Composition for improving homocysteine metabolism and preparation method and application thereof

Abstract

The embodiment of the invention discloses a composition for improving homocysteine metabolism and a preparation method and application thereof, and belongs to the technical field of homocysteine metabolism improvement. The composition is prepared from the following raw materials in parts by weight: 500 to 700 parts of choline, 800 to 1100 parts of betaine, 200 to 400 parts of glycine, 350 to 500 parts of serine, 3 to 5 parts of vitamin B6, 0.1 to 1 part of vitamin B12, 0.1 to 1 part of 5-methyltetrahydrofolic acid and 200 to 700 parts of a carrier. According to the composition provided by the invention, the 5-methylenetetrahydrofolic acid is converted into the 5-methyltetrahydrofolic acid by the glycine, and the 5-methyltetrahydrofolic acid in the raw materials is combined, so that the methionine-induced increase of the SAM concentration of the liver is inhibited; betaine and serine enable Hcy to be metabolized into cysteine or to be methylated again into methionine, a plurality of effective components are combined to inhibit a methionine conversion pathway, Hcy metabolism is promoted, and the concentration of plasma Hcy and the concentration of liver Hcy are greatly reduced.

Description

Technical Field

[0001] The embodiments of the present invention relate to the technical field of improving homocysteine ​​metabolism, and specifically to a composition for improving homocysteine ​​metabolism, and a preparation method and application thereof. Background Art

[0002] Homocysteine ​​(also known as homocysteine, Homocysteine, Hcy) is a non-essential amino acid containing sulfhydryl groups. It is an intermediate product of methionine (an amino acid contained in protein-rich foods such as meat, also called methionine, Met) in the human body after metabolism. It is harmful to the human body. Met is catalyzed by methionine adenosyltransferase (methionineadenosyltransferase, MAT) and ATP participates in the production of S-adenosylmethionine (S-adenosylmethionine, SAM). SAM transfers methyl groups to DNA, RNA, proteins and other molecules through methyltransferases (DNAmethyltransferases, DNMTs) to form S-adenosylhomocysteine ​​(S-adenosy1-L-homocysteine, SAH), which is then hydrolyzed by SAH hydrolase (SAHH) to remove adenosine and generate Hcy.

[0003] High Hcy levels can damage vascular endothelial cells, promote the proliferation of vascular smooth muscle cells, affect lipid metabolism, increase the adhesion of platelets in the blood, and disrupt the balance of coagulation and fibrinolysis in the body, thereby increasing the risk of cardiovascular and cerebrovascular diseases such as heart disease and stroke. At present, drugs are generally used to reduce the Hcy content in the blood, but these drugs often cannot meet the needs of completely reducing the Hcy level and have side effects. Therefore, based on this problem, the present invention has developed a safe, effective, and side-effect-free product that can fully dredge the Hcy metabolic channel. Summary of the invention

[0004] To this end, the embodiments of the present invention provide a composition for improving homocysteine ​​metabolism, a preparation method and an application thereof, so as to solve the problem in the prior art that the Hcy content in the blood is generally reduced by drugs, but the Hcy level cannot be completely reduced and there are side effects.

[0005] In order to achieve the above purpose, the embodiment of the present invention provides the following technical solutions:

[0006] According to a first aspect of an embodiment of the present invention, the present invention provides a composition for improving homocysteine ​​metabolism, wherein the composition comprises the following raw materials by weight: 500-700 parts of choline, 800-1100 parts of betaine, 200-400 parts of glycine, 350-500 parts of serine, 3-5 parts of vitamin B6, and 100-200 parts of vitamin B6. 12 0.1-1 part, 5-methyltetrahydrofolate 0.1-1 part, nicotinamide 15-20 parts, and a carrier 200-700 parts; the carrier is selected from one or more of microcrystalline cellulose, inorganic salts, lactose, sodium chloride, citric acid and sodium sulfite.

[0007] Among them, choline is an important methyl donor (or one-carbon unit donor) in the body and participates in DNA methylation. Betaine can be produced from choline; nicotinamide can prevent heart conduction block.

[0008] Furthermore, the composition comprises the following raw materials by weight: 600 parts of choline, 1000 parts of betaine, 300 parts of glycine, 450 parts of serine, 64 parts of vitamin B6, 12 0.3 parts, 5-methyltetrahydrofolate 0.5 parts, nicotinamide 17 parts, carrier 700 parts.

[0009] Furthermore, the dosage form of the composition includes tablets and capsules.

[0010] According to a second aspect of an embodiment of the present invention, the present invention provides a method for preparing the above-mentioned composition for improving homocysteine ​​metabolism, the method comprising the following steps:

[0011] S1: crush and sieve all raw materials, dry and set aside;

[0012] S2: Take the raw materials and mix them evenly according to the equal amount increasing method, add the carrier according to the proportion and mix them evenly, and make a soft material with ethanol solution;

[0013] S3: The soft material obtained in step S2 is sieved and dried to control the water content to 2-3%, and the dried raw material is packaged and bottled.

[0014] Furthermore, in step S1, the mesh size of the sieving is 60-80 meshes.

[0015] Furthermore, in step S2, the concentration of the ethanol solution is 95%.

[0016] Furthermore, in step S3, the mesh size of the sieving is 20-30 meshes; the drying conditions are a temperature of 30-50° C. and a time of 1-2 h; and the bottling is performed using a high-density polyethylene bottle for oral solid medicine.

[0017] Furthermore, the method is carried out in a Class 100,000 clean area.

[0018] According to a third aspect of an embodiment of the present invention, the present invention provides use of the above composition in preparing a drug for improving homocysteine ​​metabolism.

[0019] The embodiments of the present invention have the following advantages:

[0020] The composition provided by the present invention converts 5-methylenetetrahydrofolate into 5-methyltetrahydrofolate by glycine, and combines the 5-methyltetrahydrofolate in the raw material to inhibit the increase of liver SAM concentration induced by methionine; vitamin B6 is an important coenzyme in the Hcy transsulfurization pathway and an important coenzyme in the production of 5,10-methylenetetrahydrofolate, and vitamin B 12 As a coenzyme, it indirectly promotes the normal functioning of betaine-homocysteine ​​methyltransferase and other enzymes related to homocysteine ​​metabolism; betaine and serine metabolize Hcy into cysteine ​​or remethylate it into methionine; the combination of multiple active ingredients inhibits the methionine conversion pathway, promotes Hcy metabolism, and significantly reduces plasma Hcy and liver Hcy concentrations without causing side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the implementation methods of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for the implementation methods or the description of the prior art. Obviously, the drawings in the following description are only exemplary, and for ordinary technicians in this field, other implementation drawings can be derived from the provided drawings without creative work.

[0022] Figure 1 The statistical graph of plasma Hcy after rats were fed with different amounts of methionine provided in Test Example 1 of the present invention;

[0023] Figure 2 This is a statistical graph of plasma Hcy in rats after injection of different methionine contents provided in Test Example 1 of the present invention;

[0024] Figure 3 (A) plasma Hcy statistics, (B) plasma cys statistics, (C) liver SAM statistics, (D) liver SAH statistics, (E) liver Hcy statistics, (F) liver CBS activity graph after feeding methionine combined with glycine or serine to rats provided in Test Example 1 of the present invention;

[0025] Figure 4 The statistical graph of plasma Hcy of rats injected with methionine combined with glycine or serine provided in Test Example 1 of the present invention;

[0026] Figure 5(A) plasma Hcy statistics and (B) liver Hcy statistics of rats fed with methionine combined with the composition of Example 1 provided in Test Example 1 of the present invention. DETAILED DESCRIPTION

[0027] The following is a description of the implementation of the present invention by specific embodiments. People familiar with the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] Example 1

[0029] This embodiment provides a composition for improving homocysteine ​​metabolism, the raw materials of which are: 600 mg choline, 1000 mg betaine, 300 mg glycine, 450 mg serine, 64 mg vitamin B6, 12 0.3mg, 5-methyltetrahydrofolate 0.5mg, niacinamide 17mg, microcrystalline cellulose 700mg.

[0030] The preparation method of the above composition comprises the following steps:

[0031] Carry out the following steps in a Class 100,000 clean area;

[0032] S1: crush all raw materials through a 60-mesh sieve, dry and set aside;

[0033] S2: Take the raw materials and mix them evenly according to the equal amount increasing method, add the carrier according to the proportion and mix them evenly, and make a soft material with 95% ethanol solution;

[0034] S3: The soft material obtained in step S2 is passed through a 20-mesh sieve and dried at 30° C. for 2 h, and the moisture content is controlled to be 3%. The dried raw material is packaged and loaded into a solid medicinal high-density polyethylene bottle.

[0035] Example 2

[0036] This embodiment provides a composition for improving homocysteine ​​metabolism, the raw materials of which are: 500 mg choline, 800 mg betaine, 200 mg glycine, 350 mg serine, 300 mg vitamin B6, 300 mg vitamin B 12 0.1mg, 5-methyltetrahydrofolate 0.1mg, niacinamide 15mg, microcrystalline cellulose 200mg.

[0037] The preparation method of the above composition comprises the following steps:

[0038] Carry out the following steps in a Class 100,000 clean area;

[0039] S1: crush all raw materials through 80 mesh sieve, dry and set aside;

[0040] S2: Take the raw materials and mix them evenly according to the equal amount increasing method, add the carrier according to the proportion and mix them evenly, and make a soft material with 95% ethanol solution;

[0041] S3: The soft material obtained in step S2 is passed through a 30-mesh sieve and dried at 50° C. for 1 h, and the moisture content is controlled to be 2%. The dried raw material is packaged and loaded into a solid medicinal high-density polyethylene bottle.

[0042] Example 3

[0043] This embodiment provides a composition for improving homocysteine ​​metabolism, the raw materials of which are: 700 mg choline, 1100 mg betaine, 400 mg glycine, 500 mg serine, 65 mg vitamin B6, 12 1mg, 5-methyltetrahydrofolate 1mg, niacinamide 20mg, microcrystalline cellulose 150mg, lactose 75mg, sodium chloride 50mg.

[0044] The preparation method of the above composition comprises the following steps:

[0045] Carry out the following steps in a Class 100,000 clean area;

[0046] S1: crush all raw materials through a 60-mesh sieve, dry and set aside;

[0047] S2: Take the raw materials and mix them evenly according to the equal amount increasing method, add the carrier according to the proportion and mix them evenly, and make a soft material with 95% ethanol solution;

[0048] S3: The soft material obtained in step S2 is passed through a 30-mesh sieve and dried at 50° C. for 1 h, and the moisture content is controlled to be 2%. The dried raw material is packaged and loaded into a solid medicinal high-density polyethylene bottle.

[0049] Test Example 1

[0050] 1. Experimental conditions: Male 6-week-old rats (110-130 g) were selected and individually housed in an isolated room with the temperature controlled at 20-25°C, the humidity controlled at 40-70%, and the lighting cycle maintained at 12 hours. Before the start of the experiment, the rats had been acclimated to the facility;

[0051] The feed formula included the following ingredients (g / 100 g): casein 30%, corn 40.25%, sucrose 13%, corn oil 5%, mineral mixture (AIN-93) 3.5%, vitamin mixture 1%, choline 0.25% and cellulose 2%.

[0052] Testing conditions:

[0053] Plasma Hcy, cys: Separate plasma from heparinized whole blood, centrifuge at 2000 rpm for 15 min, and store at -30°C;

[0054] Liver Hcy, SAM, SAH, and CBS activities: The whole liver was quickly removed, rinsed with ice saline, blotted dry on filter paper, cut into two parts, weighed, quickly frozen in liquid nitrogen, and stored at -80°C.

[0055] 2. Verify the effect of glycine and serine in reducing homocysteine:

[0056] 2.1. Determination of methionine dosage in experiments

[0057] 2.1.1. The experimental rats were divided into four groups and fed with feed supplemented with 0, 0.5%, 1%, and 2% methionine in each group for 10 days. The weight gain, food intake, and relative liver weight of each group were recorded, and the plasma Hcy level was measured (see Appendix). Figure 1 ).

[0058] The experimental statistical results are shown in Table 1 below:

[0059] Table 1

[0060] Experiment 2.1.1 Weight gain (g / 10d) Food intake (g / 10d) Relative liver weight (%) 0% Methionine 41±3 113±1 4.62±0.3 0.5% Methionine 44±1 116±2 4.65±0.21 1% Methionine 42±2 114±3 4.64±0.02 2% Methionine 17±1 83±1 4.42±0.04

[0061] From the results in Table 1, it can be seen that when 0.5% and 1% methionine was added, there was no effect on the weight gain, food intake and relative liver weight of rats, but the 2% addition level significantly inhibited the growth and food intake; Figure 1 It can be seen that dietary methionine supplementation increased the concentration of plasma homocysteine ​​in a dose-dependent manner. At a dose of 1%, Hcy increased significantly, so the experiment was conducted with 1% methionine.

[0062] 2.1.2 Rats were divided into five groups and fed with normal diet for 7 days. The rats were injected intraperitoneally with saline containing 0, 100, 150, 300 or 400 mg / kg of L-methionine. The plasma Hcy level was measured (see Appendix). Figure 2 ).

[0063] Depend on Figure 2 It can be seen that intraperitoneal injection of methionine also increased plasma homocysteine ​​concentration, which almost reached a plateau level at a dose level of 300 mg / kg body weight.

[0064] 2.2. Verification of the effects of glycine and serine on plasma Hcy in rats

[0065] Rats were divided into four groups. The first group was fed with ordinary feed, the second group was fed with feed supplemented with 1% methionine, during the process, the third group was fed with feed supplemented with 1% methionine and 1.5% glycine, and the fourth group was fed with feed supplemented with 1% methionine and 1.8% serine. The four groups were fed for a total of 10 days. On the 10th day, the plasma Hcy concentration and liver SAM (S-adenosylmethionine), SAH (S-adenosylhomocysteine), and liver CBS activity (cystathionine β-synthase) concentrations of rats in each group were counted.

[0066] Depend on Figure 3 It can be seen that the addition of glycine or serine to the diet can significantly inhibit the increase in plasma homocysteine ​​concentration induced by methionine ( Figure 3 A); Compared with homocysteine, plasma cysteine ​​concentrations were slightly reduced after inhibition by glycine and serine ( Figure 3 B); 1% methionine supplementation in the diet significantly increased the concentrations of SAM, SAH, and homocysteine ​​in the liver, whereas these increases were significantly inhibited by glycine and serine ( Figure 3 C, D and E); the addition of methionine promoted the increase of CBS activity in the liver, while serine significantly inhibited this trend ( Figure 3 F); In the feed, adding 1.5% glycine or 1.8% serine has similar inhibitory levels on various indicators.

[0067] 2.3. Verification of the effect of glycine and serine on plasma Hcy in rats by intraperitoneal injection

[0068] After being fed with feed for 7 days, the rats were divided into 4 groups. The first group was injected with normal saline as the control group, the second group was injected with saline containing methionine (300 mg / kg), the third group was injected with saline containing methionine (300 mg / kg) and glycine (370 mg / kg), and the fourth group was injected with saline containing methionine (300 mg / kg) and serine (450 mg / kg). The rats were killed 2 hours after the injection, and the plasma Hcy level was detected.

[0069] Depend on Figure 4 It can be seen that the plasma homocysteine ​​concentration was significantly inhibited by serine and glycine, and the effect of serine was slightly greater than that of glycine, which verified that intraperitoneal injection of methionine would also affect the plasma Hcy level.

[0070] Principle analysis: Both glycine and serine can provide a single carbon unit and eventually convert into 5-methyltetrahydrofolate, thereby stimulating the remethylation of homocysteine ​​catalyzed by methionine synthase. Both glycine and serine inhibit the increase in liver SAM concentration induced by methionine.

[0071] 3. Experimental method: The rats were divided into three groups. The first group was fed with ordinary feed, the second group was fed with feed supplemented with 1% methionine, and the third group was fed with feed supplemented with 1% methionine and 2.5% of the composition for improving homocysteine ​​metabolism obtained in Example 1. The three groups were fed for a total of 10 days. On the 10th day, the plasma and liver Hcy concentrations of the rats in each group were counted.

[0072] Depend on Figure 5 As can be seen from A and B, the composition obtained in this embodiment 1 is relative to Figure 3 The single use of glycine or serine has a stronger inhibitory effect on the increase of plasma Hcy and liver Hcy caused by methionine, and can basically reduce them to a near normal level.

[0073] Principle analysis: Glycine and serine can both provide a single carbon unit and eventually be converted into 5-methyltetrahydrofolate. Combined with 5-methyltetrahydrofolate in Example 1, the increase in liver SAM concentration induced by methionine was inhibited. Vitamin B 12 Responsible for transferring the methyl group of 5-methyltetrahydrofolate to Hcy, vitamin B6 is an important coenzyme in the Hcy transsulfurization pathway, betaine and serine metabolize Hcy into cysteine ​​or remethylate it into methionine; the combination of multiple active ingredients inhibits the methionine conversion pathway, promotes Hcy metabolism, and significantly reduces plasma Hcy and liver Hcy concentrations.

[0074] Although the present invention has been described in detail above by general description and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements can be made to the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A composition for improving homocysteine ​​metabolism, characterized in that: The composition comprises the following raw materials by weight: 500-700 parts of choline, 800-1100 parts of betaine, 200-400 parts of glycine, 350-500 parts of serine, 3-5 parts of vitamin B6, and 100-200 parts of vitamin B6. 12 0.1-1 part, 5-methyltetrahydrofolate 0.1-1 part, nicotinamide 15-20 parts, and a carrier 200-700 parts; the carrier is selected from one or more of microcrystalline cellulose, inorganic salts, lactose, sodium chloride, citric acid and sodium sulfite.

2. The composition according to claim 1, characterized in that The composition comprises the following raw materials by weight: 600 parts of choline, 1000 parts of betaine, 300 parts of glycine, 450 parts of serine, 64 parts of vitamin B6, and 1000 parts of betaine. 12 0.3 parts, 5-methyltetrahydrofolate 0.5 parts, nicotinamide 17 parts, carrier 700 parts.

3. The composition according to claim 1, characterized in that Dosage forms of the composition include tablets and capsules.

4. The method for preparing the composition for improving homocysteine ​​metabolism according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: S1: crush and sieve all raw materials, dry and set aside; S2: Take the raw materials and mix them evenly according to the equal amount increasing method, add the carrier according to the proportion and mix them evenly, and make a soft material with ethanol solution; S3: The soft material obtained in step S2 is sieved and dried to control the water content to 2-3%, and the dried raw material is packaged and bottled.

5. The method for preparing the composition for improving homocysteine ​​metabolism according to claim 4, characterized in that: In step S1, the mesh size of the sieving is 60-80 meshes.

6. The method for preparing the composition for improving homocysteine ​​metabolism according to claim 4, characterized in that: In step S2, the concentration of the ethanol solution is 95%.

7. The method for preparing the composition for improving homocysteine ​​metabolism according to claim 4, characterized in that: In step S3, the mesh size of the sieving is 20-30 meshes; the drying conditions are a temperature of 30-50° C. and a time of 1-2 hours; and the bottling is performed using a high-density polyethylene bottle for oral solid medicine.

8. The method for preparing the composition for improving homocysteine ​​metabolism according to claim 4, characterized in that: The method is carried out in a 100,000-class clean area.

9. Use of the composition according to any one of claims 1 to 8 in the preparation of a medicament for improving homocysteine ​​metabolism.

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