HYPOLIPIDEMIC COMPOSITION AND USE THEREOF

Abstract

A composition has ornithine, aspartic acid and vitamin B6, and it is used in preparation of hypolipidemic drugs, health-care products, foods or food additives.

Claims

1. A hypolipidemic composition, comprising ornithine, aspartic acid, vitamin B6, vitamin C, and one or more of the following auxiliary components: citric acid, pantothenic acid, biotin and folic acid; by a weight ratio: ornithine:asparticacid:VB6=1:0.1-1.2:0.2-1.5; ornithine:VC=1:0.05-1.2; ornithine:citric acid=1:0.001-0.05; ornithine:pantothenic acid=1:0.00001-0.001; ornithine:biotin=1:0.000001-0.0005; ornithine:folic acid=1:0.000001-0.0005.

2. The composition according to claim 1, comprising the following auxiliary components by a weight ratio: asparticacid:VB6=1:0.3-0.7:0.4-0.8.

3. The composition according to claim 2, comprising the following auxiliary components by a weight ratio: asparticacid:VB6=1:0.5:0.6.

4. The composition according to claim 1, comprising the following auxiliary components by a weight ratio: ornithine:VC=1:0.2-0.8.

5. The composition according to claim 4, comprising the following auxiliary components by a weight ratio: ornithine:VC=1:0.5.

6. The composition according to claim 1, comprising the following auxiliary components by a weight ratio: ornithine:citric acid=1:0.001-0.03.

7. The composition according to claim 6, comprising the following auxiliary components by a weight ratio: ornithine:citric acid=1:0.01.

8. The composition according to claim 1, comprising the following auxiliary components by a weight ratio: ornithine:pantothenic acid=1:0.00005-0.0008.

9. The composition according to claim 8, comprising the following auxiliary components by a weight ratio: ornithine:pantothenic acid=1:0.0005.

10. The composition according to claim 1, comprising the following auxiliary components by a weight ratio: ornithine:biotin=1:0.000001-0.0001.

11. The composition according to claim 10, comprising the following auxiliary components by a weight ratio: ornithine:biotin=1:0.000003.

12. The composition according to claim 1, comprising the following auxiliary components by a weight ratio: ornithine:folic acid=1:0.000003-0.0001.

13. The composition according to claim 12, comprising the following auxiliary components by a weight ratio: ornithine:folic acid=1:0.00005.

14. The composition according to claim 1, wherein the ornithine refers to L-ornithine, D-ornithine or DL-ornithine; and the aspartic acid refers to L-aspartic acid, D-aspartic acid or DL-aspartic acid.

15. The composition according to claim 1, wherein the dosage form of the composition as a health-care product or a drug is any one of pharmaceutically acceptable dosage forms

16. The composition according to claim 15, wherein the dosage forms are granules, tablets, capsules, pulvis, pills, powders, medicinal liquors, ointments, pellets, granules, membranes, oral solutions and injections.

17. A method comprising preparing hypolipidemic health-care products, drugs, foods or food additives with the composition according to claim 1.

Description

DETAILED DESCRIPTION

[0027] Hereinafter, the present invention will be further described in detail in conjunction with the examples, but the present invention is not limited to the following examples.

Example 1: Preparation of Hypolipidemic Sandwich Biscuit by Using Hypolipidemic Composition as Food Additive

[0028] The preparation process comprises the following steps:

[0029] 1. blending wheat flour, eggs, a sweetener, baking soda, vegetable oil and water into dough according to a weight ratio, putting in a refrigerator for cold storage, resting for 1 hour, then taking out, rolling into 2 to 3 mm slices, pressing into a shape using a biscuit mold, one being hollow and the other being solid, and preparing into a biscuit ectoderm;

[0030] 2. putting in an oven for baking, and cooling for standby use;

[0031] 3. weighing an appropriate amount of jam, the total weight of the jam, L-ornithine, L-aspartic acid and vitamin B6 being 100 parts, evenly mixing the following raw materials in parts by weight: 3 parts of the L-ornithine, 2 parts of the L-aspartic acid, 3 parts of the vitamins B6 and 92 parts of the jam, preparing a food additive, and then smearing the food additive on a hollow part of the biscuit.

Example 2: Preparation of Healthcare Oral Solution

[0032] A hypolipidemic health-care oral solution was prepared by the following steps: weighing the following raw materials by weight: 20 g of L-ornithine, 5 g of L-aspartic acid, 25 g of vitamin B6, 15 g of vitamin C, 5 g of xylitol and 20 ml of water, mixing evenly, canning a mixture into a 5-50 mL bottle, sealing, and sterilizing at a temperature of 110 C. for 20 min.

Example 3: Preparation of Pharmaceutical Composition

[0033] A pharmaceutical composition capsule preparation comprises the following components: 70 g of L-ornithine, 60 g of L-aspartic acid, 70 g of vitamin B6, an appropriate amount of 1% polyvinylpyrrolidone ethanol solution and 2 g of magnesium stearate, and 800 capsules were prepared in total.

[0034] The preparation method comprises the following steps: weighing the L-ornithine, the L-aspartic acid and the vitamin B6, mixing evenly, preparing a soft material with 40 mL of the 1% polyvinylpyrrolidone ethanol solution, granulating with a 20-mesh sieve, drying until the moisture does not exceed 3%, adding 2 g of the magnesium stearate, mixing evenly, granulating with the 20-mesh sieve, sub-packaging, polishing and packaging, thus obtaining a capsule preparation through the above process.

Example 4: Preparation of Pharmaceutical Composition

[0035] A pharmaceutical composition tablet comprises the following components: 70 g of L-ornithine, 60 g of L-aspartic acid, 70 g of vitamin B6, an appropriate amount of 1% polyvinylpyrrolidone ethanol solution and 1 g of magnesium stearate, and 1000 tablets were prepared in total.

[0036] The preparation method comprises the following steps: weighing the L-ornithine, the L-aspartic acid and the vitamin B6, mixing evenly, preparing a soft material with 20 mL of the 1% polyvinylpyrrolidone ethanol solution, granulating with a 20-mesh sieve, drying, adding 1 g of magnesium stearate, mixing evenly, granulating with the 20-mesh sieve, tabletting, polishing and packaging, thus obtaining a composition tablet through the above process.

Example 5: Preparation of Pharmaceutical Composition

[0037] A pharmaceutical composition comprises 250 mL of a mixed substance injection containing 6 g of L-ornithine, 4 g of L-aspartic acid, 6 g of vitamin B6, 3.5 g of vitamin C, and 0.1 mg of biotin, and was added into 250 mL of a 5% glucose and sodium chloride injection (0.9% sodium chloride injection used for diabetic patients).

Example 6

[0038] A pharmaceutical composition granule comprises the following components: 70 g of L-ornithine, 60 g of L-aspartic acid, 70 g of vitamin B6, 0.5 g of citric acid, 5 mg of pantothenic acid, 0.2 mg of biotin, 0.3 mg of folic acid and 15 g of vitamin C. An appropriate amount of 20% ethanol solution was used as a wetting agent, so that the granule was prepared,

[0039] The preparation method comprises the following steps: weighing the above-mentioned components, mixing evenly, adding 40 ml of 20% ethanol solution, preparing a soft material, preparing the granule by an extrusion-spheronization method, and drying until the moisture is not more than 3%.

Example 7

[0040] A pharmaceutical composition granule comprises the following components: 70 g of L-ornithine, 60 g of D-aspartic acid, 70 g of vitamin B6, 0.5 g of citric acid, 0.2 mg of biotin and 20 g of vitamin C. An appropriate amount of 20% ethanol solution was used as a wetting agent, so that the granule was prepared.

[0041] The preparation method comprises the following steps: weighing the above-mentioned components, mixing evenly, adding 40 ml of 20% ethanol solution, preparing a soft material, preparing the granule by an extrusion-spheronization method, and drying until the moisture is not more than 3%.

Example 8

[0042] A pharmaceutical composition granule comprises the following components: 70 g of DL-ornithine, 50 g of L-aspartic acid, 60 g of vitamin B6, 30 mg of pantothenic acid, 0.5 mg of biotin and 20 g of vitamin C. An appropriate amount of 20% ethanol solution was used as a wetting agent, so that the granule was prepared.

[0043] The preparation method comprises the following steps: weighing the above-mentioned components, mixing evenly, adding 40 ml of 20% ethanol solution, preparing a soft material, preparing the granule by an extrusion-spheronization method, and drying until the moisture is not more than 3%.

Example 9

[0044] A pharmaceutical composition granule comprises the following components: 70 g of L-ornithine, 50 g of DL-aspartic acid, 60 g of vitamin B6, 30 mg of pantothenic acid, 3 mg of folic acid and 5 g of vitamin C. An appropriate amount of 20% ethanol solution was used as a wetting agent, so that the granule was prepared.

[0045] The preparation method comprises the following steps: weighing the above-mentioned components, mixing evenly, adding 40 ml of 20% ethanol solution, preparing a soft material, preparing the granule by an extrusion-spheronization method, and drying until the moisture is not more than 3%.

Example 10

[0046] A pharmaceutical composition granule comprises the following components: 70 g of L-ornithine, 50 g of DL-aspartic acid, 35 g of vitamin B6 and 45 g of vitamin C. An appropriate amount of 20% ethanol solution was used as a wetting agent, so that the granule was prepared.

[0047] The preparation method comprises the following steps: weighing the above-mentioned components, mixing evenly, adding 40 ml of 20% ethanol solution, preparing a soft material, preparing the granule by an extrusion-spheronization method, and drying until the moisture is not more than 3%.

Example 11: Hypolipidemic Animal Experiment of Composition Provided by the Invention

[0048] 1. Experimental materials: 150 healthy SD male and female rats in clean grade, with body weight of (150.28.9) g.

[0049] 2. Feed: general feed, high-fat feed formula: 72.7% of basic feed, 2% of cholesterol, 5% of egg yolk powder, 10% of lard, 0.2% of propylthiouracil, 10% of sucrose and 0.1% of sodium cholate.

[0050] 3. Grouping and administration of animals: the purchased experimental rats were adaptively fed for 1 week in a lab, original numbers were assigned according to the weighing order, and the rats were randomly divided into a blank control group, a model control group, a pharmaceutical composition (respectively prepared as in Examples 3, 6, 8 and 10, and added with 50 ml of water per 10 g to be dissolved to obtain a solution) low-dose group (5 ml/kg.Math.d), a middle-dose group (10 ml/kg-d), a high-dose group (15 ml/kg.Math.d), a positive drug (simvastatin) control group (1.5 mg/kg, volume: 10 ml/kg) by looking up a random number table, and there were 10 rats in each group. From the day of experiment, the blank control group and the model control group were intragastrically administered with normal saline (volume: 10 ml/kg), the administration group was intragastrically administered with corresponding drugs once a day, the body weight was weighed once a week, and the dosage was adjusted according to the body weight. The blank control group was fed with the normal feed, the other groups was fed with high-fat feed. During the experiment, free feeding, free drinking, continuous molding and drug administration for prevention were carried out for 4 weeks.

[0051] 4. Observation indexes: after the last administration, the rats fasted for 12 h without fasting water. The rats were anesthetized with 3% pentobarbital sodium, blood was collected from the abdominal aorta, serum was centrifugally separated, and the serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were measured.

[0052] 5. Results

[0053] a) Effect of the Composition Provided by the Invention on Blood Lipid Levels in Rats

[0054] As shown in Table 1, compared with the normal group, the levels of TC, TG and LDL-C in the serum of the rats in the model group were significantly increased (P<0.05), showing typical lipid metabolism disorder, thus indicating that an experimental hyperlipidemia model was successfully replicated.

Compared with the model group, the contents of TC, TG and LDL-C in the serum in the treatment group were significantly decreased (P<0.05), and the HDL-C content of the serum was significantly increased (P<0.01) in a dose-dependent manner.

TABLE-US-00001 TABLE 1 Changes of blood lipids of rats in various groups(X S, n = 10) TC TG HDL-C LDL-C Groups (mmol/L) (mmol/L) (mmol/L) (mmol/L) Normal control group 1.63 0.53 0.71 0.42 1.36 0.25 0.26 0.27 Model control group 12.34 3.17 1.20 0.45 0.94 0.36 5.67 3.37 Example 3: Low-dose group 6.19 1.70 0.70 0.27 1.56 0.15 2.40 1.87 Drug Middle-dose group 5.91 3.01 0.67 0.20 1.64 0.10 1.88 1.49 High-dose group 1.65 0.21 0.57 0.19 1.66 0.69 0.99 0.83 Example 6: Low-dose group 6.17 1.62 0.69 0.22 1.53 0.11 2.33 1.76 Drug Middle-dose group 4.67 3.18 0.60 0.15 1.62 0.08 1.85 1.40 High-dose group 1.61 0.21 0.53 0.16 1.65 0.61 0.97 0.71 Example 8: Low-dose group 6.05 1.71 0.60 0.24 1.46 0.13 2.28 1.80 Drug Middle-dose group 4.51 3.21 0.52 0.19 1.55 0.10 1.80 1.46 High-dose group 1.52 0.23 0.43 0.18 1.59 0.61 0.95 0.73 Example 10: Low-dose group 6.10 1.69 0.65 0.27 1.49 0.10 2.29 1.83 Drug Middle-dose group 4.58 3.25 0.58 0.17 1.59 0.15 1.83 1.50 High-dose group 1.56 0.19 0.50 0.16 1.63 0.65 0.96 0.76 Positive drug control group 8.42 4.79 0.49 0.18 1.23 0.17 1.68 1.91

[0055] b) Effect of the Composition Provided by the Invention on Liver Function of Rats

[0056] The liver function could be reflected by ALT and AST in the serum. The levels of ALT and AST in the high-fat feed group were significantly higher than those in the basic feed group (P<0.01), indicating that there was a certain damage to the liver. The levels of ALT and AST in the serum in each administration group were lower than those in the model control group, and there was a significant difference between the middle-dose group, the high-dose group and the model control group (P<0.01), indicating that the composition provided by the invention has a significant effect on protection of liver function, and a significant protecting effect on the organism.

TABLE-US-00002 TABLE 2 Changes of liver function of rats in each group (X S, n = 10) Dose ALT AST Groups (ml/kg-d) (U/L) (U/L) Normal control group 40.39 6.80 19.74 3.16 Model control group 55.44 2.88 31.51 5.68 Example 3 Low-dose 5 48.19 5.52 26.71 1.66 Drug group Middle-dose 10 44.33 3.94 20.88 7.01 group High-dose 15 42.55 4.49 18.39 5.70 group Example 6 Low-dose 5 48.16 5.57 26.66 1.64 Drug group Middle-dose 10 44.27 3.91 20.81 7.11 group High-dose 15 42.46 4.47 18.37 5.77 group Example 8 Low-dose 5 48.05 5.59 26.63 1.60 Drug group Middle-dose 10 44.19 3.95 20.77 7.15 group High-dose 15 42.43 4.40 18.34 5.79 group Example 10 Low-dose 5 48.18 5.57 26.67 1.65 Drug group Middle-dose 10 44.22 3.99 20.84 7.11 group High-dose 15 42.49 4.47 18.38 5.70 group Positive drug control group 1.5 mg/Kg-d 45.85 5.21 22.32 7.56

[0057] The contents of TC, TG and LDL-C were significantly decreased while the content of HDL-C was increased after the hyperlipidemia rats were drenched with the composition provided by the present invention; and the increase in ALT and AST in the serum caused by the high-fat feed was inhibited. It was indicated that the composition provided by the invention promoted fatty acid metabolism, improved intrahepatic lipid metabolism, protected liver cells and regulated lipids and protected liver, and was especially suitable for hyperlipidemia patients with high risk caused by liver function damage. Pharmacological experiments proved that the ornithine, the aspartic acid and the vitamin B6 had a synergistic effect, and could enhance the efficacy each other.

Example 12: Effect of Composition Provided by the Invention in Clinical Treatment

[0058] 1. Case Selection

[0059] Patients with more than 5.7 mmol/L of serum total cholesterol (TC) and (or) more than 1.7 mmol/L of triglyceride (TG) were selected as observation objects, and there were 24 cases in total, including 14 males and 10 females, aged 26 to 69 years.

[0060] 2. Diagnostic Criteria

[0061] Referring to Internal Medicine published by People's Medical Publishing House in 2010, the diagnostic criteria of hyperlipidemia was as follows: serum total cholesterol (TC) was more than or equal to 5.72 mmol/L, triglyceride (TG) was more than or equal to 1.70 mmol/L, low-density lipoprotein cholesterol (LDL-C) was more than or equal to 3.10 mmol/L, and high-density lipoprotein (HDL-C) was less than or equal to 1.04 mmol/L for males, and less than or equal to 1.17 mmol/L for females.

[0062] 3. Treatment Method

[0063] All patients were prohibited from drinking alcohol and eating excessive lipid food at dinner on the day before blood drawing, and TC, TG, HDL-C, and LDL-C were measured by drawing venous blood after the patients fasted for more than 12 hours. Then, the composition provided by the present invention (prepared as in Example 3) was administered three times a day for four continuous weeks, two pills were taken once, each pill contained about 0.25 g of the composition provided by the present invention, and spicy food, especially alcohol was restrained during treatment.

[0064] 4. Efficacy Evaluation Standards

[0065] Markedly effective: After treatment, the blood lipid was detected to conform to any one of the following standards: TC was decreased by more than or equal to 20%, or TG was decreased by more than or equal to 40%, or HDL-C was increased by more than or equal to 0.26 mmol/L, or HDL-C/LDL-C was decreased by more than or equal to 20%, or LDL-C was decreased by more than or equal to 30%.

[0066] Effective: the blood lipid was detected to conform to any one of the following standards: TC was decreased by more than or equal to 10% and less than 20%, or TG was decreased by more than or equal to 20% and less than 40%, or HDL-C was increased by more than or equal to 0.14 mmol/L and less than 0.26 mmol/L, or HDL-C/LDL-C was decreased by more than or equal to 10% and less than 20%, or LDL-C was decreased by more than or equal to 20%.

[0067] Ineffective: the blood lipid was obviously improved or the improvement on the blood lipid did not conform to the standards before and after treatment.

[0068] 5. Treatment Effects

[0069] After 24 cases of patients were treated with the composition provided by the invention for two weeks, the composition was markedly effective in 8 cases, effective in 11 cases, and ineffective in 5 cases, and TC and TG were decreased to different degrees in they ineffective cases. After the composition provided by the invention was continuously administered for two weeks, the composition was markedly effective in 14 cases, effective in 9 cases, and ineffective in 1 case, the inefficiency was 4.2%, and the total efficiency was 95.8%.

[0070] 6. Description of Specific Cases

[0071] (1) Gao, male, 33 years old, hyperlipidemia. Before treatment, the total cholesterol (TC) was 6.31 mmol/L and the triglyceride (TG) was 2.16 mmol/L. The total cholesterol (TC) was decreased to 4.92 mmol/L and the triglyceride (TG) was decreased to 0.99 mmol/L two weeks after administration of the composition provided by the present invention.

[0072] (2) Xu, female, 69 years old, hyperlipidemia. Before treatment, the total cholesterol (TC) was 5.79 mmol/L and the triglyceride (TG) was 4.12 mmol/L. The total cholesterol (TC) was decreased to 5.46 mmol/L and the triglyceride (TG) was decreased to 1.50 mmol/L two weeks after administration of the composition provided by the present invention.