阅读说明：本技术 一种苍麻组合物在制备降脂药物中的用途 (Application of fructus xanthil and fructus cannabis composition in preparation of lipid-lowering drugs ) 是由 胡馨 刘红旭 周明学 李思耐 秦小妹 于 2019-11-29 设计创作，主要内容包括：本发明提供了一种苍麻组合物在制备降脂药物中的用途。以重量份计,苍麻组合物包括5～20份的苍术和5～20份的麻黄。将苍术和麻黄的组合物应用于制备降脂药物中时,经过试验验证所制备的降脂药物具有突出的降甘油三酯、降胆固醇、促进脂肪代谢的作用,开拓了苍术和麻黄的适应症范围。(The invention provides an application of a xanthium and ephedra composition in preparing a lipid-lowering drug. The xanthium and ephedra herb composition comprises 5-20 parts of rhizoma atractylodis and 5-20 parts of ephedra herb in parts by weight. When the composition of the rhizoma atractylodis and the ephedra is applied to preparing the lipid-lowering medicine, tests prove that the prepared lipid-lowering medicine has the outstanding effects of lowering triglyceride and cholesterol and promoting fat metabolism, and the range of indications of the rhizoma atractylodis and the ephedra is expanded.)

1. The application of the xanthium and ephedra composition in preparation of a lipid-lowering drug is characterized by comprising 5-20 parts of rhizoma atractylodis and 5-20 parts of ephedra according to parts by weight.

2. The use according to claim 1, wherein the xanthium composition comprises 10 to 15 parts of the atractylodes rhizome and 8 to 12 parts of the ephedra herb in parts by weight.

3. The use of claim 1, wherein the lipid-lowering drug is an oral formulation.

4. The use according to claim 3, wherein the oral formulation is a decoction, an oral liquid, a powder, a capsule or a tablet.

5. The use according to claim 4, wherein each 100mL of the decoction or the oral liquid contains 25 to 100 μ L of the fructus xanthil water extract, the fructus xanthil water extract is 200mL of the fructus xanthil composition obtained by water extraction, and the fructus xanthil composition comprises 5 to 20g of rhizoma atractylodis and 5 to 20g of herba ephedrae.

6. The use as claimed in claim 5, wherein the decoction or the oral liquid contains 100 μ L of the aqueous extract of Siberian cocklebur fruit per 100 mL.

7. The use of claim 1, wherein said lipid-lowering agent further comprises a pharmaceutically acceptable carrier.

8. The use of claim 1, wherein the lipid-lowering drug is xanthium and ephedra pill.

9. The use according to claim 1, wherein said use comprises a process for the preparation of said lipid lowering drug, said process comprising:

carrying out water extraction or alcohol extraction on the xanthium and hemp composition to obtain an extracting solution;

the lipid-lowering medicine is prepared by adopting the extracting solution as a raw material.

10. The use of claim 9, wherein the step of preparing the lipid-lowering medicament from the extract comprises:

concentrating the extracting solution to obtain a concentrate;

mixing the concentrate with a pharmaceutically acceptable carrier to obtain the lipid-lowering medicine.

Technical Field

The invention relates to the technical field of lipid-lowering medicines, and particularly relates to an application of a xanthium and ephedra composition in preparation of a lipid-lowering medicine.

Background

Hyperlipidemia (Hyperlipidemia) is a disorder of lipid metabolism, is mainly characterized by elevated blood Triglycerides (TG), cholesterol (TC), low-density lipoproteins (LDL-C) and reduced high-density lipoproteins (HDL-C), and can cause a series of diseases such as arteriosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, renal failure, and the like. Recent studies have shown that hyperlipidemia is closely associated with the occurrence of neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD). With the improvement of living standard and the change of life style of people, the incidence rate of hyperlipidemia is increasing year by year. Hyperlipemia has become an important public health problem at present, and has a remarkable rising trend in all age groups, thus arousing wide attention of scholars.

Lipid-lowering drugs clinically used at present mainly comprise statins, fibrates and the like, and although the curative effect is obvious, in recent years, researches show that the statins can possibly cause adverse reactions such as liver injury, rhabdomyolysis, new tumors, diabetes and the like. Therefore, the development of new lipid-lowering drugs is urgently required.

Disclosure of Invention

The invention mainly aims to provide application of a xanthium and ephedra composition in preparation of a lipid-lowering drug, so as to solve the problem of great side effect of a clinical lipid-lowering drug in the prior art.

In order to achieve the purpose, according to one aspect of the invention, the invention provides a use of a xanthium and ephedra composition in preparation of a lipid-lowering drug, wherein the xanthium and ephedra composition comprises 5-20 parts of rhizoma atractylodis and 5-20 parts of ephedra according to parts by weight.

Further, the xanthium and ephedra composition comprises 10-15 parts of rhizoma atractylodis and 8-12 parts of ephedra according to parts by weight.

Furthermore, the lipid-lowering medicine is an oral preparation.

Further, the oral preparation is decoction, oral liquid, powder, capsule or tablet.

Furthermore, each 100mL of decoction or oral liquid contains 25-100 μ L of fructus xanthil water extract, the fructus xanthil water extract is 200mL of water extract obtained by water extraction of fructus xanthil composition, and the fructus xanthil composition comprises 5-20 g of rhizoma atractylodis and 5-20 g of herba ephedrae.

Furthermore, each 100mL of decoction or oral liquid contains 100 μ L of fructus Xanthii water extract.

Furthermore, the lipid-lowering medicine also comprises a pharmaceutically acceptable carrier.

Further, the lipid-lowering medicine is a xanthium and ephedra pill.

Further, the application comprises a preparation method of the lipid-lowering medicine, and the preparation method comprises the following steps: carrying out water extraction or alcohol extraction on the xanthium and hemp composition to obtain an extracting solution; the extract is used as a raw material to prepare the lipid-lowering medicine.

Further, the step of preparing the lipid-lowering medicine by using the extract as a raw material comprises the following steps: concentrating the extracting solution to obtain a concentrate; mixing the concentrate with pharmaceutically acceptable carrier to obtain the lipid-lowering medicine.

When the technical scheme of the invention is applied to the preparation of the lipid-lowering medicine, the experiment proves that the prepared lipid-lowering medicine has the outstanding effects of lowering triglyceride, lowering cholesterol and promoting fat metabolism, and the scope of indications of the rhizoma atractylodis and the ephedra herb is expanded.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate embodiments of the invention and, together with the description, serve to explain the invention and not to limit the invention. In the drawings:

FIG. 1 shows a photomicrograph of the blood fat analysis area (dotted box area) after staining zebra fish oil red O according to example 2 of the present invention;

FIG. 2 shows a typical pattern of vascular staining of the tail of zebra fish after treatment in each experimental group of example 2;

figure 3 shows the blood fat reduction results of the xanthane square treated zebrafish of example 2 at different concentrations, wherein p <0.01 and p <0.001, compared to the model control group;

FIG. 4 shows a typical pattern of fluorescent staining of zebra fish fat after treatment in each experimental group of example 4;

fig. 5 shows the blood fat reduction curves of the xanthane squares treated zebrafish of example 4 at different concentrations, wherein p is <0.01 compared to the model control group.

Detailed Description

It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail below with reference to the embodiments with reference to the attached drawings.

As analyzed in the background art of the present application, statins, fibrates and the like in the prior art have significant efficacy, but in recent years, studies find that statins may cause adverse reactions such as liver injury, rhabdomyolysis, new tumors, diabetes and the like, and in order to solve the problem, the present application provides an application of a traditional Chinese medicine composition in preparation of lipid-lowering drugs.

The traditional Chinese medicine research shows that the rhizoma atractylodis and the ephedra are combined with lung and spleen to be concocted, and the platycodon grandiflorum and the radish seed are used for diffusing qi and transforming cold-dampness, so that the clinical indication is that phlegm-dampness is in the interior and heat-condition is not obvious, namely, cold-dampness is in the interior. From the six meridians, the indication of the cang ma wan is phlegm-damp accumulation in the category of taiyin disease. From the zang-fu organs, it pertains to the lung and spleen due to phlegm-dampness and cold-dampness. Clinically, cold phlegm-dampness and internal pathogens are manifested by excessive and sticky phlegm, fullness and stuffiness in the chest and epigastrium, poor appetite, weakness of limbs, abdominal distension, sticky stool, thirst-free and thick and greasy tongue coating, which are typical indications of the cang-ma pills. At present, the rhizoma atractylodis and the ephedra are clinically applied to eliminating phlegm, relieving cough and removing dampness.

The applicant discovers that the rhizoma atractylodis and the ephedra herb have the effect of reducing blood fat when researching the pharmacological effect of the rhizoma atractylodis and the ephedra herb, and therefore, in a typical embodiment of the application, the application provides the application of the fructus xanthil and ephedra herb composition in preparing the lipid-reducing medicine, wherein the fructus xanthil and ephedra herb composition comprises 5-20 parts of the rhizoma atractylodis and 5-20 parts of the ephedra herb in parts by weight.

When the composition of the rhizoma atractylodis and the ephedra is applied to preparing the lipid-lowering medicine, tests prove that the prepared lipid-lowering medicine has the outstanding effects of lowering triglyceride and cholesterol and promoting fat metabolism, and the scope of indications of the rhizoma atractylodis and the ephedra is expanded.

In order to further exert the synergistic effect of the rhizoma atractylodis and the ephedra herb, the rhizoma atractylodis and ephedra herb composition comprises 10-15 parts of the rhizoma atractylodis and 8-12 parts of the ephedra herb by weight.

The lipid-lowering medicine can be prepared into the dosage form of the conventional lipid-lowering medicine at present, and preferably, the lipid-lowering medicine is an oral preparation. So as to promote the absorption of the effective components and exert the drug effect.

The oral preparation can be the conventional dosage form of the traditional Chinese medicine at present, and preferably, the oral preparation is decoction, oral liquid, powder, capsule or tablet.

In order to further improve the blood fat reducing effect of the rhizoma atractylodis composition and not generate any obvious toxic or side effect, preferably, each 100mL of the decoction or the oral liquid contains 25-100 μ L of the fructus xanthil water extract, the fructus xanthil water extract is 200mL of water extract obtained by water extraction of the fructus xanthil composition, and the fructus xanthil composition comprises 5-20 g of rhizoma atractylodis and 5-20 g of ephedra. Preferably, each 100mL of decoction or oral liquid contains 100 μ L of fructus Xanthii water extract.

For convenience of taking, the lipid-lowering medicine can be prepared into a Chinese patent medicine, and preferably, the lipid-lowering medicine also comprises a pharmaceutically acceptable carrier. Such as sweeteners, dispersants, and the like.

When the xanthium and ephedra composition is used for preparing the lipid-lowering medicine, the xanthium and ephedra pills clinically used at present can be directly applied to the lipid-lowering medicine.

Of course, in addition to the fructus xanthil pills, the fructus xanthil composition can be prepared into other forms for preparing lipid-lowering medicines, and preferably, the use comprises a preparation method of the lipid-lowering medicines, wherein the preparation method comprises the following steps: carrying out water extraction or alcohol extraction on the xanthium and hemp composition to obtain an extracting solution; the extract is used as a raw material to prepare the lipid-lowering medicine. The effective components in the fructus xanthil composition are extracted by water extraction or alcohol extraction to obtain an extracting solution, and the obtained extracting solution can be directly taken as a lipid-lowering medicament or can be processed according to the conventional operation of a traditional Chinese medicine preparation to form the lipid-lowering medicament.

In order to facilitate storage and circulation of the lipid-lowering drug, preferably, the step of preparing the lipid-lowering drug by using the extract as a raw material comprises: concentrating the extracting solution to obtain a concentrate; mixing the concentrate with pharmaceutically acceptable carrier to obtain the lipid-lowering medicine.

The advantageous effects of the present application will be further described below with reference to examples and comparative examples.

Laboratory animal

1. Melanin allele mutant translucent Albino strain zebrafish, in a natural pairwise mating breeding mode. The age was 7 days after fertilization, total 330, and 30 in each experimental group (for Maximum Tolerated Concentration (MTC) determination of herbal decoction).

2. Melanin allele mutant translucent Albino strain zebrafish, in a natural pairwise mating breeding mode. The age is 5 days after fertilization, 360 tails in total, and 30 tails in each experimental group (used for evaluating the effect of the traditional Chinese medicine decoction on reducing blood fat).

3. Melanin allele mutant translucent Albino strain zebrafish, in a natural pairwise mating breeding mode. The age is 7 days after fertilization, 360 tails in total, and 30 tails in each experimental group (used for evaluating the blood fat reducing effect (biochemical index) of the traditional Chinese medicine decoction).

4. Melanin allele mutant translucent Albino strain zebrafish, in a natural pairwise mating breeding mode. The age is 5 days after fertilization, 360 tails in total, and 30 tails in each experimental group (used for the influence of traditional Chinese medicine decoction on fat catabolism).

The zebra fish are all raised in water for fish culture at 28 ℃ (water quality: 200mg of instant sea salt is added into per 1L of reverse osmosis water, the conductivity is 480-510 muS/cm, the pH is 6.9-7.2, and the hardness is 53.7-71.6 mg/L CaCO₃) The license number for experimental animals is as follows: SYXK (Zhe) 2012-0171. The feeding management meets the requirements of international AAALAC certification.

Experimental sample

Raw formula of cang ma: wherein the preparation and packaging are provided by Beijing Chinese medical hospital affiliated to the university of capital medical science, and the extracting solution is used for experiments.

Adding fructus Xanthii and fructus Cannabis, wherein rhizoma Atractylodis 12g, herba Ephedrae 10g, Raphani semen 30g, radix Platycodi 12g, decocting with water to obtain brown extractive solution, 200 mL/bag × 14, collecting and registering in 2019 in 03 month and 19 days, storing at 4 deg.C, and preparing and packaging the extractive solution provided by Beijing Chinese medicine hospital affiliated to capital medical university.

Simvastatin, a white powder with lot number UZDBF-2K, purchased from echiei (shanghai) chemical industry development limited. The stock solution is prepared into 4mg/mL mother solution by 100% dimethyl sulfoxide (DMSO) for standby at the time of clinical application, and is diluted by 100% DMSO as required, and the DMSO concentration in the final working solution is 0.1%.

Resveratrol, white granules, lot number 36794, was purchased from Shanghai Allantin Biotechnology Ltd. The stock solution was prepared at the time of use with 100% DMSO at 14.4mg/mL, final DMSO concentration was 0.1%.

Instruments and reagents

Fluorescence stereomicroscope (Nikon AZ 100, Japan); dissecting microscopes (SZX7, OLYMPUS, Japan); a camera (VertA1) connected to the microscope; precision electronic balances (CP214, OHAUS, America); multifunctional microplate readers (Mithras LB940, Berthold Technologies); 6-well plates (Nest Biotech, China); 96-well microplate (costar, USA); methylcellulose (Sigma, USA); egg yolk powder (Beijing Kaiyuan, lot number 20170626); oil red O (OilRed O, lot SLBP5248V, Sigma); dimethyl sulfoxide (DMSO, Sigma, France); nile red (CAS number 7385-67-3, Sigma); triglyceride (TG) test box (lot No. 20190320, buika beijing); total cholesterol (T-CHO) test kit (batch No. 20190321, Nanjing Keoho).