CN100337662C - Medicinal composition for treating hyperlipemia and its preparing method - Google Patents
Medicinal composition for treating hyperlipemia and its preparing method Download PDFInfo
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- CN100337662C CN100337662C CNB2005100520079A CN200510052007A CN100337662C CN 100337662 C CN100337662 C CN 100337662C CN B2005100520079 A CNB2005100520079 A CN B2005100520079A CN 200510052007 A CN200510052007 A CN 200510052007A CN 100337662 C CN100337662 C CN 100337662C
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Abstract
The present invention relates to a medicine for treating hyperlipemia and a preparing method. The medicine is mainly formed by preparing raw medicinal medicines as follows: 80 to 120 portions of prepared fleece-flower roots, 80 to 120 portions of hawthorn fruits, 45 to 72 portions of lotus leaves, 60 to 95 portions of water plantains, 80 to 120 portions of cattail pollen and 60 to 95 portions of saute cassia seeds. The composition of the present invention is applicable to clinical rehabilitation of the hyperlipemia and has preferable improving effect on vertigo, numbness of limbs and oppression in the chest.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method for the treatment of hyperlipidemia, said composition is particularly useful for the rehabilitation of hyperlipidemia clinically, to dizzy, limb is numb, uncomfortable in chest has a better role.
Background technology
Atherosclerosis and hyperlipidemia are one of main reason of cardiovascular and cerebrovascular disease, can cause diseases such as hypertension, coronary heart disease, diabetes, the patient's blood vessel infringement is on the rise, cause hemorrhage or thrombosis, and make the blood supply of some organ limited, cause a series of clinical symptoms such as organ injury.
The Chinese medicine of China has own unique theory of medicine and Therapeutic Method to this disease, " expectorant is turbid " reaches " the turbid viscous of expectorant is in blood vessels " though belong to the different theoretical system of Chinese and western medicine in hyperlipidemia, atherosclerosis and the traditional Chinese medical science, but they are the indication basically identical on pathology, physiology, and close corresponding relation is arranged.The traditional Chinese medical science is thought: eating and drinking without temperance, comfortable food rich and fatty diet, and taste are injured, fortuneization mistake department, the spleen being the source of producing phlegm, expectorant is given birth to for wet, and turbid damp fills the air middle Jiao, check clearly sun, body fluid stagnates, simultaneously the hepatic and renal YIN deficiency then catharsis transfer smooth mistake department, it is turbid that body fluid can not be failed the then living expectorant of cloth, and phlegm-damp accumulates long-pending, obstruction of meridian, stay and do not go, viscous is in arteries and veins, and sering is blocked, influence QI-blood circulation, so that phlegm and blood stasis, become and give birth to all diseases.The rule of treatment when with invigorating the liver and kidney, transfer taste, dampness removing turbid, the clots absorbing collateral dredging makes that phlegm-damp is stagnant to be eliminated, spleen is transported multiple, QI and blood and smooth, then the stiffness of the body body is good for, then life lengthening is also.
Domestic by retrieval relevant document and data base find that some contains the blood fat reducing Chinese medicine of Dioscoreaceae plant, the dry cough symptom occurs continuing; Some contains the hypolipidemic of Chinese medicines such as artificial musk, Monas cuspurpureus Went, and the patient takes the back and not untoward reaction such as two numbnesss of lower limbs occur; Untoward reaction such as abdominal discomfort or ALT one property crossed rising appear in the Chinese medicine hypolipidemic that other has the part patient to take and contains Rhizoma Polygoni Cuspidati.
Domestic by retrieval patent database, find relevant Chinese medicine blood fat reducing one piece of the patent documentation in aspect (CN1088450), be No.2 Pharmaceutical Factory of Zichuan Dist., Zibo City's patent documentation, it provides a kind of Chinese medicine preparation " excellent blood fat reducing " for the treatment of hyperlipidemia, comprise Chinese crude drugs such as tonic, promoting blood circulation and hemostasis medicine, digestants, damp-clearing drug and antipyretic, wherein tonic can be selected Radix Polygoni Multiflori, and blood circulation promoting medicine can be selected Pollen Typhae etc., and its dosage form can be an oral liquid etc.But its prescription is excessive, and the kidney invigorating and YANG supporting flavour of a drug are on the high side, makes the function embodiment of blood fat reducing, vessel softening not obvious, and does not carry out prescription by the monarch of theory of Chinese medical science.
From the deficiency of above existing product and technology, as can be seen, be necessary to continue choosing and look for better Chinese medicine lipid lowerers.
Summary of the invention
The present invention is guidance with the theory of Chinese medical science, seeks the Chinese medicine composition of treatment hyperlipidemia, overcomes the defective of existing Chinese medicine, and the inventor is through a large amount of animal and clinical trial, and screening has obtained the sure Chinese prescription of curative effect, thereby has finished the present invention.
Primary and foremost purpose of the present invention provides a kind of medicine for the treatment of hyperlipidemia, and next provides the preparation method and the corresponding preparation of this Chinese medicine composition.
The present invention treats the pharmaceutical composition of hyperlipidemia, and its crude drug is formed the weight portion ratio and comprised Radix Polygoni Multiflori Preparata 80-120 part, Fructus Crataegi 80-120 part, Folium Nelumbinis 45-72 part, Rhizoma Alismatis 60-95 part, Pollen Typhae 80-120 part, Semen Cassiae (parched) 60-95 part.
The preferred portfolio ratio of the pharmaceutical composition of described treatment hyperlipidemia is: 100 parts of Radix Polygoni Multiflori Preparatas, 100 parts of Fructus Crataegis, 60 parts on Folium Nelumbinis, 75 parts of Rhizoma Alismatis, 100 parts of Pollen Typhaes, 75 parts of Semen Cassiae (parched).
Extraction of active ingredients adopts decoction and alcohol sedimentation technique: above Six-element medicine adds 6-14 times of water gaging immersion after 6-12 hour by recipe quantity, heating decocts extracts secondary, each half an hour, filter merging filtrate, be evaporated to proportion 1.05-1.10 (heat is surveyed 70 ℃), add 2-4 and doubly measure 95% ethanol, left standstill 12-48 hour, filter, decompression filtrate recycling ethanol is not to there being the alcohol flavor, and to be condensed into relative density be that the 1.05-1.40 clear paste is standby.
The clear paste of preparation is added conventional oral formulations adjuvant, make corresponding oral formulations.
Oral liquid formulation: clear paste is added water to full dose, filter, fill, sterilization, promptly.
The granule dosage form: 1 part of qinghuo reagent, lactose 2.5-5 part, dextrin 0.1-1 part, that correctives reaches ethanol in right amount is an amount of, makes granule, drying, promptly.
Tablet: 1 part of qinghuo reagent, starch 0.5-3 part, dextrin 0.1-1 part, that magnesium stearate reaches ethanol in right amount is an amount of, makes granule, drying, and tabletting, coating, promptly.
Capsule: 1 part of qinghuo reagent, starch 0.5-3 part, dextrin 0.1-2 part, make granule, drying, encapsulated, promptly.
The present invention is monarch with the Radix Polygoni Multiflori Preparata, and its property bitter but sweet flavor is puckery, and tepor has the effect of invigorating the liver and kidney, benefiting essence-blood, relieving constipation; Fructus Crataegi is that minister, its sour in the mouth are sweet, tepor, and with relieving dyspepsia, strengthening the spleen and stomach, blood circulation promoting and blood stasis dispelling; Folium Nelumbinis is bitter flat, and Rhizoma Alismatis is sweet salty-cold, two medicines 5 for assistant, with clearing away heat-damp and promoting diuresis, tonneau urine and draw turbid descending; Pollen Typhae is sweet flat, the promoting the circulation of blood repercussive; The Semen Cassiae (parched) hardship is slightly cold, the liver heat removing and eyesight improving intestine moistening, and two medicines are dredged the disaster stasis of blood in the blood altogether for making.All medicines share, invigorating the liver and kidney, strengthening the spleen stomach, turbid, the promoting blood circulation of expectorant.It is main that we are effected a permanent cure, and it is auxilliary taking stopgap measures, and treating both the principal and secondary aspects of a disease brings out the best in each other, should be as the small wooden raft drum.
So having screened by the Radix Polygoni Multiflori, Fructus Crataegi, Pollen Typhae, Folium Nelumbinis, Semen Cassiae, Rhizoma Alismatis Six-element Chinese medicine, the present invention forms blood fat reducing side in treatment hyperlipidemia side medicine.Clinical observation has curative effect preferably.This side not only has good effect for reducing fat, and the function of the hemorheological property that changes.Radix Polygoni Multiflori invigorating the liver and kidney, benefiting essence-blood in the side remove dizziness due to wind pathogen, and " book on Chinese herbal medicine justice " calls it, " specially going into Liver and kidney; take a tonic or nourishing food to build up one's health Kidney-Yin ... meet " with the reason of part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels envelope Tibetan, with the pure and honest gentleness of its nature and flavor, merit is arrogated to oneself and is filled out tonifying YIN gas, flat secret negative and positive, so energy the kidney invigorating regulating liver-QI, benefit is smart in dizzy, and modern pharmacological research proof this product has the lipoid and reducing blood pressure effect that necessarily disappears, so the present invention as monarch drug in the prescription, plays the effect of blood fat reducing cholesterol with Radix Polygoni Multiflori Preparata with nourishing the liver and kidney.And oral liquid formulation of the present invention and XUEZHILING PIAN are carved ball and are being contrasted aspect pharmacological effect and the clinical experiment, the result shows that the present invention is at blood fat reducing, the effect aspect of vessel softening is far superior to XUEZHILING PIAN and carves ball, and concrete data are seen embodiment 13---and 17.
The present invention finds to have compared characteristics such as rapid-action, that curative effect is high, and side effect is little with domestic other like product by zoopery and clinical experiment, is treatment and prevention hyperlipoproteinemia and the comparatively ideal medicine of atherosclerosis.
The specific embodiment
The oral liquid formulation of embodiment one preparation medicine of the present invention
Prescription: Radix Polygoni Multiflori Preparata 80g Fructus Crataegi 80g Folium Nelumbinis 45g Rhizoma Alismatis 60g
Pollen Typhae 80g Semen Cassiae (parched) 60g
Preparation method:
(1) pre-treatment: Semen Cassiae (parched) is ground into coarse powder, the single bag of Pollen Typhae, and other medical material is removed impurity;
(2) extract: above Six-element medicine adds 6 times of water gagings immersions after 6 hours by recipe quantity, decoct secondary, each half an hour, filter merging filtrate, filtrate decompression is concentrated into proportion 1.05 (heat is surveyed 70 ℃), add 2.5 times of amount ethanol, left standstill below 4 ℃ 24 hours, filter, decompression filtrate recycling ethanol is not to there being the alcohol flavor, and to be condensed into relative density be 1.08 clear paste;
(3) preparation oral liquid: add purified water to 1000ml, fill, sterilization, promptly.
Character: this product is the liquid of yellowish-brown to rufous; Distinguish the flavor of little acid, little hardship.
Check: relative density: be 1.015 (an appendix VII of Chinese Pharmacopoeia version in 2000 A)
PH value: be 4.53 (an appendix VI of Chinese Pharmacopoeia version in 2000 G).
Other: meet every regulation relevant under the mixture item (an appendix I of Chinese Pharmacopoeia version in 2000 J)
The granule dosage form of embodiment two preparations medicine of the present invention
Prescription is with embodiment one
Preparation method:
(1) pre-treatment, leaching process are with embodiment one, and the clear paste relative density is 1.36.
(2) make granule: 1 part of qinghuo reagent, 2.5 parts of lactose, 1 part in dextrin, that correctives reaches ethanol in right amount is an amount of, makes granule, drying, promptly.
Character: this product is that yellowish-brown is to brown granular; It is little sweet to distinguish the flavor of.
Check: should meet every regulation relevant under the granule item (an appendix appendix of Chinese Pharmacopoeia version in 2000 IC)
The hard capsule dosage form of embodiment three preparations medicine of the present invention
Prescription is with embodiment one
Preparation method:
(1) pre-treatment, leaching process are with embodiment one, and the clear paste relative density is 1.32.
(2) make capsule: 1 part of qinghuo reagent, 1.5 parts of starch, 1 part in dextrin, make granule, drying, encapsulated, promptly.
Character: this product content is that yellowish-brown is to brown granular.
Check: should meet every regulation relevant under the capsule item (an appendix appendix of Chinese Pharmacopoeia version in 2000 IL)
The Tabules of embodiment four preparations medicine of the present invention
Prescription is with embodiment one
Preparation method:
(1) pre-treatment, leaching process are with embodiment one, and the clear paste relative density is 1.28
(2) preparation tablet: 1 part of qinghuo reagent, 2 parts of starch, 1 part in dextrin, that magnesium stearate reaches ethanol in right amount is an amount of, makes granule, drying, and tabletting, coating, promptly.
Character: this product Film coated tablets, remove and show yellowish-brown behind the film-coat to sepia; Distinguish the flavor of little acid, little hardship.
Check: should meet every regulation relevant under the tablet item (appendix ID of Chinese Pharmacopoeia version in 2000)
The granule dosage form of embodiment five preparations medicine of the present invention
Prescription: Radix Polygoni Multiflori Preparata 90g Fructus Crataegi 90g Folium Nelumbinis 55g Rhizoma Alismatis 70g
Pollen Typhae 90g Semen Cassiae (parched) 70g
Preparation process is with embodiment two, amount of water is that 8 times of amounts were soaked 8 hours, it is 1.08 that decocting boils the back relative density, add 3 times of amount ethanol precipitate with ethanol, room temperature left standstill 30 hours, and reclaiming alcohol back relative density is 1.33,1 part of qinghuo reagent, 3 parts of lactose, 1 part in dextrin, that correctives reaches ethanol in right amount is an amount of, make granule, drying, promptly.
Character: this product is that yellowish-brown is to brown granular; It is little sweet to distinguish the flavor of.
Check: should meet every regulation relevant under the granule item (an appendix appendix of Chinese Pharmacopoeia version in 2000 IC)
The oral liquid formulation of embodiment six preparations medicine of the present invention
Prescription: Radix Polygoni Multiflori Preparata 90g Fructus Crataegi 90g Folium Nelumbinis 50g Rhizoma Alismatis 70g
Pollen Typhae 90g Semen Cassiae (parched) 70g
Preparation process is with embodiment one, and amount of water is that 12 times of amounts were soaked 12 hours, and it is 1.10 that decocting boils the back relative density, adds 3.5 times of amount ethanol precipitate with ethanol, and 4 ℃ left standstill 20 hours, and reclaiming alcohol back relative density is 1.10, adds purified water to 1000ml, fill, and sterilization, promptly.
Character: this product is the liquid of yellowish-brown to rufous; Distinguish the flavor of little acid, little hardship.
Check: relative density: be 1.017 (an appendix VII of Chinese Pharmacopoeia version in 2000 A)
PH value: be 4.83 (an appendix VI of Chinese Pharmacopoeia version in 2000 G).
Other: meet every regulation relevant under the mixture item (appendix IJ of Chinese Pharmacopoeia version in 2000)
The oral liquid formulation of embodiment seven preparations medicine of the present invention
Prescription: Radix Polygoni Multiflori Preparata 100g Fructus Crataegi 100g Folium Nelumbinis 60g Rhizoma Alismatis 75g
Pollen Typhae 100g Semen Cassiae (parched) 75g
Preparation process is with embodiment one, and amount of water is that 12 times of amounts were soaked 24 hours, and it is 1.12 that decocting boils the back relative density, adds 4 times of amount ethanol precipitate with ethanol, and 4 ℃ left standstill 24 hours, and reclaiming alcohol back relative density is 1.08, adds purified water to 1000ml, fill, and sterilization, promptly.
Character: this product is the liquid of yellowish-brown to rufous; Distinguish the flavor of little acid, little hardship.
Check: relative density: be 1.019 (an appendix VII of Chinese Pharmacopoeia version in 2000 A)
PH value: be 3.83 (an appendix VI of Chinese Pharmacopoeia version in 2000 G).
Other: meet every regulation relevant under the mixture item (appendix IJ of Chinese Pharmacopoeia version in 2000)
The granule dosage form of embodiment eight preparations medicine of the present invention
Prescription is with embodiment seven
Preparation process is with embodiment seven, and the clear paste relative density is 1.34, and 1 part of qinghuo reagent, 2.8 parts of lactose, 1 part in dextrin, that correctives reaches ethanol in right amount is an amount of, makes granule, drying, promptly.
Character: this product is that yellowish-brown is to brown granular; It is little sweet to distinguish the flavor of.
Check: should meet every regulation relevant under the granule item (an appendix appendix of Chinese Pharmacopoeia version in 2000 IC)
The hard capsule dosage form of embodiment nine preparations medicine of the present invention
Prescription is with embodiment seven
Preparation process is with embodiment seven, and the clear paste relative density is 1.34, and 1 part of qinghuo reagent, 2.5 parts of starch, 1 part in dextrin are made granule, and drying is encapsulated, promptly.
Character: this product content is that yellowish-brown is to brown granular.
Check: should meet every regulation relevant under the capsule item (an appendix appendix of Chinese Pharmacopoeia version in 2000 IL)
The Tabules of embodiment ten preparations medicine of the present invention
Prescription is with embodiment seven
Preparation process is with embodiment seven, and the clear paste relative density is 1.29, and 1 part of qinghuo reagent, 2.5 parts of starch, 1 part in dextrin, that magnesium stearate reaches ethanol in right amount is an amount of, makes granule, drying, and tabletting, coating, promptly.
Character: this product Film coated tablets, remove and show yellowish-brown behind the film-coat to sepia; Distinguish the flavor of little acid, little hardship.
Check: should meet every regulation relevant under the tablet item (appendix ID of Chinese Pharmacopoeia version in 2000)
The granule dosage form of embodiment 11 preparations medicine of the present invention
Prescription: Radix Polygoni Multiflori Preparata 110g Fructus Crataegi 110g Folium Nelumbinis 70g Rhizoma Alismatis 85g
Pollen Typhae 110g Semen Cassiae (parched) 85g
Preparation process is with embodiment eight, amount of water is that 14 times of amounts were soaked 14 hours, it is 1.02 that decocting boils the back relative density, add 4 times of amount ethanol precipitate with ethanol, room temperature left standstill 36 hours, and reclaiming alcohol back clear paste relative density is 1.34,1 part of qinghuo reagent, 2.8 parts of lactose, 1 part in dextrin, that correctives reaches ethanol in right amount is an amount of, make granule, drying, promptly.
Character: this product is that yellowish-brown is to brown granular; It is little sweet to distinguish the flavor of.
Check: should meet every regulation relevant under the granule item (an appendix appendix of Chinese Pharmacopoeia version in 2000 IC)
The Tabules of embodiment 12 preparations medicine of the present invention
Prescription: Radix Polygoni Multiflori Preparata 120g Fructus Crataegi 120g Folium Nelumbinis 72g Rhizoma Alismatis 95g
Pollen Typhae 120g Semen Cassiae (parched) 95g
Preparation process is with example ten, and amount of water is that 16 times of amounts were soaked 24 hours, and it is 1.02 that decocting boils the back relative density, adds 3.5 times of amount ethanol precipitate with ethanol, and 4 ℃ left standstill 24 hours, and reclaiming alcohol back relative density is 1.38.1 part of qinghuo reagent, 2.3 parts of starch, 1 part in dextrin, that magnesium stearate reaches ethanol in right amount is an amount of, makes granule, drying, and tabletting, coating, promptly.
Character: this product Film coated tablets, remove and show yellowish-brown behind the film-coat to sepia; Distinguish the flavor of little acid, little hardship.
Check: should meet every regulation relevant under the tablet item (appendix ID of Chinese Pharmacopoeia version in 2000)
Blood fat reducing and the study of anti-atherogenic effect of 13 pairs of high fat rabbit of embodiment
Experimentation:
The oral liquid of [medicine] (1) product of the present invention: embodiment seven preparations
(2) nicotinic acid tablet: (100mg/ sheet)
(3) XUEZHINING
(4) JIANGZHINING KELI
(5) cholesterol
Rabbit 1.8-2.2kg plants in [animal] male New Zealand
[test method] is divided into oral liquid high dose group of the present invention at random with rabbit, and (0.6ml/kg/d is equivalent to 6 times of people's clinical dosage, P.O), low dose group (0.3ml/kg/d, P.O), high fat matched group (0.6ml/kg/d tap water P.O), nicotinic acid matched group (30mg/kg/d, P.O), XUEZHINING matched group (4.0mg/kg/d, P.O), JIANGZHINING KELI matched group (4.0mg/kg/d, P.O), blank group (0.6ml/kg/d tap water P.O), except that the blank group, add every of all the other each treated animal every day and feed cholesterol 0.5g, every animal sub-cage rearing, each treated animal ear vein blood sampling mensuration blood lipid level (T-CHOL TC respectively when experiment 1.5 months and 3 months, high density lipoprotein HDL-C, low density lipoprotein, LDL LDL-C and triglyceride TG), weigh simultaneously.When experiment is carried out 1.5 months, the beginning administration, experiment was carried out after three months, put to death all animals, do the atherosis pathology inspection of aorta, coronary artery and renal artery, measure liver coefficient (liver weight/body weight * 100%) and blood lipid level (assay method is the same) and MDA (the sulfo-crust is than peace acid ratio color method).
The exponential comparative descriptions of respectively organizing of [result] (1) the weight of animals and liver, oral liquid of the present invention does not have obvious influence to animal weightening finish and liver index.The results are shown in Table 1, table 2.
Table 1: oral liquid of the present invention is to the influence of rabbit body weight
| Group | Dosage ml/kg | Number of animals (only) | Before the experiment | Tested 1.5 months | Tested three months |
| The high fat contrast of the peaceful JIANGZHINING KELI of oral liquid of the present invention oral liquid nicotinic acid of the present invention blood fat blank | 0.6 0.3 30mg/kg 4.0g/kg 4.0g/kg, 0.6 tap water, 0.6 tap water | 10 10 10 10 10 10 10 | 2075±387 2025±193 2015±196 2097±208 2098±218 2055±324 2067±208 | 2520±359 2317±233 2470±256 2502±324 2612±225 2556±213 2512±267 | 2572±442 2467±197 2528±360 2561±267 2658±307 2661±122 2701±293 |
X±S.D. g
Table 2: oral liquid of the present invention is to the influence of liver coefficient
| Group | Dosage ml/kg | Number of animals (only) | The liver coefficient |
| The high fat contrast of the peaceful JIANGZHINING KELI of oral liquid of the present invention oral liquid nicotinic acid of the present invention blood fat blank | 0.6 0.3 30mg/kg 4.0g/kg 4.0g/kg, 0.6 running water, 0.6 running water | 10 10 10 10 10 10 10 | 5.30±0.71 5.27±0.68 5.00±0.91 5.31±0.93 5.34±0.82 5.21±0.81 5.03±0.69 |
(2) the lipid determination result shows: except that the blank group, each was organized blood fat and all obviously raises when high fat was raised 1.5 months, P＜0.01, and group difference is not remarkable.And after the experiments in 1.5 months that add the medicine feed thing afterwards, the lipid determination result shows, compares with high fat matched group, and medicine all has obvious lipid-lowering effect, and two dosage of oral liquid promptly of the present invention all can obviously reduce TC and TG, and is not fairly obvious to HDL and LDL influence.The results are shown in Table 3, table 4.
Table 3: the blood lipid level of high fat rabbit experiment each group in the time of 1.5 months
| Group | Dosage ml/kg | Number of animals (only) | TC | HDL | LDL | TG |
| The high fat contrast of the peaceful JIANGZHINING KELI of oral liquid of the present invention oral liquid nicotinic acid of the present invention blood fat blank | 0.6 0.3 30mg/kg 4.0g/kg 4.0g/kg, 0.6 tap water, 0.6 tap water | 10 10 10 10 10 10 10 | 516.8±87.5 499.9±86.0 486.8±85.5 489.8±91.2 498.6±92.2 506.1±92.1 221.6±67.5 | 115.1±54.6 106.8±51.9 95.5±34.0 99.2±60.0 98.5±58.2 97.8±42.1 42.1±12.3 | 374.1±82.3 326.3±58.5 398.7±67.1 359.6±78.1 367.6±76.3 389.2±69.3 190.6±39.6 | 241.1±73.6 ※ 281±74.1 242.6±46.0 261.1±58.1 ※ 259.8±56.6 ※ 256.3±71.2 82.5±10.6 |
X±S.D. mg/dl
Table 4: when testing three months, oral liquid of the present invention is to the influence of high fat rabbit blood fat
| Group | Dosage ml/kg | Number of animals only | TC | HDL | LDL | TG |
| The high fat contrast of the peaceful JIANGZHINING KELI of oral liquid of the present invention oral liquid nicotinic acid of the present invention blood fat blank | 0.6 0.3 30mg/kg 4.0g/kg 4.0g/kg, 0.6 running water, 0.6 running water | 10 10 10 10 10 10 10 | 706.1±97.8 ※※ 761.0±175.4 ※※ 819.0±173.4 ※ 821.1±89.9 ※ 823.3±88.9 ※ 1009.1±215.4 212.5±61.0 | 419.8±158.8 371.8±72.6 541.0±141.5 ※ 528.1±98.0 ※ 526.2±98.9 ※ 421.7±91.2 41.9±10.1 | 437.6±81.1 455.8±105.1 327.0±96.7 ※※ 341.0±79.5 ※※ 348.2±78.4 ※※ 502.1±103.2 185.6±64.0 | 117.3±75.0 ※※193.8±87.1 ※181.4±89.7 ※※185.1±79.9 ※186.4±78.6 ※269.2±80.6 89.2±29.1 |
X ± S.D. mg/dl and high fat matched group be ※ P＜0.05 ※ ※ P＜0.01 relatively
(3) oral liquid of the present invention can also obviously reduce lipid peroxide---MDA generation.
The results are shown in Table 5.
Table 5: oral liquid of the present invention is to the influence of high fat rabbit MDA
| Group | Dosage | Number of animals (only) | MDA | nmol/ml |
| Individual month 1.5 (not administration) | 3 months (administration) | |||
| The high fat contrast of the peaceful JIANGZHINING KELI of oral liquid of the present invention oral liquid nicotinic acid of the present invention blood fat blank | 0.6 0.3 30mg/kg 4.0g/kg 4.0g/kg, 0.6 tap water, 0.6 tap water | 10 10 10 10 10 10 10 | 2.20±0.34 2.29±0.25 2.20±0.30 2.31±0.27 2.28±0.37 2.25±0.31 1.81±0.41 | 1.22±0.25 ※※ 1.96±0.17 ※※ 2.47±0.24 2.38±0.21 ※ 2.42±0.31 ※ 2.68±0.29 1.39±0.37 |
X ± S.D.nmol/ml and high fat matched group be ※ P＜0.05 ※ ※ P＜0.01 relatively
(4) pathology detection result
1. atherosclerosis of aorta pathologic finding: aorta is taken off from aortic orifice to common iliac artery crotch, peel off the fat of aorta outside, aorta is cut off in stringer, be tiled on the filter paper, use 10% formaldehyde fixed, soudan III dyeing is traced the size of whole aortic tunica intima and lipid speckle on slide then, slide is placed that (each little lattice is 1mm on the scale paper again
2), calculate the area (Applied Anatomy microscope) of aortal area of each bar and lipid speckle respectively, obtain the percentage ratio that fat speckle area accounts for the aorta area.Pathologic finding finds that fat speckle character all is intimal thickenings, and a large amount of foam cells gather smooth muscle cell and proliferation of fibrous tissue.The fat speckle average area percentage ratio of high fat matched group is 44.9 ± 7.1%, and high dose oral liquid group of the present invention is 19.3 ± 3.2%, compares P＜0.01 with the former; Low dose group is 17.8 ± 4.3%, compares P＜0.01 with the former, and the nicotinic acid group is 38.6 ± 6.9%; The XUEZHINING group is 37.6 ± 4.9%, and JIANGZHINING KELI is 38.4 ± 4.5, compares P＜0.05 with high fat.The blank group is 4.4 ± 1.1%, compares P＜0.05 with high fat matched group.
2. coronary atherosclerosis pathologic finding: check left anterior descending branch: at distance coronary sulcus 0.5cm place, begin to cut a block organization every 0.5cm, every animal is got the 3-4 piece, carries out cut sections for microscopic examination, finds that the arteria coronaria left anterior descending branch of high fat matched group has 4 examples that the fat speckle is arranged; Oral liquid high dose group of the present invention has an example; Low dose group has an example; The nicotinic acid group has 3 examples; The XUEZHINING group has 2 examples, and JIANGZHINING KELI has 2 examples, and the blank group does not have.
3. the atherosis pathology inspection of renal artery, the piece of tissue inspection is got at the place of hardening in renal artery part, both sides, 2 of every side-draws, the high fat matched group of result has 3 routine renal artery that the fat speckle is arranged, oral liquid high and low dose group of the present invention respectively has an example, and the nicotinic acid group has 3 examples, and the XUEZHINING group has 2 examples, JIANGZHINING KELI has 2 examples, and the blank group does not have.The results are shown in Table 6.
Table 6: oral liquid study of anti-atherogenic effect of the present invention
| Group | Dosage ml/kg | Number of animals (only) | Aorta AS area percentage % | Several of examples take place for every group in AS | |
| Coronary artery | Renal artery | ||||
| The high fat contrast of the peaceful JIANGZHINING KELI of oral liquid of the present invention oral liquid nicotinic acid of the present invention blood fat blank | 0.6 0.3 30mg/kg 4.0g/kg 4.0g/kg, 0.6 tap water, 0.6 tap water | 10 10 10 10 10 10 10 | 19.3±3.2 ※※ 17.8±4.3 ※※ 38.6±6.9 37.6±4.6 ※ 38.4±4.5 ※ 44.9±7.1 4.4±1.1 | 1 ※ 1 ※ 3 2 2 4 0 | 1 1 3 2 2 3 0 |
X ± SD.% and high fat matched group be ※ P＜0.05 ※ ※ P＜0.01 relatively
Embodiment 14 animal acute toxicity experiments
Experimentation:
The oral liquid of [medicine] oral liquid of the present invention: embodiment seven preparations
[animal] Kunming mouse 18-21g, male and female half and half
[test method] gets 40 white mice, male and female half and half are divided by the 75ml/kg oral liquid and to be irritated stomach for three times, observe and irritate behind the stomach diet, feces, hair color, mucosa, breathing, activity and the death condition of animal in seven days, if in time dissect and do pathology, see toxicity performance situation in death.
[result] is after stomach is irritated in first and second time (early 8:00, afternoon 13:00), all are movable normal for animal, irritating stomach (18:00 in afternoon) back for the third time in half an hour, animal sees quiet few moving slightly, recover normal after half an hour, animal diet followed, feces, hair color, mucosa, breathing, activity be all normal in then seven days, and none example is dead.The results are shown in Table 7.
Table 7: oral liquid maximum tolerated dose experiment of the present invention
| Medicine | Dosage ml/kg | Number of animals (only) | Response situation | Dead |
| Diet, feces, hair color, mucosa, breathing, activity | ||||
| Oral liquid of the present invention | 75 | 40 | Normally | 0 |
[conclusion] oral liquid maximum tolerated dose of the present invention has surpassed 150 times (people's clinical dosage is 30ml/ day/people) of people's clinical dosage greater than 75ml/kg.
Embodiment 15 long-term toxicity test for animals
Experimentation:
Said preparation is every milliliter of oral liquid that contains the 0.5g crude drug, and clinical consumption is each 1 (10ml), every day three times, if the adult presses the 60kg weighing machine, takes 30ml, per kilogram of body weight 0.5ml/kg/d everyone every day.
Not forming because the Chinese medicine of this Chinese medicine compound has eighteen incompatible medicaments, nineteen medicaments of mutual restraint, avirulence medical material, again without chemical treatment, is again that our province distinguished veteran doctors of TCM Zhang Baishi teaches in the clinical practice of five more than ten years and do not find toxic and side effects, and acute toxicity testing also is difficult to measure LD
50, the maximum tolerated dose mice is oral greater than 75ml/kg (surpass people's clinical dosage 150 times), so require spiritually according to pharmaceutical control law, establishes two dosage groups, two months rat long term toxicity tests.
The oral liquid of [medicine] oral liquid of the present invention: embodiment seven preparations.For implementing the heavy dose of gastric infusion of rat, its drug level is five times of clinical oral administration liquid, promptly contains crude drug 250%.
[animal] S.D rat, male and female half and half, body weight 135 ± 10g
[test method]
One, selects healthy white rat for use, male and female half and half, be divided into high dose group (5.0ml/kg/d at random, be equivalent to 50 times of people's clinical dosages), low dose group (1.0ml/kg/d, be higher than zoopery effective dose 0.6ml/kg/d) and blank group, each 10 of every group of male and female, gastric infusion every day once (matched group give tap water), continuous irrigation stomach two months, each group all awards normal diet, free diet and drinking-water.Respectively claim body weight one time before and after the experiment, routine blood test and hepatic and renal function are measured in the phase blood sampling before, during and after the test.When experiment finished in two months, put to death 50% animal and survey hepatic and renal function, routine blood test and get important organ (heart, liver, spleen, lung, kidney, brain, adrenal gland), when no abnormal, put to death all the other animals again.Important organ is all weighed and is done pathological section.
Institute's employing method is the conventional method of present clinical regulation in the biochemical investigation.Adopt Switzerland to produce COBAS MIRAS type automatic biochemistry analyzer and analyze, agents useful for same is fastened the import reagent of extra large Long March company packing: blood urea nitrogen adopts that urease method is measured, total protein adopts that biuret method is measured, albumin adopts that the bromocresol green method is measured, GPT adopts enzymatic assays, TTT adopts the thymol method to measure.
During [result] fed in one, two month, no significant difference between each group of beverage day's expenditure, 11.3 ± 2.5g/ only amount of drinking water 39 ± 5ml/, belonged to normal range.
Two, no matter high dose group or low dose group, the activity of animal, hair color, feces and body weight gain and matched group relatively, all Non Apparent Abnormality sees Table 8.
Table 8: rat body weight gain situation
| Group | Dosage ml/kg | Number of animals (only) | Body weight (g) before the experiment | Body weight (g) when experiment finishes |
| Oral liquid high dose group of the present invention | 5.0 | 20 | 121.1±11.8 | 246.5±19.6 |
| Oral liquid low dose group of the present invention | 1.0 | 20 | 118.2±10.6 | 251.4±21.0 |
| Matched group | 20 | 126.3±11.3 | 239.1±23.2 |
X±S.D.
Three, also no significant difference of the weight of the heart, liver, spleen, lung, kidney, brain and organ index is respectively organized in experiment, illustrates that oral liquid of the present invention does not have obvious influence to important organ weights or index.
The results are shown in Table 9.
Table 9: oral liquid of the present invention is to the exponential influence of Rats Organs and Tissues
| Group | Dosage ml/kg | Number of animals (only) | The heart | Liver | Spleen | Lung | Kidney | Brain |
| Oral liquid high dose group of the present invention | 5.0 | 20 | 0.84±0.02 | 4.03±0.05 | 0.74±0.04 | 1.20±0.09 | 0.89±0.06 | 0.81±0.06 |
| Oral liquid low dose group of the present invention | 1.0 | 20 | 0.81±0.03 | 3.89±0.08 | 0.68±0.05 | 1.18±0.07 | 0.85±0.07 | 0.79±0.07 |
| Matched group | 20 | 0.83±0.04 | 4.11±0.9 | 0.72±0.06 | 1.22±0.06 | 0.91±0.08 | 0.83±0.07 |
X±S.D.
Four, oral liquid of the present invention is two months, routine blood test, the hepatic and renal function of rat is not also had obvious influence, all within range of normal value.The results are shown in Table 10, table 11.
Table 10: oral liquid of the present invention is to the influence of rat serum routine
| Group | Dosage ml/kg | Number of animals (only) | Get the blood time | Leukocyte * 109/L | Erythrocyte * 1012/L | Platelet * 109/L | Reticulocyte % | Hematochrome g/L |
| Oral liquid high dose group of the present invention | 5.0 | 20 | Experiment end in the experiment before the experiment | 6.88±1.31 7.13±2.14 6.98±2.03 | 5.61±1.21 5.23±1.30 5.91±1.91 | 140.1±10.5 132.2±12.1 145.0±11.5 | 3.5±0.7 3.7±0.5 3.7±0.8 | 111.8±11.8 109.1±9.01 123.6±11.2 |
| Oral liquid low dose group of the present invention | 1.0 | 20 | Experiment end in the experiment before the experiment | 6.99±1.54 7.24±1.98 7.21±2.01 | 6.01±1.04 5.29±1.10 5.41±1.32 | 153.6±15.3 157.8±20.1 149.2±19.2 | 3.2±0.8 3.4±0.9 3.6±0.7 | 125.6±10.5 120.5±12.0 135.1±11.1 |
| Matched group | 20 | Experiment end in the experiment before the experiment | 7.23±2.12 6.78±1.93 6.91±1.78 | 5.81±1.12 6.02±0.98 6.01±1.12 | 158.2±17.1 161.3±20.1 148.2±23.1 | 3.6±0.9 3.9±0.9 3.3±0.5 | 121.6±9.16 111.2±7.12 131.7±9.25 |
X±S.D.
Table 11: oral liquid of the present invention is to the influence of rats'liver, renal function
| Group | Dosage ml/kg | Number of animals (only) | Get the blood time | Blood urea nitrogen mmol/l | Total protein g/l | Albumin g/l | GPT Lai Shi u/l | TTT Maxwell u |
| Oral liquid high dose group of the present invention | 5.0 | 20 | Experiment end in the experiment before the experiment | 4.8±1.2 4.9±1.0 4.7±0.8 | 58.1±9.8 61.2±7.8 63.7±7.3 | 22.6±3.1 21.5±2.4 24.5±2.4 | 30.2±10.1 25.2±8.3 29.2±10.3 | ＜6 ＜6 ＜6 |
| Oral liquid low dose group of the present invention | 1.0 | 20 | Experiment end in the experiment before the experiment | 4.9±1.1 5.0±1.2 4.7±0.9 | 59.9±9.5 60.3±8.6 66.8±10.5 | 20.7±2.7 19.6±3.2 23.4±1.9 | 25.3±9.8 31.5±10.6 32.6±8.9 | ＜6 ＜6 ＜6 |
| Matched group | 20 | Experiment end in the experiment before the experiment | 5.1±1.2 4.8±1.3 4.5±0.8 | 57.3±6.9 65.7±9.9 60.9±8.9 | 24.6±1.8 20.8±1.1 23.6±1.7 | 22.4±10.1 24.1±9.9 28.1±10.5 | ＜6 ＜6 ＜6 |
X±S.D.
Five, pathology detection result
Liver: the liver of experimental group and control animals is all existing obviously congested, no significant difference between organizing on the degree, the visible liver degeneration of matched group one routine liver, experimental group liver no abnormality seen.
Kidney: all existing tangible congestion of blood vessel of the kidney of experimental group and matched group and nearly curved tube epithelial cell cloudy swelling, no significant difference between organizing on the degree.Matched group has 3, high dose group to have in 2 dirty collecting tubules the protein material to occur, like irrelevant with drug effect.
Lungs: all existing tangible congestion of blood vessel of experimental group and matched group and chronic matter must inflammation, at no significant difference between group on the degree.Matched group and high dose group respectively have the visible pulmonary abscess of the lungs of 1 animal.
Be thought of as the Foreign body aspiration and cause, irrelevant with medicine.Internal organs such as the heart of experimental group and matched group, brain, spleen, epinephrine, except that tangible hyperemia, (at no significant difference between group on the congested degree), this may be to put to death animal to enter institute and cause other no abnormal discovery.
The preventive effect of 16 pairs of rat disorders of lipid metabolism of embodiment
[medicine] (1) oral liquid of the present invention
(2) XUEZHILING PIAN
(3) Colestid capsule
(4) cholesterol (import packing)
[animal] S.D white mouse 180-200g, magnificence
[experimental technique] is divided into oral liquid high dose group of the present invention (6.0ml/kgP.O), low dose group (3.0ml/kg P.O) at random with rat, known medicine XUEZHILING PIAN (4g/kg P.O), Colestid capsule (4g/kg P.O), matched group and blank group (6.0ml/kg tap water P.O) and high fat matched group (also being 6.0ml/kg tap water P.O).Except that the blank group was fed common mixed fodder, other each group added again and feeds 3% cholesterol, 10% Adeps Sus domestica and 0.2% methylthiouracil on 87% basic mixed fodder basis every day.Oral administration gavage 10 days is then got the hematometry blood fat: T-CHOL TC, high density lipoprotein HDL, low density lipoprotein, LDL LDL and triglyceride TG.
TC and LDL measure and adopt the CHOD-PAP method, and reagent is provided by Beijing Zhongsheng Biological Engineering High Technology Company; HDL adopts phosphoglycerol oxidase peroxidase---and end-point method mensuration, reagent is provided by Beijing Chemical Plant's clinical reagent subsidiary factory.
[result] application rat is set up high blood lipid model has raising convenient, the advantage that resistance is strong, feeding habits are close with the people.Experimental result explanation, oral liquid of the present invention have the effect of obvious reduction TC and TG, compare with high fat matched group, and through data t test statistics processing in groups, difference has significance, P＜0.05.Not obvious to HDL, LDL influence.The results are shown in Table 12.
Table 12: oral liquid of the present invention is to the preventive effect of disorders of lipid metabolism
| Medicine | Dosage ml/kg | Number of animals (only) | TC | LDL | HDL | TG |
| The high fat contrast of oral liquid of the present invention oral liquid XUEZHILING PIAN of the present invention Colestid capsule blank | 6.0 3.0 4.0g 4.0g, 6.0 tap waters, 6.0 tap waters | 10 10 10 10 10 10 | 235.1±49.1 ※ 250.5±32.1 ※ 258.5±47.9 ※ 256.9±47.6 ※ 292.2±40.8 70.9±7.9 | 211.5±57.2 218.1±50.1 233.6±81.2 234.5±82.4 227.5±50.3 41.2±8.1 | 27.2±9.2 28.3±6.0 11.6±3.6 ※ 10.9±3.2 ※ 32.3±5.0 38.0±15.9 | 127.6±29.6 ※ 135.1±33.4 107.6±33.9 ※ 106.8±32.9 ※ 163.2±42.4 83.0±38.7 |
X ± S.D.mg/dl and high fat matched group be ※ P＜0.05 relatively
[conclusion] oral liquid of the present invention has hypercholesterolemia reducing and triglyceride effect.And it reduces TC, the TG effect is better than XUEZHILING PIAN and Colestid capsule, and rising HDL effect also is better than XUEZHILING PIAN.
Embodiment 17 clinical trials
1. clinical trial design
1.1 test objective
Estimate the clinical effectiveness and the safety of oral liquid treatment hyperlipidemia of the present invention.
1.2 testing program
1.2.1 study subject
Hyperlipidemia patient: adopt at random, contrast, double blinding dual analog multi-center clinical trial research method.Going into to organize case load altogether is 238 examples, oral liquid treatment group 118 examples wherein of the present invention, male's 60 examples, women's 58 examples, age 58a ± s8a; XUEZHINING WAN matched group 120 examples; Male's 61 examples, women's 59 examples, age 57a ± 8a.
Hyperlipidemia diagnostic criteria: formulate with reference to " new drug (Chinese medicine) clinical research guideline ": the dyslipidemia patient, through diet propaganda and education, blood sampling is 2 times in 2～4wk, as 2 serum TCs all＞5.98mmol/L or triglyceride (TG) 〉=2.26mmol/L,＜5.65mmol/L person.HDL-Ch value male≤1.04mmol/L, women≤1.17mmol/L are as the reference condition.
The Chinese medical discrimination standard of expectorant stasis of blood retardance disease: sleepy, the uncomfortable in chest or chest pain of limbs, indigestion and loss of appetite, the gastral cavity abdomen is glutted, fat, tongue is dark or ecchymosis is arranged, thick fur is greasy, rolling pulse or heavy.
● inclusion criteria:
1) meets the constitutional hyperlipidemia patient that above-mentioned hyperlipidemia diagnosis and Chinese medical discrimination belong to expectorant stasis of blood retardance card.
2) 30～65 years old age, male or female;
3) liver, renal function and hemogram are normal; Tried voluntarily.
● exclusion standard:
1) once suffered from myocardial infarction in the 0.5a, cerebrovascular accident, severe trauma or capital operation person.
2) nephrotic syndrome, hypothyroidism, acute or chronic liver, biliary diseases, diabetes and gout patient.
3) family hypercholesterolemia (the subtype hypercholesterolemia of isozygotying).
4) hyperlipidemia that causes by medicine (as phenothiazines, epinephrine beta-blocker, 17-hydroxy-11-dehydrocorticosterone and some contraceptive class).
5) using heparin, thyroid curative and other to influence the patient who adopts other blood fat reducing measures in the patient of blood lipid metabolism medicine and the nearly 4wk.
6) anemia of pregnant woman and women breast-feeding their children.
7) be associated with other serious organic disease doctors and think the person of being not suitable for.
8) allergic constitution and psychosis patient.
1.2.2 medication:
● oral liquid group of the present invention: use oral liquid of the present invention, each 1, take blank soft gelatin capsule 2 balls simultaneously, every day 3 times, oral; 8 weeks of the course of treatment
● the XUEZHINING WAN group: use XUEZHINING WAN, each 2 balls are taken 1 of blank oral liquid simultaneously, and are every day 3 times, oral; 8 weeks of the course of treatment.
1.2.3 observed content:
1.2.3.1 safety indexes:
(1) comprise blood, urine, just conventional, electrocardiogram, liver function (ALT), renal function (Cr, BUN), creatine kinase (CK);
(2) untoward reaction symptom and sign may appear.
1.2.3.2 health giving quality index:
(1) serum lipids (comprising TC, TG, HDL-Ch, LDL-Ch, Apo AI, Apo B100).
(2) clinical related symptoms and sign.
1.2.4 observe time point and method
Lipid metabolism index: TC, TG, HDL-C and LDL-C check that the back of taking medicine was respectively looked into 1 time in the 4th, 8 weeks 2 times in preceding 2 weeks of taking medicine.TC, TG, HDL-C measure and use enzyme process.LDL presses the Friedewald formula and calculates.Blood lipids index is all used parallel double tube, and requires to carry out in strict accordance with Quality Control.Other index: routine blood test, routine urinalysis, blood glucose, blood creatine kinase (CK) and liver, renal function are in taking medicine preceding and taking medicine back respectively looking into 1 time in 4,8 weeks.
1.2.5 curative effect determinate standard contrast " new drug Chinese medicine clinical research guideline " is formulated:
● clinic control---the every index of blood fat recovers normal.
● produce effects---blood fat does not recover normal fully but reaches following each person, and TC descends 〉=20%, and TG descends 〉=40%, HDL-Ch rising 〉=0.26mmol/L; TG-HDL-Ch/HDL-Ch descends 〉=20%.
● effectively---blood fat recovers to reach following any one person, and TC descends 10%～20%, and TG descends 20%～40%; HDL-Ch rising 0.104mmol/L～＜0.26mmol/L;
TC-HDL-Ch/HDL-Ch descends 10%～＜20%.
● invalid: experimental check does not reach effective standard person.
1.2.6 the relatively employing x2 of date processing enumeration data check, measurement data relatively with the t check, the relatively employing Ridit of ranked data analyzes.
2. clinical test results
2.1 relatively harmonious:
Various baseline case such as the sex when going into to organize between two groups, age, occupation, body weight, the course of disease, blood fat, clinical symptoms, physico-chemical examination more all have comparability (P＞0.05).
2.2 curative effect relatively
2.2.1 blood fat curative effect: oral liquid clinic control 56 examples of the present invention, produce effects 39 examples, effective 15 examples, obvious effective rate is 80.51%, total effective rate is 93.2%; XUEZHINING WAN group clinic control 42 examples, produce effects 43 examples, effective 12 examples, obvious effective rate is 70.83%, total effective rate is 80.83% (P＜0.05).Do not find obvious adverse reaction.
P＜0.05 sees Table 1
2 groups of hyperlipidemia curative effects of table 1 are [example (%)] relatively
| Group | The example number | Control | Produce effects | Effectively | Invalid |
| Oral liquid XUEZHINING WAN of the present invention | 118 120 | 56(47.46) 42(35.00) | 39(33.05) 43(35.83) | 15(12.71) 12(10.00) | 8(6.78) 23(19.17) |
Analyze through Ridit: R mountain=0.5, R blood=0.5446, P＜0.05.
2.2.2 blood lipid level relatively before and after the treatment: oral liquid group of the present invention and XUEZHINING WAN group treatment back TG, TC, LDL-Ch and atherogenic index (TC-HDL-Ch/HDL-Ch) all have obvious reduction, and P is all＜0.01, TC reduces amplitude oral liquid group of the present invention and is better than the XUEZHINING WAN group, P＜0.05; P＜0.01, zero difference between rising amplitude group all raise to some extent after the treatment of HDL-Ch group.Oral liquid group treatment back Apo AI of the present invention raises to some extent, and Apo B100 decreases, all P＜0.01; The XUEZHINING WAN group changes little, all P＞0.05.Comparing difference has highly significant or remarkable meaning (P＜0.01 or P＜0.05) between 2 groups of groups, sees Table 2.
The comparison that blood fat, apolipoprotein level and atherogenic index change before and after 2 groups of treatments of table 2 (x ± s)
| Project | Group | Unusually routine | Before the treatment | After the treatment | Difference |
| TC (mmol/L) | XUEZHINING WAN | 60 | 6.9±1.4 | 5.6±0.8 | -1.3±0.9 c |
| Oral liquid of the present invention | 59 | 6.8±1.3 | 5.3±0.9 | -1.6±1.0 cc | |
| 0.9TG (mmol/L) | XUEZHINING WAN | 102 | 3.3±1.1 | 2.2±1.0 | -1.0±0.9 c |
| Oral liquid of the present invention | 116 | 3.3±1.4 | 2.2±1.1 | -1.0±1.2 cd | |
| HDL-Ch (mmol/L) | XUEZHINING WAN | 56 | 0.95±0.12 | 1.15±0.17 | -0.20±0.17 c |
| Oral liquid of the present invention | 58 | 0.95±0.15 | 1.2±0.3 | -0.2±0.7 cd | |
| LDL-Ch (mmol/L) | XUEZHINING WAN | 115 | 3.8±1.4 | 3.1±1.1 | -0.7±0.8 c |
| Oral liquid of the present invention | 112 | 3.7±1.7 | 3.0±1.9 | -0.7±0.7 cd | |
| Apo Ai (g/L) | XUEZHINING WAN | 53 | 1.29±0.25 | 1.31±0.21 | -0.02±0.18 a |
| Oral liquid of the present invention | 52 | 1.2±0.3 | 1.91±0.29 | -0.10±0.13 cf | |
| Apo B100 (g/L) | XUEZHINING WAN | 34 | 1.05±0.27 | 0.99±0.24 | -0.06±0.19 a |
| Oral liquid of the present invention | 46 | 1.06±0.25 | 0.94±0.25 | -0.12c±0.16 cc | |
| TC-HDL-Ch/ HDL-Ch | XUEZHINING WAN | 112 | 4.4±1.7 | 3.1±1.1 | -1.3cd±1.3 c |
| Oral liquid of the present invention | 114 | 4.6±1.7 | 3.0±1.5 | -1.6±2.3 cd |
Relatively check before and after the treatment through t:
aP＞0.05,
CP＜0.01; Relatively check between group through t:
dP＞0.05,
cP＜0.05,
fP＜0.01.
2.2.3 doing well,improving situation: oral liquid group of the present invention is being improved that patient's limbs are sleepy, uncomfortable in chest, better action is being arranged aspect the tcm symptoms such as chest pain, indigestion and loss of appetite, distension and fullness in the abdomen, but with XUEZHINING WAN group difference nonsignificance (P＞0.05) relatively, see Table 3.
2 groups of doing well,improvings of table 3 are (example) relatively
| Symptom | The XUEZHINING WAN group | Oral liquid group of the present invention | ||
| Before the treatment | After the treatment | Before the treatment | After the treatment | |
| The indigestion and loss of appetite distension and fullness in the abdomen of the sleepy feeling of oppression and pain in the chest of limbs | 93 72 61 113 118 | 21 c 24 c 27 c 27 c 44 c | 117 76 84 109 112 | 48 cd 22 cd 42 cd 24 cd 36 cd |
Compare through X before and after 2 groups of treatments
2Check
CP＜0.01; Compare through X between 2 groups of treatment back groups
2Check:
dP＞0.05.
2.3 safety evaluatio
2.3.1 the adverse events incidence rate relatively
2.3.2 untoward reaction tabulation
3. clinical trial discussion
Modern medicine study, the generation of hyperlipidemia is dirty relevant with the liver spleen kidney three of the traditional Chinese medical science, wherein close with the kidney relation of the traditional Chinese medical science, hyperlipidemia is this with weakened body resistance, expectorant is turbid, blood stasis is mark, and the traditional Chinese medical science is suffered from a deficiency of the kidney, and can to belong to hypothalamus-hypophysis-target gland s function low, some hypothalamic and pituitary hormone have environment dynamic equilibrium in the combined regulating blood fat directly or indirectly from steady function.Suffering from a deficiency of the kidney to make the HDL-CH level reduce, a little less than the atherosclerosis ability.TC increases relevant with insufficiency of kidney-YANG, and TG increases relevant with deficiency of the kidney yin, and the relation that all is proportionate.The effect of the invigorating the liver and kidney of monarch drug Radix Polygoni Multiflori, benefiting essence-blood in the side, and mend and not dry, can reduce TC, TG, can improve HDL again; Be improved superoxide dismutase activity and increase the vigor of endogenous free radical and cleaning system of modern pharmacological research proof Radix Polygoni Multiflori and Fructus Crataegi suppresses the generation of low density lipoprotein, LDL, makes its decline, thereby reaches prevention and treat atherosclerotic purpose.
This clinical trial proves: oral liquid of the present invention contains Radix Polygoni Multiflori Preparata, Fructus Crataegi, Pollen Typhae, Rhizoma Alismatis, Folium Nelumbinis, Semen Cassiae (stir-fry), with XUEZHINING the effect of hypercholesterolemia reducing and triglyceride is arranged all, but oral liquid of the present invention is aspect hypercholesterolemia reducing, obviously be better than XUEZHINING, this may obviously to be better than XUEZHINING aspect the APOB100 relevant reducing with oral liquid of the present invention; This is relevant with the Pollen Typhae and the Rhizoma Alismatis that are contained in the prescription, prove according to modern pharmacological research: Pollen Typhae utilizes phytosterol can suppress the hydrolysis of sterin in the enteric cavity and the fatization again of the interior free sterin of intestinal wall, and occupy the position of micelle inner cholesterol competitively, influence the chance that cholesterol contacts with intestinal mucosa, to prevent its absorption; The Rhizoma Alismatis effective ingredient is a triterpenoid compound, can influence the decomposition of fat, reduce the synthetic of cholesterol raw material (S-acetyl-coenzyme-A), thereby influence the synthetic of TC, and there is the prevention lipoids in serum, to be detained or to be penetrated into the ability of tremulous pulse inwall, promote transportation and the removing of TC in the blood plasma, and the HDL that can raise.So three lotus oral liquids curative effect aspect atherosclerosis also is better than XUEZHINING.
In sum: oral liquid of the present invention has effect for reducing blood fat preferably, and mends with rushing down and combine the report that has no adverse reaction.Therefore we think that oral liquid of the present invention is a kind of determined curative effect, safe and reliable lipid-regulation medicine.
Claims (8)
1, a kind of pharmaceutical composition for the treatment of hyperlipidemia, the composition and the weight portion ratio that it is characterized in that making the crude drug of this medicine are: Radix Polygoni Multiflori Preparata 80-120 part, Fructus Crataegi 80-120 part, Folium Nelumbinis 45-72 part, Rhizoma Alismatis 60-95 part, Pollen Typhae 80-120 part, Semen Cassiae (parched) 60-95 part.
2, the pharmaceutical composition of treatment hyperlipidemia according to claim 1, wherein the consumption of each crude drug is: 100 parts of Radix Polygoni Multiflori Preparatas, 100 parts of Fructus Crataegis, 60 parts on Folium Nelumbinis, 75 parts of Rhizoma Alismatis, 100 parts of Pollen Typhaes, 75 parts of Semen Cassiae (parched).
3, the preparation of drug combination method of claim 1 or 2 described treatment hyperlipidemias, comprise the following steps: that extraction of active ingredients adopts decoction and alcohol sedimentation technique: above Six-element medicine adds 6-14 times of water gaging immersion after 6-12 hour by recipe quantity, heating decocts extracts secondary, each half an hour, filter, merging filtrate, be evaporated to proportion 1.05-1.10, add 2-4 and doubly measure 95% ethanol, left standstill 12-48 hour, filter, decompression filtrate recycling ethanol is not to there being the alcohol flavor, and to be condensed into relative density be that the clear paste of 1.05-1.40 is standby.
4, the preparation of drug combination method of treatment hyperlipidemia according to claim 3 is characterized in that the clear paste of preparation is added conventional oral formulations adjuvant, makes corresponding oral formulations.
5. the preparation of drug combination method of treatment hyperlipidemia according to claim 4 is characterized in that the clear paste of preparation is added water to full dose, filters, and fill, sterilization promptly gets oral liquid.
6, the preparation of drug combination method of treatment hyperlipidemia according to claim 4 is characterized in that 1 part of qinghuo reagent, lactose 2.5-5 part, dextrin 0.1-1 part, that correctives reaches ethanol in right amount is an amount of, makes granule, and drying promptly gets granule.
7, the preparation of drug combination method of treatment hyperlipidemia according to claim 4 is characterized in that 1 part of qinghuo reagent, starch 0.5-3 part, dextrin 0.1-1 part, that magnesium stearate reaches ethanol in right amount is an amount of, makes granule, dry, tabletting, coating promptly gets tablet.
8, the preparation of drug combination method of treatment hyperlipidemia according to claim 4 is characterized in that 1 part of qinghuo reagent, starch 0.5-3 part, dextrin 0.1-2 part, makes granule, and drying is encapsulated, promptly gets capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102670869B (en) * | 2012-06-04 | 2014-01-08 | 黄芸 | Chinese medicine oral fluid containing cattail pollen for relieving hyperlipoidemia and preparing method thereof |
| CN102886024A (en) * | 2012-10-10 | 2013-01-23 | 湖北省宏源药业有限公司 | Composition with function of aiding to reduce blood fat and preparation method of composition |
| CN104055962A (en) * | 2013-03-22 | 2014-09-24 | 王文才 | Dietotherapy composition for reducing blood lipid |
| CN103285275A (en) * | 2013-06-18 | 2013-09-11 | 冯宇伟 | Medicament for preventing and treating atherosclerosis and preparation method thereof |
| CN103330097B (en) * | 2013-07-19 | 2014-09-03 | 杜兆侠 | Pet food with function of reducing blood lipid, as well as preparation method of pet food |
| CN104173495A (en) * | 2014-08-01 | 2014-12-03 | 通化新东日药业股份有限公司 | Jiangzhining granule and preparation method thereof |
| CN104288392A (en) * | 2014-11-07 | 2015-01-21 | 田丽华 | Traditional Chinese medicine for treating atherosclerosis |
| CN104435585A (en) * | 2015-01-03 | 2015-03-25 | 孟红琳 | Traditional Chinese medicine composition for treating phlegm stagnation middle energizer type hyperlipemia |
| CN104547779A (en) * | 2015-02-09 | 2015-04-29 | 王士国 | Lipid lowering and meridian unblocking medicament for treating chronic arteriosclerosis and preparation method of medicament |
| CN108272087A (en) * | 2018-01-30 | 2018-07-13 | 山东汇润膳食堂股份有限公司 | A kind of blood fat reducing food and preparation method thereof |
| CN108355087A (en) * | 2018-05-16 | 2018-08-03 | 重庆跃龙生物制药有限公司 | Chinese medicine composition and preparation method thereof for treating hyperlipemia |
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| CN1253809A (en) * | 1999-09-29 | 2000-05-24 | 周文志 | Chinese medicine tea for diluting blood fat |
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