CN1582919A - Preparation of medicines for reducing blood sugar and triglyceride from hippophae rhamnoides flavone - Google Patents

Abstract

The invention discloses a method for preparing medicines for lowering blood sugar and triglycerides by using seabuckthorn flavonoids, which belongs to the technical field of traditional Chinese medicine preparation. Take seabuckthorn flavonoids as the active substance, add excipients, microcrystalline cellulose, hydroxypropyl cellulose, sodium carboxymethyl starch, talcum powder, gelatin, glycerin, water, and parts of refined vegetable oil to make tablets or drug capsules The medicinal raw materials are processed into tablets or filled into capsules to obtain a drug that can simultaneously reduce high blood sugar levels and high blood lipid levels. The method has the advantages of simple method, low production equipment requirement, low production cost and easy implementation.

Description

Method for preparing medicine for lowering blood sugar and triglyceride by using seabuckthorn flavonoids

                    

The invention relates to a method for preparing medicines for lowering blood sugar and triglycerides by using seabuckthorn flavonoids, and belongs to the technical field of preparation of traditional Chinese medicines.

Background technique

Seabuckthorn flavonoids are active substances extracted from seabuckthorn, a traditional Chinese medicine, namely seabuckthorn leaves, seabuckthorn fruit, seabuckthorn juice or seabuckthorn oil.

Modern pharmacological studies have shown that seabuckthorn flavonoids have good curative effects on diseases of the cardiovascular and cerebrovascular systems, respiratory system, digestive system, and immune system. , 2001, 14(2): 27-29, Zhu Wanjing and Ni Peide et al.'s paper "The Best Extraction Technology of Flavonoids from Seabuckthorn Pomace", China Oils and Fats, 2001, 26(1): 35-37, Zhu Wanjing Ni Peide et al. Thesis "Development of Seabuckthorn Resources and Extraction of Seabuckthorn Flavonoids", China Oils and Oils, 2000, 25(5): 46-48, Yu Changqing and Yang Huiwen's paper "Characteristics of Seabuckthorn Oil and Supercritical CO ₂ Extraction Technology", Gansu Light Fang Science and Technology, 1998, (4): 22-27 and Cheng Tijuan, Bu Jikang et al.'s paper "Hepatoprotective Effect and Mechanism of Seabuckthorn Seed Oil", Chinese Journal of Traditional Chinese Medicine, 1994, 19(6): 367-370. In addition, seabuckthorn flavonoids also have the functions of promoting metabolism, anti-tumor, protecting organs, anti-inflammation and muscle growth, strengthening brain and improving intelligence, promoting development and resisting aging. , Tianjin Traditional Chinese Medicine, 1997, 14(4): 173-174, Xin Weijun and Chen Ping's paper "Treating Hyperlipidemia and Hyperviscosity with Acetaloflavone", New Drugs and Clinics, 1997, 16(1) : 17-18, the achievement "seabuckthorn flavonoids" of the Institute of Biophysics, Chinese Academy of Sciences, achievement record number: 181349 and Zou Yuansheng's patent, "seabuckthorn oil compound capsule", patent application number: 98103550, approval announcement number: 1063959.

Contents of the invention

So far, there have been no domestic and foreign research reports on the medicinal use of seabuckthorn flavonoids in simultaneously reducing high blood sugar levels, anti-glycosylation and high triglyceride levels.

The technical problem to be solved by the present invention is to propose a method for preparing medicines for lowering blood sugar and triglycerides by using seabuckthorn flavonoids. The technical scheme of the present invention to solve the above-mentioned technical problems is characterized in that, taking seabuckthorn flavonoids as an active substance, with auxiliary materials, microcrystalline cellulose (MCC), hydroxypropyl cellulose (HPC), sodium carboxymethyl starch (CMS-Na ), talcum powder, gelatin, glycerin, water, and parts in refined vegetable oils to obtain medicinal raw materials for tablets or drug capsules, and then process the medicinal raw materials into tablets or fill them into capsules to obtain simultaneously reducing hyperglycemia Levels and drugs for high blood lipid levels.

The technical solution of the present invention is now described in detail. A method for preparing hypoglycemic and lipid-lowering medicines with seabuckthorn flavonoids, characterized in that seabuckthorn flavones are used as active substances, and the medicine is prepared in the form of tablets, and the specific operation steps are as follows:

Step 1 Ingredients

Prepare the number of tablets as required and each tablet contains: 1 part by weight of seabuckthorn flavonoids, 0.1 to 0.3 parts by weight of microcrystalline cellulose, 0.05 to 0.2 parts by weight of sodium hydroxypropyl cellulose, and 0.01 to 0.06 parts by weight of sodium carboxymethyl starch , the proportioning ingredients of 0.001～0.03 parts by weight of talcum powder;

The second step preparation

Seabuckthorn flavonoids are sieved and mixed with microcrystalline cellulose and hydroxypropyl cellulose sodium, sieved, then mixed with carboxymethyl starch sodium and talcum powder to obtain medicinal raw materials, and the medicinal raw materials are pressed into tablets to obtain Each tablet of the required number of tablets contains 1 part by weight of seabuckthorn flavonoids while reducing high blood sugar levels and high blood fat levels.

A further feature of the technical solution of the present invention is that the dosage form of the preparation medicine is a soft capsule, and the specific operation steps are:

Step 1 Ingredients

Prepare the number of medicine capsules as required and each medicine capsule contains: 1 part by weight of seabuckthorn flavonoids, 0.8 to 1.2 parts by weight of refined vegetable oil, 1 part by weight of gelatin, 0.55 to 0.65 parts by weight of glycerin, and 1 part by weight of water;

The second step preparation

Dissolve seabuckthorn flavonoids in refined vegetable oil to obtain capsule core material, stir and dissolve with water, glycerin and gelatin to obtain capsule wall material, put the capsule core material and capsule wall material into a capsule machine to obtain the required number of capsules Each medicine capsule containing seabuckthorn flavonoids for reducing high blood sugar level and high blood fat level at the same time by 1 part by weight.

The invention has the advantages of simple method, low production equipment requirement, low production cost and easy implementation, and the raw material active substance is seabuckthorn flavone, which is a pure natural substance.

Detailed ways

All examples are operated according to the operation steps of the above-mentioned preparation method.

Example 1

The first step is to prepare 1000 tablets as required, each containing 0.1 g of seabuckthorn flavonoids, 0.03 g of microcrystalline cellulose, 0.02 g of sodium hydroxypropyl cellulose, 0.006 g of sodium carboxymethyl starch, and 0.003 g of talcum powder The ratio of ingredients for g;

In the second step, seabuckthorn flavonoids are mixed with microcrystalline cellulose and hydroxypropyl cellulose, then mixed with carboxymethyl starch sodium and talcum powder, and pressed into tablets to obtain 1000 tablets each containing 0.1 g of seabuckthorn flavonoids. Tablets that lower high blood sugar levels and high blood fat levels.

Example 2

The first step is to prepare 1000 tablets as required, each containing 0.1 g of seabuckthorn flavonoids, 0.02 g of microcrystalline cellulose, 0.0125 g of hydroxypropyl cellulose sodium, 0.0035 g of sodium carboxymethyl starch, and 0.0015 g of talcum powder The ratio of ingredients for g;

The second step is to mix seabuckthorn flavonoids with microcrystalline cellulose and hydroxypropyl cellulose according to the conventional method, then mix with carboxymethyl starch sodium and talcum powder, and press into tablets to obtain 1000 tablets each containing seabuckthorn Flavonoids 0.1g Tablets that reduce high blood sugar levels and high blood fat levels at the same time.

Example 3

The first step is to prepare 1000 tablets as required, each containing 0.1 g of seabuckthorn flavonoids, 0.01 g of microcrystalline cellulose, 0.005 g of hydroxypropyl cellulose sodium, 0.001 g of sodium carboxymethyl starch, and 0.0001 g of talcum powder The ratio of ingredients for g;

In the second step, seabuckthorn flavonoids are mixed with microcrystalline cellulose and hydroxypropyl cellulose, then mixed with carboxymethyl starch sodium and talcum powder, and pressed into tablets to obtain 1000 tablets each containing 0.1 g of seabuckthorn flavonoids. Tablets that lower high blood sugar levels and high blood fat levels.

Example 4

In the first step, the number of drug capsules required to be prepared is 1000, and each drug capsule contains: 0.1 g of seabuckthorn flavonoids, 0.12 g of refined vegetable oil, 0.1 g of gelatin, 0.065 g of glycerin, and 0.1 g of water;

The second step is to dissolve seabuckthorn flavonoids in refined vegetable oil to obtain the capsule core material, heat glycerin and water to 70-80°C, add gelatin, stir and dissolve, and obtain the capsule wall material, and mix the capsule core material and the capsule wall material Put it into a capsule machine for preparation, and prepare 1000 medicinal capsules each containing 0.1 g of seabuckthorn flavonoids, which can reduce high blood sugar levels and high blood fat levels.

Example 5

In the first step, the number of drug capsules required to be prepared is 1000, and each drug capsule contains 0.1 g of seabuckthorn flavonoids, 0.1 g of refined vegetable oil, 0.1 g of gelatin, 0.06 g of glycerin, and 0.1 g of water;

The second step is to dissolve seabuckthorn flavonoids in refined vegetable oil to obtain the capsule core material, heat glycerin and water to 70-80°C, add gelatin, stir and dissolve, and obtain the capsule wall material, and mix the capsule core material and the capsule wall material Put it into a capsule machine for preparation, and prepare 1000 medicinal capsules each containing 0.1 g of seabuckthorn flavonoids, which can reduce high blood sugar levels and high blood fat levels.

Example 6

In the first step, the number of drug capsules required to be prepared is 1000, and each drug capsule contains 0.1 g of seabuckthorn flavonoids, 0.08 g of refined vegetable oil, 0.1 g of gelatin, 0.055 g of glycerin, and 0.1 g of water;

The second step is to dissolve seabuckthorn flavonoids in refined vegetable oil to obtain the capsule core material, heat glycerin and water to 70-80°C, add gelatin, stir and dissolve, and obtain the capsule wall material, put the capsule core material and the capsule wall material Prepare in a capsule machine, and prepare 1000 medicinal capsules each containing 0.1 g of seabuckthorn flavonoids that can reduce high blood sugar levels and high blood fat levels.

Animal experiments to investigate the efficacy of seabuckthorn flavonoids in lowering blood sugar and triglycerides:

1. Male Kunming mice with a body weight of about 25 g were fed with alloxan intraperitoneally at a dose of 180 mg/kg of mouse body weight after 3 days of adaptive feeding. Fasting serum glucose (hereinafter referred to as blood sugar) value was measured after 72 hours. Select mice whose blood sugar level is higher than 14mmol/L to form a positive control group, a positive administration control group, and a seabuckthorn flavonoid treatment group (divided into low, medium, and high dosage groups), and the blood sugar level difference between each group is less than 1.1mmol/L. L. A normal control group was also set up, with 12 mice in each of the above groups. Positive administration control dose was 100mg/kg, and the control drug-Jiangtangling was fed once a day, and the seabuckthorn flavone treatment group was given three doses of 50mg/kg, 100mg/kg, and 150mg/kg, respectively, once a day. The seabuckthorn flavonoids were fed continuously for 18 days, and the positive control and the normal control were fed with the same amount of distilled water once a day.

The fasting blood glucose level was measured every 6 days when the test was recorded as zero at the beginning.

The results showed that compared with the positive control group, the blood sugar level of each test group was lowered by 38.04% in the low-dose treatment group at 18 days (P<0.05). Middle-dose treatment group: on day 12 and day 18, the hypoglycemic ranges were 36.19% (P<0.01) and 36.91% (P<0.05). High-dose treatment group: at 6, 12 and 18 days, the hypoglycemic ranges were 45.06%, 46.34% and 61.16%, respectively (all P<0.01). Compared with the positive administration control group, there was no significant difference in the therapeutic effect between the low and middle doses and the control drug Jiangtangling, and the high dose could significantly increase the hypoglycemic range by about 17% compared with the control drug Jiangtangling. See Table 1.

2. While measuring the blood sugar level, analyze the insulin sensitivity index and triglyceride level of the mice in the high-dose treatment group and the positive control group. On day 18, the insulin sensitivity index of the mice in the positive control group was -7.00±0.30, and the insulin sensitivity index of the mice in the positive control group was -6.59±0.61. The insulin sensitivity index of mice in the high-dose treatment group was -6.27±0.41, which was 10.42% higher than that of the positive control group and 4.85% higher than that of Jiangtangling in the positive control group. The analysis results show that seabuckthorn flavonoids have the tendency to enhance the release of insulin under the pathological state of hyperglycemia, and significantly improve the sensitivity index of insulin. The triglyceride value of the mice in the positive control group was 1.75±0.42mmol/L, and that of the positive control group was 1.64±0.52. There was no significant difference between the latter and the positive control group. The triglyceride value of the mice in the high-dose treatment group The value is 1.39±0.16mmol/L, which is 20.57% lower than the positive control and 14.79% lower than the positive control. The results of the analysis showed that seabuckthorn flavonoids can reduce the level of triglycerides. see table

3. Normal male SD rats with a body weight of 253.07 ± 16.17g were adaptively fed for 5 days, and after fasting for 10 hours, 4% streptozotocin (STZ) solution prepared with citric acid buffer (pH4.6) , by intraperitoneal injection at a dose of 57 mg/kg to prepare hyperglycemic rats. After 96 hours, blood was collected from the tail vein, and the fasting blood glucose value after 6 hours of fasting was measured, and those with a fasting blood glucose value greater than 15.00 mmol/L were selected to randomly form a positive control group, a positive administration control group, and a treatment group, with 12 rats in each group. mouse. The blood glucose difference among each group was less than 0.1mmol/L. Another normal control group was set up.

The treatment group was given 150 mg/kg of seabuckthorn flavonoids, the positive control group was given 200 mg/kg of metformin by intragastric administration once a day, and the positive and normal control groups were given intragastric administration of the same volume of distilled water once a day. 4 consecutive weeks. Check blood sugar once a week.

The results showed that after intragastric administration for 1, 2, 3 and 4 weeks, the blood sugar levels of the rats in the treatment group were significantly lower than those of the positive control group rats, and the range of hypoglycemic levels increased week by week, respectively by 5.66% (P< 0.05), 14.86% (P<0.01), 16.68% (P<0.05), 23.33% (P<0.01), and better than the metformin hypoglycemic effect of the positive administration control group, the highest value of metformin hypoglycemic was 15.84% (P<0.05). See Table 3.

4. In order to determine the stability of seabuckthorn flavonoids in effectively lowering blood sugar, while seabuckthorn flavonoids were used to reduce the hyperglycemia level in rats induced by streptozotocin, the serum fructosamine, which can reflect the stability of blood sugar in 2 to 3 weeks, was measured. The results It showed that compared with metformin, seabuckthorn flavonoids can reduce serum fructosamine level by 11.69% (P<0.05).

At 5 and 4 weeks, the rats with hyperglycemia induced by streptozotocin were tested for triglycerides, and the results were consistent with the previous ones. Compared with metformin, seabuckthorn flavonoids can effectively reduce the triglyceride level of the test rats at the same time, and the reduction rate is 36.50% (P<0.05).

In conclusion, (1) one-time feeding of seabuckthorn flavonoids at a dose of 50-150 mg/kg per day for 18 consecutive days can effectively reduce the hyperglycemia level of mice with hyperglycemia induced by alloxan and increase the degree of hyperglycemia induced by alloxan. Insulin sensitivity index of rats; one-time feeding of seabuckthorn flavonoids at a dose of 150 mg/kg per day for 28 consecutive days can effectively reduce the hyperglycemia and fructosamine levels of streptozotocin-induced hyperglycemia SD rats.

(2) One-time feeding of 50-150 mg/kg of seabuckthorn flavonoids per day for 18 consecutive days can also reduce the level of high blood sugar, reduce the level of triglycerides and improve the antioxidant capacity of the tested animals.

Conclusion: Two different hyperglycemic animal experiments have proved that the seabuckthorn flavonoid drug prepared by the method of the present invention can effectively reduce the hyperglycemia level and hypertriglyceride level of hyperglycemia mice and rats tested simultaneously.

Table 1. Effect of seabuckthorn flavonoids on serum glucose in alloxan-induced hyperglycemia model mice

Group Dose Mice Serum Glucose (mmol/L)

(mg/kg) (only) 0d 6d 12d 18d

Normal Distilled water equivalent 8 9.63±0.63 9.53±3.12 10.08±0.87 8.43±1.31

Positive control Equal volume of distilled water 8 25.50±7.45 22.68±8.69 28.98±6.65 36.35±11.20

Positive administration 100 8 25.41±8.21 15.52±7.28 ^* 18.96±6.12 ^* 17.06±7.56 ^**

Low dose 50 10 25.33±9.12 20.12±10.68 19.39±11.86 22.52±14.23 ^*

Medium dose 100 10 25.36±9.15 21.69±8.60 18.49±7.47 ^** 22.93±10.98 ^*

High dose 150 10 25.11±7.17 12.46±4.09 ^** 15.55±4.59 ^** 14.12±5.77 ^**

^* P<0.05, ^** P<0.01 vs positive control.

Table 2. Effect of seabuckthorn flavonoids on blood lipids in mice with hyperglycemia induced by alloxan

Group Dose Cholesterol Triglycerides

(mg/kg) (mmol/L) (mmol/L)

Normal Equivalent distilled water 2.92±0.47 1.16±0.22 ^**

Positive control Equivalent distilled water 3.53±0.81 1.75±0.42

Positive administration 100 3.21±0.60 1.64±0.52

High dose 150 3.08±0.76 1.39±0.16 ^*

^* P<0.05, ^** P<0.01, compared with positive control.

Table 3. Effect of seabuckthorn flavonoids on serum glucose in streptozotocin-induced hyperglycemia rats

Groups Number of Rats Serum Glucose (mmol/L)

(only) 0 weeks 1 week 2 weeks 3 weeks 4 weeks

Normal 10 5.81±0.23 5.78±0.22 5.77±0.44 5.71±0.47 5.73±0.67

Positive control 10 27.29±1.58 27.74±1.65 31.15±3.18 30.93±5.12 30.95±2.61

Positive administration 11 27.25±2.70 27.01±2.24 29.21±2.63 26.03±5.61 ^* 28.70±1.87 ^*

High dose 11 27.24±1.71 26.17±2.11 ^* 26.52±4.38 ^** 25.77±5.45 ^* 23.73±7.55 ^**

*P<0.05, **P<0.01 compared with positive control.

Claims (3)

1. one kind prepares the method for blood sugar lowering and triglyceride medicine with Fructus Hippophae flavone, it is characterized in that, and with the Fructus Hippophae flavone active substance, be equipped with adjuvant, microcrystalline Cellulose, hydroxypropyl cellulose, carboxymethyl starch sodium, Pulvis Talci, gelatin, glycerol, water, the part in the refining vegetable oil makes the medicinal raw material of tablet or medicament capsule, again this medicinal raw material is processed into tablet or charges into capsule, make the medicine that reduces hyperglycemia level and hyperlipidemia level simultaneously.

2. the method for preparing medicine according to claim 1 is characterized in that, the type of preparation medicine is a tablet, the concrete operations step:

First step batching

Contain by required preparation tablet sheet number and every: 1 part of weight of Fructus Hippophae flavone, 0.1～0.3 part of weight of microcrystalline Cellulose, 0.05～0.2 part of weight of HPMC, 0.01～0.06 part of weight of carboxymethyl starch sodium, the proportion ingredient of 0.001～0.03 part of weight of Pulvis Talci;

The preparation of second step

Fructus Hippophae flavone is sieved and microcrystalline Cellulose and HPMC mixing, sieve, again with carboxymethyl starch sodium and Pulvis Talci mixing, make medicinal raw material, the medicinal raw material tabletting reduces the tablet of hyperglycemia level and hyperlipidemia level when making every of required number and contain 1 part of weight Fructus Hippophae flavone.

3. the method for preparing medicine according to claim 1 is characterized in that, the dosage form of preparation medicine is a soft capsule, the concrete operations step:

First step batching

Contain by required preparation medicament capsule number and each medicament capsule: 1 part of weight of Fructus Hippophae flavone, 0.8～1.2 part of weight of refining vegetable oil, 1 part of weight of gelatin, 0.55～0.65 part of weight of glycerol, the proportion ingredient of 1 part of weight of water;

The preparation of second step

Fructus Hippophae flavone is dissolved in refining vegetable oil, make the capsule core material material, after water, glycerol and gelatin stir and dissolve, make the cyst wall material, capsule core material material and cyst wall material are put into capsule machine, reduce the medicament capsule of hyperglycemia level and hyperlipidemia level when each that makes required number contains 1 part of weight of Fructus Hippophae flavone.