CN101411765B - Use of Chinese medicinal composition in preparing medicament for treating metabolism syndrome - Google Patents
Use of Chinese medicinal composition in preparing medicament for treating metabolism syndrome Download PDFInfo
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Abstract
The invention discloses an application of a Chinese medicine composition to the preparation of a medicine for treating metabolic syndrome. Tests prove that the Chinese medicine composition has effects of reducing the blood sugar of the metabolic syndrome, regulating the blood fat, improving the impaired glucose tolerance and the like, and can also decrease the left ventricular end systolic volume, improve the systolic function of the heart and reduce the thickens of the carotid wall; moreover, while improving the heart function of the patient suffered from the metabolic syndrome, the invention can obviously improve the blood vessel function of the patient suffered from the metabolic syndrome, and has the effect of treating the metabolic syndrome.
Description
Technical field
The present invention relates to a kind of new purposes of Chinese medicine composition, particularly, the present invention relates to the application of a kind of Chinese medicine composition in the medicine of preparation treatment metabolic syndrome, belong to Chinese medicine application.
Background technology
Metabolic syndrome (MS) is under the stimulation of envirment factor, immunity and inflammation etc., by tumor susceptibility gene, produces, and morbidity is relevant with acquired, environment and hereditary factors, but the current cause of disease is not yet clear and definite, also lacks specific treatment.MS has the Clinical symptoms such as hypertension, hyperglycemia, lipid metabolic disorder, obesity, and principal character is insulin resistant (IR).The metabolism disorder of IR and secondary thereof be produce coronary heart disease, diabetes and hypertensive common soil [Stern. diabetes and cardiovascular disease: common soil hypothesis. diabetes 1995,44 (4): 369-374. (Stern MP.Diabetes and cardiovasculardisease:The " Common soil " hypothesis.Diabetes, 1995,44 (4): 369-374.)], the prognosis of above-mentioned disease is played to harmful effect.
The diagnostic criteria of MS has the ATPIII of u.s. national cholesterol education program (NCEP) and the diagnostic criteria of World Health Organization (WHO), and wherein the dyslipidemia in ATPIII diagnostic criteria connects IR and cardiovascular diseases's danger.Diabetes branches of Chinese Medical Association in 2004 suggestion is applicable to the MS diagnostic criteria of Chinese population, comprises overweight, blood pressure and fasting glucose raises, blood fat (triglyceride raises, HDL-C reduce) etc. is abnormal, has that wherein 3 above abnormal indexes are diagnosable.Central obesity, first at global unified definition MS, be take as core in IDF in 2005, merge blood pressure, blood glucose, triglyceride raises and or in reducing 2 of HDL-C can be diagnosed as MS.
At present treatment MS is that to take its different components be feature, the guide of each relevant component of take is basis, drug combination on the basis of therapeutic life change (therapeutic lifestyle changes, TLC), intervenes respectively the Clinical symptoms such as blood pressure, blood glucose, blood fat and obesity.This administrated method has evidence-based medicine EBM support, for there being the patient of organic change can bring the benefit for the treatment of, but the HDL and improve the medicine of IR of also not having at present significantly to raise.Rising HDL and improve IR, can improve the metabolism disorder of secondary, by strengthen cholesterol counter transport de-rotation pulse atherosclerosis [metabolism and the function of the molecular regulation of you .HDL of Randt: the prompting of new Therapeutic Method. clinical investigation .2006, 116 (12): 3090-100.2006, 116 (12): 3090-100. (Rader DJ.Molecular regulation of HDL metabolism andfunction:implications for novel therapies.J Clin Invest.2006, 116 (12): 3090-100.)], and may further improve patient's clinical prognosis.
Aspect adjusting lipid metabolism, conventional medicine is Statins, nicotinic acid class, the special class of shellfish, cholic acid chelating agent etc. at present, only has Statins and fibrate can improve prognosis, but limited to the improvement of low HDL and insulin resistant.Select and find significantly to raise HDL and improve the medicine of insulin resistant is current research direction.There is traditional advantage in China aspect Chinese medicine, therefrom may can search out effective medicine.
The present invention is the improvement invention of carrying out on the basis of No. 01131203.3 and No. 200410048292.2 patent, at this, quotes in full the content that this two patent document is recorded.The application of unexposed this Chinese medicine composition of above-mentioned two patents in the medicine of preparation treatment metabolic syndrome.The present invention has carried out correlational study on its basis, and the application of this Chinese medicine composition in the medicine of preparation treatment metabolic syndrome is provided.
Summary of the invention
The object of the invention is to provide the application of a kind of Chinese medicine composition in the medicine of preparation treatment metabolic syndrome, and described Chinese medicine composition is made by the crude drug of following weight portion:
Radix Ginseng 3-10 Hirudo 3-11 Eupolyphaga Seu Steleophaga 5-10 Olibanum (system) 1-5 Radix Paeoniae Rubra 3-9 Lignum Dalbergiae Odoriferae 1-5
Lignum Santali Albi 1-5 Scorpio 3-9 Periostracum Cicadae 3-12 Scolopendra 1-3 Borneolum Syntheticum 1-7 Semen Ziziphi Spinosae (stir-fry) 3-10;
Preferably, this Chinese medicine composition is made by the crude drug of following weight portion:
Radix Ginseng 6 Hirudo 10 Eupolyphaga Seu Steleophaga 7 Olibanums (system) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferaes 2
Lignum Santali Albi 2 Scorpio 7 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosaes (stir-fry) 5; Or:
Radix Ginseng 10 Hirudo 8 Eupolyphaga Seu Steleophaga 7 Olibanums (system) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferaes 2
Lignum Santali Albi 2 Scorpio 9 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosaes (stir-fry) 5; Or:
Radix Ginseng 6 Hirudo 11 Eupolyphaga Seu Steleophaga 7 Olibanums (system) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferaes 2
Lignum Santali Albi 2 Scorpio 3 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosaes (stir-fry) 5;
More preferably, the active component of above-mentioned Chinese medicine composition is comprised of following ingredients:
A mean diameter is less than Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga, Periostracum Cicadae and the Olibanum (processed) medicated powder of 100 μ m;
B Borneolum Syntheticum medicated powder;
The volatile oil that c is extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi;
D Radix Ginseng is the alcohol-extracted extract after concentrated with the alcohol extract after ethanol extraction;
The water extracted immersing paste being condensed into after water extraction liquid after Lignum Dalbergiae Odoriferae after e extraction composition c and water extraction liquid, Radix Paeoniae Rubra and the Semen Ziziphi Spinosae (parched) of Lignum Santali Albi medicinal residues decoct with water and the water extraction liquid of the medicine residues of Radix Ginseng after extraction ingredient d filter, mix.
The invention also discloses that to contain above-mentioned Chinese medicine composition be capsule, tablet, granule, powder, oral liquid or pill as the pharmaceutical preparation of active component.
The present invention also provides this Chinese medicine composition to improve the application in the medicine of metabolic syndrome cardiac function in preparation.
The present invention also provides this Chinese medicine composition to improve the application in the medicine of metabolic syndrome vascular function in preparation.
In Chinese medicine composition of the present invention, as the title of the crude drug of active component and Preparation process method thereof from < < Chinese medicine voluminous dictionary > > (in July, 1977, front page, Shanghai science tech publishing house) and < < Chinese Pharmacopoeia > > (2005 Nian Ban， Chemical Industry Press).
Chinese medicine composition of the present invention can also be routinely extraction and preparation process, for example, the preparation technology that the green booth < of model < pharmacy of Chinese materia medica > > (Shanghai Science Press 1997 December the 1st edition) records, make the acceptable any conventional dosage form of pharmaceutics, such as capsule, tablet, granule, powder, oral liquid or pill etc.
In application of the present invention, described Chinese medicine composition is a kind of in capsule, tablet, granule, powder, oral liquid or pill preparation, for above-mentioned dosage form can be realized, need when these dosage forms of preparation, add the acceptable adjuvant of pharmacy, such as: filler, disintegrating agent, lubricant, suspending agent, binding agent, sweeting agent, correctives, antiseptic, substrate etc.Filler comprises: starch, pregelatinized Starch, lactose, mannitol, chitin, microcrystalline Cellulose, sucrose etc.; Disintegrating agent comprises: starch, pregelatinized Starch, microcrystalline Cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose etc.; Lubricant comprises: magnesium stearate, sodium lauryl sulphate, Pulvis Talci, silicon dioxide etc.; Suspending agent comprises: polyvinylpyrrolidone, microcrystalline Cellulose, sucrose, agar, hydroxypropyl emthylcellulose etc.; Binding agent comprises, starch slurry, polyvinylpyrrolidone, hydroxypropyl emthylcellulose etc.; Sweeting agent comprises: saccharin sodium, Aspartane, sucrose, cyclamate, enoxolone etc.; Correctives comprises: sweeting agent and various essence; Antiseptic comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its esters, benzalkonium bromide, acetic acid chloroethene are determined, Folium eucalypti globueli (Eucalyptus globulus Labill.) wet goods; Substrate comprises: PEG6000, PEG4000, insect wax etc.
Preparation of the present invention is preferably made by following preparation method: the five kinds of Chinese medicine such as the Hirudo of said ratio, Scorpio, Periostracum Cicadae, Eupolyphaga Seu Steleophaga, Scolopendra cleaned, and oven drying at low temperature, standby; Lignum Santali Albi, Lignum Dalbergiae Odoriferae extract volatile oil, and medicinal residues and aqueous solution are standby; Radix Ginseng extracts secondary with 70% alcohol heating reflux, and 3 hours for the first time, 2 hours for the second time, merge extractive liquid,, reclaimed ethanol extremely without alcohol taste; The medicinal residues of medicine residues of Radix Ginseng and Lignum Santali Albi, Lignum Dalbergiae Odoriferae merge with aqueous solution, add Radix Paeoniae Rubra, Semen Ziziphi Spinosae (stir-fry), decoct with water secondary, 3 hours for the first time, 2 hours for the second time, collecting decoction, filters, and filtrate is concentrated into the clear paste that relative density is 1.20-1.25 (60 ℃), add above-mentioned panaxynol extract, mix, cold drying, is ground into fine powder; The five tastes such as Olibanum (system) and Hirudo are ground into fine powder altogether; Borneolum Syntheticum porphyrize, with above-mentioned fine powder facing-up, mixes respectively, sprays into volatile oil, mixes, and incapsulates, and obtains.
Or preparation of the present invention is preferably made by following preparation method:
A) weight ratio of crude drug is: Radix Ginseng 3-10 part, Hirudo 3-11 part, Eupolyphaga Seu Steleophaga 5-10 part, Olibanum (processed) 1-5 part, Radix Paeoniae Rubra 3-9 part, Lignum Dalbergiae Odoriferae 1-5 part, Lignum Santali Albi 1-5 part, Scorpio 3-9 part, Periostracum Cicadae 3-12 part, Scolopendra 1-3 part, Borneolum Syntheticum 1-7 part, Semen Ziziphi Spinosae (parched) 3-10 part;
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter be less than 100 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae decoct with water again, after water extraction liquid filters, and one-tenth extractum to be concentrated; Radix Ginseng is with after ethanol extraction, then uses water extraction, and alcohol extract reclaims after ethanol, is condensed into alcohol-extracted extract, and water extraction liquid is condensed into the water extracted immersing paste after filtering and mixing with all water extraction liquid;
D) preparation process:
In Fluidbedgranulatingdrier, adding superfine powder flour, then by step c) gained extracts extractum and sprays into granulation; The granule of making, through granulate, is added to Borneolum Syntheticum fine powder, spray into the volatile oil being extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, after mixing, by capsule filler filling, make capsule.
Or preparation of the present invention is preferably made by following preparation method:
A) weight ratio of crude drug is: Radix Ginseng 3-10 part, Hirudo 3-11 part, Eupolyphaga Seu Steleophaga 5-10 part, Olibanum (system) 1-5 part, Radix Paeoniae Rubra 3-9 part, Lignum Dalbergiae Odoriferae 1-5 part, Lignum Santali Albi 1-5 part, Scorpio 3-9 part, Periostracum Cicadae 3-12 part, Scolopendra 1-3 part, Borneolum Syntheticum 1-7 part, Semen Ziziphi Spinosae (parched) 3-10 part;
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter be less than 100 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae decoct with water again, after water extraction liquid filters, and one-tenth extractum to be concentrated; Radix Ginseng is with after ethanol extraction, then uses water extraction, and alcohol extract reclaims after ethanol, is condensed into alcohol-extracted extract, and water extraction liquid is condensed into the water extracted immersing paste after filtering and mixing with all water extraction liquid, and extractum Direct spraying is dried to spray powder;
D) preparation process:
By superfine powder flour and step c) be added in Fluidbedgranulatingdrier together with gained spray drying powder, then spray solvent granulation; The granule of making, through granulate, is added to Borneolum Syntheticum fine powder, spray into the volatile oil being extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, after mixing, by capsule filler filling, make capsule.
The compound preparation that medicine of the present invention is comprised of Radix Ginseng, Hirudo, Scorpio, Eupolyphaga Seu Steleophaga, Radix Paeoniae Rubra, Periostracum Cicadae etc., the effect that medicine of the present invention has blood circulation promoting and blood stasis dispelling, blood fat reducing, anticoagulant, reduction platelet aggregation and sticks.After pharmaceutical intervention MS rat 4 weeks, low, high dose medicine group of the present invention body weight and blood pressure all reduce compared with matched group.After propylthiouracil adds high lipid food, the more general food group of body weight declines, may be relevant with this medicine inhibition rat appetite and basal metabolism.Intervention group body weight lower than matched group and self modeling after, illustrate that medicine of the present invention has the effect that reduces body weight; High dose group blood pressure is compared with significantly declining after self modeling, and that low dose group changes is little, and prompting high dose medicine of the present invention may have the effect of blood pressure lowering.
Biochemical indicator from intervening, low, high dose medicine group of the present invention all can reduce the fasting glucose of rat, and rising HDL reduces c reactive protein and LDL/HDL level.Because lipid metabolism feature and the mankind of rat are different, so the variation situation of its triglyceride is larger, after pharmaceutical intervention, do not produce curative effect.
Medicine of the present invention is low, high dose group all can reduce T-CHOL, and relevant to dosage.LDL is had to the trend of reduction and relevant to dosage, but do not reach significant difference.Medicine of the present invention is on not impact of Fibrinogen.The equal difference of hepatic and renal function of respectively organizing rat after intervention is little, illustrates that high fat diet and medicine are little on hepatic and renal function impact.
The result of carbohydrate tolerance test is presented at after pharmaceutical intervention, after oral glucose 15,30,60 and 120 minutes, the instant blood glucose of drug intervention groups of the present invention all significantly declines compared with matched group, illustrates that the use of medicine of the present invention can significantly improve the degree of experimental MS rat impaired glucose tolerance.Pharmaceutical intervention group of the present invention is higher than each time point blood glucose value of Wistar rat carbohydrate tolerance test, but be better than normal diet, feeds SHR group rat.
Echocardiography shows that low dosage pharmaceutical intervention group of the present invention EF, FS significantly increase compared with matched group, and ESV reduces, and high dose group has the trend increasing but do not reach significant difference.These results suggest that medicine of the present invention has the advantages that to improve myocardium shrinkage function.That carotid ultrasound is shown is low, high dose medicine of the present invention all significantly reduces right carotid wall thickness, and relevant to dosage.Studies have shown that in a large number carotid wall thickness is the sensitive indicator of reaction systemic atherosclerosis degree, MS rat model carotid wall thickness is the highest, and after Drug therapy of the present invention, there is the effect of the minimizing carotid wall thickness that dosage is relevant, illustrate that this medicine has significant study of anti-atherogenic effect, high dose is especially obvious.And produce these effect, may with the carbohydrate metabolism that improves MS rat, Blood pressure drop, the HDL that especially raises is relevant.
Use Drug therapy MS of the present invention all to there is the body weight of reduction, blood pressure, fasting glucose, blood fat, rising HDL, reduce LDL/HDL, improve impaired glucose tolerance, reduce the effect that left chamber is shunk last volume and strengthened cardiac systolic function, and be dose dependent reduction carotid wall thickness, and there is antiatherogenic effect, to the treatment of MS, may there is good prospect.
The consumption of pharmaceutical composition of the present invention, is converted to the weight of raw medicinal material, is each 0.8-3 gram, and take 2-4 every day, is preferably each 1.11-2.22 gram, takes every day three times.
The specific embodiment
Embodiment 1:
A) crude drug formula is:
Radix Ginseng 39.6g Hirudo 72.6g Eupolyphaga Seu Steleophaga 46.2g Olibanum (system) 13.2g
Radix Paeoniae Rubra 33g Lignum Dalbergiae Odoriferae 13.2g Lignum Santali Albi 13.2g Scorpio 19.8g
Periostracum Cicadae 46.2g Scolopendra 6.6g Borneolum Syntheticum 33g Semen Ziziphi Spinosae (stir-fry) 33g;
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter be less than 30-40 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae add suitable quantity of water and decoct secondary again, and each 3 hours, merge water extraction liquid, after filtration, one-tenth extractum to be concentrated; Appropriate 70% ethanol extraction secondary for Radix Ginseng, each 3 hours, merge extractive liquid,, reclaim ethanol extremely without alcohol taste, use again water extraction, it is 0.9～1.1 (60 ℃) alcohol-extracted extract that alcohol extract is condensed into relative density, and water extraction liquid is concentrated into the clear paste that relative density is 0.9～1.1 (60 ℃) after filtering and mixing with above-mentioned all water extraction liquid, standby;
D) preparation process:
In Fluidbedgranulatingdrier, adding superfine powder flour, then by step c) gained extracts extractum and sprays into granulation; The granule of making, through granulate, is added to Borneolum Syntheticum fine powder, spray into the volatile oil being extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, after mixing, by capsule filler filling, make 1000 capsules.
The consumption of medicine of the present invention, for each 2-4 grain, takes three times every day.
For illustrating the therapeutic activity of Chinese medicine composition of the present invention to metabolic syndrome, with the Capsule content fine powder making by above-described embodiment 1 method (hereinafter referred to as medicine of the present invention), carried out following test to prove its curative effect, but it can not form any restriction to scope of the present invention.
experimental example:
The therapeutical effect of medicine of the present invention to metabolic syndrome rat model
1, materials and methods
1.1 laboratory animals and grouping are divided into general food matched group (A group), MS model control group (B group), low dosage medication therapy groups of the present invention (C group) and high dose medication therapy groups of the present invention (D group) at random by the bull spontaneous hypertensive rat (SHR) of body weight 300～400g 32 (being purchased from Shanghai Slac Experimental Animal Co., Ltd.), and to take 10 of male Wistar rats be general food reference matched group (E group).
Each group rat is weighed in 1.2 experimental model preparations, measure after blood pressure and tail venous blood sampling, A, E group are fed with normal diet, B-D group is with high lipid food (10% Adeps Sus domestica containing propylthiouracil, 10% sucrose, cholesterol 4% and normal feedstuff etc.) feed altogether modeling 4w wherein, pharmaceutical intervention 4w 8 weeks.After modeling, measure blood pressure and tail venous blood sampling and measure biochemical indicator, determine and set up MS animal model.
1.3 medicines of the present invention (Hebei Yi Ling Pharmaceutical Group provides) are with low dosage (0.2g/kg) to C group, and high dose (0.8g/kg), to the treatment of D group gavage, 1 times/day, is treated 4 weeks altogether.
1.4 arteria caudalis blood pressure measurements by rat 38 ℃ of lucifuge oven heat after 5-10 minute, adopt physiograph (Powerlab, Australia) measure rat tail artery blood pressure, choosing wherein 3 times (differing in 10mmHg between each measured value) is averaged as rat blood pressure.
1.5 biochemical indicators are measured after modeling and intervention, by rat limosis 12h, from tail venous blood sampling 2mL is centrifugal, get blood plasma, adopt automatic biochemistry analyzer (Beckman LX20, the U.S.) to carry out Analysis of Biochemical.
When 4w is intervened in 1.6 oral glucose tolerance tests (OGTT), each group rat limosis was weighed after 12 hours, from tail vein end otch, get blood 50 μ L, adopt blood glucose meter (Advantage IV, Germany Roche Holding Ag) measure fasting glucose, with 20% glucose solution, with 2g/kg, to each, organize rat oral gavage again, after gavage, from tail vein end incision, get the same mensuration of blood 50 μ L blood glucose at once 15,30,60 and 120 minutes time.
When 1.7 echocardiography cardiac function are intervened 4w, after each group rat is anaesthetized with stable (3mg/kg) and ketamine (30mg/kg), adopt ultrasound cardiograph (the Vivid I of General Electric (U.S.A.)) to measure Cardiac Function in Rat index, row carotid ultrasound is measured internal diameter of carotid and wall thickness simultaneously.
1.8 statistical procedures test datas all with
represent, adopt SPSS11.5 statistical software to carry out statistical analysis, each is organized mean and relatively uses multivariate analysis of variance, and P < 0.05 is significant difference.
2, result
After 2.1 body weight and the modeling of blood pressure index and intervention, C group body weight, blood pressure are all lower than matched group.D modeling and intervene after body weight lower than B group, after blood pressure modeling with B group zero difference, after intervention lower than B group (P < 0.05).E group body weight and blood pressure are all lower than B group, in Table 1.
Table 1 respectively organize body weight, blood pressure determination value (n=8-10,
)
Each group compares with B group
ap < 0.05
2.2 biochemical indicators are respectively organized hepatic and renal function Non Apparent Abnormality, in Table 2.
Table 2 after intervening, respectively organize hepatic and renal function index comparison (n=5-10,
)
Each group compares with B group
ap < 0.05
After table 3 pharmaceutical intervention, respectively organize fasting glucose, blood fat, c reactive protein and fibrinogen assay value
Each group compares * P < 0.05, * * P < 0.01 with B group.
2.3 oral glucose tolerance tests (OGTT) show that C, D group impaired glucose tolerance significantly improves, in Table 3.
After table 3 pharmaceutical intervention, respectively organize the comparison of blood glucose after glucose gavage
| Grouping | A group | B group | C group | D group | E group |
| 0 minute | 4.71±0.47 | 5.25±1.26 | ?4.52±0.87 | 4.15±0.84* | 4.62±0.86 |
| 15 minutes | 8.83±1.61 | 7.61±1.52 | ?5.82±1.87* | 4.96±0.80** | 5.51±0.76** |
| 30 minutes | 9.48±1.06 | 8.87±1.76 | ?7.06±1.98* | 6.72±1.43** | 5.43±0.44** |
| 60 minutes | 9.21±1.62* | 11.44±3.08 | ?7.62±2.60** | 9.14±1.41* | 5.27±0.54** |
| 120 minutes | 6.44±2.75** | 10.84±4.00 | ?6.77±1.59** | 7.87±2.82* | 4.41±0.46** |
Each group compares * P < 0.05, * * P < 0.01 with B group.
2.4 echocardiography C, D group ESV, LVsMass reduce compared with B group, and C group EF, FS significantly raise compared with B group, and D group has the trend of rising.There was no significant difference between each group of other indexs, in Table 4.
Table 4 after intervening, respectively organize echocardiographic parameters comparison (n=8-10,
)
Each group compares aP < 0.05 with B group
2.5 carotid ultrasonography show that C, D group all reduces carotid artery thickness and relevant to dosage, in Table 5.
Table 5 after intervening, respectively organize Carotid Artery comparison (n=8-10,
)
| Grouping | A group | B group | C group | D group | E group |
| Internal diameter of carotid (cm) | 0.21±0.02 | ?0.20±0.05 | ?0.22±0.03 | 0.22±0.01 | 0.23±0.04 a |
| Carotid artery thickness (mm) | 0.70±0.07 | ?0.80±0.15 | ?0.63±0.16 a | 0.47±0.07 a | 0.50±0.15 a |
Each group compares aP < 0.01 with B group
3, conclusion
We using male spontaneous hypertensive rat (SHR) as experimental subject, and with the male Wistar rat of same strain in contrast, set up MS animal model.Indices shows that SHR rat exists hypertension, hyperglycemia, impaired glucose tolerance, inflammation state of activation, HDL reduces and Fibrinogen increasing high relatively, by the high lipid food containing propylthiouracil, feed and amplified impaired glucose tolerance and the relative degree reducing of HDL, strengthened inflammatory reaction, can be as much as possible and the feature matching of clinical MS.
After pharmaceutical intervention MS rat 4 weeks, medicine of the present invention is low, high dose group body weight and blood pressure all reduce compared with matched group.After propylthiouracil adds high lipid food, the more general food group of body weight declines, may be relevant with this medicine inhibition rat appetite and basal metabolism.Intervention group body weight lower than matched group and self modeling after, illustrate that medicine of the present invention has the effect that reduces body weight; High dose group blood pressure is compared with significantly declining after self modeling, and that low dose group changes is little, and prompting high dose medicine of the present invention may have the effect of blood pressure lowering.
Biochemical indicator from intervening, medicine of the present invention is low, high dose group all can reduce the fasting glucose of rat, and rising HDL reduces c reactive protein and LDL/HDL level.Because lipid metabolism feature and the mankind of rat are different, so the variation situation of its triglyceride is larger, after pharmaceutical intervention, do not produce curative effect.
Medicine of the present invention is low, high dose group all can reduce T-CHOL, and relevant to dosage.LDL is had to the trend of reduction and relevant to dosage, but do not reach significant difference.Medicine of the present invention is on not impact of Fibrinogen.The equal difference of hepatic and renal function of respectively organizing rat after intervention is little, illustrates that high fat diet and medicine are little on hepatic and renal function impact.
The result of carbohydrate tolerance test is presented at after pharmaceutical intervention, after oral glucose 15,30,60 and 120 minutes, the instant blood glucose of drug intervention groups of the present invention all significantly declines compared with matched group, illustrates that the use of medicine of the present invention can significantly improve the degree of experimental MS rat impaired glucose tolerance.Pharmaceutical intervention group of the present invention is higher than each time point blood glucose value of Wistar rat carbohydrate tolerance test, but be better than normal diet, feeds SHR group rat.
Echocardiography shows that low dosage pharmaceutical intervention group of the present invention EF, FS significantly increase compared with matched group, and ESV reduces, and high dose group has the trend increasing but do not reach significant difference.These results suggest that medicine of the present invention has the advantages that to improve myocardium shrinkage function.That carotid ultrasound is shown is low, high dose medicine of the present invention all significantly reduces right carotid wall thickness, and relevant to dosage.Studies have shown that in a large number carotid wall thickness is the sensitive indicator of reaction systemic atherosclerosis degree, MS rat model carotid wall thickness is the highest, and after Drug therapy of the present invention, there is the effect of the minimizing carotid wall thickness that dosage is relevant, illustrate that this medicine has significant study of anti-atherogenic effect, high dose is especially obvious.And produce these effect, may with the carbohydrate metabolism that improves MS rat, Blood pressure drop, the HDL that especially raises is relevant.
Use Drug therapy MS of the present invention all to there is the body weight of reduction, blood pressure, fasting glucose, blood fat, rising HDL, reduce LDL/HDL, improve impaired glucose tolerance, reduce the effect that left chamber is shunk last volume and strengthened cardiac systolic function, and be dose dependent reduction carotid wall thickness, and there is antiatherogenic effect, to the treatment of MS, may there is good prospect.
Claims (1)
1. Chinese medicine composition is treated the application in the medicine that improves impaired glucose tolerance in metabolic syndrome in preparation, and described Chinese medicine composition is prepared by the following method:
A) crude drug formula is:
Radix Ginseng 39.6g Hirudo 72.6g Eupolyphaga Seu Steleophaga 46.2g Olibanum (processed) 13.2g
Radix Paeoniae Rubra 33g Lignum Dalbergiae Odoriferae 13.2g Lignum Santali Albi 13.2g Scorpio 19.8g
Periostracum Cicadae 46.2g Scolopendra 6.6g Borneolum Syntheticum 33g Semen Ziziphi Spinosae (parched) 33g;
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter be less than 30-40 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae add suitable quantity of water and decoct secondary again, and each 3 hours, merge water extraction liquid, after filtration, one-tenth extractum to be concentrated; Appropriate 70% ethanol extraction secondary for Radix Ginseng, each 3 hours, merge extractive liquid,, reclaim ethanol extremely without alcohol taste, use again water extraction, it is 0.9～1.1 alcohol-extracted extract that alcohol extract is condensed into 60 ℃ of mensuration relative densities, and water extraction liquid is concentrated into 60 ℃ after filtering and mixing with above-mentioned all water extraction liquid and measures the clear paste that relative densities are 0.9～1.1, standby;
D) preparation process:
In Fluidbedgranulatingdrier, adding superfine powder flour, then by step c) gained extracts extractum and sprays into granulation; The granule of making, through granulate, is added to Borneolum Syntheticum fine powder, spray into the volatile oil being extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, after mixing, by capsule filler filling, make 1000 capsules.
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| CN1124153C (en) * | 2001-08-31 | 2003-10-15 | 石家庄以岭药业股份有限公司 | Medicinal composition for restoring cardiac collaterals and its application |
| CN1709291A (en) * | 2004-06-18 | 2005-12-21 | 河北以岭医药研究院有限公司 | Supermicro heart-meridians-activating Chinese medicine composition and its preparing method |
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| CN1124153C (en) * | 2001-08-31 | 2003-10-15 | 石家庄以岭药业股份有限公司 | Medicinal composition for restoring cardiac collaterals and its application |
| CN1709291A (en) * | 2004-06-18 | 2005-12-21 | 河北以岭医药研究院有限公司 | Supermicro heart-meridians-activating Chinese medicine composition and its preparing method |
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| 国家药典委员会.通心络胶囊.《中华人民共和国药典 2005年版第一部》.化学工业出版社,2005,第586页. * |
| 通心络对实验性代谢综合症动物模型的治疗作用;黄晓忠等;《第二届国际络病学大会论文集》;20061001;第264-265页 * |
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