CN103623189A - Compound traditional Chinese medicine preparation with effect of atherosclerotic plaque regression and reversal - Google Patents

Abstract

The present invention relates to a compound traditional Chinese medicine preparation with an effect of atherosclerotic plaque regression and reversal. The compound traditional Chinese medicine preparation is characterized by comprising three main traditional Chinese medicines such as fructus trichosanthis, longstamen onion bulb and sanchi and a certain auxiliary herb, wherein a weight percentage ratio of the sanchi to the longstamen onion bulb to the fructus trichosanthis is 1:1-3:1-4, and the amount of the three main traditional Chinese medicines is 50-100% of the total weight of the preparation. According to the present invention, during use, based on effective and stable inhibition of atherosclerosis pathological change progression, plaque regression induction is achieved so as to achieve the pre-displacement of the whole treatment time window, such that the occurrence probability of various types of cardiovascular and cerebrovascular events caused by atherosclerosis pathological changes can be fundamentally reduced. In addition, compatibility of the compound traditional Chinese medicine preparation is optimized and improved so as to reduce burdens on liver, kidney and other organs and reduce risks of liver and kidney toxicity caused by the traditional statin drug intensification therapy.

Description

A kind ofly disappear and reverse Chinese traditional compound medicine of atheromatous plaque and preparation method thereof

Technical field

The present invention relates to medical technical field, specifically a kind ofly disappear and reverse Chinese traditional compound medicine of atheromatous plaque and preparation method thereof.

Background technology

Raising along with human living standard, the quickening of Working Life rhythm and the aggravation of social senilization, with atherosclerosis (atherosclerosis, AS) be the cardiovascular and cerebrovascular disease of pathologic basis, due to higher sickness rate, fatality rate and disability rate, become the main disease of serious harm human health, the sickness rate of China is the trend rising year by year, and develop to rejuvenation, in China, the number of dying from every year vascular conditions reaches more than 300 ten thousand people, accounted for the 35%-40% of the annual total death toll of China, be used for the treatment of the expense of AS angiopathy more than hundred billion yuan, countries in the world are the most important thing of research using the research of AS and complication thereof as cardiovascular and cerebrovascular disease all.Although the acute phase mortality that current comprehensive medicine and interventional therapy effectively reduce this type of patient, but improve still more limited to patient's long-term prognosis, more lack active and effective early-stage preventive measures, even the most effectively his spit of fland and aspirin Drug therapy also can only reduce the generation of 30% cardiocerebrovasculaevents events, how further to reduce all the other 70% residual risks, becoming pressing issues urgently to be resolved hurrily at present, is also the focus of current medical research.

Studies confirm that in a large number: cardiovascular and cerebrovascular disease and endovascular atheromatous plaque are directly closely related, Mottling formation is a long-term chronic pathology process simultaneously, once will constantly accelerate and speckle forms its progress, thereby cause various cardiovascular and cerebrovascular diseases, such as: apoplexy, heart infarction and lower limb ischemia or internal organs thromboembolism etc.Although the serum regulating drug extensive uses clinically such as his spit of fland, but it is not obvious to disappearing of the established speckle of industry, and often needing heavy dose of long-term taking, this brings again the problems such as corresponding Liver and kidney and musclar toxicity, is a clinical key issue in the urgent need to address.

Summary of the invention

The object of the present invention is to provide and a kind ofly improvedly disappear and reverse Chinese traditional compound medicine of atheromatous plaque and preparation method thereof, it can overcome in prior art improves still more limited to patient's long-term prognosis, his spit of fland and aspirin Drug therapy more lack active and effective early-stage preventive measures, even the most effectively also can only reduce the some shortcomings of the generation of 30% cardiocerebrovasculaevents events.

To achieve these goals, technical scheme of the present invention is: a kind of Chinese traditional compound medicine that disappears and reverse atheromatous plaque, it is characterized in that: described Chinese traditional compound medicine consists of this three tastes Chinese medicine of Fructus Trichosanthis, Bulbus Allii Macrostemonis and Radix Notoginseng, and the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 1:1-3:1-4.

A kind of Chinese traditional compound medicine that disappears and reverse atheromatous plaque, it is characterized in that: the major ingredient that described Chinese traditional compound medicine is 50-100% by percentage by weight and 0-50% adjuvant are made, described major ingredient comprises by this three tastes Chinese medicine of Fructus Trichosanthis, Bulbus Allii Macrostemonis and Radix Notoginseng and forms, and the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 1:1-3:1-4.

A kind of preparation method that disappears and reverse the Chinese traditional compound medicine of atheromatous plaque, it is characterized in that: described preparation method is water decoction-alcohol sedimentation preparation method, concrete steps are as follows: a, Fructus Trichosanthis, Bulbus Allii Macrostemonis and Radix Notoginseng crude drug are mixed according to the proportioning of 1:1-3:1-4, add to account for medical material gross weight 10-20 decocting doubly and boil, decocting time is 2-6 hour; The decoction liquor obtaining after b, decoction is through 40 order vibrating screen devices, carry out solid-liquid separation, the aqueous extract that separation is obtained carries out concentrating under reduced pressure (pressure is-740mmHg) on thin-film concentrator, then be transferred to that in Stainless steel pressure cooking-vessel, to carry out normal pressure concentrated, the extractum after concentrated is that every 1ml is equivalent to Chinese crude drug 6-10g; C, in above-mentioned extractum, add 95% amount of alcohol, make it to reach 60% containing alcohol amount, stir evenly and within latter standing 48 hours, obtain alcohol deposit fluid, after alcohol deposit fluid is filtered, be placed in ethanol recovery pot again and reclaim ethanol to also again obtaining extractum without alcohol taste, above-mentioned extractum continues to be concentrated into every 1ml extractum and is equivalent to Chinese crude drug 8-12g; D, add and account for the ethanol modulation soft material that extractum percentage by weight is 6% polyvinylpolypyrrolidone and 70%, the subsequently wet grain of system in 16 order stainless steel mesh oscillating granulators again; E, the grain that will wet are evenly distributed in drip pan at stand, then send into forced air drying in heated-air circulation oven, and oven temperature is controlled at 75 ℃, make granule water content interior cooling to prescribed limit (lower than 6%), finally use the artificial granulate of 16 eye mesh screen, obtain Chinese traditional compound medicine.

The invention still further relates to a kind of capsule, in said the compound preparation stable and atheromatous plaque that disappears is incapsulated, the atherosclerosis compound capsule of must stablizing and disappear.

The invention still further relates to a kind of buccal tablet, add the magnesium stearate that accounts for total weight percent 1% to mix 30 minutes in the said granule medicated powder that disappears and reverse the Chinese traditional compound medicine of atheromatous plaque, the herbal mixture buccal tablet of atheromatous plaque can be disappeared and be reversed to compacting in flakes, again.

The invention still further relates to a kind of coated tablet, add the magnesium stearate that accounts for total weight percent 1% to mix 30 minutes in the said granule medicated powder that disappears and reverse the Chinese traditional compound medicine of atheromatous plaque, be pressed into label, outer wrapping sugar-coat or macromolecule membrane subsequently, can be disappeared and be reversed the herbal mixture coated tablet of atheromatous plaque.

The invention still further relates to a kind of ultrafine preparation, the said granule that disappears and reverse the Chinese traditional compound medicine of atheromatous plaque is processed through micronizing rod mill again, the ultrafine preparation that acquisition particle diameter is 10-40um, subpackage is standby, and it can be used as inner stuffing prepared by capsule preparation, buccal tablet preparation and coated tablet.

During use, the present invention is effectively stably suppressing on the basis of atherosclerotic lesion progress, realizing induction speckle disappears, thereby realize the reach of wholistic therapy time window, fundamentally reduce the occurrence probability of all kinds of cardiocerebrovasculaevents events that atherosclerotic lesion causes, in addition the compatibility of this compound recipe, through optimizing improvement, has reduced the burdens such as Liver and kidney, has reduced the risk that traditional statins intensive treatment causes Liver and kidney toxicity.

Accompanying drawing explanation

Fig. 1 is the inhibitory action icon of compound preparation of the present invention to experimental rabbit Carotid Atherosclerosis speckle.

The specific embodiment:

Below in conjunction with drawings and Examples, the invention will be further described.

A kind of Chinese traditional compound medicine that disappears and reverse atheromatous plaque of the present invention, its difference with the prior art is: described Chinese traditional compound medicine consists of this three tastes Chinese medicine of Fructus Trichosanthis, Bulbus Allii Macrostemonis and Radix Notoginseng, and the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 1:1-3:1-4.

A kind of Chinese traditional compound medicine that disappears and reverse atheromatous plaque, its difference with the prior art is: the major ingredient that described Chinese traditional compound medicine is 50-100% by percentage by weight and 0-50% adjuvant are made, described major ingredient comprises by this three tastes Chinese medicine of Fructus Trichosanthis, Bulbus Allii Macrostemonis and Radix Notoginseng and forms, and the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 1:1-3:1-4.Described adjuvant is by Bulbus Fritillariae Uninbracteatae 1-60 part, and Rhizoma Pinelliae 1-40 part and Rhizoma Coptidis 1-12 part mix; Described adjuvant is by Fructus Aurantii Immaturus 1-60 part, and Radix Platycodonis 1-60 part and Poria 1-60 part mix; Described adjuvant is by Pericarpium Citri Reticulatae 1-60 part, and Fructus Gardeniae 1-60 part and Radix Angelicae Sinensis 1-40 divide and mix; Described adjuvant is by Fructus Amomi 1-35 part, and Radix Aucklandiae 1-35 part and Radix Glycyrrhizae 1-40 part mix.

In described Chinese traditional compound medicine formula, major ingredient accounts for 65-70%, adjuvant accounts for 30-35%, in major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 3:2:1, described adjuvant is made by this three tastes Chinese medicine of Bulbus Fritillariae Uninbracteatae, the Rhizoma Pinelliae and Rhizoma Coptidis, wherein, the ratio of the percentage by weight of Bulbus Fritillariae Uninbracteatae, the Rhizoma Pinelliae and Rhizoma Coptidis is 1:1:1.In described Chinese traditional compound medicine formula, major ingredient accounts for 65-70%, adjuvant accounts for 30-35%, in major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 3:2:1, described adjuvant is made by this three tastes Chinese medicine of Fructus Aurantii Immaturus, Radix Platycodonis and Poria, wherein, the ratio of the percentage by weight of Fructus Aurantii Immaturus, Radix Platycodonis and Poria is 2:1:1.In described Chinese traditional compound medicine formula, major ingredient accounts for 65-70%, adjuvant accounts for 30-35%, in major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 3:2:1, described adjuvant is made by this three tastes Chinese medicine of Pericarpium Citri Reticulatae, Fructus Gardeniae and Radix Angelicae Sinensis, wherein, the ratio of the percentage by weight of Pericarpium Citri Reticulatae, Fructus Gardeniae and Radix Angelicae Sinensis is 1:2:1.In described Chinese traditional compound medicine formula, major ingredient accounts for 65-70%, adjuvant accounts for 30-35%, in major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 3:2:1, described adjuvant is made by this three tastes Chinese medicine of Fructus Amomi, the Radix Aucklandiae and Radix Glycyrrhizae, wherein, the ratio of the percentage by weight of Fructus Amomi, the Radix Aucklandiae and Radix Glycyrrhizae is 1:1:1.

A kind of preparation method that disappears and reverse the Chinese traditional compound medicine of atheromatous plaque, it is characterized in that: described preparation method is water decoction-alcohol sedimentation preparation method, concrete steps are as follows: the major ingredient that a, described Chinese traditional compound medicine are 50-100% by percentage by weight and 0-50% adjuvant are made, described major ingredient comprises by this three tastes Chinese medicine of Fructus Trichosanthis, Bulbus Allii Macrostemonis and Radix Notoginseng and forms, in above-mentioned compound, add to account for medical material gross weight 10-20 decocting doubly and boil, decocting time is 2-6 hour; The decoction liquor obtaining after b, decoction is through 40 order vibrating screen devices, carry out solid-liquid separation, the aqueous extract that separation is obtained carries out concentrating under reduced pressure on thin-film concentrator, is then transferred to that in Stainless steel pressure cooking-vessel, to carry out normal pressure concentrated, and the extractum after concentrated is that every 1ml is equivalent to Chinese crude drug 6-10g; C, in above-mentioned extractum, add 95% amount of alcohol, make it to reach 60% containing alcohol amount, stir evenly and within latter standing 48 hours, obtain alcohol deposit fluid, after alcohol deposit fluid is filtered, be placed in ethanol recovery pot again and reclaim ethanol to also again obtaining extractum without alcohol taste, above-mentioned extractum continues to be concentrated into every 1ml extractum and is equivalent to Chinese crude drug 8-12g; D, add and account for the ethanol modulation soft material that extractum percentage by weight is 6% polyvinylpolypyrrolidone and 70%, the subsequently wet grain of system in 16 order stainless steel mesh oscillating granulators again; E, the grain that will wet are evenly distributed in drip pan at stand, then send into forced air drying in heated-air circulation oven, and oven temperature is controlled at 75 ℃, make granule water content interior cooling to prescribed limit, finally use the artificial granulate of 16 eye mesh screen, obtain Chinese traditional compound medicine granule.

In a step, in described major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 1:1-3:1-4; In described adjuvant, adopting the proportioning of four kinds of heterogeneities, is respectively that Bulbus Fritillariae Uninbracteatae 1-60 part, Rhizoma Pinelliae 1-40 part and Rhizoma Coptidis 1-12 part mix; Fructus Aurantii Immaturus 1-60 part, Radix Platycodonis 1-60 part and Poria 1-60 part mix; Pericarpium Citri Reticulatae 1-60 part, Fructus Gardeniae 1-60 part and Radix Angelicae Sinensis 1-40 divide and mix; Fructus Amomi 1-35 part, Radix Aucklandiae 1-35 part and Radix Glycyrrhizae 1-40 part mix.In b step, the pressure limit of concentrating under reduced pressure is negative 650mmHg-negative 750mmHg; In d step, granule water content is cooling lower than carrying out after 6%.

In the Chinese traditional compound medicine granule obtaining in e step, add the magnesium stearate that accounts for Chinese traditional compound medicine weight percentage 1% to mix 30 minutes, the granule after total mixing, selects 0# gelatin Capsules, carries out capsule-filling and obtains capsule, the heavy 0.35g/ grain of grain.

In the Chinese traditional compound medicine granule obtaining in e step, add the magnesium stearate that accounts for compound preparation particle medicinal powder percentage by weight 1% to mix 30 minutes, then compacting in flakes, can obtain buccal tablet, the heavy 0.35g/ sheet of sheet.

In the Chinese traditional compound medicine granule obtaining in e step, add the magnesium stearate that accounts for compound preparation particle medicinal powder percentage by weight 1% to mix 30 minutes, become label, outer wrapping sugar-coat or macromolecule membrane, can obtain coated tablet subsequently, the heavy 0.35g/ sheet of sheet.

The Chinese traditional compound medicine granule obtaining in e step is processed through micronizing rod mill again, the ultrafine preparation that acquisition particle diameter is 10-40um, and subpackage is standby, and it can be used as inner stuffing prepared by capsule preparation, buccal tablet preparation and coated tablet.

Although motherland's medical science successive dynasties document does not have atherosclerotic record, in the traditional Chinese medical science, be attributable to that the expectorant of deficiency in origin and excess in superficiality is turbid, the category of blood stasis.The endogenous cause of ill that expectorant generates is visceral dysfunction, and surfeit Sorghum vulgare Pers. savoury is its exopathogenic factor, from hereditary angle, says that tcm constitution situation is also key factor as " fertile people's excessive phlegm ".The paathogenic factor such as hyperlipemia and hyperglycemia can be referred to as " expectorant in blood is turbid ", the traditional Chinese medical science is attributed to phlegm syndrome, Shen Jin huge legendary turtle < < miscellaneous diseases source and course rhinoceros candle > > says: " expectorant be thing; the accident of flowing, thus its cause harm, upper to top, top; down to spring; fall with gas lift, all arrive inside and outside all over the body, the vital organs of the human body all have." have and easily gather the easily feature of row.Under Earlier atherosclerotic lesion lipid striped, inner membrance, foam cell gathers and is the solidifying not loose imbody of the turbid retardance of expectorant, expectorant, has the also easy pathological characters of dissipation of easy formation.Blood stasis refers to there is blood stasis in body, is mainly that blood circulating out of vessels is accumulated in body, or blood fortune is not smooth, blocks the blood in passages through which vital energy circulates and internal organs.The traditional Chinese medical science is plaque rupture, platelet activation and high coagulation, and thrombosis is considered as syndrome of blood stasis category.Expectorant is turbid, blood stasis is atherosclerotic main pathological product, is again paathogenic factor, and both reciprocal causations, can transform mutually, and expectorant can cause the stasis of blood, and the stasis of blood can be given birth to expectorant, runs through the overall process that AS pathology occurs, and phlegm and blood stasis is atherosclerotic Etiological pathogenesis.Expectorant comes from Tianjin, the stasis of blood this in blood, but different stream and homology can mutually transform under certain specified conditions.They belong to " homogeny of clear fluid and blood " on physiology in brief, are " the expectorant stasis of blood is with sick " on pathology.As < < Ling Shu Miraculous Pivot or Divine Axis carbuncle > > cloud: " body fluid and tune, change and red be blood ".In < < Plain Questions numbness opinion > >, there is " obstruction of heart-QI pain person also has the dead blood of pertinacious phlegm "; < < treatise on blood trouble water fire of moxibustion blood opinion > > cloud: " blood stasis is both of a specified duration, also can turn to expectorant water ".And it is long-standing for the theory of thoracic obstruction removing both phlegm and blood stasis at the same time.As large in < < Plain Questions YIN YANG classification of natural phenomena opinion > > proposes " blood reality person should determine it ", and < < Ling Shu Miraculous Pivot or Divine Axis five tastes > > also has the suggestion of " pained should eat Chinese onion "; The two is that obstruction of qi in the chest and cardialgia is from the thinking blank of expectorant, stasis of blood treatment.

This traditional Chinese medical science has been provided to the corresponding method for the treatment of rule for the treatment of to phlegm and blood stasis diseases such as atherosclerosiss theoretically, such as < < Treatise on Febrile and Miscellaneous Disease > > sums up Qin Han theory of medicine in the past, found differentiation of febrile diseases in accordance with the theory of the six meridians and treatment rule, proposed first the relation of " expectorant and blood ".Cure mainly all expectorant sides in " obstruction of qi in the chest and cardialgia lose heart abnormal pulse card control " piece of writing in, being equipped with the fluent QI and blood of Chinese liquor, is the thinking that has implied removing both phlegm and blood stasis at the same time.The Tang Dynasty < < Essential Recipes for Emergent Use Worth A Thousand Gold > > soldier is sent out to obstruction of qi in the chest and cardialgia controls with Radix Et Rhizoma Rhei, Ramulus Euonymi blood circulation promoting and blood stasis dispelling, Rhizoma Dysosmae Versipellis expectorant powder junction, removing blood stasis, Radix Platycodonis reduces phlegm; Song dynasty < < Shengji Zonglu thoracic obstruction door > > controls the thoracic obstruction, ties loose mass in the abdomen, with fluffy cowherb promoting the circulation of blood blood stasis dispelling in the four loose sides of temperature with Fructus Aurantii Immaturus expectorant.The red small stream heart of Jin Dynasty < < mirror > > " expectorant diseases caused by retention of fluid stops the loose name of a knot thoracic obstruction side " gets Fructus Trichosanthis, Rhizoma Atractylodis, Fructus Aurantii and reduces phlegm except painful abdominal mass knot, and Radix Paeoniae is invigorated blood circulation.Cao Renbai clearly proposition in < < continues will hall case stagnated QI door > > " chest pain radiating to the back is a thoracic obstruction ..., only expectorant is not turbid for this pain, and has blood stasis, hands between resistance diaphragm.Fructus Trichosanthis, Bulbus Allii Macrostemonis, Semen Persicae, Flos Carthami for side ", not only recognize that the thoracic obstruction and the expectorant stasis of blood are closely related, and adopted the method for removing both phlegm and blood stasis at the same time.

The present invention is the famous prescription GUALOUXIEBAI TANG based in the well-known doctor's Zhang Zhongjing < < Medical Treasures of the Golden Chamber > > of Han dynasty, according to the up-to-date atherosclerosis new theory of " removing both phlegm and blood stasis at the same time ", in conjunction with long-term clinical practice, improve and obtain simultaneously.Gualou Xiebai Baijiu Tang activating YANG and eliminating stagnation, under eliminating phlegm, Radix Notoginseng and battalion hemostasis, the clots absorbing of promoting blood circulation, both close and add taste, remove Chinese liquor simultaneously, the function the chest stuffiness relieving of regulating the flow of vital energy, clearing away phlegm eliminating stagnation, blood circulation promoting and blood stasis dispelling, removing both phlegm and blood stasis at the same time.Fructus Trichosanthis nature and flavor sweetness and bitterness, cold, enter lung, stomach, large intestine channel, cure mainly lung moistening, reduce phlegm, eliminating stagnation, intestine moistening.Control phlegm-heat cough, the thoracic obstruction, blocked-up chest, consumptive lung disease hemoptysis, quenches one's thirst, jaundice, constipation, carbuncle from the beginning of; Bulbus Allii Macrostemonis nature and flavor are pungent, bitter, and temperature, with entering lung, stomach, large intestine channel, cures mainly activating YANG and eliminating stagnation, circulation of qi promoting intestinal stasis relieving.For thoracic obstruction pain, phlegm retention cough with asthma, lets out after dysentery heavy; Sweet, the micro-hardship of Radix Notoginseng nature and flavor, warm in nature, return liver, stomach, the heart, lung, large intestine channel, cure mainly to fall and flutter congestive edema, thoracic obstruction angor, lump in the abdomen, blood stasis amenorrhea, dysmenorrhea, the cloudy stomachache of the stasis of blood in puerperal, sore, carbuncle and painful swelling.According to the principles of formulating prescriptions of " monarch ", monarch drug is that Fructus Trichosanthis is real, the chest stuffiness relieving of regulating the flow of vital energy, and clearing away phlegm eliminating stagnation, controls the key medicine of thoracic obstruction chest pain, ministerial drug is Bulbus Allii Macrostemonis, the logical sliding profit of temperature, activating YANG and eliminating stagnation, promoting the circulation of QI to relieve pain, two medicines match, and for controlling the key medicine of the thoracic obstruction, then help with pseudo-ginseng blood-circulation-invigovating blood stasis dispelling, strengthen the merit that Bulbus Allii Macrostemonis circulation of qi promoting activates yang.Three taste medicines are mutually auxiliary is use, with the chest stuffiness relieving of regulating the flow of vital energy, and clearing away phlegm eliminating stagnation, blood circulation promoting and blood stasis dispelling, removing both phlegm and blood stasis at the same time.

Zoopery proves, medicine of the present invention, and toxicity is less, even if take in a large number, also has no side effect.Stable and the atheromatous plaque compound preparation acute toxicity testing result that disappears shows, press the maximum concentration of ordinary dissolution of medicine, maximum administration capacity, SPF rank kunming mice gavage gives 285g(crude drug) only after administration, in 2 hours, there is the phenomenons such as lethargy, few moving, few feed in the compound preparation extractum of/kg.d body weight (containing adjuvant), administration recovers for 2 hours later successively, tested mice is none death in experimental period, median lethal dose(LD 50) LD50 does not measure, therefore only do maximum dosage-feeding (MTD) experiment.Result shows, the MTD>285g(that mice gives compound preparation amounts to crude drug and calculates)/kg.d, for referrer's clinical dosage (body weight press 60kg calculating) 21.4 times, illustrate that this medicine is nontoxic, clinical drug safety.

Laboratory animal grouping and dosage thereof: 8 week age, SPE kunming mice was totally 26, body weight: 19.0～22.0g, male and female half and half, by Shanghai, western pul-Bi Kai experimental animal company limited provides, laboratory animal production licence number: SCXK(Shanghai) 2008-0016, raise: The 2nd Army Medical College INM Animal House, the quality certification number: the moving word the 0075045th of doctor.

Experimental technique:

1) with the extractum of embodiment 1, make suspension, measuring and calculating maximum acceptable concentration 9.5g/ml.

2) animal fasting (12-16 hour), can't help water, and according to body weight gastric infusion, every mice is with 30ml/kg body weight, and disposable gastric infusion is observed after administration the poisoning and death condition of animal in 14 days.

3) observation index: observe toxic reaction and death condition after animals administer.Toxic reaction primary part observation symptom, degree, toxic reaction initial time, persistent period and recovery time etc.

4) maximum acceptable concentration and the maximum volume that allows are not measured LD50 yet, can only demand maximum tolerated dose (MTD) value.Method: the maximum of once pressing Cmax allows volume medicine to 20 animals, and Continuous Observation 14 days, has no any animal dead, MTD>XXg/kg.If only there is indivedual death,

Result: 1) preliminary experiment: select 6 of Kunming kind white mice, male and female half and half, body weight 20 ± 2g.Fasting, can't help water 12～16 hours.Every each gavage of mice gives concentration for the speckle capsule extractum dawn 30ml/kg(body weight containing crude drug 9.5g/ml), gavage 1 time, then raises routinely.Observe the situations such as mice outward appearance, behavioral activity, breathing, secretions, defecation, death and weigh continuous 7 days.Because being subject to the impact of drug level and volume, single administration is not all measured median lethal dose(LD 50) (LD50) with Cmax, heap(ed) capacity, therefore only do maximum dosage-feeding experiment; 2) maximum dosage-feeding experiment: select 20 of Kunming kind white mice, male and female half and half, body weight 20 ± 2g.Fasting, can't help water 12～16 hours.Every each gavage of mice gives concentration for the speckle capsule extractum dawn 30ml/kg(body weight containing crude drug 9.5g/ml), gavage 1 time, after administration 2 hours, mice occur lethargy in various degree, few moving, do not take food or the phenomenon such as few feed, but recovered successively after 2 hours, mice shows no obvious abnormalities reaction, activity freely, diet, feces and other situations be all without abnormal, hair color light next to the skin.After administration, 7 days and 14 days animal subject body weight are all significantly increased (in Table 1), and within the 14th day, mice is put to death by cuing open inspection perusal no abnormality seen.Result shows the MTD>285g/kg of mice to compound preparation.

Stable and the atheromatous plaque compound preparation that disappears of table 1 is to acute toxicity test in mice body weight change

Stable and the atheromatous plaque compound preparation that disappears shows the result of study of new zealand rabbit carotid artery atherosclerosis plaques: the compound preparation stable and atheromatous plaque that disappears has the effect that regulates blood fat and suppress atheromatous plaque progress, the established carotid artery atherosclerosis plaques of industry is had to significant regressive effect simultaneously.

Laboratory animal grouping and dosage thereof:

48 of purebred new zealand white rabbits, male and female half and half, body weight 2.50kg ± 0.5kg ，You The 2nd Army Medical College Experimental Animal Center provides.Animal production licence number: SCXK(Shanghai) 2007-0003; Animal occupancy permit number: SYXK(Shanghai) 2007-0003.

Experimental technique:

1) capsule 's content making with embodiment 6 is made into suspension with normal saline, and its dosage is 3.4mg/ (kg.d), and laboratory animal list cage routine feeding, freely drinks water, movable unrestricted.The full diet that first all animals experience 1 week is after the laundering period, 48 high fat of rabbit are fed after 5 weeks and carried out modeling, the high fat of postoperative continuation (high lipid food formula: 5% triglyceride, 1% cholesterol, 94% rabbit normal feedstuff) diet, then be divided at random matched group, compound preparation capsule intervention group and atorvastatin group 10mg/(kg.d), all with normal saline, be made into suspension same volume gastric infusion, matched group gives isopyknic normal saline gavage.Carotid atherosclerosis adopts the method induction of inner membrance collagenase digesting damage.Within 4 weeks after surgery, give carotid ultrasound assessment speckle situation, finally at experiment terminal, within 24 weeks, repeat ultrasonic evaluation, put to death subsequently animal, leave and take blood sample, the pathological analysis of the promoting the circulation of blood pipe of going forward side by side.

Table 2 compound preparation capsule to the regulating action of experimental rabbit blood fat (

)

* p<0.05 and matched group comparison, #p<0.05 and the comparison of atorvastatin intervention group

Table 2 result shows: 24 weekends, compound preparation intervention can significantly reduce the level of cholesterol, triglyceride and the low-density lipoprotein cholesterol of laboratory animal serum, its effect and control drug atorvastatin are similar, compound preparation can also improve the hdl level of laboratory animal serum simultaneously, and its effect will obviously be better than positive control medicine.

2) suppress rabbit carotid atherosclerosis progress

Adopt 770 pairs of experimental rabbits of toy ultrasonic image system Vevo to carry out the ultrasonic examination of carotid artery body surface, along blood vessel major axis, measure tube chamber and measure tremulous pulse rear wall inner membrance-intima-media thickness (IMT), left common carotid artery internal diameter (LCCAD).Put to death and to leave and take carotid artery specimen after animal and carry out specimens paraffin embedding slices analysis, concrete outcome is in Table 2 and Fig. 1.

Table 3 compound preparation to the inhibitory action of experimental rabbit Carotid Atherosclerosis speckle (

)

* p<0.05 and matched group comparison

The result of table 3 and Fig. 1 shows: give the progress that compound preparation intervention can significantly suppress carotid artery atherosclerosis plaques pathological changes due to new zealand rabbit inner film injury that high fat feeds, increase lumen diameter simultaneously, his spit of fland of this effect and control drug is compared stronger, although significant difference not significantly (p>0.05).

3) the stable and rabbit carotid atherosclerosis that disappears

Carotid ultrasound dynamic evaluation prompting: although spontaneous regression group has changed regular diet into, plaque area still has increase, and internal diameter of carotid is dwindled (#p<0.05 and comparison in 4 weeks), the compound preparation intervention rabbit carotid artery atherosclerosis plaques pathological changes of can effectively stablizing and disappear, plaque area is significantly dwindled (#p<0.05 and comparison in 4 weeks), strengthening his spit of fland intervention has similar effect, but speckle regressive effect is obviously weaker than compound preparation intervention group.

Table 4 compound preparation to the regressive effect of experimental rabbit Carotid Atherosclerosis speckle (

)

* p<0.05 and matched group comparison #p<005 and comparison clinical practice in 4 weeks prove, the Chinese traditional compound medicine of the stable and atheromatous plaque that disappears of the present invention, for patients with coronary heart disease, there is very significant curative effect, general dosage is 5-20mg/kg body weight every day, specifically can by doctor, be determined according to patient's the concrete conditions such as the age state of an illness.

Embodiment 1

The manufacturing process of the stable and atherosclerosis compound preparation granule medicated powder that disappears, by Fructus Trichosanthis, Bulbus Allii Macrostemonis, after Radix Notoginseng three taste crude drugs mix according to the part by weight of 3:2:1, adding 10 times of decoctings boils, extraction time is 5 hours, through 40 order vibrating screen devices, carry out solid-liquid separation, the aqueous extract that separation is obtained carries out concentrating under reduced pressure on thin-film concentrator, then be transferred to that in Stainless steel pressure cooking-vessel, to carry out normal pressure concentrated, fluid extract amount after concentrated should be controlled at every 1ml and be equivalent to Chinese crude drug 6-10g, add 95% amount of alcohol, containing alcohol amount 60%, stir evenly latter standing 48 hours, after alcohol deposit fluid is filtered, put ethanol and reclaim the interior ethanol that reclaims of pot extremely without alcohol taste, above-mentioned extractum continues to be concentrated into every 1ml extractum and is equivalent to Chinese crude drug 8-12g, add again 6% polyvinylpolypyrrolidone-70% ethanol modulation soft material, in 16 order stainless steel mesh oscillating granulators, make subsequently wet grain.Wet granular is evenly distributed in drip pan at stand, then sends into forced air drying in heated-air circulation oven, oven temperature is controlled at 75 ℃, makes granule water content cooling to <6%, finally uses the artificial granulate of 16 eye mesh screen, obtains.

Embodiment 2

Just Fructus Trichosanthis is 3 parts, 2 parts of Bulbus Allii Macrostemonis, 1 part of Radix Notoginseng, 1 part of Bulbus Fritillariae Uninbracteatae, 1 part of the Rhizoma Pinelliae, after 1 part of mixing of Rhizoma Coptidis, adding 10 times of decoctings boils, extraction time is 5 hours, through 40 order vibrating screen devices, carry out solid-liquid separation, the aqueous extract that separation is obtained carries out concentrating under reduced pressure on thin-film concentrator, then be transferred to that in Stainless steel pressure cooking-vessel, to carry out normal pressure concentrated, fluid extract amount after concentrated should be controlled at every 1ml and be equivalent to Chinese crude drug 6-10g, add 95% amount of alcohol, containing alcohol amount 60%, stir evenly latter standing 48 hours, after alcohol deposit fluid is filtered, put ethanol and reclaim the interior ethanol that reclaims of pot extremely without alcohol taste, above-mentioned extractum continues to be concentrated into every 1ml extractum and is equivalent to Chinese crude drug 8-12g, add again 6% polyvinylpolypyrrolidone-70% ethanol modulation soft material, in 16 order stainless steel mesh oscillating granulators, make subsequently wet grain.Wet granular is evenly distributed in drip pan at stand, then sends into forced air drying in heated-air circulation oven, oven temperature is controlled at 75 ℃, makes granule water content cooling to <6%, finally uses the artificial granulate of 16 eye mesh screen, obtains.

Embodiment 3

By 3 parts of Fructus Trichosanthis, 2 parts of Bulbus Allii Macrostemonis, 1 part of Radix Notoginseng, 2 parts of Fructus Aurantii Immaturuss, 1 part of Radix Platycodonis, after 1 part of mixing of Poria, adding 10 times of decoctings boils, extraction time is 5 hours, through 40 order vibrating screen devices, carry out solid-liquid separation, the aqueous extract that separation is obtained carries out concentrating under reduced pressure on thin-film concentrator, then be transferred to that in Stainless steel pressure cooking-vessel, to carry out normal pressure concentrated, fluid extract amount after concentrated should be controlled at every 1ml and be equivalent to Chinese crude drug 6-10g, add 95% amount of alcohol, containing alcohol amount 60%, stir evenly latter standing 48 hours, after alcohol deposit fluid is filtered, put ethanol and reclaim the interior ethanol that reclaims of pot extremely without alcohol taste, above-mentioned extractum continues to be concentrated into every 1ml extractum and is equivalent to Chinese crude drug 8-12g, add again 6% polyvinylpolypyrrolidone-70% ethanol modulation soft material, in 16 order stainless steel mesh oscillating granulators, make subsequently wet grain.Wet granular is evenly distributed in drip pan at stand, then sends into forced air drying in heated-air circulation oven, oven temperature is controlled at 75 ℃, makes granule water content to cooling after <5%, finally uses the artificial granulate of 16 eye mesh screen, obtains.

Embodiment 4

By 3 parts of Fructus Trichosanthis, 2 parts of Bulbus Allii Macrostemonis, 1 part of Radix Notoginseng, 1 part of Pericarpium Citri Reticulatae, 2 parts of Fructus Gardeniae, after Radix Angelicae Sinensis mixes for 1 minute, adding 10 times of decoctings boils, extraction time is 5 hours, through 40 order vibrating screen devices, carry out solid-liquid separation, the aqueous extract that separation is obtained carries out concentrating under reduced pressure on thin-film concentrator, then be transferred to that in Stainless steel pressure cooking-vessel, to carry out normal pressure concentrated, fluid extract amount after concentrated should be controlled at every 1ml and be equivalent to Chinese crude drug 6-10g, add 95% amount of alcohol, containing alcohol amount 60%, stir evenly latter standing 48 hours, after alcohol deposit fluid is filtered, put ethanol and reclaim the interior ethanol that reclaims of pot extremely without alcohol taste, above-mentioned extractum continues to be concentrated into every 1ml extractum and is equivalent to Chinese crude drug 8-12g, add again 6% polyvinylpolypyrrolidone-70% ethanol modulation soft material, in 16 order stainless steel mesh oscillating granulators, make subsequently wet grain.Wet granular is evenly distributed in drip pan at stand, then sends into forced air drying in heated-air circulation oven, oven temperature is controlled at 75 ℃, makes granule water content to cooling after <6%, finally uses the artificial granulate of 16 eye mesh screen, obtains.

Embodiment 5

By 3 parts of Fructus Trichosanthis, 2 parts of Bulbus Allii Macrostemonis, 1 part of Radix Notoginseng, 1 part of Fructus Amomi, 1 part of the Radix Aucklandiae, after 1 part of mixing of Radix Glycyrrhizae, adding 10 times of decoctings boils, extraction time is 5 hours, through 40 order vibrating screen devices, carry out solid-liquid separation, the aqueous extract that separation is obtained carries out concentrating under reduced pressure on thin-film concentrator, then be transferred to that in Stainless steel pressure cooking-vessel, to carry out normal pressure concentrated, fluid extract amount after concentrated should be controlled at every 1ml and be equivalent to Chinese crude drug 6-10g, add 95% amount of alcohol, containing alcohol amount 60%, stir evenly latter standing 48 hours, after alcohol deposit fluid is filtered, put ethanol and reclaim the interior ethanol that reclaims of pot extremely without alcohol taste, above-mentioned extractum continues to be concentrated into every 1ml extractum and is equivalent to Chinese crude drug 8-12g, add again 6% polyvinylpolypyrrolidone-70% ethanol modulation soft material, in 16 order stainless steel mesh oscillating granulators, make subsequently wet grain.Wet granular is evenly distributed in drip pan at stand, then sends into forced air drying in heated-air circulation oven, oven temperature is controlled at 75 ℃, makes granule water content to cooling after <6%, finally uses the artificial granulate of 16 eye mesh screen, obtains.

By the above-mentioned Chinese traditional compound medicine making, give following case and take, concrete effect is as follows:

Model case 1: man, 53 years old, business manager, patient has coronary heart disease medical history 10 years, and feeling of oppression and pain in the chest accompanies dizzy symptom repeatedly within 3 years, to increase the weight of January, and after being admitted to hospital, row inspection is found: blood lipid level significantly raises, moderate fatty liver; Angiography prompting: arteria coronaria triple vessel disease, left anterior descending branch moderate stenosis; Carotid ultrasound prompting: the visible area in right carotid artery bifurcation is about 3.52 ± 0.04mm ²soft speckle, give the stable and atherosclerotic compound preparation intervention of disappearing of embodiment 6, each 3, every day 3 times, after February patient's feeling of oppression and pain in the chest and dizzy remission obvious, after half a year, check the visible speckle of carotid ultrasound and significantly dwindle.

Model case 2: female, 41 years old, company clerk, patient's routine work pressure is large, live irregular, before 2 years, found that blood fat raises, give the oral blood fat of fat-reducing medicament such as his spit of fland and substantially recover normal, often with dizzy symptom uncomfortable in chest, increase the weight of 2 months, Lai Wo institute Electrocardioscopy prompting myocardial ischemia, carotid ultrasound prompting bilateral carotid arteries inner membrance significantly thickens, IMT is 2.75mm, stable and the atherosclerotic compound preparation intervention of disappearing that to give embodiment 4 be content, each 2, every day 3 times, after January, patient's dizzy remission uncomfortable in chest is obvious, electrocardiogram prompting ST obviously improves before forcing down, after half a year, check the visible carotid artery intima IMT of carotid ultrasound and be reduced to 1.75mm.

Model case 3: female, 65 years old, housewife, patient has coronary heart disease medical history 15 years, taking the symptoms such as the Western medicine chest pain dizzinesses such as his spit of fland controls not good, with weakness of the lower extremities, in the recent period because of Changes in weather, the dizzy symptom of chest pain increases the weight of, come my Out-patient Department medical, electrocardiogram prompting ST section is forced down obviously, the ultrasonic visible several specklees of carotid artery and artery of lower extremity, angiostenosis is obvious, row coronary angiography and two lower extremities ct angiography are clear and definite: left anterior descending branch interrupts narrow 80%, right hat narrow 40%, two lower extremity blood flow are not smooth, visible many places filling defect, intravascular ultrasound prompting left anterior descending branch stenosis speckle is eccentric unstable spot, its lactone core is larger, stable and the atherosclerotic compound preparation intervention of disappearing that to give embodiment 2 be content, each 4, every day 3 times, after February, the remission of patient's chest pain is obvious, lower extremity motor function recovers substantially, after half a year, check intravascular ultrasound prompting: left anterior descending branch stenosis unstable spot tends towards stability before, its fat core dwindles obviously, plaque area is significantly dwindled, stenosis is improved as 50%.

Model case 4: man, 51 years old, leading cadre, patient has hypertension history 20 years, coronary heart disease medical history 10 years, 400 years of smokings, daily dinner party is more, 3 liang of Chinese liquor every days, there is the dizzy weak symptom of chest pain companion uncomfortable in chest in nearly first quarter moon, the emergency treatment of Lai Wo institute is medical, electrocardiogram prompting left ventricular hypertrophy, ST section is significantly raised, the visible severe fatty liver of abdominal part MRI, coronary angiography prompting triple vessel disease, with left anterior descending branch, attach most importance to, its opening part narrow 70%, right hat many places filling defect, the multiple speckle of the ultrasonic prompting bilateral carotid arteries of cervical region, stable and the atherosclerotic compound preparation intervention of disappearing that to give embodiment 1 be content, each 4, every day 3 times, coordinate the life style adjustment such as discontinue the habit of smoking and drinking simultaneously, after January, the dizzy weak remission of patient's chest pain companion uncomfortable in chest is obvious, after half a year, checking coronary angiography prompting left anterior descending branch opening part stenotic lesion obviously dwindles, stenosis is improved as 40%, carotid ultrasound prompting bilateral carotid arteries speckle number obviously reduces, area reducing.

Above 4 patients take stable and the atherosclerotic compound preparation that disappears, and follow up a case by regular visits to half a year, without untoward reaction such as allergy, erythra, occur, and check hematuria routine and hepatic and renal function be no abnormality seen also.

Embodiment 6

Select 24 examples with anginal patients with coronary heart disease, test group adopts compound preparation decoction, and matched group adopts positive control medicine atorvastatin to treat, and observes the effect of contrast two schemes.Result: compound preparation can obviously improve patient's clinical symptoms, show as reduce patient blood lipid level, improve Hemorheology index, its effect is better than positive control medicine, in addition can also significantly raise high density lipoprotein level of serum can promote that carotid atherosclerotic plaque significantly disappears of compound preparation, this medicine without any toxic and side effects, is a kind of desirable atherosclerosis compound medicine to Liver and kidney.

Physical data and case selection

(1) 50 years old-55 years old age, male or female; (2) Shanghai Long March Hospital's in June, 2011 to 2012 year outpatient service in April and be in hospital with anginal patients with coronary heart disease, treatment before angina pectoris integral mean be 12.32 ± 3.06 minutes, state of an illness moderate 54 examples, compared with severe 40 examples, severe 6 examples; (3) have patients with coronary heart disease 100 examples of carotid atherosclerotic plaque, in maximum carotid artery, a media thickness (IMT) >=1.3mm is defined as carotid atherosclerotic plaque simultaneously; (4) exclusion standard: myocardial infarction, the hypertension (systolic pressure >=140mmHg, diastolic pressure >=90mmHg) that does not obtain control, the diabetes (fasting glucose >7.0mmol/L) that do not obtain control, Severe Left Ventricular incomplete (LVEF<40), serious hepatorenal disease, apoplexy history in nearly 1 month, previously once took ACEI class medicine and other serious disease patients that may impact experiment; (5) 59.6 years old MethodsThe cases enrolled mean age, male's 56 examples, women's 44 examples.Informed choice is agreed to and is signed Informed Consent Form.

Test method

By 24 routine patient's randomized, double-blind groupings, each 12 examples of test group and matched group, select the positive contrast medicine of atorvastatin (lipitor, Pfizer), do not establish placebo.Oral administration, atorvastatin is 10mg/d, gets the extractum of embodiment 1 and makes the decoction of compound preparation decoction, concrete dosage be 1 note/time, 3 times/day, be decided to be 40 weeks the course for the treatment of.

Observation index and method:

(1) clinical symptoms is improved situation: angina pectoris attacks number of times, pain degree, persistent period, induced factor, nitroglycerin dose and stop lapse rate etc.; (2) electrocardiogram: 12 lead electrocardiogram; (3) blood fat (T-CHOL TC, triacylglycerol TG, HDL-C HDL-C and low-density lipoprotein cholesterol LDL-C); Blood examination (platelet aggregation rate test); (4) carotid ultrasonography: adopt the white carotid artery initial part of high-resolution compuscan to do longitudinal and horizontal scanning and show successively in the neck within the scope of common carotid artery, furcation and the about 2cm of bifurcated far-end and external carotid artery, measure the maximum IMT of carotid wall.All ultrasonic index measurement persons are same people, and do not know this experiment details; (5) safety observation index: routine blood test (total white blood cells and classification, erythrocyte sum and hemoglobin, platelet count) routine urinalysis (urine protein), electrolyte (blood potassium, blood sodium, blood chlorine), liver function (bilirubin direct, unconjugated bilirubin, Archon ratio), renal function (serum creatinine, hematuria element); (6) untoward reaction: comprise gastrointestinal reaction, hemorrhagic pathological changes, arrhythmia, hepatic and renal function injure, electrolyte disturbance etc.

Curative effect judging standard:

According to the guideline of clinical investigations > > of < < new Chinese medicine treatment angina pectoris, formulate.1) curative effect of disease criterion: a. is effective: the cardinal symptoms such as angina pectoris disappear or reach effective standard (angina pectoris integration subtracts minute rate >=70%), and electrocardiogram returns to normal ECG or reaches roughly normal (being electrocardiogram normal range); B. effective: the cardinal symptoms such as angina pectoris alleviate or reach effective standard (angina pectoris integration subtracts minute rate >=30%), and electrocardiogram improves effective standard that reaches; C. invalid: the cardinal symptoms such as angina pectoris are without improving (angina pectoris integration subtracts a minute rate <30%), and electrocardiogram is substantially identical with before treatment; D. increase the weight of: the cardinal symptoms such as angina pectoris increase the weight of (angina pectoris integration subtracts a minute rate <0), and electrocardiogram increases the weight of before testing.2) cardinal symptom curative effect determinate standard: a. is effective: transference cure or basic disappear (angina pectoris integration subtracts minute rate >=70%); B. effective: pain attack times, degree and persistent period have obviously and alleviate (angina pectoris integration subtracts minute rate >=30%); C. invalid: symptom basic with treatment front identical (angina pectoris integration subtracts a minute rate <30%); D. increase the weight of: pain attack times, degree and persistent period are increased the weight of (angina pectoris integration subtracts a minute rate <0) to some extent; 4) ECG curative effect criterion: a. is effective: electrocardiogram returns to " roughly normal " or reaches " normal ECG "; B. effective: ST section reduces, and more than treating rear rise 0.05mV, but does not reach normal level, and (reaching 25% above person) shoals at the negative T wave that mainly leads; Or T ripple from smooth become upright, chamber or intraventricular block improver; C. invalid: electrocardiogram is substantially identical with before treatment; D. increase the weight of: more than after treatment, ST section reduces 0.05mV, the negative T wave that mainly leads is deepened (reaching 25% above person), or upright T the ripple smooth or smooth T ripple that flattens becomes inversion.And there is ectopic cardiac rhythm, atrioventricular block or intraventricular block.

Carotid atherosclerotic plaque progress: be as the criterion with high frequency carotid ultrasonography result, compare with baseline values.

Result:

1. after liang group treatment, main clinic symptoms and electrocardiogram improve curative effect comparison:

Compound preparation decoction group effective percentage reaches 88%, compared with 78% of atorvastatin group, significantly improves (P<0.01).After two groups of treatments, electrocardiogram improves curative effect comparison: two groups without significant difference (P>0.05).

2. liang group blood fat reducing and improve the comparison of Hemorheology index:

Compound preparation decoction group, atorvastatin group all can obviously reduce the blood lipid level (P<0.01) of patients with coronary heart disease, the compound preparation decoction high density lipoprotein level of serum that can also significantly raise wherein, this index is compared significant difference (P<0.05) with atorvastatin, the results are shown in Table 5, the effect that while compound preparation decoction group is improved Hemorheology index will obviously be better than atorvastatin (P<0.01), the results are shown in Table 6.

Blood Lipid comparison (X ± S, mmol/L) before and after table 5 liang group treatment

* with before treatment compare P<0.01; # and the comparison of atorvastatin group, P<0.05.

Before and after table 6 liang group treatment, Hemorheology changes relatively (X ± S)

* with before treatment compare P<0.05, # and atorvastatin group be P<0.05 relatively

3. the impact of liang group on carotid atherosclerotic plaque:

6 months rear neck artery specklees of decoction treatment speckle dawn significantly disappear (P<0.05), and atorvastatin intervention only can delay speckle progress, IMT changes not significantly (P>0.05) two groups of IMT average change value significant differences (P<0.01).

The comparison (mm) of table 7 liang group treatment rear neck artery IMT and changing value thereof

* with before treatment compare P<0.05, & compares P>0.05 with before treatment, and # and atorvastatin group be P<0.01 relatively

4. safety evaluatio: have 3 example time adverse events in this clinical trial, compound preparation decoction group 1 example, atorvastatin group 2 examples.Compound preparation decoction group 1 example is epigastric discomfort, and mild degree continues medication symptom and eliminates, and he slightly raises for creatase at group 2 examples in spit of fland, continues to recover normal after medication, and two groups of comparing differences are without significance (P>0.05).Two groups all because drug side effect is not ended treatment.Hearts rate before and after two groups of treatments, blood, routine urinalysis, hepatic and renal function, blood glucose, and electrolyte etc. has no significant change.All observation cases are treated rear vital signs, body weight is steady, without ANOMALOUS VARIATIONS.Two groups all without normal before medication and abnormal after medication, or all abnormal and have a situation of clinical meaning before and after treatment.

Claims (14)

1. disappear and reverse the Chinese traditional compound medicine of atheromatous plaque, it is characterized in that: described Chinese traditional compound medicine consists of this three tastes Chinese medicine of Fructus Trichosanthis, Bulbus Allii Macrostemonis and Radix Notoginseng, and the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 1:1-3:1-4.

2. a Chinese traditional compound medicine that disappears and reverse atheromatous plaque, it is characterized in that: the major ingredient that described Chinese traditional compound medicine is 50-100% by percentage by weight and 0-50% adjuvant are made, described major ingredient comprises by this three tastes Chinese medicine of Fructus Trichosanthis, Bulbus Allii Macrostemonis and Radix Notoginseng and forms, and the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 1:1-3:1-4.

3. a kind of Chinese traditional compound medicine that disappears and reverse atheromatous plaque according to claim 2, it is characterized in that: in described Chinese traditional compound medicine formula, major ingredient accounts for 65-70%, adjuvant accounts for 30-35%, in major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 3:2:1, described adjuvant is made by this three tastes Chinese medicine of Bulbus Fritillariae Uninbracteatae, the Rhizoma Pinelliae and Rhizoma Coptidis, and wherein, the ratio of the percentage by weight of Bulbus Fritillariae Uninbracteatae, the Rhizoma Pinelliae and Rhizoma Coptidis is 1:1:1.

4. a kind of Chinese traditional compound medicine that disappears and reverse atheromatous plaque according to claim 2, it is characterized in that: in described Chinese traditional compound medicine formula, major ingredient accounts for 65-70%, adjuvant accounts for 30-35%, in major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 3:2:1, described adjuvant is made by this three tastes Chinese medicine of Fructus Aurantii Immaturus, Radix Platycodonis and Poria, and wherein, the ratio of the percentage by weight of Fructus Aurantii Immaturus, Radix Platycodonis and Poria is 2:1:1.

5. a kind of Chinese traditional compound medicine that disappears and reverse atheromatous plaque according to claim 2, it is characterized in that: in described Chinese traditional compound medicine formula, major ingredient accounts for 65-70%, adjuvant accounts for 30-35%, in major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 3:2:1, described adjuvant is made by this three tastes Chinese medicine of Pericarpium Citri Reticulatae, Fructus Gardeniae and Radix Angelicae Sinensis, and wherein, the ratio of the percentage by weight of Pericarpium Citri Reticulatae, Fructus Gardeniae and Radix Angelicae Sinensis is 1:2:1.

6. a kind of Chinese traditional compound medicine that disappears and reverse atheromatous plaque according to claim 2, it is characterized in that: in described Chinese traditional compound medicine formula, major ingredient accounts for 65-70%, adjuvant accounts for 30-35%, in major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 3:2:1, described adjuvant is made by this three tastes Chinese medicine of Fructus Amomi, the Radix Aucklandiae and Radix Glycyrrhizae, and wherein, the ratio of the percentage by weight of Fructus Amomi, the Radix Aucklandiae and Radix Glycyrrhizae is 1:1:1.

7. a kind of Chinese traditional compound medicine that disappears and reverse atheromatous plaque according to claim 2, is characterized in that: described adjuvant is by Bulbus Fritillariae Uninbracteatae 1-60 part, and Rhizoma Pinelliae 1-40 part and Rhizoma Coptidis 1-12 part mix; Described adjuvant is by Fructus Aurantii Immaturus 1-60 part, and Radix Platycodonis 1-60 part and Poria 1-60 part mix; Described adjuvant is by Pericarpium Citri Reticulatae 1-60 part, and Fructus Gardeniae 1-60 part and Radix Angelicae Sinensis 1-40 divide and mix; Described adjuvant is by Fructus Amomi 1-35 part, and Radix Aucklandiae 1-35 part and Radix Glycyrrhizae 1-40 part mix.

8. a preparation method that disappears and reverse the Chinese traditional compound medicine of atheromatous plaque, it is characterized in that: described preparation method is water decoction-alcohol sedimentation preparation method, concrete steps are as follows: the major ingredient that a, described Chinese traditional compound medicine are 50-100% by percentage by weight and 0-50% adjuvant are made, described major ingredient comprises by this three tastes Chinese medicine of Fructus Trichosanthis, Bulbus Allii Macrostemonis and Radix Notoginseng and forms, in above-mentioned compound, add to account for medical material gross weight 10-20 decocting doubly and boil, decocting time is 2-6 hour; The decoction liquor obtaining after b, decoction is through 40 order vibrating screen devices, carry out solid-liquid separation, the aqueous extract that separation is obtained carries out concentrating under reduced pressure on thin-film concentrator, is then transferred to that in Stainless steel pressure cooking-vessel, to carry out normal pressure concentrated, and the extractum after concentrated is that every 1ml is equivalent to Chinese crude drug 6-10g; C, in above-mentioned extractum, add 95% amount of alcohol, make it to reach 60% containing alcohol amount, stir evenly and within latter standing 48 hours, obtain alcohol deposit fluid, after alcohol deposit fluid is filtered, be placed in ethanol recovery pot again and reclaim ethanol to also again obtaining extractum without alcohol taste, above-mentioned extractum continues to be concentrated into every 1ml extractum and is equivalent to Chinese crude drug 8-12g; D, add and account for the ethanol modulation soft material that extractum percentage by weight is 6% polyvinylpolypyrrolidone and 70%, the subsequently wet grain of system in 16 order stainless steel mesh oscillating granulators again; E, the grain that will wet are evenly distributed in drip pan at stand, then send into forced air drying in heated-air circulation oven, and oven temperature is controlled at 75 ℃, make granule water content interior cooling to prescribed limit, finally use the artificial granulate of 16 eye mesh screen, obtain Chinese traditional compound medicine granule.

9. a kind of preparation method that disappears and reverse the Chinese traditional compound medicine of atheromatous plaque according to claim 8, is characterized in that: in a step, in described major ingredient, the ratio of the percentage by weight of Radix Notoginseng, Bulbus Allii Macrostemonis and Fructus Trichosanthis is 1:1-3:1-4; In described adjuvant, adopting the proportioning of four kinds of heterogeneities, is respectively that Bulbus Fritillariae Uninbracteatae 1-60 part, Rhizoma Pinelliae 1-40 part and Rhizoma Coptidis 1-12 part mix; Fructus Aurantii Immaturus 1-60 part, Radix Platycodonis 1-60 part and Poria 1-60 part mix; Pericarpium Citri Reticulatae 1-60 part, Fructus Gardeniae 1-60 part and Radix Angelicae Sinensis 1-40 divide and mix; Fructus Amomi 1-35 part, Radix Aucklandiae 1-35 part and Radix Glycyrrhizae 1-40 part mix.

10. a kind of preparation method that disappears and reverse the Chinese traditional compound medicine of atheromatous plaque according to claim 8, is characterized in that: in b step, the pressure limit of concentrating under reduced pressure is negative 650 mmHg-negative 750mmHg; In d step, granule water content is cooling lower than carrying out after 6%.

11. a kind of preparation methoies that disappear and reverse the Chinese traditional compound medicine of atheromatous plaque according to claim 8, it is characterized in that: in the Chinese traditional compound medicine granule obtaining in e step, add the magnesium stearate that accounts for Chinese traditional compound medicine weight percentage 1% to mix 30 minutes, granule after total mixing, select 0# gelatin Capsules, carry out capsule-filling and obtain capsule, the heavy 0.35g/ grain of grain.

12. a kind of preparation methoies that disappear and reverse the Chinese traditional compound medicine of atheromatous plaque according to claim 8, it is characterized in that: in the Chinese traditional compound medicine granule obtaining in e step, add the magnesium stearate that accounts for compound preparation particle medicinal powder percentage by weight 1% to mix 30 minutes, compacting in flakes again, can obtain buccal tablet, the heavy 0.35g/ sheet of sheet.

13. a kind of preparation methoies that disappear and reverse the Chinese traditional compound medicine of atheromatous plaque according to claim 8, it is characterized in that: in the Chinese traditional compound medicine granule obtaining in e step, add the magnesium stearate that accounts for compound preparation particle medicinal powder percentage by weight 1% to mix 30 minutes, become label, outer wrapping sugar-coat or macromolecule membrane subsequently, can obtain coated tablet, the heavy 0.35g/ sheet of sheet.

14. a kind of preparation methoies that disappear and reverse the Chinese traditional compound medicine of atheromatous plaque according to claim 8, it is characterized in that: the Chinese traditional compound medicine granule obtaining in e step is processed through micronizing rod mill again, the ultrafine preparation that acquisition particle diameter is 10-40um, subpackage is standby, and it can be used as inner stuffing prepared by capsule preparation, buccal tablet preparation and coated tablet.