CN101485769A - Technique for preparing medicinal material in leaf of Zanthoxylum bungeanum or Zanthoxylum schnifolium and use thereof - Google Patents

Abstract

The invention provides technology for preparing pepper leave medicinal substances and application thereof, and belongs to the field of technology for preparation process and application of traditional Chinese medicine. The preparation method mainly comprises the following steps: firstly, using 8 to 12 times of water to decoct pepper leaves for 2 times and 1 to 2 hours for each time, mixing and filtering a decocted fluid, concentrating the decocted fluid into a relative density of between 1.15 and 1.20, performing spray drying, and encapsulating particles or pressing the particles into tablets; and secondly, using 50 to 90 percent ethanol to soak the pepper leaves, reclaiming the ethanol, drying and crushing the pepper leaves, and encapsulating fine powder or pressing the fine powder into tablets. As proved by animal experimental research and clinical tests, the reagent has the function of obviously reducing blood fat and has no obvious untoward reaction. The medicine has rich sources of raw materials, low production cost and wide application prospect due to factors such as large hyperlipemia groups.

Description

The technology of preparing of Folium Zanthoxyli Bungeani medical substance and application thereof

Affiliated technical field

The invention belongs to the technology of preparing of treatment hyperlipidemia, specifically is to extract water-soluble and pure dissolubility mixture and be prepared into medicine from the Folium Zanthoxyli Bungeani medical substance.

Background technology

Hyperlipemia is called " hiding killer " by WHO, and hypertension is also referred to as " noiseless killer ", hypertension, and hyperlipidemia, hyperglycemia, super body weight (obesity) are called as " dead quartet " (X syndrome).

People are along with the change of growth in the living standard and rhythm of life, are called as the cardiovascular and cerebrovascular disease M ﹠ M that " three-hypers disease " (being hypertension, hyperglycemia and hyperlipidemia) of " affluenza " cause and rise year by year.

Hyperlipemia (hyperlipidemia) claim hyperlipoproteinemia again, mainly is because lipid metabolism or running disorder cause dyslipidemia, shows as serum total cholesterol, triglyceride and low-density lipoprotein cholesterol rising and high density lipoprotein and reduce.Hyperlipemia is one of common ailment of middle-aged and old, it also is one of risk factor of numerous cardiovascular and cerebrovascular disease, the most important thing is that wherein dyslipidemia can cause atherosclerosis, cause the blood supply obstacle of vitals then, mainly show as coronary heart disease and cerebral infarction clinically.

Though there is no the name of disease of " hyperlipemia " in the classic of TCM, the argumentations such as disease of " interior warp " relevant " fat ", " cream " and fat meat and fine grain are the origin of the traditional Chinese medical science to hyperlipemia understanding." Ling Shu Miraculous Pivot or Divine Axis disorder of defensive QI " piece of writing cloud: " people has fertilizer, cream is arranged, meat is arranged (original work " interior " according to hereinafter, should be the "flesh" (nonproductive construction) word)." " the cream person, many gas and skin are vertical slow, so it is vertical fertile to indulge abdomen.The meat person, health holds big.The fat person, its body is received little." " the cream person, many gas, many gas person heat, hot person is cold-resistant.The many blood of meat person then shape fill, and shape is filled then flat.Its serum of fat person, gas is sliding few, thus can not be big, this is not in everybody yet." " everybody, skin and flesh fat can not addition also, blood can not be many mutually with gas, so its shape is not little little, each claims its body, life is said everybody." this be in the body fat what, the inference QI and blood what, and then judge that in vivo normally whether fat, cream.

It is reported that there is 35% population in China, promptly 4.8 hundred million people have the hyperlipemia tendency.The U.S., European hyperlipemia person's ratio are then higher, only the reimbursement treatment hyperlipemia expense person of insurance company, just surpass 100,000,000 people.Hyperlipemia can make the blood thickness that becomes, and forms lipidosis on blood vessel wall, causes infraction.When blood vessels caliber stopped up 30%～50%, human body can have only to surpass at 70% o'clock without any sensation, and human body just has symptom and occurs.Occur in cardiovascular as pathological changes and then can show as coronary heart disease, occur in cerebrovascular and can show as apoplexy, occur in liver and can cause fatty liver etc.The U.S. not Lay Framingham studies show that, blood TC continues to be higher than 7.8mmol/L and the people that do not obtain intervention, and 90% coronary heart disease can take place also to die from.Continue to be higher than 3.51mmol/L, the every rising 10% of blood fat, death risk just increases by 23%.Over 40 years, the sickness rate of China's cardiovascular and cerebrovascular disease and case fatality rate are always and increase trend year by year, and its cause of the death has accounted for 40% in the dead population in city at present.

At present, the medicine of adjusting blood fat is also many, mainly is divided into following three classes: (1) Statins, based on cholesterol reducing, as simvastatin, Provastain etc.; (2) the special class of shellfish: based on triglyceride reducing, as gemfibrozil, lipanthyl etc.; (3) natural drug class (as Xuezhikang etc.) is all effective to cholesterol reducing and triglyceride, and can high density lipoprotein increasing, have the effect of comprehensive adjustment blood fat, and side effect is little, and this class fat-reducing medicament has become present research focus.

Summary of the invention

It is definite to the purpose of this invention is to provide clinical efficacy, and toxic and side effects is little, the cheap and hyperlipidemia medicine that has wide range of applications.Produce dried cream powder with the decoction of Folium Zanthoxyli Bungeani water or with pure dipping method, be prepared into capsule, tablet etc. according to the conventional formulation Technology.

Folium Zanthoxyli Bungeani is the dried leaves of rutaceae green pepper Zanthoxylum schinifolium Sieb.et Zucc. or Pericarpium Zanthoxyli Zanthoxylum Bungeanum Maxim.Contain quintessence oil in the Pericarpium Zanthoxyli leaf, Japan pepper essential oil is one of traditional flavouring agent goods of China.Contain volatile oil 1.4% in the Folium Zanthoxyli Bungeani approximately, analyze through GC-MS and confirm that contain 22 kinds of compositions in the Folium Zanthoxyli Bungeani volatile oil, wherein 5 kinds is the composition that has with Pericarpium Zanthoxyli, Radix Zanthoxyli Bungeani and Air Bladder pseudosciaenae seu Acipenser skin.The higher composition of several content is sabinene (Sabinene; C ₁₀H ₁₆) 13.60%, limonene (Limonene; C ₁₀H ₁₆) 19.31%, linalool (Linalool; C ₁₀H ₁₈O) 15.26%, ethyl cinnamate (met hyl cinnamate; C ₁₀H ₁₀O ₂) 7.24%, α-absinthol (α-Thujone; C ₁₀H ₁₆O) 4.40%.Infer that thus Folium Zanthoxyli Bungeani volatile oil also might have other pharmacologically active effects except having the effect of Semen zanthoxyli oil pharmacologically active.The a large amount of extract of Folium Zanthoxyli Bungeani should flavonoid and alkaloids substance.Be that the present invention utilizes the water of Folium Zanthoxyli Bungeani and ethanol extraction to make Chinese medicines such as treatment hyperlipemia.

Specific embodiments

Technology of preparing embodiment of the present invention is: the one, Folium Zanthoxyli Bungeani is boiled 2 times with 8-12 times of decocting, and each 1-2 hour, merge decoction liquor, filter, be concentrated into relative density 1.15-1.20, spray drying, granule incapsulates, or is pressed into tablet.The 2nd, Folium Zanthoxyli Bungeani with 50%～90% alcohol dipping, is reclaimed ethanol, drying is pulverized, and fine powder incapsulates or is pressed into tablet.Show that after deliberation reagent of the present invention can significantly reduce the blood lipid level of hyperlipemia model rat; Clinical trial confirms to have obvious blood fat reducing curative effect.

Animal experiment study and clinical treatment hyperlipemia observation of curative effect

One, reagent of the present invention is to the effect of hyperlipemia model animal

1, material water extract of the present invention (lot number 2008060801) and ethanol extraction (lot number 2008060802) are by my Drug Manufacturing Room of institute preparation; Positive control drug is the total glycoside of Jiaogulan sheet, authentication code: (90) are defended the accurate word Z-04 of medicine number, lot number: 20080627, and the Ankang pharmaceutical factory of traditional Chinese medicine; Cholesterol, Cholesterol A.R. China Hui Xing Shanghai biochemical reagents company produces lot number 080315.Cholesterol (TC), triglyceride (TG) detectable, high density lipoprotein (HDL-C) detectable are by Beijing Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd..Instrument has: the KY2000 of Hitachi semi-automatic biochemical analyzer.XN-2 type blood viscosity instrument, Shanghai Medical Univ produces.TDZ-5-4.0 multitube frame autobalance centrifuge, Hunan instrument head factory.

2, method healthy SD rat is 50, the cleaning level, and male and female half and half, body constitution amount 150～200g provides [certificate of competency: SCXK (army) 2002006] by The Fourth Military Medical University's Experimental Animal Center.After adaptability fed for 1 week, be divided into 5 groups at random: normal control group (calling matched group in the following text), model group with hyperlipemia (calling model group in the following text), water extract group, ethanol extract group and positive controls, 10 every group.Normal control group normal diet is fed, all the other four groups of high lipid foods are fed, the high lipid food prescription is: 2% cholesterol, 0.3% sodium deoxycholate, 7.5% Adeps Sus domestica, 5% yolk powder, 85.2% normal feedstuff, and feed the SD rat and set up hyperlipemia model, freely ingest, drink water.

In 4 weeks of continuous irrigation stomach after the modelling, irritate stomach of the present invention reagent (water and ethanol extract) by 1.0g/kg body weight (in crude drug) every day; Matched group is irritated stomach with the equal-volume physiological saline solution; Matched group is irritated stomach and is given total glycoside of Jiaogulan sheet 32mg/kg, in continuous 4 weeks, weighs satellite recanalization dosage weekly 2 times.Fasting in evening on the same day is 12 hours after the last administration, does not limit drinking-water; Next day, eye socket was got blood, measured the content and the blood viscosity of cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C).

Gained The data statistics software SPLM handles, and variance analysis is used in check between group, and the t check is adopted in check between two groups.

3, result's experiment the results are shown in Table 1.After 4 weeks, the TC of rat model, TG detect index and significantly raise, and HDL-C significantly reduces; Reagent of the present invention is that TC, TG and the model group of water extract group and ethanol extraction group and Herb Gynostemmae Pentaphylli group significantly descends, and learns by statistics to handle to have remarkable meaning (P＜0.05 or P＜0.01); HDL-C then significantly raises, and relatively has statistical significance (P＜0.05 or P＜0.01) with model group.

Blood Lipid (x ± the s of table 1 medication 4 all each treated animals; Mmol/L; N=10)

^aP＜0.05, ^bCompare with matched group P＜0.01; ^cP＜0.05, ^dCompare with model group P＜0.01.

The blood viscosity in 4 weeks of rat medication detects and shows, give 4 weeks of reagent of the present invention after, the whole blood height of rat model cut viscosity, in cut viscosity and the low viscosity of cutting all significantly reduces, with model group statistical significance (P＜0.05 or P＜0.01 is arranged relatively; Table 2).

4 weeks of table 2 medication are respectively organized rat blood viscosity change (x ± s; Mpa.s; N=10)

^aP＜0.05, ^bCompare with matched group P＜0.01; ^cP＜0.05, ^dCompare with model group P＜0.01.

Two, clinical trial

1, clinical data 140 routine patients are my the outpatient service prescription on individual diagnosis person of school Affiliated Hospital, and are diagnosed as hyperlipidemia patient.37 years old mean age (22～62 years old), average course of disease 4.5 years (1.5 years～19 years).All patients are tried not accept other drug in preceding 1 month and are treated.140 routine patients are divided into matched group 48 examples at random, reagent water extract group 45 examples of the present invention, ethanol extract group 47 examples.Three groups of patients have comparability at aspects such as age, sex, the courses of disease.

2,2 treatment groups of administrated method and the present invention's course of treatment are used 9 of capsules respectively every day, divide 3 times oral meal, continuous 6 weeks; Matched group decoction being taken at a draught in evening every day simvastatin 10mg～30mg (just determining dosage according to plasma cholesterol), by specification uses.Medication 6 week, the back judged that curative effects also write down untoward reaction, occurred then termination test at once of serious adverse reaction midway as treatment.

3, curative effect determinate standard is formulated according to table 3 literature method.

4, the result is through the clinical treatment of contrast at random, and the present invention is to the treatment of hyperlipemia, and obvious effective rate and effective percentage all approach matched group (simvastatin group), but total effective percentage does not have significant difference.The The above results proof originally

The diagnosis of table 3 hyperlipemia and treatment standard

Invention aspect the treatment of hyperlipemia with the therapeutic equivalence of contrast medicine simvastatin.

Table 4 liang group hyperlipidemia patient treatment back curative effect relatively

^*Annotate: compare with matched group.

At present, simvastatin is one of domestic most widely used blood lipid-lowering medicine, also is the medicine of the maximum cholesterol reducing of home sale, and researcher finds that it except that lowering cholesterol, has the effect of obviously stablizing the coronary artery calcium speckle, reduces cardiovascular event; But bigger to the liver side effect, also have symptoms of digestive tract such as stomachache, constipation, flatulence.

Water extract of the present invention and ethanol extract are executed and are controlled hyperlipemia 92 examples, not only have better effect for reducing blood fat, and all do not find untoward reaction, through to the treatment before and after a big young waiter in a wineshop or an inn just, the detection of routine blood test, Liver and kidney merit etc. confirms that its These parameters is all in normal range.Illustrate that reagent of the present invention is safe in utilization effectively.

Claims (3)

1, a kind of medicine for the treatment of hyperlipemia, the leaf that adopts the medicinal plants Pericarpium Zanthoxyli are that the raw material extraction is prepared from;

2, the preparation method of treatment hyperlipidemia according to claim 1, its feature one are that Folium Zanthoxyli Bungeani is boiled 2 times with 8-12 times of decocting, each 1-2 hour, merge decoction liquor, filter, be concentrated into relative density 1.15-1.20, spray drying, granule incapsulates, or is pressed into tablet.The 2nd, Folium Zanthoxyli Bungeani with 50%～90% alcohol dipping, is reclaimed ethanol, drying is pulverized, and fine powder incapsulates or is pressed into tablet.

3, medicine according to claim 2, it is mainly used in the treatment of hyperlipemia clinically, and its detailed directions is oral and follows the doctor's advice.