CN106912952B

CN106912952B - Pharmaceutical composition with blood fat reducing function and preparation method of capsule preparation of pharmaceutical composition

Info

Publication number: CN106912952B
Application number: CN201710103102.XA
Authority: CN
Inventors: 李钦; 梁晓炜; 李培杉; 丁艳霞; 张峰
Original assignee: Henan University
Current assignee: Henan University
Priority date: 2017-02-24
Filing date: 2017-02-24
Publication date: 2020-12-08
Anticipated expiration: 2037-02-24
Also published as: CN106912952A

Abstract

The invention discloses a pharmaceutical composition with a blood fat reducing function, which comprises the following raw materials in parts by weight: 640-890 parts of eucommia seed oil, 450-690 parts of linseed oil, 20-60 parts of eucommia male pollen, 1-20 parts of vitamin E, 20-60 parts of beeswax and 450-690 parts of main material powder, wherein the main material powder is one of monascus powder, natto powder and smelly fermented soya bean powder; also discloses a preparation method of the medicinal composition capsule preparation. All the components of the invention are pure natural medicines or components extracted from natural medicines, the properties are stable, the bioavailability is high, a plurality of active ingredients are mutually cooperated, the defects of the existing medicines that the medicines need to be combined, the medicine price is high, the side effect is large and the like are overcome, the preparation process is simple, and the invention is suitable for industrial mass production.

Description

Pharmaceutical composition with blood fat reducing function and preparation method of capsule preparation of pharmaceutical composition

Technical Field

The invention belongs to the technical field of health care products, and particularly relates to a pharmaceutical composition with a function of reducing blood fat and a preparation method of a capsule preparation thereof.

Background

With the aging, the change of eating habits, air pollution and other reasons, people's bodies are also polluted to different degrees. Blood is also inevitably polluted, so that the color of the blood becomes dark, the blood quality becomes thick, the blood circulation becomes slow, excessive garbage impurities such as cholesterol, fat, triglyceride and the like are accumulated in the blood, the blood vessel wall becomes hard, the blood vessel channel becomes narrower, and diseases such as hypertension, hyperlipidemia, coronary arteriosclerosis, cardiovascular and cerebrovascular diseases and the like are caused, thereby seriously threatening the health of human beings.

Since lipid metabolism or abnormal movement causes one or more lipids in plasma to be higher than normal, called hyperlipidemia, lipids that are insoluble or slightly soluble in water must be bound to proteins in the form of lipoproteins, and thus hyperlipidemia is often hyperlipoproteinemia (hyperlipidemia), manifested by hypercholesterolemia, hypertriglyceridemia or both. The incidence of hyperlipidemia is a major public health problem and has been increasing at an alarming rate. It can significantly increase its risk of developing cardiovascular disease, such as atherosclerosis, which is also one of the most common causes of morbidity and mortality worldwide, with up to 1700 million deaths each year, and still the leading cause of mortality most likely in the future.

Hyperlipidemia can be classified into familial hyperlipidemia or secondary hyperlipidemia. Familial hyperlipidemia is caused by specific genetic abnormalities, especially mutations in LDL receptors in liver tissue, and thus, elevated plasma low density lipoprotein cholesterol (LDL-C) levels have been the causative agent of early heart disease progression. In addition to cardiovascular diseases, familial hyperlipidemia can also lead to a number of other complications such as xanthoma, macular tumor, and obesity. Secondary hyperlipidemia or diet-induced hyperlipidemia is non-inherited as compared to familial hyperlipidemia, and is characterized by elevated LDL-C levels and reduced high density lipoprotein cholesterol (HDL-C) levels, which are more common than the former.

The incidence of non-hereditary hypercholesterolemia has been rapidly increasing, probably due to several external factors such as obesity and improper diet, and foods containing high saturated fat and cholesterol are considered to be the most important factors causing hyperlipidemia. In addition, clinical studies have shown that high cholesterol diet and high lipid proteins, especially LDL-C in serum, can significantly affect liver cholesterol metabolism, and can also lead to the formation of fatty liver or non-alcoholic fatty liver disease (NAFLD). Since cholesterol and low density lipoproteins have the potential to cause cardiovascular disease, their relationship has been of interest for many years, and this problem also needs to be solved as quickly as possible. There are several approaches to the prevention of cardiovascular disease, such as increasing HDL-C or decreasing Total Cholesterol (TC) and LDL-C intake by a rational diet. In addition, the use of lipid-lowering drugs, such as statins, is currently the most common and widely used method for treating hyperlipidemia, but due to their expensive price and the side effects of these drugs, research and development of more effective and safer alternative products for lowering blood lipids have been initiated.

Disclosure of Invention

The invention aims to provide a pharmaceutical composition with the function of reducing blood fat and also provides a preparation method of the health-care product composition.

In order to achieve the purpose, the invention adopts the technical scheme that:

a pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 640-890 parts of eucommia seed oil, 450-690 parts of linseed oil, 20-60 parts of eucommia male pollen, 1-20 parts of vitamin E, 20-60 parts of beeswax and 450-690 parts of main material powder;

wherein the main material powder is one of red rice powder, natto powder and fermented soya bean powder.

Preferably, the pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 700-820 parts of eucommia seed oil, 520-620 parts of linseed oil, 520-620 parts of main material powder, 30-50 parts of eucommia male pollen, 5-15 parts of vitamin E and 30-50 parts of beeswax.

Preferably, the pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 764 parts of eucommia seed oil, 573 parts of flaxseed oil, 573 parts of red yeast powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 40 parts of beeswax.

Preferably, the pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 760 parts of eucommia seed oil, 570 parts of linseed oil, 570 parts of natto powder or fermented smelly beans, 40 parts of eucommia male pollen, 10 parts of vitamin E and 40 parts of beewax.

The preparation method of the medicinal composition capsule preparation with the function of reducing blood fat comprises the following steps:

(1) weighing the raw materials according to the weight ratio;

(2) heating eucommia seed oil, linseed oil and beewax to be molten (the heating temperature is 70-80 ℃), uniformly stirring, stopping heating to reduce the temperature to 30-40 ℃, adding vitamin E, and uniformly stirring;

(3) uniformly mixing the main material powder and the eucommia male pollen, sieving, adding the sieved mixture into the product obtained in the step (2), and uniformly mixing;

(4) and (4) grinding, filtering and encapsulating the product obtained in the step (3) into capsules.

Preferably, the eucommia seed oil is subjected to subcritical extraction, and the method comprises the following steps: screening and removing impurities from eucommia seeds, crushing to 55-65 meshes, sieving, and then putting into an extractor, wherein butane is used as an extraction solvent, the mass ratio of material liquid is 1: 3.5-4.5, the extraction temperature is 35-45 ℃, the extraction time is 40-50 minutes, the extraction pressure is 0.4-0.6 MPa, and the extraction times are 3-5 times.

Preferably, the capsule in the step (4) is a soft capsule, and the specification is 0.1-2.0 g/capsule.

The flax seed oil, the eucommia male pollen, the vitamin E, the beewax and the main material powder in the raw materials are all common commercial products.

Eucommia ulmoides is dry bark of Eucommia ulmoides Oliv. of family Eucommiaceae, namely Eucomia ulmoides Oliv, and is also called as follows: duan Si Pi, Si Gong Pi, Si Xian, Si Zhong, mu Mian, Shi Si Xian and Si Lian Pi, which were listed as the top grade in Shen nong Ben Cao Jing. Eucommia bark is a common traditional Chinese medicine and has the functions of tonifying liver and kidney, strengthening waist and knees, preventing miscarriage and reducing blood pressure. Modern researches show that the eucommia bark has the functions of enhancing the immunity of organisms and showing a two-phase adjustment effect on cellular immunity. Can promote the synthesis and decomposition of protein collagen in skin, bones and muscles of human body, has the functions of promoting metabolism and preventing aging, and can be used for preventing the deterioration of bones and muscles caused by space weightlessness of a character navigator. The eucommia ulmoides leaves contain chemical components which are about the same as bark, pharmacological experiments show that the eucommia ulmoides leaves also have the effects of reducing blood pressure, easing pain, resisting inflammation and enhancing body immunity, and the eucommia ulmoides leaves are processed into the eucommia ulmoides tea which has the effects of strengthening brain and refreshing.

The method comprises the steps of carrying out shelling treatment on dried eucommia seeds, crushing the eucommia seeds by a crusher, carrying out treatment by using a supercritical carbon dioxide extraction method, obtaining eucommia seed crude oil under the extraction conditions that the extraction pressure is 25-35MPa, the extraction temperature is 45-50 ℃ and the extraction time is 1.5-2.5h, then carrying out alkali refining, washing dehydration, decoloration and deodorization treatment on the eucommia seed crude oil, refining the oil, and finally obtaining the eucommia seed refined oil with qualified quality. The specific method is seen in an extraction and refining method of eucommia seed oil, and Chinese patents: CN 201210565015.3.

The eucommia seed oil obtained by squeezing eucommia seeds is rich in unsaturated fatty acid, and 10 kinds of fatty acid are identified by analyzing the fatty acid (in a methyl ester form) in the eucommia through a capillary gas chromatography-mass spectrometry combined method, wherein the fatty acid comprises 61.50% of linolenic acid, 12.60% of linoleic acid, 17.80% of oleic acid, 2.10% of stearic acid and 6.00% of palmitic acid. The alpha-linolenic acid has the effects of regulating blood fat and blood pressure, resisting tumors, improving human immunity, promoting brain cell development and the like, and is very beneficial to human health.

The metabolic pathway indicates that the human body needs to carry out a series of metabolic processes for synthesizing the cholesterol, wherein the key point is that hydroxymethyl pentadecanyl coenzyme A (HMG-CoA) generates mevalonic acid under the action of reductase (HMG-CoA-R) of the hydroxymethyl pentadecanyl coenzyme A, and then the cholesterol is further synthesized. The effective components in the red yeast rice are competitive inhibitors of HMG-CoA reductase, thereby blocking the pathway of synthesizing cholesterol and playing the role of treating and preventing cardiovascular and cerebrovascular diseases.

Linseed oil is particularly beneficial for pregnant women and infants, and is therefore also commonly referred to as lunar oil and smart oil. The ratio of omega-3 series (alpha-linolenic acid) to omega-6 series (gamma-linolenic acid) in unsaturated fatty acid in the flaxseed is close to (4-6): 1. the linseed oil is rich in omega-3, wherein the omega-3 belongs to 'essential unsaturated fatty acid', is extremely important for human bodies, but cannot be synthesized by the linseed oil per se, and can meet important substances required by the human bodies only by being taken in vitro. Omega-3 is rich in marine animals and plants such as seal, deep sea cold water fish, seaweed and the like, flax plants and walnut nuts. Linseed oil is rich in omega-3, and the content of the linseed oil is as high as more than 56%. After omega-3 is absorbed, it is metabolized to DHA according to the needs of the body, and is therefore called "liquid gold". In recent years, researches and clinical experiments prove that the linseed oil has the effects of enabling skin to be tender and bright, consuming redundant body fat, improving premenstrual syndrome of women, improving stress resistance, relieving anaphylactic reaction, reducing blood fat, reducing cholesterol and the like.

The Eucommia male flower superfine powder is flowers of Eucommia Eucomia ulmoides Oliver male plants of Eucommiaceae, and in the full-bloom period of Eucommia ulmoides male flowers blooming in spring every year, the male stamens and male flower buds of fresh Eucommia ulmoides male flowers are collected, freeze-dried by adopting a freeze-drying method, crushed into superfine powder by a jet mill and sieved by a 300-mesh sieve. Research shows that the eucommia male flower contains more than 300 nutrient substances, more than 80 active ingredients, including 18 amino acids, more than 20 mineral elements and various vitamins, and has the characteristics of high protein and low fat of health food. Wherein the content of vitamin C is 10 times of that of spirulina, and the beta carotene is 63 times of pollen pini. The eucommia male flower superfine powder is freeze-dried by adopting a freeze-drying method, and then is crushed into superfine powder by a jet mill, so that the active ingredients and the pharmacological activity of the eucommia male flower are retained to the maximum extent.

Red yeast is one of traditional Chinese medicinal materials in China, is prepared by fermenting monascus and polished round-grained rice serving as raw materials, has the effects of strengthening spleen and stomach, helping digestion, promoting blood circulation, removing blood stasis and relieving pain, and has a long history of medicinal use and eating in China. In 1979, Japanese academy of academic distant creeper separated lovastatin from Monascus fermentation broth, which was called Monacolin K. The statin substance is the only statin substance currently applied in health food because of remarkable curative effect, small toxic and side effect and good tolerance, which is gradually paid attention to. The composition also avoids the oily smell of the eucommia seed oil and the special fermentation taste of the red yeast rice, the active ingredient lovastatin in the red yeast rice is a hydrophobic substance, has poor water solubility, low gastrointestinal tract absorption and poor bioavailability, and the lovastatin is mixed with carriers such as the eucommia seed oil and the linseed oil and then filled into soft capsules, so that the bioavailability of the lovastatin can be greatly improved, and the lovastatin is a better choice for red yeast rice medicines.

The natto powder contains more than 150 kinds of physiologically active substances including Bacillus natto, natto polypeptide, superoxide dismutase (SOD), nattokinase, and vitamin K₂And various mineral substances and the like, and has the effects of improving arteriosclerosis, gastritis, bone density, diabetes and complications and the like. The natto freeze-dried powder is solid fermented natto and is obtained by vacuum freeze drying, although the processing method has higher cost, the natto freeze-dried powder reserves the physiological active substances in the natto to the maximum extent, and has higher nutritional value.

Fermented soya beans are prepared by fermenting soybeans and are listed in non-material cultural heritage in Zhongmuui county. The traditional manufacturing method of Zhongmu smelly fermented soya beans is that in 2 months (best in the beginning of 2 months) of the lunar calendar every year, soybeans are soaked and swelled, boiled to be soft, taken out and put into a burlap bag while the soybeans are hot (60-70 ℃), then buried into rice bran or wheat bran, fermented for 5-7 days until the soybeans can be stretched into viscose, the fermented soya beans become yellow brown, and dried or baked, so that the fermented soya beans are obtained. Pulverizing Chinese mumuji fermented beans into fine powder, i.e. fermented bean powder.

In conclusion, the invention has the following advantages:

(1) all the components of the invention are pure natural medicines or components extracted from natural medicines, and no preservative or pigment is added, thus ensuring the edible safety;

(2) the invention reduces the use of auxiliary materials as much as possible, only uses natural beeswax as a suspending agent and natural vitamin E oil as an antioxidant, and increases the specific gravity of the effective components on the premise of ensuring the stability of the mixture;

(3) compared with other eucommia seed oil soft capsules, the eucommia seed oil soft capsule has high bioavailability and good curative effect, simultaneously, compared with simple lovastatin, the composition has the advantages that various active ingredients are mutually cooperated, the defects that the existing medicine needs combined administration, the medicine price is high, the side effect is large and the like are overcome, and animal experiments prove that the health food composition has a remarkable blood fat reducing function compared with the common soft capsule;

(4) the health food composition has simple preparation process and is suitable for industrial production.

Drawings

FIG. 1 is a gas chromatogram of methyl alpha-linolenate;

FIG. 2 is a gas chromatogram of the pharmaceutical composition prepared in example 5;

FIG. 3 is a liquid chromatogram of lovastatin lactone;

FIG. 4 is a lovastatin open-loop (acid form qualitative) liquid chromatogram;

fig. 5 is a liquid chromatogram of the pharmaceutical composition prepared in example 5.

Detailed Description

The present invention will be described in further detail with reference to preferred examples, but the scope of the present invention is not limited thereto.

Example 1

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 640 parts of eucommia seed oil, 690 parts of linseed oil, 450 parts of red yeast powder, 60 parts of eucommia male pollen, 20 parts of vitamin E and 20 parts of beeswax.

The preparation method of the pharmaceutical composition with the function of reducing blood fat comprises the following steps:

(1) weighing the raw materials in parts by weight; wherein, the eucommia seed oil is obtained by the following steps: screening eucommia seeds, removing impurities, crushing to 55 meshes, sieving, filling into a subcritical extractor, taking butane as an extraction solvent, wherein the mass ratio of material liquid to liquid is 1:3.5, extracting for 40 minutes at 35 ℃, under 0.4MPa for 5 times to obtain eucommia seed oil;

(2) heating eucommia seed oil, linseed oil and beeswax to 70 ℃ for melting, uniformly stirring, stopping heating, reducing the temperature to 30 ℃, adding vitamin E, and uniformly stirring;

(4) and (4) grinding, filtering and encapsulating the product obtained in the step (3) into capsules with the specification of 0.2 g/capsule to obtain the capsule.

Example 2

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 890 parts of eucommia seed oil, 450 parts of linseed oil, 690 parts of red yeast powder, 20 parts of eucommia male pollen, 1 part of vitamin E and 60 parts of beeswax.

(1) weighing the raw materials in parts by weight; wherein, the eucommia seed oil is obtained by the following steps: screening eucommia seeds, removing impurities, crushing to 65 meshes, sieving, filling into a subcritical extractor, taking butane as an extraction solvent, wherein the mass ratio of material liquid to liquid is 1: 4.5, extracting at 45 ℃ for 50 minutes under 0.6MPa for 3 times to obtain eucommia seed oil;

(2) heating eucommia seed oil, linseed oil and beeswax to 80 ℃ for melting, uniformly stirring, stopping heating to reduce the temperature to 40 ℃, adding vitamin E, and uniformly stirring;

(4) and (4) grinding, filtering and encapsulating the product obtained in the step (3) into capsules with the specification of 1.2 g/capsule to obtain the capsule.

Example 3

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 700 parts of eucommia seed oil, 620 parts of linseed oil, 520 parts of red yeast powder, 50 parts of eucommia male pollen, 15 parts of vitamin E and 30 parts of beeswax.

(1) weighing the raw materials in parts by weight; wherein, the eucommia seed oil is obtained by the following steps: screening eucommia seeds, removing impurities, crushing to 60 meshes, sieving, filling into a subcritical extractor, taking butane as an extraction solvent, wherein the mass ratio of material liquid to liquid is 1: 4, extracting for 4 times at 40 ℃ under 0.5MPa for 45 minutes to obtain eucommia seed oil;

(2) heating eucommia seed oil, linseed oil and beeswax to 75 ℃ for melting, uniformly stirring, stopping heating to reduce the temperature to 35 ℃, adding vitamin E, and uniformly stirring;

(4) and (4) grinding, filtering and encapsulating the product obtained in the step (3) into capsules with the specification of 0.1 g/capsule to obtain the capsule.

Example 4

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 820 parts of eucommia seed oil, 520 parts of linseed oil, 620 parts of red yeast powder, 30 parts of eucommia male pollen, 5 parts of vitamin E and 50 parts of beeswax.

(4) and (4) grinding, filtering and encapsulating the product obtained in the step (3) into capsules with the specification of 2.0 g/capsule to obtain the capsule.

Example 5

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 764 parts of eucommia seed oil, 573 parts of flaxseed oil, 573 parts of red yeast powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 40 parts of beeswax.

(4) and (4) grinding, filtering and encapsulating the product obtained in the step (3) into capsules with the specification of 1.0 g/capsule to obtain the capsule.

Example 6

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 640 parts of eucommia seed oil, 690 parts of linseed oil, 450 parts of natto powder, 60 parts of eucommia male pollen, 20 parts of vitamin E and 20 parts of beeswax.

Example 7

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 890 parts of eucommia seed oil, 450 parts of linseed oil, 690 parts of natto powder, 20 parts of eucommia male pollen, 1 part of vitamin E and 60 parts of beeswax.

Example 8

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 700 parts of eucommia seed oil, 620 parts of linseed oil, 520 parts of natto powder, 50 parts of eucommia male pollen, 15 parts of vitamin E and 30 parts of beeswax.

Example 9

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 820 parts of eucommia seed oil, 520 parts of linseed oil, 620 parts of natto powder, 30 parts of eucommia male pollen, 5 parts of vitamin E and 50 parts of beeswax.

Example 10

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 760 parts of eucommia seed oil, 570 parts of linseed oil, 570 parts of natto powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 40 parts of beeswax.

Example 11

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 640 parts of eucommia seed oil, 690 parts of linseed oil, 450 parts of smelly fermented soya bean powder, 60 parts of eucommia male pollen, 20 parts of vitamin E and 20 parts of beeswax.

Example 12

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 890 parts of eucommia seed oil, 450 parts of linseed oil, 690 parts of smelly fermented soya bean powder, 20 parts of eucommia male pollen, 1 part of vitamin E and 60 parts of beeswax.

Example 13

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 700 parts of eucommia seed oil, 620 parts of linseed oil, 520 parts of smelly fermented soya bean powder, 50 parts of eucommia male pollen, 15 parts of vitamin E and 30 parts of beeswax.

Example 14

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 820 parts of eucommia seed oil, 520 parts of linseed oil, 620 parts of smelly fermented soya bean powder, 30 parts of eucommia male pollen, 5 parts of vitamin E and 50 parts of beeswax.

Example 15

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 760 parts of eucommia seed oil, 570 parts of linseed oil, 570 parts of smelly fermented soya bean powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 40 parts of beewax.

Comparative example 1

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 760 parts of eucommia seed oil, 570 parts of linseed oil, 570 parts of monascus powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 60.31 parts of beeswax.

Comparative example 2

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 764 parts of eucommia seed oil, 573 parts of flaxseed oil, 573 parts of red yeast powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 81.25 parts of beeswax.

Comparative example 3

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 764 parts of eucommia seed oil, 573 parts of flaxseed oil, 573 parts of monascus powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 102.63 parts of beeswax.

Comparative example 4

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 760 parts of eucommia seed oil, 570 parts of linseed oil, 570 parts of natto powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 60.31 parts of beeswax.

Comparative example 5

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 764 parts of eucommia seed oil, 573 parts of flaxseed oil, 573 parts of natto powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 81.25 parts of beeswax.

Comparative example 6

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 764 parts of eucommia seed oil, 573 parts of flaxseed oil, 573 parts of natto powder, 40 parts of eucommia male pollen and 10 parts of vitamin E.

Comparative example 7

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 760 parts of eucommia seed oil, 570 parts of linseed oil, 570 parts of smelly fermented soya bean powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 60.31 parts of beeswax.

Comparative example 8

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 764 parts of eucommia seed oil, 573 parts of flaxseed oil, 573 parts of smelly fermented soya bean powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 81.25 parts of beeswax.

Comparative example 9

A pharmaceutical composition with the function of reducing blood fat comprises the following raw materials in parts by weight: 764 parts of eucommia seed oil, 573 parts of flaxseed oil, 573 parts of smelly fermented soya bean powder, 40 parts of eucommia male pollen and 10 parts of vitamin E.

In order to ensure that the content (liquid medicine) is pressed into qualified soft capsules, the soft capsules which are easy to fill (good liquid medicine fluidity) are required to be stable (uniform) during filling, so that the dosage of the beeswax needs to be considered.

Respectively taking the pharmaceutical compositions with the blood fat reducing function prepared in the above embodiments and comparative examples, uniformly stirring, measuring about 30mL of each pharmaceutical composition, transferring the pharmaceutical compositions into a 50mL centrifuge tube, and recording the initial height h₀Centrifuging at 400r/min for 20min, taking out, standing and recording the height h of a layering part₁The sedimentation ratio is h₁/h₀. Another 30mL of the solution was placed in a beaker and observed for fluidity (proper amount of the contents was taken with a spatula until the contents remained stably on the spatula at an angle of 45 ℃ from the surface of the solution, the flow was uniform and continuous without dropping in the form of "pellets"), and cutting property (proper amount of the contents was taken with a spatula)The contents, when they tended to stop flowing, shrank very quickly towards the spoon without a "line flow" suspension in segments, i.e. with a proper "cut-off", and the results are shown in tables 1, 2 and 3, respectively ("-" shows bad, "+" shows good and "+" shows good).

TABLE 1 examination of beeswax dosage (Red rice powder as main material)

TABLE 2 examination of beeswax dosage (Natto powder as principal material)

Table 3 inspection of beeswax dosage (the main material powder is smelly fermented beans powder)

As shown in tables 1-3, when the dosage of beeswax reaches 2%, the suspension is in the form of ointment, the uniformity and the fluidity are good, the liquid surface flows down linearly stably at an angle of 45 degrees from the spoon, and no sectional 'linear flow' suspension occurs; when the suspension tends to stop flowing, the liquid medicine can be quickly contracted on the medicine spoon body, and simultaneously, a better suspension effect can be ensured, so that the quality of the prepared liquid medicine is stable and controllable by selecting 2% of the dosage of the beeswax.

The eucommia seed oil is extracted by adopting a CBE-5L subcritical fluid extraction test device (subcritical biotechnology limited, Henan province), the extraction rate of the eucommia seed oil is about 95.4%, the active ingredient alpha-linolenic acid is retained to the maximum extent, and the content of the alpha-linolenic acid is measured according to a gas chromatography.

Preparation of control solutions: 64.73mg of alpha-methyl linolenate standard is precisely weighed and placed in a 2mL volumetric flask, and is diluted to scale by isooctane, and the concentration of the solution is 32.365 mg/mL.

Treatment of the test solution: precisely weighing 0.25g of the pharmaceutical composition with the auxiliary blood fat reducing function prepared in the embodiment 5, placing the pharmaceutical composition into a 50mL conical flask, adding 6mL of 0.5mol/L sodium hydroxide methanol solution, refluxing in water bath at 70 ℃ for 10min, precisely adding 7mL of boron trifluoride methanol solution into a boiling solution, continuing to boil for 30min, precisely adding 5mL of isooctane into the boiling mixed solution, taking down a condensation device, taking out the conical flask, immediately adding 20mL of saturated sodium chloride solution, covering the mouth of the conical flask, shaking for 15 s, continuing to add the saturated sodium chloride solution to the top of the conical flask, and standing for layering. Sucking supernatant, filtering with 0.22 μm microporous membrane, and placing filtrate in liquid phase vial to obtain sample solution for sample injection.

Chromatographic conditions are as follows: gas chromatograph Thermo 1310; column TG-WAXMS, 30 m.times.0.32 m.times.0.50 μm; the temperature of the column is programmed to rise, 160 ℃ and 250 ℃, 10 ℃/min, 160 ℃ is reserved for 1min, 250 ℃ is reserved for 4min, and the temperature of the injection port is 250 ℃; the temperature of the detector is 250 ℃; 3 mu L of sample volume; the split ratio was 33.3: 1; air flow 350mL/min, nitrogen flow 40mL/min, hydrogen flow 35mL/min, detector hydrogen flame detector, separation R all greater than 1.5.

The control solution and the sample solution were each precisely aspirated by 3. mu.L each, and the solutions were injected into a gas chromatograph, and the measurement results are shown in FIG. 1 and FIG. 2, respectively. As can be seen from FIGS. 1 and 2, the alpha-linolenic acid content of the composition of the present invention is not less than 30%.

The effective component lovastatin in the red yeast rice is increasingly emphasized due to obvious curative effect, small toxic and side effect and good tolerance, is the only statin substance applied in health food at present, and the content of the lovastatin in the pharmaceutical composition prepared in the embodiment 5 is determined by high performance liquid chromatography.

Chromatographic conditions are as follows: chromatography column Agilent TC-C18 chromatography column (5 μm, 4.6 × 250mm) (Agilent); the mobile phase is methanol-water-phosphoric acid (385: 115: 0.14); the flow rate is 1.0mL/min, the detection wavelength is 238nm, the column temperature is 20 ℃, and the sample injection amount is 10 mu L.

Preparation of control solutions

a. Lovastatin standard stock solution: 0.02002g lovastatin (lactone) standard was weighed out accurately, added to the mobile phase for detection and made to volume of 50 mL. The concentration of this solution was 0.4004 mg/mL.

b. Lovastatin standard use solution: taking 1mL of lovastatin standard stock solution, and fixing the volume to a 10mL volumetric flask by using a mobile phase. The concentration of this solution was 0.04004 mg/mL.

c. Qualitative use of acid form (ring-opened) lovastatin control: 2.04mg of lovastatin (lactone) standard substance is accurately weighed, the volume is determined to be 50mL by 0.2mol/L sodium hydroxide solution, ultrasonic conversion is carried out for 1h at the temperature of 50 ℃, and the lovastatin (lactone) standard substance is naturally cooled to room temperature and then stands for 1h in a dark place. The concentration of this solution was 0.0408 mg/mL.

Preparation of a test solution: taking 20 soft capsules of the health-care food composition with the function of assisting in reducing blood fat, which is prepared in example 5, removing capsule shells, grinding, precisely weighing 0.25g of the soft capsules into a 50mL centrifugal tube, adding 10.0mL of aqueous solution of phosphoric acid with pH value of 3, covering a plug, performing ultrasonic extraction for 10min, then adding 10.0mL of trichloromethane, placing the mixture in a vortex suspension device for 3min, standing, removing an upper-layer water phase, and centrifuging a trichloromethane layer for 3min at 3000 rpm/min. Accurately sucking 1.0-5 mL of lower-layer trichloromethane liquid into a rotary evaporation bottle, drying in a water bath at 50 ℃ under reduced pressure by using a vacuum pump until all solvents are volatilized, adding a small amount of mobile phase into the rotary evaporation bottle, continuously transferring for many times, fixing the volume to 5.0mL, thoroughly mixing, and filtering by using a 0.45-micrometer microporous filter membrane to obtain a test solution.

Respectively measuring 10 μ L of lovastatin standard use solution, qualitative acid lovastatin reference solution and test solution, injecting into a liquid chromatograph, determining the quality by retention time of the measured component and the standard solution, and determining the quantity by the ratio of the sum of the peak areas of the lactone and acid lovastatin of the measured component to the peak area of lactone lovastatin in the standard use solution, with the results shown in FIG. 3, FIG. 4 and FIG. 5. As can be seen from the figure, the lovastatin content in the pharmaceutical composition prepared in example 3 was not less than 0.3%.

Pharmacological experiments can prove that the pharmaceutical composition has the effects of assisting in reducing blood fat and controlling weight, has no toxic or side effect, and is subjected to pharmacodynamic and toxicological experiments.

Test materials: SPF-grade KM male mice, 18-20g in body weight, license number: SCXK (Yu) 2015-. The animal basic feed is provided by the experimental animal center in Henan province, and the license number is as follows: SCXK (Yu) 2015-; high-fat feed: 1.5% cholesterol, 20% fat, 10% sucrose, 10% egg yolk powder, 0.15% sodium cholate; lovastatin capsules (Yangziang pharmaceutical industry group Co., Ltd.), product batch number: 15121642, respectively; heparin sodium injection (Jiangsu Wanbang Biochemical medicine, Inc.); mouse LDL-C, HDL-C, TC, TG enzyme linked immunoassay kit (Shanghai enzyme linked immunosorbent assay, Inc.).

Test method

Establishing a mouse high fat model: 60 mice were acclimatized for 5 days, weighed and randomized into 6 groups, each: blank control group, lovastatin positive control group, high-fat model control group, composition low-dose group, medium-dose group and high-dose group. The blank control group was fed with basal diet during the experimental period, and the other 5 groups were fed with high-fat diet after the adaptation period, and the body mass was measured weekly. Wherein, the compositions are respectively taken from the pharmaceutical compositions prepared in example 5, example 10 and example 15.

The administration method of the mice comprises the following steps: after two weeks of molding, the low, medium and high dosage components of the three compositions are respectively subjected to intragastric administration according to 167mg/Kg, 333mg/Kg and 1g/Kg which are 5 times, 10 times and 30 times of the recommended dosage of a human body, the positive lovastatin control group is administered with 10mg/Kg of lovastatin, and the blank control group and the high-fat model control group are administered with 0.3mL of 0.5 percent CMC-Na for intragastric administration. The stomach is irrigated once a day, and the body mass is weighed every two days.

Determination of lipid levels in mouse plasma and calculation of liver coefficients

After each group of mice are continuously gavaged for 4 weeks, fasting is not forbidden for 12 hours, blood is collected from orbital venous plexus, the mice are placed in a centrifuge tube which is soaked in heparin overnight and dried, the centrifugation is carried out for 15min at 3000r/min, supernatant is sucked, and TC, TG and HDL-C, LDL-C are measured as soon as possible. After blood is taken from the mouse, the mouse is dislocated and killed, the abdominal cavity is opened to separate the liver, the mouse is rinsed in cold normal saline to remove the blood, the filter paper is wiped dry, the wet weight is weighed, and the liver coefficient is calculated.

Test results

When the main material powder is red koji powder (example 5), the test results of mouse HDL-C and LDL-C are shown in Table 4, wherein p is less than 0.01, and the difference is very significant compared with the control group of the high-fat model; represents the significant difference of p <0.05 compared with the control group of the high fat model.

As can be seen from Table 4, the comparative content of the white control group and the high-fat model control group in the HDL-C of the mouse is obviously increased, and the P is less than 0.05, so that the significant difference exists, and the success of molding is proved; compared with a high-fat model control group, the content of the positive lovastatin control group, the low, medium and high composition dose groups is remarkably increased (P <0.01), the significant difference is achieved, and the three composition dose groups are dose-related and have significant statistical significance.

As can be seen from Table 4, the LDL-C content in the serum of the mice in the white control group and the high-fat model control group of the mice has very significant difference (p is less than 0.01) compared, which proves that the modeling of the hyperlipemia model is successful; the positive lovastatin control group and the composition high-dose group have obvious reduction (p is less than 0.01) compared with the high-fat model control group; compared with the content of a high-fat model control group, the content of a dose group in the composition has a significant difference that P is less than 0.05; and three dose groups of the composition are dose-related and have significant statistical significance.

TABLE 4 mouse HDL-C and LDL-C test results

When the base powder was natto powder (example 10), the results of the mouse HDL-C and LDL-C tests are shown in table 5, wherein p is <0.01, which is a very significant difference compared to the control group of the high fat model; represents the significant difference of p <0.05 compared with the control group of the high fat model.

TABLE 5LDL-C and HDL-C test results

When the main material powder is fermented odorous beans (example 15), the test results of mouse HDL-C and LDL-C are shown in Table 6, wherein the x in the table represents that p is less than 0.01 and has very significant difference compared with a high-fat model control group; represents the significant difference of p <0.05 compared with the control group of the high fat model.

TABLE 6LDL-C and HDL-C test results

As can be seen from tables 5 and 6, the blank control group had a significantly lower LDL-C content (p <0.01) than the high-fat model control group, which demonstrated successful molding; the LDL-C content of the low, medium and high dose groups is lower than that of the high fat model control group, the content is obviously reduced, and the dose correlation exists. The HDL-C content of the three dose groups is obviously higher than that of the high-fat model control group, and the three dose groups are in measurement correlation and have statistical significance.

When the main meal was red koji (example 5), the results of the TC and TG tests in mice are shown in table 7, where p <0.01, which is a very significant difference compared to the control group of the high fat model; represents the significant difference of p <0.05 compared with the control group of the high fat model.

TABLE 7 mouse TC and TG test results

As can be seen from Table 7, the blank control group, the positive lovastatin control group and the high-fat model control group of the mouse TC have obviously lower comparative contents, and the success of molding is proved; the content of the composition in the high and medium dose groups is obviously lower than that of the high fat model control group (P <0.05), and the composition is in dose correlation and has obvious statistical significance.

Meanwhile, the comparison content of a blank control group and a positive lovastatin control group of mouse TG and a high-fat model control group is obviously lower (P is less than 0.01), and the success of molding is proved; the content of the three dose groups of the composition is obviously lower than that of the high-fat model control group, the composition has dose correlation and has obvious statistical significance.

When the base meal was natto (example 10), the results of the TC and TG tests in mice are shown in table 8, wherein p <0.01, which is a very significant difference compared to the control group of the high fat model; represents the significant difference of p <0.05 compared with the control group of the high fat model.

TABLE 8 mouse TC and TG test results

When the main material powder is fermented odorous soy (example 15), the test results of TC and TG of the mice are shown in table 8, wherein p is less than 0.01, and the difference is very significant compared with the control group of the high-fat model; represents the significant difference of p <0.05 compared with the control group of the high fat model.

TABLE 9 mouse TC and TG test results

As can be seen from tables 8 and 9, the blank control group had significantly lower TG and TC contents than the high-fat model control group, which proved successful molding (p < 0.01); the TG and TC contents of the low, medium and high dose groups are obviously lower than those of the high-fat model control group, and the high-fat model control group is dose-related and has statistical significance.

The results of comparing the body weight and liver factor of mice when the main meal was red koji (example 5) are shown in table 10, wherein p <0.01, a very significant difference compared to the high fat model control group; represents the significant difference of p <0.05 compared with the control group of the high fat model.

TABLE 10 mouse body weight and liver factor test results

The results of comparing the body weight and liver factor of mice when the base meal was natto (example 10) are shown in table 11, wherein p <0.01, a very significant difference compared to the high fat model control group; represents the significant difference of p <0.05 compared with the control group of the high fat model.

TABLE 11 mouse body weight and liver factor test results

When the main material powder is fermented odorous soy bean powder (example 15), the comparison results of the mouse weight and the liver coefficient are shown in table 12, wherein x represents that p is less than 0.01 and the difference is very significant compared with a high-fat model control group; represents the significant difference of p <0.05 compared with the control group of the high fat model.

Table 12 mouse body weight and liver factor test results

As can be seen from tables 10-12, the weights and liver coefficients of the mice at the end of the experimental period of the three dose groups of the composition are significantly reduced compared with those of the high-fat model control group, and the composition has statistical significance.

From the above results, it is clear that the present invention has a good hypolipidemic effect, respectively manifested by a decrease in LDL-C, TG, and TC contents and an increase in HDL-C, and is capable of controlling the weight gain of diet-induced hyperlipidemic mice.

Acute oral toxicity test: the maximum oral tolerance of the mouse is more than 10g/Kg, which is equivalent to 250 times of the dosage of human body, and the maximum oral tolerance of the mouse is more than 10g/Kg, which is shown in the specification.

Claims

1. A pharmaceutical composition with a function of reducing blood fat is characterized by comprising the following raw materials in parts by weight: 764 parts of eucommia seed oil, 573 parts of flaxseed oil, 573 parts of red yeast powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 40 parts of beeswax;

the preparation method of the capsule preparation of the pharmaceutical composition with the function of reducing blood fat comprises the following steps:

(1) weighing the raw materials according to the weight ratio;

(2) heating eucommia seed oil, linseed oil and beeswax to be molten, uniformly stirring, stopping heating to reduce the temperature to 30-40 ℃, adding vitamin E, and uniformly stirring;

(3) uniformly mixing red koji powder and eucommia male pollen, sieving, adding into the product obtained in the step (2), and uniformly mixing;

(4) grinding, filtering and encapsulating the product obtained in the step (3) into capsules to obtain the compound preparation;

the eucommia seed oil is subjected to subcritical extraction, and the method comprises the following steps: screening and removing impurities from eucommia seeds, crushing to 55-65 meshes, sieving, and then putting into an extractor, wherein butane is used as an extraction solvent, the mass ratio of material liquid is 1: 3.5-4.5, the extraction temperature is 35-45 ℃, the extraction time is 40-50 minutes, the extraction pressure is 0.4-0.6 MPa, and the extraction times are 3-5 times;

the capsule in the step (4) is a soft capsule, and the specification is 0.1-2.0 g/capsule.

2. A pharmaceutical composition with a function of reducing blood fat is characterized by comprising the following raw materials in parts by weight: 760 parts of eucommia seed oil, 570 parts of linseed oil, 570 parts of natto powder or fermented smelly beans powder, 40 parts of eucommia male pollen, 10 parts of vitamin E and 40 parts of beewax;

(1) weighing the raw materials according to the weight ratio;

(3) uniformly mixing natto powder or fermented odorous bean powder and eucommia male pollen, sieving, adding into the product obtained in the step (2), and uniformly mixing;