of (100 mg-1000 mg) / 300 ml, more preferably in the range of 100 mg / 300 ml, 250 mg / 300 ml, 500 mg / 300 ml, 750 mg / 300 ml, 1000 mg / 300 ml.

[0013] In one embodiment, after rutin is dissolved in water, it does not precipitate crystals within at least 1 hour, preferably within 2 hours, within 6 hours, within 18 hours, within 44 hours, or within 72 hours.

[0014] In one embodiment, the concentration of the rutin solution is greater than or equal to 100 mg / 300 ml, and no crystals are precipitated within 44 hours after naturally cooling to room temperature after dissolution, preferably within 48 hours, and more preferably within 72 hours.

[0015] In one embodiment, the concentration of the rutin solution is greater than or equal to 250 mg / 300 ml, and no crystals are precipitated within 18 hours after naturally cooling to room temperature after dissolution, preferably within 20 hours and 30 minutes.

[0016] In one embodiment, the concentration of the rutin solution is greater than or equal to 500 mg / 300 ml, and no crystals are precipitated within 6 hours after naturally cooling to room temperature after dissolution, preferably within 7 hours.

[0017] In one embodiment, the concentration of the rutin solution is greater than or equal to 750 mg / 300 ml, and no crystals are precipitated within 2 hours after naturally cooling to room temperature after dissolution, preferably within 2 hours and 40 minutes.

[0018] In one embodiment, the concentration of the rutin solution is greater than or equal to 1000 mg / 300 ml, and no crystals are precipitated within 1 hour after naturally cooling to room temperature after dissolution, preferably within 1 hour and 20 minutes.

[0019] In one embodiment, based on a molar ratio, 1 part of rutin corresponds to 0.8 parts or more of amino acid compounds, preferably 1 part of rutin corresponds to 1 part or more of amino acid compounds, and more preferably 1 part of rutin corresponds to 1.5 parts or more of amino acid compounds.

[0020] In one embodiment, the amino acid compound is an α-amino acid, a β-amino acid or a γ-amino acid, or a pharmaceutically acceptable salt, amide or peptide thereof. More specifically, the amino acid compound is aminoacetic acid, glutamic acid, glutathione, taurine, 3-aminopropionic acid or γ-aminobutyric acid, or a pharmaceutically acceptable salt, amide or peptide thereof. More specifically, the amino acid compound is 20 kinds of amino acids in the human body or their amides or peptides, and the 20 kinds of amino acids refer to glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine and histidine, glutathione, taurine, 3-aminopropionic acid or γ-aminobutyric acid, or its amides or peptides.

[0021] In one embodiment, the temperature of the hot water is above 50°C, preferably above 80°C, more preferably above 90°C, and most preferably boiling water.

[0022] In one embodiment, the heating temperature is 50°C or higher, preferably 80°C or higher, more preferably 90°C or higher.

[0023] At the same time, the present invention provides a method for preparing a stable supersaturated solution of rutin, which comprises adding 1 part of rutin and 0.5 or more parts of amino acid compounds to hot water for dissolution, or adding 1 part of rutin and 0.5 or more parts of amino acid compounds to water and then heating and dissolving, and optionally cooling naturally to room temperature. In the supersaturated solution of rutin obtained by the preparation method, the concentration of rutin in water is greater than 37.5 mg / 300 ml, preferably in the range of (100 mg-1000 mg) / 300 ml, and more preferably in the range of 100 mg / 300 ml, 250 mg / 300 ml, 500 mg / 300 ml, 750 mg / 300 ml, and 1000 mg / 300 ml.

[0024] In the above preparation method, the stability means that after rutin is dissolved in water, no crystals are precipitated within at least 1 hour, preferably no crystals are precipitated within 2 hours, no crystals are precipitated within 6 hours, no crystals are precipitated within 18 hours, no crystals are precipitated within 44 hours, or no crystals are precipitated within 72 hours.

[0025] In one embodiment of the above preparation method, based on molar ratio, 1 part of rutin corresponds to 0.8 parts or more of amino acid compounds, preferably 1 part of rutin corresponds to 1 part or more of amino acid compounds, and more preferably 1 part of rutin corresponds to 1.5 parts or more of amino acid compounds.

[0026] In one embodiment of the above preparation method, the amino acid compound is an α-amino acid, a β-amino acid or a γ-amino acid, or a pharmaceutically acceptable salt, amide or peptide thereof. More specifically, the amino acid compound is aminoacetic acid, glutamic acid, glutathione, taurine, 3-aminopropionic acid or γ-aminobutyric acid, or a pharmaceutically acceptable salt, amide or peptide thereof. More specifically, the amino acid compound is 20 kinds of amino acids or their amides or peptides in the human body, and the 20 kinds of amino acids refer to glycine, alanine, valine, leucine, isoleucine, methionine (methionine), proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine and histidine, glutathione, taurine, 3-aminopropionic acid or γ-aminobutyric acid, or its amides or peptides.

[0027] In one embodiment of the above preparation method, the temperature of the hot water is above 50°C, preferably above 80°C, more preferably above 90°C, and most preferably boiling water.

[0028] In one embodiment of the above preparation method, the heating temperature is above 50°C, preferably above 80°C, and more preferably above 90°C.

[0029] The present invention discloses the conjugated system characteristics of rutin molecules, such as Figure 1 As shown, the electrons are delocalized to form a large π bond, resulting in the positive and negative charge centers in the molecule being located at the 1-ether bond oxygen atom and the 4-carbonyl oxygen atom, respectively. The distance between these charge centers is fixed, forming a rigid ring structure of a five-atom chain. On the other hand, amino acid compounds also have positive and negative charge centers, and the distance between the positive and negative charge centers is similar to that of rutin, so that they can form relatively stable double unsaturated charge adsorbates with rutin, such as attached Figure 2 As shown, it is equivalent to inserting a "wedge" between rutin molecules to prevent the rutin molecules from stacking neatly to form crystals, thereby increasing the solubility of rutin molecules in water, making it difficult for supersaturated solutions to precipitate crystals at room temperature.

[0030] Although the solubility of rutin in hot water is higher than that at room temperature, even if rutin is dissolved in hot water without adding amino acid compounds, crystals will soon precipitate once cooled to room temperature. The present invention surprisingly found that a mixture of α-amino acid, β-amino acid or γ-amino acid and rutin is dissolved in hot water, and the supersaturated solution formed after cooling to room temperature can still remain stable for a long time without crystallization.

[0031] Since the solubility of rutin in hot water is greatly improved compared with that at room temperature, hot water is used to dissolve the solid mixture of rutin and amino acid compounds, the purpose of which is to dissolve as much rutin as possible in a smaller volume of water. The hot water can be boiling water, or it can have a water temperature that allows a specified amount of rutin to dissolve at a higher solubility than at room temperature, for example, above 50°C, preferably above 80°C, and more preferably above 90°C. The long time is a longer time for crystallization of a rutin solution of the same concentration compared to the absence of amino acid compounds, for example, 1 hour, 2 hours, 6 hours, 18 hours, 44 hours or 72 hours.

[0032] Furthermore, the solution of the rutin-amino acid mixture can prevent rutin from crystallizing and precipitating in the digestive tract. Figure 3 As shown in the figure, in the absence of amino acids, rutin in the solution encounters protons to form pseudo salts and crystallize out. In the presence of amino acids, amino acids can prevent rutin from forming pseudo salts in gastric acid, thereby increasing the solubility and absorption rate of rutin in the body.

[0033] Rutin can penetrate the blood-brain barrier and enter the central and peripheral nervous systems due to its high fat solubility. The present invention can greatly improve the bioavailability of rutin in the body, thereby improving the therapeutic effect of rutin, for example, having a more rapid effect on improving diabetic complications such as blurred vision, hearing loss, skin itching, cold limbs, edema and ulcers.

[0034] Therefore, the present invention also relates to the use of the above-mentioned composition for preparing medicines, cosmetics or food with medicinal and edible properties.

[0035] Therefore, the present invention also relates to the use of the above-mentioned composition in the preparation of drugs for treating cardiovascular and cerebrovascular diseases, antibacterial and anti-inflammatory, antiviral, antihypertensive, antihyperglycemic, antihyperlipidemic and the like. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 It is the conjugated system and positive and negative unsaturated charge center of rutin.

[0037] Figure 2 It is the adsorption of double unsaturated charges between rutin and amino acids (taking aminoacetic acid as an example).

[0038] Figure 3 This is the reaction process in which rutin in the solution encounters protons to generate pseudo salts and crystallizes in the absence of amino acids.

[0039] Figure 4 Comparison of rutin precipitation time when rutin and amino acids (taking aminoacetic acid as an example) form supersaturated solutions at different concentrations: the X-axis is the time from when rutin is completely dissolved to when rutin crystals begin to precipitate, and the Y-axis is the mass of rutin in every 300 ml of aqueous solution (calculated in mg). DETAILED DESCRIPTION

[0040] Preparation and stability test of rutin composition of the present invention

[0041] Example 1. 100 mg of rutin was added with 11 mg of aminoacetic acid (molar ratio of about 1:1), dissolved in 300 ml of boiling water and then left at room temperature for 72 hours without the precipitation of rutin crystals.

[0042] Example 2. 100 mg of rutin was added with 22 mg of glutamic acid (molar ratio of about 1:1), dissolved in 300 ml of boiling water and placed at room temperature, pH 4. After 44 hours, rutin began to slowly crystallize. Glutamic acid is an acidic amino acid and can accelerate the precipitation of rutin.

[0043] Example 3. 100 mg of rutin was added with 46 mg of glutathione (molar ratio of about 1:1), dissolved in 300 ml of boiling water and allowed to stand for 48 hours without rutin crystal precipitation.

[0044] Example 4. 100 mg of rutin and 25 mg of taurine (molar ratio of about 1:1) were added to 300 ml of boiling water and dissolved. After being placed for 48 hours, no rutin crystals were precipitated. The charge distance is suitable, the solution is fast, and no crystals will be formed even if it is placed for a long time.

[0045] Example 5. 100 mg of rutin and 25 mg of 3-aminopropionic acid (molar ratio of about 1:1) were added to 200 ml of boiling water and dissolved. After being left for 48 hours, no rutin crystals were precipitated. The charge distance is suitable, the solution is fast, and no crystals will be formed even if it is left for a long time.

[0046] Example 6. 100 mg of rutin was added with 16 mg of γ-aminobutyric acid (molar ratio of about 1:1), dissolved in 300 ml of boiling water and allowed to stand for 48 hours without the precipitation of rutin crystals.

[0047] Example 7. 1000 mg of rutin was added with 110 mg of aminoacetic acid (molar ratio 1:1), and 300 ml of boiling water was added to dissolve the mixture. The mixture was then left at room temperature for 1 hour and 20 minutes, and rutin crystals were precipitated.

[0048] Example 8. 750 mg of rutin was added with 82.5 mg of aminoacetic acid (molar ratio 1:1), dissolved in 300 ml of boiling water and then left at room temperature for 2 hours and 40 minutes, and rutin crystals were precipitated.

[0049] Example 9. 500 mg of rutin was added with 55 mg of aminoacetic acid (molar ratio 1:1), dissolved in 300 ml of boiling water and then left at room temperature for 7 hours, and rutin crystals were precipitated.

[0050] Example 10. 250 mg of rutin was added with 27.5 mg of aminoacetic acid (molar ratio 1:1), dissolved in 300 ml of boiling water and then allowed to stand at room temperature for 20 hours and 35 minutes, and rutin crystals were precipitated.

[0051] Examples 1 and 7-10 show the time for which the mixture of rutin and amino acid (taking aminoacetic acid as an example) at different concentrations remains stable without crystallization after being dissolved in boiling water, as shown in the attached Figure 4 As shown, it can be seen that rutin solutions at different concentrations can remain crystallized for a long time.

[0052] In vivo simulation experiment of the rutin composition of the present invention

[0053] The artificial gastric juice used in the following Examples 11-16 was prepared according to Part IV of the Chinese Pharmacopoeia 2015 Edition: 16.4 mL of dilute hydrochloric acid was added to 800 mL of water and 10 g of pepsin, and the mixture was shaken to fully dissolve, and the pH value was adjusted to 1.3, and the mixture was diluted with water to a volume of 1000 ml.

[0054] Example 11. Prepared (100 mg rutin and 5.5 mg aminoacetic acid (molar ratio 1:0.5) were heated and completely dissolved in 300 ml water and allowed to stand at room temperature. 150 ml of room temperature aqueous solution of rutin and aminoacetic acid was mixed evenly with 150 ml of artificial gastric juice, and rutin crystals were precipitated after 24 hours and 10 minutes.

[0055] Example 12: 150 ml of room temperature aqueous solution of rutin and aminoacetic acid (100 mg rutin and 11 mg aminoacetic acid were heated (molar ratio 1:1) and completely dissolved in 300 ml water and allowed to stand at room temperature) was mixed evenly with 150 ml of artificial gastric juice, and rutin crystals were precipitated in 25 hours.

[0056] Example 13: 150 ml of room temperature aqueous solution of rutin and aminoacetic acid (500 mg rutin and 27.5 mg aminoacetic acid were heated (molar ratio 1:0.5) and completely dissolved in 300 ml water and allowed to stand at room temperature) were mixed evenly with 150 ml of artificial gastric juice, and rutin crystals were precipitated in 55 minutes.

[0057] Example 14: 150 ml of the prepared (500 mg rutin and 55 mg aminoacetic acid were heated (molar ratio 1:1) and completely dissolved in 300 ml water and allowed to stand at room temperature) rutin and aminoacetic acid room temperature aqueous solution were mixed evenly with 150 ml of artificial gastric juice, and rutin crystals were precipitated in 1 hour and 40 minutes.

[0058] Example 15: 150 ml of the prepared (200 mg rutin and 11 mg aminoacetic acid were heated (molar ratio 1:0.5) and completely dissolved in 300 ml water and allowed to stand at room temperature) rutin and aminoacetic acid room temperature aqueous solution were mixed evenly with 150 ml of artificial gastric juice, and rutin crystals were precipitated after 8 hours and 30 minutes.

[0059] Example 16. 150 ml of the prepared (200 mg rutin and 22 mg aminoacetic acid were heated (molar ratio 1:1) and completely dissolved in 300 ml water and allowed to stand at room temperature) rutin and aminoacetic acid room temperature aqueous solution were mixed evenly with 150 ml of artificial gastric juice, and rutin crystals were precipitated after 12 hours and 25 minutes.

[0060] Examples 11-16 show that the rutin composition of the present invention can still maintain stability for a long time in the in vivo environment simulated by artificial gastric fluid, thereby preventing or delaying the precipitation of rutin in the form of crystalline solid in gastric fluid.

[0061] Comparative Example without Adding Amino Acid Compounds

[0062] Comparative Example 1. 1000 mg of rutin was dissolved in 300 ml of boiling water and then allowed to stand at room temperature for 10 minutes, during which rutin crystals were precipitated.

[0063] Comparative Example 2: 750 mg of rutin was dissolved in 300 ml of boiling water and then allowed to stand at room temperature for 23 minutes, during which rutin crystals were precipitated.

[0064] Comparative Example 3. 500 mg of rutin was dissolved in 300 ml of boiling water and then allowed to stand at room temperature for 41 minutes, during which rutin crystals were precipitated.

[0065] Comparative Example 4. 250 mg of rutin was dissolved in 300 ml of boiling water and then allowed to stand at room temperature for 128 minutes, during which rutin crystals were precipitated.

[0066] Comparative Example 5. 100 mg of rutin was dissolved in 300 ml of boiling water and then left at room temperature for 365 minutes, during which rutin crystals were precipitated.

[0067] Comparative Example 6. 100 mg of rutin was completely dissolved in 300 ml of water by heating and allowed to stand at room temperature. Before rutin crystallized, 150 ml of rutin solution was mixed with 150 ml of artificial gastric juice. Rutin crystallized in 63 minutes.

[0068] Comparative Example 7: 500 mg of rutin was completely dissolved in 300 ml of water after heating. When left to stand at room temperature, rutin had already precipitated and could no longer be mixed with artificial gastric juice for testing.

[0069] Comparative Example 8. 200 mg of rutin was completely dissolved in 300 ml of water by heating and allowed to stand at room temperature. Before rutin crystallized, 150 ml of rutin solution was mixed with 150 ml of artificial gastric juice. Rutin crystallized in 23 minutes.

[0070] Comparing the examples of the present invention with the comparative examples, it can be clearly seen that the composition of the present invention significantly prolongs the stability of the rutin solution, especially prolongs the time that the supersaturated rutin solution at room temperature does not precipitate crystals. In an in vivo simulation experiment of artificial gastric juice, the composition of the present invention also has the effect of preventing or delaying the precipitation of rutin, thereby promoting the absorption of rutin in the body and improving the bioavailability of rutin.

Claims

1. A composition comprising rutin and an amino acid compound, wherein, by molar ratio, 1 part of rutin corresponds to 0.5 or more parts of the amino acid compound.

2. The composition according to claim 1, wherein The composition is solid, and the rutin and amino acid compounds therein are in the form of a physical mixture.

3. The composition according to claim 1, wherein The composition is liquid, which is a rutin solution obtained by adding rutin and amino acid compounds into hot water and dissolving them, or adding rutin and amino acid compounds into water and then heating and dissolving them.

4. The composition according to claim 3, wherein After the rutin solution is allowed to cool to room temperature, the concentration of rutin in water is greater than 37.5 mg / 300 ml, preferably in the range of (100 mg-1000 mg) / 300 ml, more preferably 100 mg / 300 ml, 250 mg / 300 ml, 500 mg / 300 ml, 750 mg / 300 ml, or 1000 mg / 300 ml.

5. The composition according to claim 3 or 4, wherein After rutin is dissolved in water, no crystals are precipitated within at least 1 hour, preferably no crystals are precipitated within 2 hours, no crystals are precipitated within 6 hours, no crystals are precipitated within 18 hours, no crystals are precipitated within 44 hours, or no crystals are precipitated within 72 hours.

6. The composition according to any one of claims 1 to 5, wherein Calculated by molar ratio, 1 part of rutin corresponds to 0.8 parts or more of the amino acid compound, preferably 1 part of rutin corresponds to 1 part or more of the amino acid compound, and more preferably 1 part of rutin corresponds to 1.5 parts or more of the amino acid compound.

7. The composition according to any one of claims 1 to 6, wherein The amino acid compound is an α-amino acid, a β-amino acid or a γ-amino acid, or a pharmaceutically acceptable salt, amide or peptide thereof.

8. The composition according to any one of claims 3 to 7, wherein The temperature of the hot water is 50° C. or higher, preferably 80° C. or higher, more preferably 90° C. or higher, and most preferably boiling water.

9. The composition according to any one of claims 3 to 7, wherein The heating temperature is 50° C. or higher, preferably 80° C. or higher, and more preferably 90° C. or higher.

10. The composition according to any one of claims 1 to 9, wherein It is composed of rutin and amino acid compounds.

11. A method for preparing a stable supersaturated rutin solution, characterized in that: In terms of molar ratio, 1 part of rutin and 0.5 parts of amino acid compound or more are added to hot water to dissolve, or 1 part of rutin and 0.5 parts of amino acid compound or more are added to water and heated to dissolve, and optionally cooled naturally to room temperature.

12. The preparation method according to claim 11, characterized in that: The concentration of rutin in water is greater than 37.5 mg / 300 ml, preferably in the range of (100 mg-1000 mg) / 300 ml, and more preferably in the range of 100 mg / 300 ml, 250 mg / 300 ml, 500 mg / 300 ml, 750 mg / 300 ml, and 1000 mg / 300 ml.

13. The preparation method according to claim 11 or 12, characterized in that: The term "stable" means that after rutin is dissolved in water, no crystals are precipitated within at least 1 hour, preferably no crystals are precipitated within 2 hours, no crystals are precipitated within 6 hours, no crystals are precipitated within 18 hours, no crystals are precipitated within 44 hours, or no crystals are precipitated within 72 hours.

14. The preparation method according to claim 11 or 12, characterized in that: In terms of molar ratio, 1 part of rutin corresponds to 0.8 parts or more of the amino acid compound, preferably 1 part of rutin corresponds to 1 part or more of the amino acid compound, and more preferably 1 part of rutin corresponds to 1.5 parts or more of the amino acid compound.

15. The preparation method according to any one of claims 11 to 14, characterized in that: The amino acid compound is an α-amino acid, a β-amino acid or a γ-amino acid, or a pharmaceutically acceptable salt, amide or peptide thereof.

16. The preparation method according to any one of claims 11 to 15, characterized in that: The temperature of the hot water is 50° C. or higher, preferably 80° C. or higher, more preferably 90° C. or higher, and most preferably boiling water.

17. The preparation method according to any one of claims 11 to 15, characterized in that: The heating temperature is 50° C. or higher, preferably 80° C. or higher, and more preferably 90° C. or higher.

18. Use of the composition according to any one of claims 1 to 10 for preparing medicines, cosmetics or foods having both medicinal and edible properties.

19. Use of the composition according to any one of claims 1 to 10 in the preparation of drugs for treating cardiovascular and cerebrovascular diseases, antibacterial and anti-inflammatory, antiviral, antihypertensive, antihyperglycemic, and antihyperlipidemia.

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