阅读说明：本技术 降香檀叶提取物在制备降血脂药物中的应用及其泡腾片 (Application of dalbergia odorifera leaf extract in preparation of hypolipidemic drugs and effervescent tablets thereof ) 是由 邵峰 吕燕妮 梅慧 胡慧明 洪舟 唐芳瑞 石强 申晨晓 于 2021-01-19 设计创作，主要内容包括：本发明公开了降香檀叶提取物在制备降血脂药物中的应用及其泡腾片,属于医药技术领域。该降香檀叶提取物可按下述方法得到：将降香檀叶采用水或有机溶剂进行化学成分提取,将提取液过滤,减压浓缩,干燥,获得提取物。经本发明药理实验研究结果表明：降香檀叶提取物具有良好的降血脂作用。降香檀叶提取物泡腾片,按以下质量份数制备：降香檀叶提取物1～8份、酸源10-35份、碱源10-35份、辅助崩解剂10-35份、填充剂10-45份、润滑剂1-10份、黏合剂1-8份。本发明降香檀叶提取物不仅表现出良好的降血脂作用,而且其泡腾片制备工艺简单,成本低廉,易于工业化生产,有利于林业废弃物降香檀叶的综合利用开发。(The invention discloses an application of dalbergia odorifera leaf extract in preparation of a blood fat reducing medicine and an effervescent tablet thereof, belonging to the technical field of medicines. The dalbergia wood leaf extract can be obtained by the following method: extracting lignum Dalbergiae Odoriferae leaf with water or organic solvent, filtering the extractive solution, concentrating under reduced pressure, and drying to obtain extract. The pharmacological experiment research result of the invention shows that: the dalbergia wood leaf extract has good effect of reducing blood fat. The dalbergia odorifera leaf extract effervescent tablet is prepared from the following components in parts by mass: 1-8 parts of dalbergia odorifera leaf extract, 10-35 parts of an acid source, 10-35 parts of an alkali source, 10-35 parts of an auxiliary disintegrating agent, 10-45 parts of a filling agent, 1-10 parts of a lubricant and 1-8 parts of a binder. The dalbergia wood leaf extract disclosed by the invention not only shows a good blood fat reducing effect, but also has the advantages of simple preparation process and low cost of the effervescent tablet, is easy for industrial production, and is beneficial to comprehensive utilization and development of forestry waste dalbergia wood leaves.)

1. An application of lignum Dalbergiae Odoriferae leaf extract in preparing medicine for reducing blood lipid is provided.

2. The use as claimed in claim 1, wherein the preparation method of the dalbergia odorifera leaf extract comprises: extracting the dalbergia wood leaves by adopting 3-10 times of water or 20-90% ethanol or methanol, extracting for 1-3 times at 60-100 ℃ by adopting a hot reflux, warm immersion or ultrasonic extraction method, wherein each time lasts for 1-5 hours, filtering, combining filtrate, concentrating under reduced pressure, and drying to obtain the dalbergia wood leaf extract.

3. The dalbergia odorifera leaf extract effervescent tablet is characterized by comprising the following components in parts by mass: 1-8 parts of dalbergia odorifera leaf extract, 10-35 parts of an acid source, 10-35 parts of an alkali source, 10-35 parts of an auxiliary disintegrating agent, 10-45 parts of a filling agent, 1-10 parts of a lubricant and 1-8 parts of a binder.

4. The dalbergia odorifera leaf extract effervescent tablet as claimed in claim 3, wherein the preparation method of the dalbergia odorifera leaf extract effervescent tablet comprises the following steps:

grinding an acid source, an alkali source, an auxiliary disintegrating agent, a filling agent, a lubricating agent, a binding agent and a dalbergia odorifera leaf extract, and then respectively sieving the ground materials by a No. 2 sieve;

step two, placing the sieved powder into a 500mL beaker, finally adding a lubricant, and stirring until the mixture is uniformly mixed;

and step three, adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

5. The rosewood leaf extract effervescent tablet of claim 4, wherein the acid source is one of citric acid and tartaric acid; the alkali source is sodium bicarbonate; the auxiliary disintegrant is one of microcrystalline cellulose, hydroxypropyl cellulose, carboxymethyl starch sodium, starch sodium glycolate and alginic acid; the filler is one of mannitol, dextrin, lactose and starch; the lubricant is one of polyethylene glycol 6000, L-leucine, magnesium stearate and benzoic acid; the adhesive is one of polyvidone K30, ethanol, sodium carboxymethylcellulose, starch slurry, acacia, sucrose, acacia slurry, and hydroxypropyl methylcellulose.

Technical Field

The invention relates to the technical field of medicines, in particular to application of dalbergia odorifera leaf extract in preparation of a blood fat reducing medicine and an effervescent tablet thereof.

Background

According to 2018, the world health organization counts that about 5700 thousands of people die of cardiovascular diseases globally, accounting for about 31 percent of the total death. Hyperlipidemia is an important cause of cardiovascular diseases such as atherosclerosis, coronary heart disease and hypertension. The clinical manifestations of the disease are that the index levels of serum Total Cholesterol (TC), Triglyceride (TG), low-density lipoprotein (LDL-C) and the like are increased, and the index level of high-density lipoprotein (HDL-C) is reduced. Generally, patients who take lipid-lowering drugs such as statins and fibrates are often accompanied by severe adverse reactions such as hyperuricemia, muscle damage and abnormal liver function. Therefore, the search for safer and more effective drugs for preventing and treating hyperlipidemia is the focus of long-term attention in the field of medicine research in the world.

Dalbergia odorifera (Dalbergia odorifera), also known as Hainan Huanghua pear, is a precious tree species and is also a basic source plant of traditional Chinese medicine Dalbergia odorifera. The plant core material mainly contains flavonoid components and volatile oil components, and has good biological activities of oxidation resistance, inflammation resistance, bacteria resistance, tumor resistance and the like. At present, the pharmaceutical research of dalbergia odorifera is mainly carried out around the core material, and the related research and comprehensive utilization of dalbergia odorifera leaves have not yet attracted attention of people. The effervescent tablet is prepared on the basis of determining that the dalbergia odorifera leaf extract has good biological activity for reducing blood fat, and an effective way is finally provided for realizing comprehensive utilization of the dalbergia odorifera leaf which is a forestry waste.

Disclosure of Invention

The invention provides application of dalbergia odorifera leaf extract in preparation of a medicine for preventing and treating blood fat reduction and an effervescent tablet thereof.

The dalbergia odorifera leaf extract has a good blood fat reducing effect, can be applied to preparation of blood fat reducing medicines, and is simple in preparation process, low in cost and easy for industrial production.

One of the technical schemes of the invention is realized by the following modes: an application of lignum Dalbergiae Odoriferae leaf extract in preparing medicine for preventing or treating osteoporosis is provided.

Preferably, the preparation method of the dalbergia odorifera leaf extract comprises the following steps: extracting the dalbergia wood leaves by adopting 3-10 times of water or 20-90% ethanol or methanol, extracting for 1-3 times at 60-100 ℃ by adopting a hot reflux, warm immersion or ultrasonic extraction method, wherein each time lasts for 1-5 hours, filtering, combining filtrate, concentrating under reduced pressure, and drying to obtain the dalbergia wood leaf extract.

The second technical scheme of the invention is realized by the following mode: an effervescent tablet of dalbergia odorifera leaf extract comprises the following components in parts by mass: 1-8 parts of dalbergia odorifera leaf extract, 10-35 parts of an acid source, 10-35 parts of an alkali source, 10-35 parts of an auxiliary disintegrating agent, 10-45 parts of a filling agent, 1-10 parts of a lubricant and 1-8 parts of a binder.

Preferably, the preparation method of the dalbergia odorifera leaf extract effervescent tablet comprises the following steps:

grinding an acid source, an alkali source, an auxiliary disintegrating agent, a filling agent, a lubricating agent, a binding agent and a dalbergia odorifera leaf extract, and then respectively sieving the ground materials by a No. 2 sieve;

step two, placing the sieved powder into a 500mL beaker, finally adding a lubricant, and stirring until the mixture is uniformly mixed;

and step three, adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

Preferably, the acid source is one of citric acid and tartaric acid; the alkali source is sodium bicarbonate; the auxiliary disintegrant is one of microcrystalline cellulose, hydroxypropyl cellulose, carboxymethyl starch sodium, starch sodium glycolate and alginic acid; the filler is one of mannitol, dextrin, lactose and starch; the lubricant is one of polyethylene glycol 6000, L-leucine, magnesium stearate and benzoic acid; the adhesive is one of polyvidone K30, ethanol, sodium carboxymethylcellulose, starch slurry, acacia, sucrose, acacia slurry, and hydroxypropyl methylcellulose.

The effervescent tablet is prepared on the basis of determining that the dalbergia odorifera leaf extract has good biological activity of reducing blood fat, and finally, an effective development way is provided for realizing comprehensive utilization of the dalbergia odorifera leaf which is a forestry waste.

Drawings

FIG. 1 is a comparison graph of blood lipid levels of various experimental groups in a pharmacological test of Dalbergia odorifera leaf extract;

FIG. 2 is a liver HE staining chart of each experimental group in a pharmacological test of dalbergia odorifera leaf extract;

FIG. 3 is a staining diagram of liver immunohistochemistry in each experimental group in the pharmacological test of Dalbergia odorifera leaf extract.

Detailed Description

The present invention is further illustrated by the following examples, which are intended to be illustrative only and not limiting, in conjunction with the results of pharmacodynamic testing.

Example 1

Extracting lignum Dalbergiae Odoriferae leaf with water at a ratio of 1:10 at 100 deg.C under reflux for 3 times (1 hr each time), filtering, mixing filtrates, concentrating under reduced pressure, and drying to obtain lignum Dalbergiae Odoriferae leaf extract.

Grinding 10 parts of citric acid, 10 parts of sodium bicarbonate, 10 parts of hydroxypropyl cellulose, 10 parts of mannitol, 1 part of magnesium stearate, 1 part of sodium carboxymethyl cellulose and 1 part of dalbergia odorifera leaf extract, and respectively sieving with a No. 2 sieve. Each powder was placed in a 500ml beaker and magnesium stearate was added last and stirred until well mixed. Adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

Example 2

Extracting lignum Dalbergiae Odoriferae leaf with water at a ratio of 1:3 at 60 deg.C under reflux for 5 hr for 1 time (balancing the number of the following 3 extraction methods), filtering, concentrating under reduced pressure, and drying to obtain lignum Dalbergiae Odoriferae leaf extract.

Grinding 35 parts of citric acid, 35 parts of sodium bicarbonate, 35 parts of sodium starch glycolate, 8 parts of ethanol, 45 parts of dextrin, 10 parts of L-leucine and 8 parts of dalbergia odorifera leaf extract, and respectively sieving with a No. 2 sieve. Each powder was placed in a 500ml beaker and L-leucine was added last and stirred until well mixed. Adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

Example 3

The dalbergia wood leaf extract is prepared by using 20% ethanol as an extraction solvent, performing warm-immersion extraction at 80 ℃ according to the material-liquid ratio of 1:10 for 3 times, each time for 1 hour, filtering, combining filtrates, concentrating under reduced pressure, and drying.

Grinding 10 parts of tartaric acid, 10 parts of sodium bicarbonate, 10 parts of microcrystalline cellulose, 1 part of starch slurry, 10 parts of lactose, 1 part of polyethylene glycol 6000 and 1 part of dalbergia odorifera leaf extract, and respectively sieving with a No. 2 sieve. Placing each powder in a 500ml beaker, adding polyethylene glycol-6000, and stirring to mix well. Adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

Example 4

Soaking lignum Dalbergiae Odoriferae leaf in 70% ethanol at a ratio of 1:7 at 60 deg.C for 2 times (each for 2 hr), filtering, mixing filtrates, concentrating under reduced pressure, and drying to obtain lignum Dalbergiae Odoriferae leaf extract.

Grinding 20 parts of tartaric acid, 25 parts of sodium bicarbonate, 20 parts of carboxymethyl starch sodium, 5 parts of povidone K30, 30 parts of starch, 5 parts of benzoic acid and 5 parts of dalbergia odorifera leaf extract, and respectively sieving the ground materials by a No. 2 sieve. Each powder was placed in a 500ml beaker and benzoic acid was added last and stirred until well mixed. Adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

Example 5

Soaking lignum Dalbergiae Odoriferae leaf with 90% ethanol as extraction solvent at a ratio of 1:3 at 100 deg.C for 1 time, each for 5 hr, filtering, concentrating under reduced pressure, and drying to obtain lignum Dalbergiae Odoriferae leaf extract.

Grinding 35 parts of tartaric acid, 35 parts of sodium bicarbonate, 35 parts of alginic acid, 8 parts of Arabic gum, 45 parts of starch, 10 parts of L-leucine and 8 parts of dalbergia odorifera leaf extract, and sieving with a No. 2 sieve respectively. Each powder was placed in a 500ml beaker and L-leucine was added last and stirred until well mixed. Adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

Example 6

The dalbergia wood leaf extract is prepared by using methanol as an extraction solvent, performing ultrasonic extraction for 1 hour according to the material-liquid ratio of 1:3, filtering, concentrating under reduced pressure, and drying.

Grinding 10 parts of citric acid, 10 parts of sodium bicarbonate, 10 parts of microcrystalline cellulose, 1 part of hydroxypropyl methyl cellulose, 10 parts of mannitol, 1 part of polyethylene glycol 6000 and 1 part of dalbergia odorifera leaf extract, and respectively sieving with a No. 2 sieve. Placing each powder in a 500ml beaker, adding polyethylene glycol-6000, and stirring to mix well. Adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

Example 7

The dalbergia wood leaf extract is prepared by using methanol as an extraction solvent, performing ultrasonic extraction for 2 hours according to the material-liquid ratio of 1:7, filtering, concentrating under reduced pressure, and drying.

Grinding 25 parts of tartaric acid, 20 parts of sodium bicarbonate, 20 parts of carboxymethyl starch sodium, 5 parts of acacia mucilage, 25 parts of dextrin, 6 parts of magnesium stearate and 5 parts of dalbergia odorifera leaf extract, and screening by a No. 2 sieve respectively. Each powder was placed in a 500ml beaker and magnesium stearate was added last and stirred until well mixed. Adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

Example 8

The dalbergia wood leaf extract is prepared by using methanol as an extraction solvent, performing ultrasonic extraction for 5 hours according to the material-liquid ratio of 1:10, filtering, concentrating under reduced pressure, and drying.

35 parts of citric acid, 35 parts of sodium bicarbonate, 35 parts of hydroxypropyl cellulose, 8 parts of sucrose, 45 parts of lactose, 10 parts of L-leucine and 8 parts of dalbergia odorifera leaf extract are ground and respectively sieved by a No. 2 sieve. Each powder was placed in a 500ml beaker and L-leucine was added last and stirred until well mixed. Adding the mixture into a tabletting machine to prepare the dalbergia odorifera leaf extract effervescent tablets.

Test case 1

Pharmacological test of dalbergia wood leaf extract:

1. animal grouping, modeling and administration

SD rats are fed with common feed for 3 days, and then are randomly divided into a normal group (Control group), a Model group (Model group) and a lignum Dalbergiae Odoriferae leaf low dose group (0.4 g.Kg)^-1) Dosage group (0.8 g.Kg) in dalbergia odorifera leaf^-1) High dose group (1.6 g.Kg) of dalbergia odorifera leaves^-1) 10 per group. Basal diet was given to the normal group, high-sugar and high-fat diet was given to the other groups continuously for 2 weeks, and drinking water was freely taken during the experiment to establish a hyperlipemia rat model. After the model building is successful, the dalbergia odorifera leaf treatment group is respectively administered with corresponding medicaments for intragastric administration every day, and the intragastric administration dose is 10mL & Kg^-1Body mass, 1 time daily, for 4 weeks. The normal group and the model group were given a corresponding volume of distilled water.

2. Blood lipid level determination

After 4 weeks of continuous administration, orbital bleeds (12 h before bleeds were fasted without water), 3500 r.min^-1Centrifuging for 10min, collecting serum, detecting TC in rat serum by full-automatic biochemical analyzer,TG, HDL-C, LDL-C content.

3. HE staining

After 4 weeks of continuous administration, blood was collected from the orbit, sacrificed by dislocation, and the liver of the rat was dissected and collected. Washing blood in tissue with normal saline, fixing liver tissue in 10% neutral formalin solution, dehydrating, embedding in paraffin, making paraffin section (3 μm), staining with hematoxylin-eosin method, gradient eluting with alcohol, clearing xylene, sealing with neutral gum, and observing tissue cell and organelle shape under microscope.

4. Immunohistochemical staining

The cut paraffin sections were dewaxed conventionally to hydration, placed in fresh 3% catalase solution, left to stand at room temperature for 15min, and washed with PBS. The antigen was heat-repaired by autoclave, serum-blocked, primary antibody (HMGCR antibody) was added dropwise, incubated for 30min, and left overnight in a refrigerator at 4 ℃. Standing at room temperature for 60min, removing the blocking solution, washing with PBS, and incubating the second antibody according to the instruction of the immunohistochemical second antibody kit. Adding DAB color development working solution dropwise for color development, performing mild counterstaining with hematoxylin, dehydrating, performing xylene transparency, adding neutral gum, sealing, and observing and taking a picture under an optical microscope.

After experimental study, as shown in fig. 1, compared with the normal group, after being fed with high-fat feed for 6 weeks, the serum TG, TC and LDL-C levels of the model group mice are all significantly increased (P <0.05, P <0.01), and the HDL-C level is significantly reduced (P <0.01), which indicates that the hyperlipidemia rat model is successfully replicated. Compared with the model group, the serum TC and LDL-C levels of rats in each administration group are obviously reduced (P < 0.01). Serum TG levels were significantly reduced in the low dose group rats (P < 0.05). The serum HDL-C level of rats in the high dose group is obviously higher than that in the model group (P < 0.01). The result shows that the dalbergia odorifera leaf extract has good hypolipidemic activity and can be applied to preparation of hypolipidemic drugs.

As shown in FIG. 2, the normal group of hepatocytes has regular morphology and clear hepatic lobule structure. In comparison with the normal group, a large number of lipid droplet vacuoles were present in hepatocytes of the model group. The nuclei were squeezed by large lipid droplets and turned to one side with significant steatosis. The liver lobules are infiltrated by a large number of inflammatory cells. Each administration group reduced symptoms of steatosis and inflammatory cell infiltration compared to the model group. The results confirm that: the dalbergia odorifera leaf extract has good biological activity of reducing blood fat.

As shown in FIG. 3, brown-positive expression was not observed in the cytoplasm of hepatocytes of the normal group, whereas the expression of the model group was more positive than that of the model group in terms of tan. Compared with the model group, the administration groups can obviously reduce the rat liver HMGCR expression. The results further confirm that: the dalbergia odorifera leaf extract has good biological activity of reducing blood fat.

Test case 2

The effervescent tablets of examples 1 to 8 were subjected to disintegration time limit test, and as shown in Table 1, the effervescent tablets prepared in each example were disintegrated within 150 seconds.

TABLE 1 disintegration time limit

While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.