CN103919854A - Application of butterflybush flower and extract thereof to preparation of medicament - Google Patents

Application of butterflybush flower and extract thereof to preparation of medicament Download PDF

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Publication number
CN103919854A
CN103919854A CN201410157986.3A CN201410157986A CN103919854A CN 103919854 A CN103919854 A CN 103919854A CN 201410157986 A CN201410157986 A CN 201410157986A CN 103919854 A CN103919854 A CN 103919854A
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extract
flos buddlejae
medicine
heart disease
flos
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CN103919854B (en
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温先敏
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Yunnan Sunsail Pharmaceutical Co.,Ltd.
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温先敏
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Priority to CN201610650497.0A priority Critical patent/CN106038701A/en
Priority to CN201610649456.XA priority patent/CN106063815A/en
Priority to CN201610649559.6A priority patent/CN106109580A/en
Priority to CN201610648733.5A priority patent/CN106038700A/en
Priority to CN201610648732.0A priority patent/CN106138210A/en
Priority to CN201410157986.3A priority patent/CN103919854B/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/56Loganiaceae (Logania family), e.g. trumpetflower or pinkroot
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/35Extraction with lipophilic solvents, e.g. Hexane or petrol ether
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/37Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/53Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to new application of a natural plant medicinal herb and/or an extract thereof to preparation of a medicament for treating heart disease. The invention relates to application of butterflybush flower and/ or an extract thereof to preparation of the medicament for treating heart disease. The butterflybush flower is buds, inflorescence or complete plant of loganiaceae plant butterflybush flower; the extract is obtained by the steps of crushing butterflybush flower and carrying out leaching or heating reflux or supercritical extraction at room temperature; the used solvent in extraction is a miscible liquid mixture of water and ethanol in a random ratio or a miscible liquid mixture of ethyl ether, petroleum ether, chloroform, ethyl acetate and other organic solvents in a random ratio or liquid state CO2. The butterflybush flower and/or extract thereof can separately serve as a main active ingredient to be prepared into a pharmaceutical preparation, and can also serve as the main active ingredient together with other components to be prepared into the pharmaceutical preparation.

Description

Flos Buddlejae and extract thereof are in the application of preparing in medicine
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to the new application in the cardiopathic medicine of preparation treatment of a kind of natural plant crude drugs and/or its extract.
Technical background
Since eighties of last century nineties, heart disease is wide with morbidity scope, frequency of disease development is high and hazardness becomes greatly the underlying cause of death of urban and rural residents of China gradually, has at present accounted for 35% of total death toll, is the first killer who endangers China's national health.Heart disease is treated mainly with operation and Western medicine at present, but because the side effect of western medicine heart disease is large, often cause many untoward reaction, cause the organ injuries such as liver to patient, kidney, intestinal, stomach very large, in the case, people attempt to find a more suitable method, and the Chinese medicine advantage of oneself just in this respect, Chinese medicine heart disease not only has one's own knack to patient's heart, and other internal organs are also had to conditioning, health-care effect.
Flos Buddlejae BuddlejaofficinalisMaxim. is loganiaceae plant, " Chinese Pharmacopoeia " 2010 editions contained functions with cure mainly as " heat clearing away nourishing the liver, improving acuity of vision and removing nebula.For conjunctival congestion and swelling pain, many tear photophobia, the nebula of looking unfamiliar film, hepatasthenia dim eyesight, blurring of vision.”
Successive dynasties book on Chinese herbal medicine and the medicinal ancient books and records of each ethnic groups all use Flos Buddlejae as " nourishing the liver to improve visual acuity " medicine, particularly use as " ophthalmology panacea ".Before this, have many patent applications of applying in the medicine aspect preparing ophthalmology and liver about Flos Buddlejae and bibliographical information, but Flos Buddlejae there is no bibliographical information at treatment cardiac disease.
Summary of the invention
The object of the present invention is to provide the new application in pharmaceutical field of a kind of Flos Buddlejae and/or its extract.
The present invention relates to the application in the cardiopathic medicine of preparation treatment of Flos Buddlejae and/or its extract.
The present invention relates to the application in the medicine of preparation treatment coronary heart disease of Flos Buddlejae and/or its extract.
The present invention relates to the application in the medicine of preparation treatment rheumatic heart disease of Flos Buddlejae and/or its extract.
The present invention relates to the application in the medicine of preparation treatment hypertensive heart disease of Flos Buddlejae and/or its extract.
The present invention relates to the application in the medicine of preparation treatment pulmonary heart disease of Flos Buddlejae and/or its extract.
The present invention relates to the application in the myocardiac medicine of preparation treatment of Flos Buddlejae and/or its extract.
The present invention relates to the application in the medicine of preparation treatment cardiac tumor of Flos Buddlejae and/or its extract.
The present invention relates to the application in the medicine of preparation treatment vascular lesion of Flos Buddlejae and/or its extract.
Flos Buddlejae of the present invention is loganiaceae plant Flos Buddlejae alabastrum, inflorescence or its Herb, described extract for Flos Buddlejae pulverize after the extract that obtains in room temperature lixiviate or reflux or supercritical extraction, extract the solvent that uses for water and ethanol are with the miscible liquid of any ratio; Or the organic solvent such as ether, petroleum ether, chloroform, ethyl acetate is with the miscible liquid of any ratio; Or liquid CO 2.
Flos Buddlejae of the present invention and/or its extract can be made pharmaceutical preparation as main active separately, also can jointly make pharmaceutical preparation as main active with other composition.
Pharmaceutical dosage form of the present invention comprises the medicinal thing preparation of the different way of administration such as various oral, injections, tract, percutaneous.The compound preparation that capsule that can be raw material of the present invention make through common process with corresponding pharmaceutic adjuvant, tablet, granule, pill, externally-applied liniment, spray, injection etc. can be also raw materials of the present invention to be formed with other Chinese crude drug.
The invention provides the new application of Flos Buddlejae and/or its extract, for disease treatment provides new natural drug plant.The present invention is mainly used in the Comprehensive Treatment to coronary heart disease, rheumatic heart disease, hypertensive cerebral heart, pulmonary heart, cardiomyopathy, cardiac tumor, vascular lesion.The made pharmaceutical preparation of the present invention shows without obvious adverse reaction and toxic and side effects through animal experiment and clinical trial, can provide safely, treat efficiently for patient cardiopathic natural drug new product.
Drug safety test of the present invention:
One, acute toxicity test
1 materials and methods
1.1.1 animal: 40 of healthy qualified clean level Kunming mouses, body weight 18~22g, male and female half and half, are provided by Kunming medical university experimental animal center.
1.1.2 tested medicine and preparation thereof: Flos Buddlejae capsule (method for making is shown in embodiment 2, lower same) is provided specification 0.5g/ grain by Yunnan Mingyang Pharmaceutical Co., Ltd..Get 40 Flos Buddlejae capsules and remove capsule shell, incline and medicated powder, in mortar, grind the sodium carboxymethyl cellulose that adds gradually 2% after 5min, join for pasty state suspension, thickness, end level is 40%, is the maximum concentration of Flos Buddlejae capsule.
1.2 test method
With reference to " study of tcm new drug guide " (pharmacy, pharmacology, toxicology), in the laboratory of 22 DEG C of room temperatures, prerun mouse gavaging capsule 40g/kg (capsule suspension Cmax and heap(ed) capacity) repeatedly, observe mouse toxicity reaction in a week and death condition, fail to measure capsule gavage LD50 value, therefore select mtd test.
Choose 20 qualified clean level Kunming mouses of health, male and female half and half, by gavage in capsule suspension 24h, administration capacity is 0.2ml/10g body weight, then freely drink water and look for food, observing one week, recording the situations such as mice appetite, body weight, position, breathing, righting reflex.
1.3 result of the test
1 week interior none example of mouse stomach capsule suspension is dead, and feed and drinking-water are without abnormal change, as shown in table 1.
Result after table 1 mouse gavaging Flos Buddlejae capsule
Observe in 7 days take medicine dead mouse and obviously abnormal phenomena generation.Put to death and dissect every animal and contrast with normal mouse through cervical vertebra dislocation, under bore hole, the heart, liver, spleen, lung, kidney, brain etc. are without anomaly.
This result of the test, mouse gavaging capsule Cmax and maximum volume, i.e. 40g/kg body weight, is 666 times of human body dose, has no toxicity and occurs.
Pharmacodynamics test of the present invention:
Two, mist Air Bladder pseudosciaenae seu Acipenser capsule anti-experimental character Atherosclerosis
1 materials and methods
1.1 reagent and medicine cholesterol, cholate are purchased from Tianjin Yong great chemical reagents corporation; Adeps Sus domestica self-control; Yolk powder and whole milk powder market are bought; Normal feedstuff is provided by Kunming medical university Experimental Animal Center.Malonaldehyde (MDA) and superoxide dismutase (SOD) detection kit: power biomedical engineering institute is gathered in Nanjing.The anti-Mus ICAM-1 of rabbit (ICAM-1) antibody, peroxidase (HRP) labelling goat anti-rabbit igg, instant SABC (peroxidase) SABC test kit and DAB nitrite ion (Wuhan Boster Biological Technology Co., Ltd.).Flos Buddlejae capsule is developed by Yunnan Mingyang Pharmaceutical Co., Ltd..
1.2 instrument 5804R low temperature supercentrifuges (German eppendorf company); UV-2401 spectrophotometer (Japanese Shimadzu); AMS-18A automatic clinical chemistry analyzer (Zhangjiakou Ao Pusen development in science and technology company limited); Olympus CH30 optical microscope.
1.3 groupings and 30 of the healthy SD rats of drawing materials, ♂, body weight (205 ± 20) g, purchased from Kunming medical university Experimental Animal Center.Rat is divided into 3 groups of groups at random: matched group, model group and Chinese drug-treated group, 10 every group.Matched group feeding is with standard feed, model group and mist flower Capsules group are fed with high lipid food (1% cholesterol, 0.1% cholate, 10% Adeps Sus domestica, 5% yolk powder, 5% whole milk powder, 78.9% normal feedstuff), and mist flower Capsules group is given Flos Buddlejae capsule in feeding with high lipid food.Each group is all freely drunk water, and feeds continuously acute execution after 8 weeks, and abdominal vein is got blood, and 20 DEG C of refrigerators of centrifuging and taking serum , – are placed, and rat opens rapidly breast and takes out aorta breast abdomen section blood vessel, removes 70 DEG C of refrigerators of surrounding tissue , – and keeps, for subsequent use.
1.4 Biochemical Indexes are measured serum cholesterol (TC), triacylglycerol (TG), low density lipoprotein, LDL (LDL-C), high density lipoprotein (HDL-C).The operation of test kit description is pressed in serum MDA level and SOD determination of activity.
1.5 light microscopic histology are drawn materials with thoracic aorta intersection at rat aorta bow, and 10% neutral formalin is fixed, paraffin embedding, preparation cross section paraffin section, approximately 4 microns of thickness, HE dyeing, om observation.
1.6 aorta tube wall ICMA-1 detect ventral aorta and shear the one section of blood vessel in 0.6cm left and right, and 10% neutral formalin is fixed, and remaining blood vessel is used for extracting albumen, 75% ethanol dehydration, the section of paraffin embedding cross section, thick 4 microns, get 1,5 slice, thin pieces of every part of vascular specimen every 4.SABC immunohistochemical method detects ICMA-1:3%H2O2 room temperature sealing min, with fire extinguishing endogenous enzyme, after boiling water bath is repaired, normal three sheep blood serum room temperature sealing blocking-up non-specific binding, 37 DEG C of 1h of the Mus ICMA-1 of rabbit Chinese People's Anti-Japanese Military and Political College antibody (1:100), 37 DEG C of biotinylation three goat anti-rabbit iggs are hatched 20min, and PBS washes rear dropping reagent SABC.DAB colour developing, haematoxylin is slightly redyed, and dehydration is transparent, mounting, microscopic examination, using the section of the Mus ICMA-1 of Bu Jia rabbit Chinese People's Anti-Japanese Military and Political College antibody as negative control, cell membrane and the Cytoplasm of positive cell are dyed yellowish-brown, and prompting has ICMA-1 to express.Choose the uniform high power field of cell distribution as observation area, positive cell number under mirror is compared with total cell number, obtain the expression rate of positive cell, every part of vascular specimen is got the meansigma methods of its 4 slice, thin pieces, draws ICMA-1 positive cell expression rate
1.7 aortic blood tube wall ICMA-1 expressing quantity Detection and Extraction albumen, protein extract is carried out to SDS-polyacrylamide gel electrophoresis, then transferring film, 5% 37 DEG C of defatted milk powder sealing 1h, TBS washes after film, first with 4 DEG C of reaction overnight of the Mus ICMA-1 of rabbit Chinese People's Anti-Japanese Military and Political College antibody (1:100), react 1h with 37 DEG C of peroxidase (HRP) labelling goat anti-rabbit iggs (1:200) again, T-TBS washes film, and DAB colour developing, analyzes.
The all experimental datas of 1.8 statistical procedures adopt SPSS11.5 software kit statistical analysis.
2 results
Comparison model group Serum TC, TG and the LDL-C level of 2.1 blood fat are apparently higher than matched group, and mist Air Bladder pseudosciaenae seu Acipenser capsule can significantly reduce atherosclerosis (AS) rat TC and LDL-C level, and on TG and HDL-C impact not obvious (in table 2).
Table 2 serum TC, TG, LDL-C and HDL-C level
With matched group comparison, cP < 0.05, bP < 0.01; With relatively cfP < 0.01 of model group.
The comparison model group rat blood serum MDA level of 2.2 oxygen-derived free radicals indexs of correlation is apparently higher than matched group,, SOD activity obviously reduces, and mist Air Bladder pseudosciaenae seu Acipenser capsule can reduce MDA level, improves SOD activity (in table 3).
Table 3 serum MDA level and SOD activity
With matched group comparison, cp < 0.05, bp < 0.01; With model group comparison cfp < 0.01.
The change naked-eye observation 3 treated animal aortic tunica intima no significant differences of 2.3 aorta wall tectologies, optical microphotograph Microscopic observation, the complete smooth not damaged of control rats arterial wall endothelium, smooth muscle marshalling; The endotheliocytic swelling of model group rat artery wall, part endothelial denudation, smooth muscle arrangement disorder, form is various, and part smooth muscle has propagation, and moves to internal layer, endothelial cell adhesion has mononuclear cell, and inner membrance has monocyte infiltration, and can be observed macrophage; Mist flower Capsules group endothelium is more complete, has no endothelial denudation, and smooth muscle is arranged also neat compared with model group, the rare monocyte infiltration of endothelium.
2.4 impacts of mist Air Bladder pseudosciaenae seu Acipenser capsule on rat aorta ICMA-1 expression
2.4.1 SABC is by SABC sections observation, and positive cell cell membrane and Cytoplasm are dyed yellowish-brown, has ICMA-1 to express.Control rats aortic endothelial cell core smooth muscle cell has micro-ICMA-1, and model group rat aortic endothelial cells core smooth muscle cell ICMA-1 is strong positive to express, and mist flower Capsules group can significantly reduce its expression.
2.4.2Western blot result control rats aorta does not detect obvious ICMA-1 albumen, and model group rat aorta ICMA-1 expressing quantity obviously increases, the expression that mist flower Capsules group can significantly be lowered aorta ICMA-1.
3 conclusions
Mist Air Bladder pseudosciaenae seu Acipenser capsule can significantly reduce AS rat TC, LDL-C and MDA level, significantly improves SOD activity, obviously lowers aorta ICMA-1 protein expression; Pathological examination also shows that mist Air Bladder pseudosciaenae seu Acipenser capsule has protective effect to aortic tunica intima, shows that mist Air Bladder pseudosciaenae seu Acipenser capsule has the atherosclerosis of alleviating, and prevents and treats the effect of coronary heart disease.
Three, the research of mist Air Bladder pseudosciaenae seu Acipenser capsule on SHR rat blood pressure and left ventricular hypertrophy impact
1 materials and methods
1.1 50 of laboratory animal spontaneous hypertensive rats (SHR), purchased from Chinese Academy of Sciences's Shanghai Experimental Animal Center, male, 11 week age, body weight (260 ± 18) g, sub-cage rearing, 2, every cage, room temperature (23 ± 2) DEG C, relative humidity (60 ± 5) %, ad lib drinking-water.
1.2 instruments and reagent RBP-1B type Hypertensive Rats measuring cell, Beijing China-Japan Friendship Hospital produces; UV-2401 spectrophotometer (Japanese Shimadzu); 5804R low temperature supercentrifuge (German eppendorf company).Mist Air Bladder pseudosciaenae seu Acipenser capsule is made by oneself by Yunnan Mingyang Pharmaceutical Co., Ltd.; Enalapril is commercially available.All the other reagent are commercially available analytical pure.
1.3 method
1.3.1 animal grouping and administration are divided into 5 groups at random by whole rats, 10 every group.Blank group gavages drinking water every day; The high, medium and low dosage group of mist Air Bladder pseudosciaenae seu Acipenser capsule gavages mist Air Bladder pseudosciaenae seu Acipenser capsule by 400mg/kg, 800mg/kg, 1200mg/kg respectively every day; Enalapril group gavages enalapril by 20mg/kg every day.Every rat is pressed 10ml/kg administration or feedwater, measures weekly body weight one time, and adjusts dosage, administration time 8 weeks according to body weight.
1.3.2 observation index and assay method blood pressure determination: experiment is front and test the pressure value of measuring rat for latter the 4th, 8 weeks, and each continuous measurement 3 times, averages.After last administration, weigh rat body weight (BW), Measure blood pressure, sacrificed by decapitation animal, takes out rapidly heart, remove trunk residue and connective tissue, cut off atrium along sexual life ring, cut off right ventricle along interventricular septum, retain interventricular septum, left compartment muscle, with normal saline flushing blood stains, after blotting with filter paper, weigh, record left ventricular mass (LVW), calculate the ratio (LVMI) of left ventricular mass and body weight.
The all experimental datas of 1.4 statistical procedures adopt SPSS11.5 software kit statistical analysis.
2 results
2.1 affect administration after 4 weeks, 8 weeks to rat blood pressure, before enalapril group and height, middle dosage group blood pressure and experiment, significantly decline (P < 0.05), and relatively there is significant difference (P < 0.05) with blank group, low dose group, enalapril group and high, middle dosage group comparing difference not statistically significant (P > 0.05); Comparing difference not statistically significant (P > 0.05) between blank group, low dose group.The results are shown in Table 4.
The variation of systolic pressure before and after the treatment of the each group of table 4 rat
Relatively front with experiment, * P<0.05; With blank, low dose group comparison, ★ P<0.05.
2.2 affect enalapril group and high, middle dosage group and the comparison of blank group to Cardiac Function in Rat, LVMI index decreased is (P < 0.05) significantly, low dose group LVMI and blank group comparing difference not statistically significant (P > 0.05); High dose group and enalapril group LVMI index comparing difference have statistical significance (P < 0.05), the results are shown in Table 5.
The variation of cardiac function after the treatment of the each group of table 5 rat
With relatively * P<0.05 of blank group; With relatively ★ P<0.05 of enalapril group.
3 conclusions
Mist Air Bladder pseudosciaenae seu Acipenser capsule can effectively reduce and control SHR rat blood pressure, alleviates and reverses SHR Left Ventricular Hypertrophy in Rats, and prompting mist Air Bladder pseudosciaenae seu Acipenser capsule has good therapeutic effect to hypertensive heart disease.
Four, the pharmacological action of mist Air Bladder pseudosciaenae seu Acipenser capsule to Rabbit Lung cardiopathia due to ferric chloride
1 materials and methods
1.1 30 of experimental animal Japan large ear rabbits, male and female half and half, body weight 2.2~3.5kg, purchased from Kunming medical university Experimental Animal Center.
1.2 instruments and reagent acetylspiramycin are produced by Baiyunshan Pharmaceutics Stock-sharing Co., Ltd., Guangzhou City; Aminophylline is produced by Shandong XinHua Pharmacy stock Co., Ltd; Mist Air Bladder pseudosciaenae seu Acipenser capsule is made by oneself by Yunnan Mingyang Pharmaceutical Co., Ltd.; Olympus CH30 optical microscope.
1.3 methods are got 30 of rabbit, divide 5 groups, blank group, model group, positive controls acetylspiramycin (0.15g/kg, oral)+aminophylline (0.02g/kg, oral), high, the middle dosage group of mist Air Bladder pseudosciaenae seu Acipenser capsule (1.2g/kg, 0.8g/kg).Except blank group, the liquor ferri trichloridi of all the other various all auricular vein injections simultaneously 1% 45 days.Front 4 week 2 times/week, 0.5ml/ time; The injection next day of later, 1ml/ time, totally four times; Then 1.5ml/ only, injects 2 times; 2.0ml/ only, injects 1 time; Finally only injection 4 days (45 days, amount to 25ml 19 times) continuously of a 2.5ml, 2.5ml, 3.0ml, 4.0ml/ respectively.On the same day of injection liquor ferri trichloridi, blank group, model group are with distilled water gavage 50ml/ only; Positive controls is with acetylspiramycin (0.15g/kg, oral)+aminophylline (0.02g/kg, oral) gavage; Mist Air Bladder pseudosciaenae seu Acipenser capsule senior middle school dosage group is respectively with 1.2g/kg, 0.8g/kg gavage.After the 45th day gastric infusion 4h, put to death animal, win thyroid, spleen, the heart, lung, adrenal gland and do pathologic finding under light microscopic, and satisfactory, lung weight, heart path length in length and breadth measured, and pulmonic ring is long.
2 results
After 2.1 sign rabbit injection liquor ferri trichloridis, fur is all not as good as blank group rabbit gloss, and mobility declines, and rapid breathing appears in most rabbit, after particularly dosage strengthens, animal breath frequency is accelerated, and kicks, drowsiness, can recover normal after about 1h, body weight gain is slow compared with blank group.
After 2.2 survival condition to experiment finishes, administration group is high compared with model group animal dis motility rate, in table 6.
The impact of table 6 mist Air Bladder pseudosciaenae seu Acipenser capsule on pulmonary heart disease Rabbits Models survival condition
With relatively * P<0.05 of model group, * * PP<0.01.
After 2.3 internal organs gross examination of skeletal muscle sacrifice of animal, dissect, naked eyes are as seen except blank group, and all animals are the visible heart, lung and thoracic cavity adhesion all, and there is edema due to disorder of QI at lungs edge, and lung surface has hemorrhage; Cardiac contour expands, full, sub-circular, and longitudinal and transverse demeter is poor to be dwindled, and heart size increases; Pulmonic ring expands.High, the middle dosage group of above-mentioned performance positive control and mist Air Bladder pseudosciaenae seu Acipenser capsule is compared with model group mild symptoms, table 7 between the heart, lung index of correlation.
The impact of table 7 mist Air Bladder pseudosciaenae seu Acipenser capsule on pulmonary heart disease Rabbits Models organ index
With relatively * P<0.05 of model group.
2.4 light microscopic pathological examination results display model groups have 4 rabbit myocytes to occur granular degeneration, interstitial congestion; There is filling the air interstitial inflammation in lungs, accidental small artery endotheliocytic swelling, and intercellular is every broadening, and limit office alveolar wall thickens, and has cell infiltration congestion; In positive control and mist Air Bladder pseudosciaenae seu Acipenser capsule, dosage group respectively has 2 rabbit lungs to occur slight pathological change, and cardiac muscle is without obviously pathological change; Mist Air Bladder pseudosciaenae seu Acipenser capsule high dose group lungs and cardiac muscle are all without obviously pathological change.Model group and each administration group Thyroid Gland of Rabbits, adrenal gland, spleen are all without obviously pathology conversion.The pathological change that the each internal organs of mist flower Capsule on Rabbit are described has stronger protective effect.
3 conclusions
The Rabbit Lung cardiopathia that mist Air Bladder pseudosciaenae seu Acipenser capsule brings out ferric chloride has the symptom of improvement, the positive role of mitigate the disease.
Clinical data:
Five, mist flower capsule for treating unstable angina pectoris observation of curative effect
Coronary heart disease unstable angina (UA) refers to one group of anginal syndrome of coming personally between stable angina pectoris and acute myocardial infarction (AMI).
1 data and method
The routine patient of 1.1 physical data 68 all meets International Society of Cardiology and WHO clinical name standardization associating specialist paper " name of ischemic heart desease and diagnostic criteria ", discharges acute myocardial infarction, serious hepatic and renal function injure.68 routine patients are divided into 2 groups at random, matched group 32 examples, wherein male's 19 examples, women's 13 examples, 40~72 years old age; Treatment group 36 examples, wherein male's 22 examples, women's 14 examples, 40~74 years old age.Two groups at the aspects such as sex, age, Clinical types, the course of disease, Electrocardiogram Feature, complication, difference not statistically significant.
The oral Tab. Isosorbidi Dinitratis of 1.2 Therapeutic Method matched group: the each 5-10mg of sublingual administration, every day 3 times; The oral mist Air Bladder pseudosciaenae seu Acipenser for the treatment of group capsule, each 3, every day 3 times, be 30 days two groups of courses for the treatment of.
1.3 observation index are observed two groups of patient treatments front and back angina pectoris attacks situations and electrocardiogram changes.
1.4 efficacy determinations are effective: angina pectoris transference cure or substantially disappear within a course for the treatment of, and electrocardiogram returns to normally or roughly normally meets taking the next item up or two as effective; Effective: angina pectoris attacks number of times, degree and persistent period obviously alleviate, reduce the above or negative T wave of ST section rise 0.05mV shoal reach more than 25% or T ripple from smooth become upright for effective; Invalid: symptom is without improvement, and basic identical before electrocardiogram and treatment is invalid.
2 results
The angina pectoris of 2.1 liang of groups, ECG curative effect are in table 8, table 9
The comparison of table 8 curative effect to treat angina pectoris
Two groups of obvious effective rates, total effective rate comparing differences have statistical significance (P<0.05).
The comparison of table 9 ECG curative effect
Two groups of obvious effective rates, total effective rate comparing differences have two groups of statistical significance (P<0.05) 2.2 untoward reaction in therapeutic process all without obvious adverse reaction.
Six, mist flower capsule for treating rheumatic heart disease observation of curative effect
Rheumatic heart disease is modal one in heart disease, is the chronic valvular heart disease that acute rheumatic valvulitis is left over, and we have obtained satisfied effect by mist flower capsule for treating rheumatic heart disease, now clinical data are summarized as follows.
1 data and method
The all patients of 1.1 physical data, after checking, are diagnosed as rheumatic heart according to the chronic rheumatic heart disease diagnostic criteria of Ministry of Public Health formulation in 1992.72 routine rheumatic heart diseases are divided into 2 groups, matched group 32 examples, wherein, and male's 14 examples, women's 18 examples, 34~61 years old age, mitral lesion person 18 examples, aortic valve disease person 16 examples, having 2 examples is two equal pathological changes of valve; Treatment group 40 examples, wherein male's 17 examples, women's 23 examples, 35~61 years old age, mitral lesion person 22 examples, aortic valve disease person 20 examples, having 2 examples is two equal pathological changes of valve.All patients are without serious liver, renal failure and other diseases, and patient has comparability in sex, age, the course of disease, P > 0.05.
1.2 Therapeutic Method matched group oral hydrochloride amiodarone sheets, loading: common one day 600mg(3 sheet), maintenance dose: can give 100~400mg on the one according to individual reaction.The oral mist Air Bladder pseudosciaenae seu Acipenser for the treatment of group capsule, each 3, every day 3 times, be 4 months two groups of courses for the treatment of.
1.3 observation index check Cardiac Function of Patients
1.4 efficacy determinations are effective: activity is not limited, and general activity is without any discomfort; Effective: physical exertion is slightly restricted, when general physical exertion, occur uncomfortable; Minor effect: physical exertion is obviously restricted, slight physical exertion has a strong impact on life; Invalid: can not orthobiosis, symptom is without any improvement.Total effective rate=(total case-Ineffective Cases)/total case × 100%.Before all patient treatments, all there are one or more in the complication such as heart failure, arrhythmia, respiratory tract infection, thromboembolism, acataposis, formulate the standard of curative effect evaluation for treatment infectious-related complication: 0~1 complication for treatment effective; Occur that 2~3 complication are for treating effectively; Occur that more than 3 complication is for failing to respond to any medical treatment.Total coincidence=(total case-effective case)/total case × 100%.
2 results
Two groups of patients of 2.1 liang of group Cardiac Function of Patients recovery situations, through treatment, follow up a case by regular visits to check cardiac function after 4 months, the results are shown in Table 10.
Table 10 heart function recovery situation
Two groups of total effective rate comparing differences have statistical significance (P<0.05).
After 2.2 complication results treatments 4 months, for the follow-up observation of rheumatic heart disease complication and add up, the results are shown in Table 11.
Table 11 complication result
Two groups of total coincidence comparing differences have statistical significance (P<0.05).
Detailed description of the invention
The present invention is carried out detailed explanation and is described the present invention by following medicine Preparation Example, but, the invention is not restricted to these embodiment.
Embodiment 1: Flos Buddlejae tablet
Formula: 1000 parts of Flos Buddlejaes, 3 parts of starch, 20 parts of lactose, 15 parts of carboxymethyl starch sodium, 4 parts of Pulvis Talci.
Method for making: get 800 parts of Flos Buddlejaes, press decocting method with drinking water and extract secondary, each 1 hour, collecting decoction (or was got Flos Buddlejae, be ground into coarse powder, in 40 DEG C of immersion secondaries, each 6~8 hours, merge immersion with the aquiferous ethanol of variable concentrations, reclaim ethanol), concentrated decocting liquid becomes thick paste, dry, pulverize into fine powder for subsequent use in 55 DEG C~65 DEG C.Separately get 200 parts of Flos Buddlejaes, be directly ground into fine powder, mix with aforementioned Flos Buddlejae extract fine powder, lactose, carboxymethyl starch sodium, make adhesive with starch slurry, granulation, dry, add Pulvis Talci and mix, tabletting and get final product.
Embodiment 2: Flos Buddlejae capsule
Formula: 1000 parts of Flos Buddlejaes, 100 parts of starch.
Method for making: get 800 parts of Flos Buddlejaes, press decocting method with drinking water or (aquiferous ethanol) and extract secondary, each 1 hour, collecting decoction (or was got Flos Buddlejae, be ground into coarse powder, with the aquiferous ethanol immersion secondary of variable concentrations, each 6~8 hours, merge immersion, reclaim ethanol), concentrated decocting liquid becomes thick paste, dry, pulverize into fine powder for subsequent use in 55 DEG C~65 DEG C.Separately get 200 parts of Flos Buddlejaes, be directly ground into fine powder, mix with aforementioned Flos Buddlejae extract fine powder and starch, incapsulate.
Embodiment 3: Flos Buddlejae capsule
Formula: 1000 parts of Flos Buddlejaes, 100 parts of starch.
Method for making: get 700 parts of Flos Buddlejaes, be ground into coarse powder, with ethyl acetate room temperature lixiviate secondary, 48 hours for the first time, 40 hours for the second time, merge immersion, reclaim ethyl acetate, extract is for subsequent use.Separately get 300 parts of Flos Buddlejaes, be directly ground into fine powder, mix homogeneously with aforementioned Flos Buddlejae extract, dry, pulverize into fine powder in 60 DEG C~70 DEG C, mix with starch, incapsulate and get final product.
Embodiment 4: Flos Buddlejae granule
Formula: 1000 parts of Flos Buddlejaes, 200 parts of Icing Sugar, 10 parts, dextrin, 20 parts of lactose.
Method for making: get Flos Buddlejae, be ground into coarse powder, with petroleum ether and ether mixed liquor (3 ﹕ 1) room temperature lixiviate secondary, 40 hours for the first time, 35 hours for the second time, merge lixiviating solution, reclaim solvent, extract adds Icing Sugar, dextrin, lactose to stir, granulation, dry, subpackage and get final product.
Embodiment 5: Flos Buddlejae pill
Formula: 1000 parts of Flos Buddlejaes, 110 parts of refined honeys.
Method for making: get 800 parts of Flos Buddlejaes, selection, washing, dry, pulverize into fine powder in 60-65 DEG C, pack extraction kettle into, get rid of all gas impurity in still, then by 31.05 DEG C of supercritical fluid CO2(temperature ﹥, pressure ﹥ 7.39MP) injection extraction kettle, extraction, high pressure CO 2 gases that are dissolved with extract flow into separating still from extraction kettle top, blood pressure lowering, and extract is separated out; Separately get 200 parts of Flos Buddlejaes, be ground into fine powder, mix with extract, add refined honey and water is appropriate, general ball, makes water-honeyed pill, to obtain final product.
Embodiment 6: Flos Buddlejae liniment
Formula: 1000 parts of Flos Buddlejaes, 200 parts of glycerol.
Method for making: get 1000 parts of Flos Buddlejaes, press decocting method with deionized water and extract secondary, each 1 hour, collecting decoction, is concentrated into relative density 1.1~1.2, adds qdx ethanol, stir, leave standstill, filter, filtrate recycling ethanol (or get Flos Buddlejae coarse powder, use the aquiferous ethanol of variable concentrations to soak secondaries, each 6~8 hours in 40 DEG C, merge immersion, reclaim ethanol), cold preservation 24 hours, filter, filtrate glycerol adding mixes, subpackage and get final product.
Embodiment 7: Flos Buddlejae spray
Formula: 1000 parts of Flos Buddlejaes, 3 parts of ethyl hydroxybenzoates.
Method for making: get 1000 parts of Flos Buddlejae Herbs, press decocting method with distilled water and extract secondary, each 1 hour, merge decocting liquid, be concentrated into relative density 1.1~1.2, add qdx ethanol, stir evenly, leave standstill, filter, filtrate recycling ethanol (or is got Flos Buddlejae coarse powder, in 40 DEG C of immersion secondaries, each 6~8 hours, merge immersion with the aquiferous ethanol of variable concentrations, reclaim ethanol), cold preservation 24 hours.Filter, add ethyl hydroxybenzoate and distilled water appropriate, mix, fill, to obtain final product.
Embodiment 8: Flos Buddlejae injection
Formula: 8 parts of 1000 parts of Flos Buddlejaes, benzyl alcohol 10ml, sodium chloride.
Method for making: get 1000 parts of Flos Buddlejaes, press decocting method with distilled water and extract secondary, each 1 hour, merge decocting liquid, be concentrated into relative density 1.1~1.2, add qdx ethanol, stir, cold preservation, precipitation, filter, filtrate recycling ethanol, be concentrated into relative density 1.05~1.06(or get Flos Buddlejae coarse powder, soak secondaries in 40 DEG C with the aquiferous ethanol of variable concentrations, each 4~6 hours, merge immersion, reclaim ethanol and be concentrated into relative density 1.05~1.06), add again ethanol to reaching 80% containing alcohol amount, cold preservation, filter, filtrate recycling ethanol is extremely without alcohol taste, add benzyl alcohol and sodium chloride, stirring and dissolving, inject water to 1000ml, filter with G4 sintered glass funnel, embedding is in the ampoule of 2ml, 100 DEG C of sterilizings 30 minutes and get final product.
Embodiment 9: compound preparation 1
Formula: 350 parts of Flos Buddlejaes, 150 parts of Radix Rubiae Yunnanensis, 240 parts of Radix Notoginseng, 260 parts of Radix Salviae Miltiorrhizaes.
Method for making: Radix Notoginseng powder is broken into coarse powder, according to the percolation under fluid extract and extractum item, makes solvent with 70% ethanol, floods and carries out percolation after 24 hours, and diacolation liquid recycling ethanol, is concentrated into relative density 1.0~1.1(60 DEG C), medicinal residues are for subsequent use.Separately get Flos Buddlejae, Radix Rubiae Yunnanensis, Radix Salviae Miltiorrhizae and Radix Notoginseng medicinal residues, add drinking water and extract secondary by decocting method, each 1 hour, collecting decoction (or is got Flos Buddlejae, Radix Rubiae Yunnanensis, Radix Salviae Miltiorrhizae powder and is broken into coarse powder, mixes with Radix Notoginseng medicinal residues, in 40 DEG C of warm macerating extraction secondaries, each 6~8 hours, merge immersion with the aquiferous ethanol of variable concentrations, reclaim ethanol), decocting liquid and the liquid of filtering are merged and is condensed into thick paste, dry, pulverize into fine powder in 55 DEG C~65 DEG C, mix with appropriate amount of auxiliary materials, incapsulate and get final product.
Embodiment 10: compound preparation 2
Formula: 550 parts of Flos Buddlejaes, 390 parts of Radix Salviae Miltiorrhizaes, 60 parts, Flos Carthami.
Method for making: above 3 tastes, it is for subsequent use that Flos Carthami powder is broken into fine powder, Flos Buddlejae, Radix Salviae Miltiorrhizae, add drinking water and extract secondary by decocting method, each 1 hour, collecting decoction (or was got Flos Buddlejae, Radix Salviae Miltiorrhizae coarse powder, in 40 DEG C of immersion secondaries, each 6~8 hours, merge immersion with the aquiferous ethanol of variable concentrations, reclaim ethanol), concentrated decocting liquid becomes thick paste, dry in 55 DEG C~65 DEG C, be ground into fine powder, mix with Flos Carthami fine powder and appropriate amount of auxiliary materials, incapsulate, to obtain final product.
More than describing is general description of the present invention.According to circumstances or actual needs, can carry out the variation of form and equivalent substituting, although adopt specific term herein, but these terms are intended to describe, instead of object in order to limit.Those skilled in the art can make various changes or modifications the present invention, within these equivalent form of values fall within the application's appended claims limited range equally.

Claims (8)

1. a Flos Buddlejae and/or its extract application in the cardiopathic medicine of preparation treatment, described Flos Buddlejae is loganiaceae plant Flos Buddlejae alabastrum, inflorescence or its Herb, described extract for Flos Buddlejae pulverize after the extract that obtains in room temperature lixiviate or reflux or supercritical extraction, extract the solvent that uses for water and ethanol are with the miscible liquid of any ratio; Or ether, petroleum ether, chloroform, ethyl acetate organic solvent are with the miscible liquid of any ratio; Or liquid CO 2.
2. Flos Buddlejae as claimed in claim 1 and/or its extract application in the medicine of preparation treatment coronary heart disease.
3. Flos Buddlejae as claimed in claim 1 and/or its extract application in the medicine of preparation treatment rheumatic heart disease.
4. Flos Buddlejae as claimed in claim 1 and/or its extract application in the medicine of preparation treatment hypertensive heart disease.
5. Flos Buddlejae as claimed in claim 1 and/or its extract application in the medicine of preparation treatment pulmonary heart disease.
6. Flos Buddlejae as claimed in claim 1 and/or its extract application in the myocardiac medicine of preparation treatment.
7. Flos Buddlejae as claimed in claim 1 and/or its extract application in the medicine of preparation treatment cardiac tumor.
8. Flos Buddlejae as claimed in claim 1 and/or its extract application in the medicine of preparation treatment vascular lesion.
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