CN1833703A - Medicine for treating peripheral nervous disease of diabets mellitus and prepn. method - Google Patents
Medicine for treating peripheral nervous disease of diabets mellitus and prepn. method Download PDFInfo
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Abstract
A Chinese medicine for treating the diabetic peripheral neuropathy is prepared from 13 Chinese-medicinal materials including astragalus root, rehmannia root, Chuan-xiong rhizome, Chinese angelica root, etc. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of medicine that is used for the treatment of diabetic peripheral neuropathy and preparation method thereof, belong to the Chinese herbal and crude drugs preparations technical field.Be mainly used in the treatment diabetic peripheral neuropathy clinically, card belongs to deficiency of both QI and YIN, channels numbness type.Disease is seen numb limbs and tense tendons, is sent out cool, pain, acroparesthesia, the soft unable disease of waiting of limb.
Background technology
Reached 30,000,000 China diabetes patient, had 100,012,000 approximately in the worldwide.According to the prediction of WHO latest data, Chinese diabetes number will reach present 4 times by 2010, and the whole world will have 2.4 hundred million diabetes patients.The West Pacific region is the Diabetes Epidemiological Investigation result show, the westization of people's lives is key factors that the onset diabetes rate increases, and non-insulin-dependent diabetes mellitus reaches 5-10% unexpectedly in crowd more than 40 years old.Although because the application of antibiotics and the appearance of insulin, diabetics is died from infection and the ketoacidosis person greatly reduces, but cardio cerebrovascular affection easily takes place in diabetes, arteriosclerotic incidence rate can reach 90%, and diabetic neuropathy, retinopathy, nephropathy become, and human beings'health and life are constituted increasing threat.Diabetic peripheral neuropathy (diabeticperipheral neuropathy, DPN) be one of diabetes modal three big chronic complicating diseases, its sickness rate can reach 90% with the prolongation of the course of disease, has become the one of the main reasons that causes the diabetics disability.
In recent years, progress along with diabetes and complication basic research thereof, as neural blood flow determination, the ultrastructure of neuropathy and enzyme dynamics, pathogenesis to DPN has had darker understanding, studies show that: metabolism disorder and vascular lesion play an important role, and neurotrophic factor, immune factor etc. also work simultaneously.These basic research have also promoted the process of clinical treatment, at the aldose reductase inhibitor (ARIs) of Developmental and Metabolic Disorder, anti-glycosylation preparation etc., be applied to prevention or treatment diabetic peripheral neuropathy, but the curative effect of medicine and safety wait further research; Neurotrophic factor also more and more comes into one's own in treatment, think to alleviate infringement to function of nervous system, but at present DPN is not still had specific Therapeutic Method, majority is emphasized Comprehensive Treatment, the main blood sugar control that also is, this is the basic measures of prevention neuropathy complication.
The Chinese medicine prevention diabetes have nearly 2,000 years history, and complete theoretical system and abundant clinical experience are arranged, and advantageous natural resources of Chinese medicinal materials is arranged, and the Chinese medicine diabetes hold out broad prospects, and especially the control to chronic complicating diseases of diabetes has more advantage.But lack very much this sick tcm product of treatment at present, performance Chinese medicine advantage, this sick Chinese medicine preparation of multipath research and development control is still very necessary.
Summary of the invention
The object of the present invention is to provide a kind of treatment evident in efficacy to treat medicine of diabetic peripheral neuropathy and preparation method thereof.
This drug invention people professor Wu Yiling finds the concealment of diabetic peripheral neuropathy onset in practice, slower development, and the state of an illness is touching, be difficult to speed more, meets the Clinical symptoms of pathogen usually intruding into collateral in protracted disease, and the network deficiency of vital energy stagnates, qi disease involving blood, finally causing the resistance of channels numbness is basic pathogenesis performance.Channels is the hinge and the path of defeated cloth of qi-blood-body fluid and circulation, has to ooze to moisten perfusion, connect the function that battalion defended, oozed mutually Tianjin blood, communication the exterior and the interior, and be the prerequisite of keeping its normal function so mechanism of qi is unobstructed, the network road is without hindrance.The numbness resistance of network road, QI and blood can not be oozed and be moistened perfusion, perforation battalion defends and then is prone to numb limbs and tense tendons pain, the lower limb weakness.Professor Wu Yiling thinks that deficiency of both QI and YIN is the pathologic basis of this disease, and new pathological factor is arranged again in the pathogen usually intruding into collateral in protracted disease.The deficiency of vital energy then blood is capable unable, obstruction of collaterals by blood stasis; Yin and fluid deficiency liquid exhausts, and anhydrous being difficult to sails a boat, and channels loses foster and causes the numbness resistance.Obstruction of collaterals by blood stasis, functional activity of QI being not smooth in the network, can make the stagnation of QI again is trouble, further increases the weight of the network resistance; With the passing of time the deficiency of YIN scorching, and liquid is thanks to pneumatic, and endogenous wind is gone into network, and the inadequate urgency of channels is obstructed; Heat in blood is fought mutually and is caused Yang Renei strongly fragrant, the cloudy blood of burning then, and blood deficiency susceptible again is cold, further consumes impairment of QI sun so that QI and blood and does not pass through and the card that changes.So treatment tightly centers on the purpose of collateral dredging, at the pathologic basis of deficiency of both QI and YIN, with invigorating qi and dredging collateral, it is main moistening logical the benefit, make logically with benefit, cooperate promoting blood circulation to remove obstruction in the collateral, the spasmolytic that relieves dizziness, high fever, infantile convulsions, epilepsy, etc. collateral dredging, the evil collateral dredging that looses dispels the wind, all methods such as hot warm cold expelling collateral dredging, normal to recover the channels function, ruton and pain is ended, play supplementing QI and nourishing YIN altogether, the effect of removing obstruction in the collateral to relieve pain.
At this disease deficiency in origin and excess in superficiality, the characteristics of simulataneous insufficiency and excessive, treatment should be with strengthening vital QI to eliminate pathogenic factors, with collateral dredging, pain relieving is purpose, at the pathologic basis of deficiency of both QI and YIN, with invigorating qi and dredging collateral, it is main moistening logical the benefit, makes logically with benefit, cooperates promoting blood circulation to remove obstruction in the collateral, the spasmolytic that relieves dizziness, high fever, infantile convulsions, epilepsy, etc. collateral dredging, the evil collateral dredging that looses that dispels the wind, all methods such as hot temperature cold expelling collateral dredging are normal to recover the channels function, play supplementing QI and nourishing YIN altogether, the effect of removing obstruction in the collateral to relieve pain.Medicine of the present invention is monarch drug with the Radix Astragali, with the Radix Rehmanniae, Caulis Spatholobi, Rhizoma Chuanxiong is ministerial drug, assistant is with Radix Angelicae Sinensis, the Rhizoma Anemarrhenae, Pheretima, Ramulus Mori, Radix Cynanchi Paniculati, Semen Litchi, Rhizoma Corydalis, Ramulus Cinnamomi, Herba Ephedrae, can supplementing QI and nourishing YIN Zhi Qiben, and can invigorate blood circulation again, dispel the wind, cold expelling, row stagnate to control its mark, treating both the principal and the secondary aspects of a disease at the same time, make channels logical, pain is ended, and healthy energy is multiple, then disease subtracts the body peace, promotes the rehabilitation of disease.
Medicine of the present invention is to be made by the crude drug of following weight portion ratio:
Radix Astragali 300-400 part Radix Rehmanniae 300-400 part Caulis Spatholobi 300-400 part Ramulus Cinnamomi 80-120 part
Radix Angelicae Sinensis 100-150 part Rhizoma Chuanxiong 150-200 part Semen Litchi 150-200 part Rhizoma Anemarrhenae 80-120 part
Ramulus Mori 80-120 part Radix Cynanchi Paniculati 80-120 part Rhizoma Corydalis 70-120 part Herba Ephedrae 50-100 part
Pheretima 30-60 part
The weight portion ratio of above-mentioned raw materials medicine is preferred:
170 parts of 136 parts of Rhizoma Chuanxiongs of 113 parts of Radix Angelicae Sinensis of 340 parts of Ramulus Cinnamomi of 340 portions of Caulis Spatholobis of 340 parts of Radix Rehmanniae of the Radix Astragali
68 parts in 91 portions of Herba Ephedraes of 102 parts of Rhizoma Corydalis of 113 parts of Radix Cynanchi Paniculatis of 113 parts of Ramulus Moris of 170 parts of Rhizoma Anemarrhenaes of Semen Litchi
45 parts of Pheretimas
Or:
150 parts of 100 parts of Rhizoma Chuanxiongs of 80 parts of Radix Angelicae Sinensis of 300 parts of Ramulus Cinnamomi of 300 portions of Caulis Spatholobis of 300 parts of Radix Rehmanniae of the Radix Astragali
50 parts in 70 portions of Herba Ephedraes of 80 parts of Rhizoma Corydalis of 80 parts of Radix Cynanchi Paniculatis of 80 parts of Ramulus Moris of 150 parts of Rhizoma Anemarrhenaes of Semen Litchi
30 parts of Pheretimas
Or:
200 parts of 150 parts of Rhizoma Chuanxiongs of 120 parts of Radix Angelicae Sinensis of 400 parts of Ramulus Cinnamomi of 400 portions of Caulis Spatholobis of 400 parts of Radix Rehmanniae of the Radix Astragali
100 parts in 120 portions of Herba Ephedraes of 120 parts of Rhizoma Corydalis of 120 parts of Radix Cynanchi Paniculatis of 120 parts of Ramulus Moris of 200 parts of Rhizoma Anemarrhenaes of Semen Litchi
60 parts of Pheretimas
Or:
150 parts of 150 parts of Rhizoma Chuanxiongs of 120 parts of Radix Angelicae Sinensis of 300 parts of Ramulus Cinnamomi of 300 portions of Caulis Spatholobis of 300 parts of Radix Rehmanniae of the Radix Astragali
100 parts in 120 portions of Herba Ephedraes of 120 parts of Rhizoma Corydalis of 120 parts of Radix Cynanchi Paniculatis of 120 parts of Ramulus Moris of 200 parts of Rhizoma Anemarrhenaes of Semen Litchi
60 parts of Pheretimas
Medicine of the present invention can be made the acceptable any conventional dosage form of pharmaceutics, for example capsule, tablet, pill, oral liquid etc. by preparation process routinely.
Medicine of the present invention can also be made by following preparation method:
1), the side's of getting Chinese crude drug, clean respectively, coarse crushing is about 5-10mm granule, in proportion weighing.
2) take by weighing the Radix Astragali, Herba Ephedrae, Ramulus Mori, Rhizoma Corydalis, Caulis Spatholobi, Rhizoma Chuanxiong, in proportion, add 8-12 respectively and doubly measure 50-80% ethanol, reflux, extract, 1-3 time, extraction time was respectively 1-3 hour.Filter, merge extractive liquid,, residue discards.Reclaim ethanol to there not being the alcohol flavor, be evaporated to relative density 1.02-1.06 (60 ℃ of heat are surveyed) fluid extract, standby.
3) take by weighing Ramulus Cinnamomi, Radix Angelicae Sinensis, Radix Cynanchi Paniculati, in proportion, add 5-8 times of water gaging, soaked 20-40 minute, steam distillation extracts volatile oil, carries time 5-8 hour, and volatile oil device is in addition collected.Decocting liquid filters, and is standby.
4) take by weighing Radix Rehmanniae, Semen Litchi, the Rhizoma Anemarrhenae, Pheretima, in proportion, and carry oil back residue and merge, add 8-12 times of water gaging, heating decocts 1-3 time, and the time was respectively 1-3 hour, filters, merge extractive liquid,, residue discards, and is evaporated to relative density 1.20-1.24 clear paste (60 ℃ of heat are surveyed), add 95% ethanol to determining alcohol 50-70%, 5-10 ℃ left standstill 18-36 hour, filtered, and decompression filtrate recycling ethanol is to there not being the alcohol flavor, be evaporated to relative density 1.02-1.06 (60 ℃ of heat are surveyed) fluid extract, standby.
5), with starch, the dextrin mixing is put in the spray granulation machine, alcohol extraction fluid extract and water extract-alcohol precipitation fluid extract is mixed spraying into granulation, granulate sprays into volatile oil, and is encapsulated airtight half an hour, promptly.
Perhaps, with step 1), 2), 3), 4) extract of preparation, formulation method is made capsule, pill, tablet or oral liquid routinely.
The specific embodiment
Example below in conjunction with the preparation of medicine capsule of the present invention, tablet, pill, oral liquid illustrates the specific embodiment of the present invention.
Embodiment 1:
170 parts of 136 parts of Rhizoma Chuanxiongs of 113 parts of Radix Angelicae Sinensis of 340 parts of Ramulus Cinnamomi of 340 portions of Caulis Spatholobis of 340 parts of Radix Rehmanniae of the Radix Astragali
68 parts in 91 portions of Herba Ephedraes of 102 parts of Rhizoma Corydalis of 113 parts of Radix Cynanchi Paniculatis of 113 parts of Ramulus Moris of 170 parts of Rhizoma Anemarrhenaes of Semen Litchi
45 parts of Pheretimas
Preparation method:
1), the side's of getting Chinese crude drug, clean respectively, coarse crushing is about 5-10mm granule, in proportion weighing.
2) take by weighing the Radix Astragali, Herba Ephedrae, Ramulus Mori, Rhizoma Corydalis, Caulis Spatholobi, Rhizoma Chuanxiong, in proportion, add 10 times of amounts, 8 times of amount 60% ethanol respectively, reflux, extract, 2 times, extraction time was respectively 2,1.5 hours.Filter, merge extractive liquid,, residue discards.Reclaim ethanol to there not being the alcohol flavor, be evaporated to relative density 1.02-1.06 (60 ℃ of heat are surveyed) fluid extract, standby.
3) take by weighing Ramulus Cinnamomi, Radix Angelicae Sinensis, Radix Cynanchi Paniculati, in proportion, add 7 times of water gagings, soaked 30 minutes, steam distillation extracts volatile oil, carries 6 hours time, and volatile oil device is in addition collected.Decocting liquid filters, and is standby.
4) take by weighing Radix Rehmanniae, Semen Litchi, the Rhizoma Anemarrhenae, Pheretima, in proportion, and carry oil back residue and merge, add 9 times of water gagings, heating decocts 2 times, and the time was respectively 2,1.5 hours, filters, merge extractive liquid,, residue discards, and is evaporated to relative density 1.20-1.24 clear paste (60 ℃ of heat are surveyed), add 95% ethanol to determining alcohol 60%, 5-10 ℃ left standstill 24 hours, filtered, and decompression filtrate recycling ethanol is to there not being the alcohol flavor, be evaporated to relative density 1.02-1.06 (60 ℃ of heat are surveyed) fluid extract, standby.
5), with starch, the dextrin mixing is put in the spray granulation machine, alcohol extraction fluid extract and water extract-alcohol precipitation fluid extract is mixed spraying into granulation, granulate sprays into volatile oil, and is encapsulated airtight half an hour, promptly.
Embodiment 2:
150 parts of 100 parts of Rhizoma Chuanxiongs of 80 parts of Radix Angelicae Sinensis of 300 parts of Ramulus Cinnamomi of 300 portions of Caulis Spatholobis of 300 parts of Radix Rehmanniae of the Radix Astragali
50 parts in 70 portions of Herba Ephedraes of 80 parts of Rhizoma Corydalis of 80 parts of Radix Cynanchi Paniculatis of 80 parts of Ramulus Moris of 150 parts of Rhizoma Anemarrhenaes of Semen Litchi
30 parts of Pheretimas
Preparation method: with among the embodiment 1 1), 2), 3), 4) step and make tablet according to a conventional method.
Embodiment 3:
200 parts of 150 parts of Rhizoma Chuanxiongs of 120 parts of Radix Angelicae Sinensis of 400 parts of Ramulus Cinnamomi of 400 portions of Caulis Spatholobis of 400 parts of Radix Rehmanniae of the Radix Astragali
100 parts in 120 portions of Herba Ephedraes of 120 parts of Rhizoma Corydalis of 120 parts of Radix Cynanchi Paniculatis of 120 parts of Ramulus Moris of 200 parts of Rhizoma Anemarrhenaes of Semen Litchi
60 parts of Pheretimas
Preparation method: with among the embodiment 1 1), 2), 3), 4) step and make pill according to a conventional method.
Embodiment 4:
150 parts of 150 parts of Rhizoma Chuanxiongs of 120 parts of Radix Angelicae Sinensis of 300 parts of Ramulus Cinnamomi of 300 portions of Caulis Spatholobis of 300 parts of Radix Rehmanniae of the Radix Astragali
100 parts in 120 portions of Herba Ephedraes of 120 parts of Rhizoma Corydalis of 120 parts of Radix Cynanchi Paniculatis of 120 parts of Ramulus Moris of 200 parts of Rhizoma Anemarrhenaes of Semen Litchi
60 parts of Pheretimas
Preparation method: with among the embodiment 1 1), 2), 3), 4) step and make oral liquid according to a conventional method.
The present invention is according to Chinese medical theory, especially the network ens morbi is applied in the treatment of diabetic peripheral neuropathy, develop in conjunction with clinical application experience for many years, being intended to provides determined curative effect, takes safe new product of Chinese medicine for the diabetic peripheral neuropathy patient.
Pharmacological action
Its capsule of medicine of the present invention (Zhou Luotong capsule by name) has carried out following animal experiment to prove its curative effect:
Summary
The Zhou Luotong capsule has the effect of collateral dredging stasis-dispelling and pain-killing, finds in clinical practice, and some peripheral nerve syndromes of diabetics such as acroparesthesia, numbness, pain etc. are had comparatively significantly improvement effect.
Streptozotocin is adopted in this research, and (Streptozotocin, STZ) diabetes rat and mouse model are observed the protective effect of Zhou Luotong capsule to STZ diabetes animal model peripheral neuropathy.
Method and result:
1 all ruton capsules are to the protective effect of diabetes model rat peripheral neuropathy
Adopt the STZ lumbar injection to cause the rat diabetes model, continuous 8 weeks of gastric infusion after the observation modeling are to the protective effect of diabetes rat peripheral neuropathy.Zhou Luotong capsule dosage is 0.80g/kg, 0.40g/kg and 0.20g/kg, is equivalent to 14 times, 7 times and 3.5 times of the clinical plan consumption of people respectively.
1.1 influence to overview indexs such as STZ diabetes rat body weight, food-intake, amount of drinking water and blood glucose
2,4,6,8 whens week after modeling, male and female diabetes rat body weight all obviously reduces (P＜0.01), average food-intake and average amount of drinking water are apparently higher than blank group rat, Zhou Luotong 0.80g/kg group female rats body weight is obviously greater than (P＜0.05) the model group during except that 2 weeks, and the Zhou Luotong capsule does not all have obvious influence to the STZ diabetes are male with female rats body weight, average food-intake and average amount of drinking water.
STZ diabetic model group rat blood sugar value is apparently higher than blank blood glucose value (P＜0.01).Except that 8 when week Zhou Luotong capsule 0.80g/kg and female group of rat blood sugar value of 0.20g/kg be lower than (P＜0.05, P＜0.01) the model group, at all the other time Zhou Luotong capsules male and female blood glucose in diabetic rats value is not all shown obvious influence.
1.2 influence to the STZ diabetes rat mechanical stimulus threshold of pain and the electricity irritation threshold of pain
The mechanical stimulus pain threshold of STZ diabetes rat obviously reduces (P＜0.01) than the blank group, electricity irritation pain threshold obviously raise (P＜0.01).Each dosage group of Zhou Luotong capsule all shows tangible antagonism (P＜0.05 or P＜0.01) to the reduction of the mechanical stimulus pain threshold of STZ diabetes rat and the rising of electricity irritation pain threshold.
1.3 influence to STZ diabetic sciatic nerve conduction velocity (MNCV)
Rat is fixing under Patients Under Ketamine Anesthesia, stimulate needle electrode to insert the incisura ischiadica place through skin, spread out of the position for sciatic nerve herein, recording electrode places the ankle joint sciatic nerve through the position, stimulate with the pulse square wave, record begins from exciting nerve time of action potential, i.e. incubation period to occur to far-end muscle.Accurately measure stimulating electrode to the distance between the recording electrode along animal body surface.Substitution formula: the distance/incubation period between motor nerve conduction velocity (m/s)=stimulating electrode and recording electrode, ask and calculate the sciatic nerve conduction velocity of ischial tuberosity to ankle.
STZ diabetic model group rat MNCV is than blank group rat obviously slow down (P＜0.01); Each dosage group of Zhou Luotong capsule is to the MNCV effect of all having clear improvement (P＜0.01 or P＜0.05) of slowing down.
1.4 influence to the change of STZ diabetic sciatic nerve pathomorphism
The dyeing of STZ diabetic model group rat sciatic nerve osmic acid shows that myelin has the obvious impairment reaction, the corrugated fold appears in the nerve fiber edge, the coagulation fritter that occurs many lipoid degenerations in the myelin, phenomenon of rupture appears in some position, local swelling or the nerve fiber degeneration of taking place of part of nerve fibers myelin.Each dosage group of Zhou Luotong has nerve fiber myelin pathological changes occurrence degree and significantly alleviates effect.
Rat sciatic nerve fibre damage count results is shown that STZ diabetic model group rat nerve fiber the ratio of above-mentioned pathological changes takes place apparently higher than normal group (P＜0.01), and the sciatic nerve fibre diameter dwindles (P＜0.01).Zhou Luotong can obviously reduce nerve fiber pathological changes incidence rate (P＜0.01), the nerve fiber diameter is reduced have obvious protective effect (P＜0.05 or P＜0.01).
2 all ruton capsules are to the protective effect of STZ diabetic mice function of peripheral nerves damage
Adopt streptozotocin (STZ) lumbar injection to cause the mice diabetes model, continuous 13 weeks of gastric infusion after the observation modeling are to the protective effect of STZ diabetic mice function of peripheral nerves damage.The Zhou Luotong dosage is 1.03g/kg, 0.51g/kg and 0.26g/kg, is equivalent to 18 times, 9 times and 4.5 times of the clinical plan consumption of people respectively.
2.1 influence to STZ diabetic mice body weight and level of sugar
STZ model group mice body weight obviously reduces and level of sugar obviously raises.Each dosage group of Zhou Luotong does not all make significant difference to mice body weight and level of sugar.
2.2 STZ diabetic mice heat, cold stimulation response time, chemical stimulation pain reactions change and heavy burden are climbed the influence of net time
Respectively 43 ℃ of hot water, 10 ℃ of cold water stimulating mices are produced thermostimulation response time and the cold stimulation response time of the time of whipping as mice; Give the formalin 0.01ml of the right back instep of mice portion subcutaneous injection 0.4%, the number of times sum of licking metapedes and playing metapedes with mice in 0～5 minute is the pain reaction index of mice to chemical stimulation; Afterbody is born the mice that is equivalent to body weight 40% weight place on the wire gauze of vertical hanging, fall time of getting off of record mice bears a heavy burden as mice and climbs the net time.
In 2 whens week after the STZ modeling, the thermostimulation response time of model group mice is obviously reduced (P＜0.01), and (P＜0.05, P＜0.01 and P＜0.01) after this obviously raises again when 5 weeks, 8 weeks and 13 weeks.The rising of Zhou Luotong 1.03g/kg, 0.51g/kg, the 0.26g/kg mice thermostimulation threshold of pain during to 8 weeks all has highly significant inhibitory action (P＜0.01); Administration is during 13 weeks, and Zhou Luotong 0.51g/kg, 0.26g/kg still show obvious inhibitory action (P＜0.05) to the rising in thermostimulation response time.
Zhou Luotong 1.03g/kg raises to 8 STZ diabetic mice cold stimulation response time in when week and has obvious suppression effect (P＜0.05), and Zhou Luotong 0.51g/kg, 0.26g/kg do not have obvious effect.
During two weeks, the pain reaction that STZ diabetic mice PARA FORMALDEHYDE PRILLS(91,95) stimulates obviously increases (P＜0.05) in modeling; When 6 weeks, then there is not significant difference (P＞0.05); During 8 weeks, the pain reaction that showing PARA FORMALDEHYDE PRILLS(91,95) again stimulates obviously weakens (P＜0.01).Chemical stimulation pain reaction variation in each period does not all show obvious influence (P＞0.05) to each dosage group of Zhou Luotong to the STZ diabetic mice.
The all significantly shortenings (P＜0.01, P＜0.01, P＜0.05) of net time are climbed in the heavy burden of model group mice when 4 weeks, 9 weeks and 13 weeks.Zhou Luotong 0.51g/kg, 0.26g/kg bear a heavy burden to the STZ diabetic mice and climb the minimizing of net time and all show tangible prolongation effect (P＜0.05).
3. all rutons are to the mechanism research of diabetic peripheral neuropathy protective effect
3.1 influence to STZ diabetic sciatic nerve polyhydric alcohol metabolic pathway
Compare with blank group rat, sorbitol, fructose, glucose and the mannose content in the STZ diabetic model group rat sciatic nerve tissue all obviously raises (P＜0.01), but inositol content is not seen marked difference (p＞0.05).Compare with model group, Zhou Luotong 0.80g/kg and 0.20g/kg can obviously reduce the sorbitol content (P＜0.05) in the nervous tissue; Zhou Luotong 0.20g/kg can also significantly reduce glucose content and the mannose content (P＜0.01) in the nervous tissue; Zhou Luotong there is no obvious influence (p＞0.05) to fructose content, inositol content.
Compare active significantly strengthen (P＜0.01) of STZ diabetic model group rat sciatic nerve aldose reductase (AR) with the blank group; Zhou Luotong 0.8g/kg, 0.4g/kg, 0.2g/kg can obviously suppress the active increase of AR.
STZ diabetes female rats sciatic nerve Na
+, K
+-atpase activity obviously reduces (P＜0.01).After 8 weeks of administration, Zhou Luotong 0.8g/kg, 0.4g/kg, 0.2g/kg have obvious improvement effect (P＜0.05 or P＜0.01) to the reduction of this enzymatic activity
3.2 influence to STZ diabetes rat free radical resisting ability
Compare with blank group rat, active obviously raise (P＜0.01) of the superoxide dismutase (SOD) of STZ diabetic sciatic nerve tissue, active obviously reduce (P＜0.05) of glutathion peroxidase (GSH-PX), active significantly raise (P＜0.01) of catalase (CAT); Compare with the blank group, sciatic nerve malonaldehyde (MDA) content significantly raises (P＜0.05), and reduced glutathion (GSH) content does not have significant change (P＞0.05).Compare with model group, Zhou Luotong 0.40g/kg, 0.20g/kg show tangible reduction effect (P＜0.05) to sciatic nerve tissue SOD activity, and Zhou Luotong 0.40g/kg, 0.20g/kg can make active obviously raise (P＜0.05) of the GSH-PX of nervous tissue; Zhou Luotong 0.80g/kg has obvious reduction effect (P＜0.05) to the CAT activity.Zhou Luotong 0.80g/kg, 0.40g/kg, 0.20g/kg can make that MDA content obviously reduces in the STZ diabetic sciatic nerve tissue, and GSH content is not all had obvious influence (P＞0.05).
3.3 influence to the formation of STZ diabetes rat glycated protein
Model group rat blood serum glycated protein and saccharification hemoglobin content be obviously rising (P＜0.01) all.Zhou Luotong 0.40g/kg and 0.20g/kg have obvious reduction effect (P＜0.05) to STZ diabetes rat saccharifying serum albumin content; Zhou Luotong 0.40g/kg can also obviously reduce saccharification hemoglobin content (P＜0.05).
3.4 all rutons are to the hemorheological influence of STZ diabetes rat
3.4.1 to the hemorheological influence of STZ diabetes rat
Compare with the blank group, the erythrocyte aggregation of male and female STZ diabetes rat all obviously strengthens (P＜0.05), and erythrocyte deformability, whole blood viscosity and plasma viscosity all do not have obvious change (P＞0.05).Zhou Luotong 0.20g/kg has obvious rising effect (P＜0.05) to male STZ diabetes rat red cell deformability, and enhancing demonstrates obvious inhibitory action (P＜0.05) to Zhou Luotong 0.40g/kg to the female rats erythrocyte aggregation; Zhou Luotong does not then see obvious influence (P＞0.05) to blood viscosity and plasma viscosity.
3.4.2 all rutons to normal stress in rats after hemorheology influence
Add on the rat blood stasis model that epinephrine stress cause at frozen water, with blank group ratio, the erythrocyte aggregation of model group rat significantly increases (P＜0.01), and red cell deformability then obviously reduces (P＜0.01).Compare with model group, Zhou Luotong 0.8g/kg, 0.4g/kg, 0.2g/kg group all have obvious reduction effect (P＜0.05 or P＜0.01) to erythrocyte aggregation, and red cell deformability is had obvious potentiation (P＜0.05 or P＜0.01).
Compare with the blank group, whole blood viscosity and the plasma viscosity of model group rat all is significantly increased (P＜0.01), Zhou Luotong 0.2g/kg has obvious reduction effect (P＜0.05) to whole blood viscosity when low cutting, but other each administration groups all do not show obvious influence (P＞0.05).
3.5 all ruton antiinflammatory actions
Zhou Luotong 1.03g/kg, 0.51g/kg and 0.26g/kg can significantly suppress the mice ear (P＜0.05) due to the dimethylbenzene; Zhou Luotong 0.40g/kg and 0.20g/kg can obviously suppress rat paw edema (P＜0.01 or P＜0.05) due to the carrageenin; Zhou Luotong 1.03g/kg has obvious inhibitory action (P＜0.05) to capillary permeability.Each dosage group of Zhou Luotong is not seen obvious influence (P＞0.05) to the subacute inflammation granulation tissue hyperplasia.
Conclusion
Zhou Luotong does not see obvious influence to the body weight of male and female STZ diabetes rat, average amount of drinking water and average food-intake; Zhou Luotong there is no the significance influence except that in 8 whens week female rats blood glucose being had the slight reduction effect to the other times blood glucose value.Body weight, glucose in urine to the STZ diabetic mice do not have obvious influence yet.
For the rising of reduction of the STZ diabetes rat mechanical stimulus threshold of pain and electricity irritation pain threshold, the Zhou Luotong tool improves significantly; Zhou Luotong can suppress slowing down of STZ diabetic sciatic nerve conduction velocity, and function of peripheral nerves is improved significantly, and diabetic peripheral neuropathy reason morphological change is also had the certain protection effect.
Zhou Luotong can obviously improve STZ diabetic mice model heat, cold stimulation are reacted bitterly, obviously strengthens muscular strength and the endurance of STZ mice, makes and climbs the net time lengthening.Zhou Luotong reacts bitterly to chemical stimulation does not have obviously influence.
The heavy dose of group of Zhou Luotong raises to the diabetes rat electricity irritation threshold of pain antagonism is arranged, and than the small dose group length of holding time; Mice cold stimulation reactions change is had obvious antagonism, and middle small dose group effect is not obvious.More than there is certain dose-effect relationship some index aspect that acts on of explanation Zhou Luotong.
Zhou Luotong can obviously suppress the increase of diabetic sciatic nerve sorbitol, glucose equal size, suppresses aldose reductase activity and increases, and the polyhydric alcohol metabolic pathway is strengthened obvious inhibitory action; Strengthen Na
+, K
+-atpase activity.More than prompting, Zhou Luotong may be its significant feature link to the inhibitory action of glucose polyhydric alcohol metabolic pathway.Effects such as the antioxidant radical effect of Zhou Luotong, anti-glycated protein and glycolated hemoglobin nucleus formation, the red cell deformability that strengthens rat, antiinflammatory have also participated in diabetic peripheral neuropathy protective effect mechanism.
Claims (9)
1, the medicine of a kind of treatment diabetic peripheral neuropathy is characterized in that being being made by the crude drug of following weight portion ratio:
Radix Astragali 300-400 part Radix Rehmanniae 300-400 part Caulis Spatholobi 300-400 part Ramulus Cinnamomi 80-120 part Radix Angelicae Sinensis 100-150 part
Rhizoma Chuanxiong 150-200 part Semen Litchi 150-200 part Rhizoma Anemarrhenae 80-120 part Ramulus Mori 80-120 part Radix Cynanchi Paniculati 80-120 part
Rhizoma Corydalis 70-120 part Herba Ephedrae 50-100 part Pheretima 30-60 part.
2, medicine according to claim 1, the weight portion ratio of its crude drug is:
170 parts of 136 parts of Rhizoma Chuanxiongs of 113 parts of Radix Angelicae Sinensis of 340 parts of Ramulus Cinnamomi of 340 portions of Caulis Spatholobis of 340 parts of Radix Rehmanniae of the Radix Astragali
68 parts in 91 portions of Herba Ephedraes of 102 parts of Rhizoma Corydalis of 113 parts of Radix Cynanchi Paniculatis of 113 parts of Ramulus Moris of 170 parts of Rhizoma Anemarrhenaes of Semen Litchi
45 parts of Pheretimas.
3, medicine according to claim 1, the weight portion ratio of its crude drug is:
150 parts of 100 parts of Rhizoma Chuanxiongs of 80 parts of Radix Angelicae Sinensis of 300 parts of Ramulus Cinnamomi of 300 portions of Caulis Spatholobis of 300 parts of Radix Rehmanniae of the Radix Astragali
50 parts in 70 portions of Herba Ephedraes of 80 parts of Rhizoma Corydalis of 80 parts of Radix Cynanchi Paniculatis of 80 parts of Ramulus Moris of 150 parts of Rhizoma Anemarrhenaes of Semen Litchi.
30 parts of Pheretimas
4, medicine according to claim 1, the weight portion ratio of its crude drug is:
200 parts of 150 parts of Rhizoma Chuanxiongs of 120 parts of Radix Angelicae Sinensis of 400 parts of Ramulus Cinnamomi of 400 portions of Caulis Spatholobis of 400 parts of Radix Rehmanniae of the Radix Astragali
100 parts in 120 portions of Herba Ephedraes of 120 parts of Rhizoma Corydalis of 120 parts of Radix Cynanchi Paniculatis of 120 parts of Ramulus Moris of 200 parts of Rhizoma Anemarrhenaes of Semen Litchi.
60 parts of Pheretimas
5, medicine according to claim 1, the weight portion ratio of its crude drug is:
150 parts of 150 parts of Rhizoma Chuanxiongs of 120 parts of Radix Angelicae Sinensis of 300 parts of Ramulus Cinnamomi of 300 portions of Caulis Spatholobis of 300 parts of Radix Rehmanniae of the Radix Astragali
100 parts in 120 portions of Herba Ephedraes of 120 parts of Rhizoma Corydalis of 120 parts of Radix Cynanchi Paniculatis of 120 parts of Ramulus Moris of 200 parts of Rhizoma Anemarrhenaes of Semen Litchi
60 parts of Pheretimas.
6,, it is characterized in that this medicine is capsule, tablet, pill or oral liquid according to the arbitrary described medicine of claim 1-5.
7, medicine according to claim 5 is characterized in that this medicine is a capsule.
8, the preparation method of the described medicine of claim 7 is characterized in that may further comprise the steps:
1), the side's of getting Chinese crude drug, clean respectively, coarse crushing is about 5-10mm granule, in proportion weighing;
2) take by weighing the Radix Astragali, Herba Ephedrae, Ramulus Mori, Rhizoma Corydalis, Caulis Spatholobi, Rhizoma Chuanxiong, in proportion, add 8-12 respectively and doubly measure 50-80% ethanol, reflux, extract, 1-3 time, extraction time was respectively 1-3 hour.Filter, merge extractive liquid,, residue discards.Reclaiming ethanol does not extremely have the alcohol flavor, and the fluid extract of relative density 1.02-1.06 is standby when being evaporated to 60 ℃ of heat surveys;
3) take by weighing Ramulus Cinnamomi, Radix Angelicae Sinensis, Radix Cynanchi Paniculati, in proportion, add 5-8 times of water gaging, soaked 20-40 minute, steam distillation extracts volatile oil, carries time 5-8 hour, and volatile oil device is in addition collected.Decocting liquid filters, and is standby;
4) take by weighing Radix Rehmanniae, Semen Litchi, the Rhizoma Anemarrhenae, Pheretima, in proportion, and carry oil back residue and merge, add 8-12 times of water gaging, heating decocts 1-3 time, and the time was respectively 1-3 hour, filters, merge extractive liquid,, residue discards, the clear paste of relative density 1.20-1.24 when being evaporated to 60 ℃ of heat surveys, add 95% ethanol to determining alcohol 50-70%, 5-10 ℃ left standstill 18-36 hour, filtered, and decompression filtrate recycling ethanol is to there not being the alcohol flavor, the fluid extract of relative density 1.02-1.06 is standby when being evaporated to 60 ℃ of heat surveys;
5), with starch, the dextrin mixing is put in the spray granulation machine, alcohol extraction fluid extract and water extract-alcohol precipitation fluid extract is mixed spraying into granulation, granulate sprays into volatile oil, and is encapsulated airtight half an hour, promptly.
9, the preparation method of the described medicine of claim 6 is characterized in that may further comprise the steps:
With step 1), 2 in the claim 8), 3), 4) preparation extract, formulation method is made pill, tablet or oral liquid routinely.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101559156B (en) * | 2008-04-18 | 2011-11-09 | 河北以岭医药研究院有限公司 | Application of traditional Chinese medicine composition in preparing medicament for curing chronic inflammatory demyelinating polyneuropathy |
| CN102631415A (en) * | 2011-03-01 | 2012-08-15 | 四川升和药业股份有限公司 | Traditional Chinese medicine composite as well as product and application thereof |
| CN102749407A (en) * | 2011-04-19 | 2012-10-24 | 河北以岭医药研究院有限公司 | Method for determining timosaponin BII content of traditional Chinese medicine composition |
| CN101361821B (en) * | 2008-10-10 | 2012-11-14 | 北京中医药大学 | Medicine combination for treating diabetic peripheral neuropathy and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101590173B (en) * | 2008-05-30 | 2012-05-30 | 河北以岭医药研究院有限公司 | Application of traditional Chinese medicine composition in preparing medicine for treating hypertensive intracerebral hemorrhage |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1124140C (en) * | 2000-02-22 | 2003-10-15 | 王兆凯 | Traditional Chinese medicine for treating diabetic peripheral neuropathy |
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2005
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101559156B (en) * | 2008-04-18 | 2011-11-09 | 河北以岭医药研究院有限公司 | Application of traditional Chinese medicine composition in preparing medicament for curing chronic inflammatory demyelinating polyneuropathy |
| CN101361821B (en) * | 2008-10-10 | 2012-11-14 | 北京中医药大学 | Medicine combination for treating diabetic peripheral neuropathy and preparation method thereof |
| CN102631415A (en) * | 2011-03-01 | 2012-08-15 | 四川升和药业股份有限公司 | Traditional Chinese medicine composite as well as product and application thereof |
| CN102631415B (en) * | 2011-03-01 | 2015-05-20 | 四川升和药业股份有限公司 | Traditional Chinese medicine composite as well as product and application thereof |
| CN102749407A (en) * | 2011-04-19 | 2012-10-24 | 河北以岭医药研究院有限公司 | Method for determining timosaponin BII content of traditional Chinese medicine composition |
| CN102749407B (en) * | 2011-04-19 | 2016-09-28 | 河北以岭医药研究院有限公司 | The content assaying method of rhizoma anemarrhenae saponin BII in a kind of Chinese medicine composition |
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