CN1459305A - Medicine for treating chronic pain, and its prepn. method - Google Patents
Medicine for treating chronic pain, and its prepn. method Download PDFInfo
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Abstract
A Chinese medicine in the form of oral liquid for treating the chronic pain caused by the peripheroneural damage is prepared from 5 Chinese medicinal materials including asarum herb, notoginseng, American ginseng, tremella, and pilose asiabell root on achyranthes bidentate through extracting polyose substances separately. The extracted polyose components have the function of repairing the nerve ending causing the chronic pain and contain no inhibitor on the nervous centralis. Its advantages are high curative effect, quickly taking its effect and no toxic by-effect.
Description
Technical field
Herbal pharmaceutical classification under the present invention in the biomedicine field.
Technical background
In state-owned several thousand civilized history also be tcm theory and application and development history simultaneously.The territory of China is vast, plant resources is abundant, the traditional Chinese medical science ought to be made bigger contribution to the world, but because the theory and the preparation way of the traditional Chinese medical science are difficult to be admitted by the west, therefore 95% cosmopolitian plant medicine market is captured by Japan and Korea S based on polish, and China only occupies less than 5%, but also is with raw material, roughly processed product is main, and added value of product is low.China accession to the WTO (WTO) afterwards, pharmacy big factory in various countries' will enter Chinese market comprehensively, China pharmacy industry be faced with unprecedented crisis.In new century, the modernization of Chinese medicine and internationalization are big pillars that makes the China's economic prosperity.
The industry that under the big general layout of economic globalization, how will the have Chinese national characters most formation new growth engines that squeezes into the international market, foreign exchange earning, the status tool of setting up China traditional medicine big country has become problem anxious to be solved.Along with China's entry into the WTO, unprecedented acute variation has taken place in the living environment of national medicine industry, the current whole world constantly increases the demand of natural drug, and the Chinese medicine industry has become the field of economic increase of outstanding, the tool potentiality of advantage, and development prospect is very wide.But China's tcm product also has suitable distance apart from international standard and market demands at present, one, Chinese medicine preparation outward appearance " thick, big, black, assorted ", because the herbal species in the prescription is various, composition mixes, middle pharmaceutically active ingredient is indeterminate, lacks significant composition, can't set up the system that can meet the foreign drugs quality inspection standard.Its two, the pharmacological action of Chinese medicine is difficult to make an explanation with the modern biomedical theory.Its three because the restriction of traditional prescription, process for producing must fall behind, and makes the Chinese medicine preparation component content complexity of producing, heavy metal and harmful substance substantially exceed international standard, have seriously hindered Chinese medicine and have entered the international market.Overcome these drawbacks, realize the modernization and the internationalization of Chinese medicine, theory of Chinese medical science must develop to some extent, must on the basis of Traditional Chinese medical theory, fully use modern cytology, physiology, biochemistry and preclinical medicine scheduling theory and test method, give traditional Chinese medical science pharmacological mechanism new theory, filter out effective site or composition, improve the added value of product of raw material of Chinese medicine, set up the quality standard of international endorsement and identify standard system, development has the Chinese medicine of independent intellectual property right and enters international medical main flow market with medicine for treatment.For reversing and change the backward situation of Chinese medicine, our company is devoted to develop the herbal species that modern scientific theory is supported, does good try for Chinese medicine moves towards the international market.
It is a kind of with the modernization of Chinese medicine and international research and development mode that our company with Chinese medicine is that resource is attempting opening.The external Chinese medicine conventional formulation of export trade has " WUJI BAIFENG WAN ", pills such as " LIUWEI DIHUANG WAN " at present; Granules such as " Radix Isatidis granules "; Read unguentum and other oral liquids such as kind Buddhist nunnery Chinese lute cream, all dosage forms all are to be formed by fried the concentrating of plurality of Chinese, chemical constituent mixes, the color dark, do not meet the medicine inspection standard that external medicine inspection department is formulated, pharmacological mechanism can't even if be main subject of a sale with minority Chinese colony just also abroad, can't enter external medical main flow market with the present state of Chinese medicine with the theoretical explanation of modern science at all.Do not change the thinking and the mode of Chinese medicine development, utilize the innovation to some extent on original traditional basis of modern theory and technological means, the modernization of Chinese medicine and internationalization will be difficult to find a breach.
Summary of the invention
The present invention is inheriting and is developing on the basis of Chinese medicine advantage and characteristic, according to China traditional Chinese medical theory and experience, utilize modern biological medicine theory and technology for instructing, from Chinese medicine, filter out the effective ingredient that to treat pain and set up extraction process and the preparation composing method, develop the tcm product that can formally enter international medical market according to the medical standards and norms of international endorsement.
We have set up the method and the theory of the screening new drug of own uniqueness according to the theoretical direction exploitation new Chinese medicine of modern cytobiology and neuro physiology.Modern science thinks that human body is a unified integral body.People's nervous system comprises that brain, spinal cord and peripheral nerve have constituted the signal granting and the conduction network of a precision jointly.The command function of brain is accepted the suffered chemistry of eye, ear, nose, tongue and periphery skin and the stimulation of physics, cooperates the reaction of adjusting stimulating by whole neural network.The nerve of human body is clouded in each corner of whole body as branch.All nerves all lead to " headquarter " brain again as telephone wire.According to statistics, if all superfine little nerve fibers of a people are all connected being aligned, can be around terrestrial equator 50 circles.The intravital nerve fiber of machine cans be compared to " telephone wire ", is made up of " leather sheath " that " copper wire " and the coated outside of nexine." copper wire " of nexine is the neurocyte fiber, and outer field " leather sheath " is epilemma.The conduction of nerve signal is that the variation by the transmembrane potential on the neuron membrane surface between the epilemma tuberosity realizes.After epilemma and neuron membrane sustain damage, resemble " leather sheath " breakage of electric wire, can cause the phenomenon such as spontaneous sparking, short circuit, electric leakage of electric wire.The depolarization threshold at the impaired place of neuron membrane can lower, and produces unusual electricity physiological signal, causes unusual neural reflex reaction.The nerve fiber of leading nociceptive reflex is a C class nerve fiber.The material that searching and discovery can be repaired C class neuron membrane surface is the basic point of our company's research and development analgesic.
Pain is a kind of neural reflex, is divided into acute pain and chronic pain usually.Chronic pain is bigger to the dependency of analgesic, is a main target of new drug development.At present domestic antalgica commonly used clinically divides two kinds of opium alkaloid class and non-steroidal anti-inflammatory classes.Opiates is a depressor of nerve centre, be called narcosis analgesic again, it is strong analgesic, as codeine, Semen Papaveris, morphine etc., the afferent conduction of nociceptive reflex is just blocked in their effect, rather than the surperficial root that produces unusual transmembrane potential granting of the neuron membrane of fundamentally eliminating damaged, though it is remarkable therefore to contain the antalgica analgesic effect of depressor of nerve centre, a kind of medicine of curing the symptoms, not the disease.A lot of antalgicas of hospital and pharmacy sale at present all contain depressor of nerve centre.Time of Administration has been grown also easy addiction and has been produced toleration.NSAID (non-steroidal anti-inflammatory drug) acts on peripheral nervous system, is the purpose that synthesizes with the blocking-up prostaglandin, as ibuprofen commonly used.Such medicine can produce allergy, gastrorrhagia and ulcer as taking for a long time, causes functional gastrointestinal disorder, obviously is not ideal medicine for the treatment chronic pain.
The existing Chinese medicine preparation that relieves the pain, RUGUI ginseng analgesic combination is made up of six kinds of Chinese medicines, the complex chemical composition of preparation, the very grave muddiness of color and luster contains Pericarpium Papaveris in the prescription, promptly a kind of depressor of nerve centre composition.This class analgesic can't reach the medicine inspection standard of US and European country at all, can't obtain Hesperian approval, does not possess the condition that goes to the world fully.
Modern science finds that the nerve fiber of leading nociceptive reflex is a C class nerve fiber.The material that searching and discovery can be repaired C class neuron membrane surface is the target of our company's new drug development.Our company is exactly the thinking of pharmacy of will breaking traditions, according to cytophysiology, molecular biology and biochemistry is basis and guiding theory, at the cytophysiology and the molecule mechanism of body morbidity, be that resource therefrom filters out medicine targetedly with various Chinese medicines.At first location screening be a class can with the material of neuron membrane surface combination, because the absorption of this class material, make the position of proper interior nerve injury obtain covering and recovering, the pathology root that will cause because of the unusual transmembrane potential granting that damage location causes is got rid of, and fundamentally treatment is because the associated conditions that nerve injury causes clinically.Through screening, from Chinese medicine Herba Asari, Radix Notoginseng, Radix Panacis Quinquefolii, Tremella, Radix Codonopsis or cattle lacquer, extract the medicine that polysaccharose substance is used to prepare the chronic pain medicine that treatment causes because of peripheral nerve injury respectively.
In the biomacromolecule that nature exists, comprise nucleic acid, protein and polysaccharide.It is minimum that polysaccharose substance is studied at present.The major function of nucleic acid is a coded protein; Protein is being born the effect of structure and biochemical function in organism; Various functional effect that polysaccharide has been proteinaceous additive.Polysaccharide is to interconnect the biomacromolecule that forms by several monosaccharide that nature exists.Because the architectural difference between the monosaccharide is little, connection between the monosaccharide and compound mode complexity are so polysaccharose substance is difficult to do structural identification and synthetic.Therefore mainly be from natural product, to extract just can obtain.Seek new medicinal ingredient from the plant resources of nature vastness is people's pursuing target always, equally also is the source of our company's new drug development.
Company finds and extracts the polysaccharose substance that a class can have affinity with the C class neuron membrane surface of causing nociceptive reflex according to theory extensively screening in Chinese medicine of neuro physiology.It can get up the surface coverage of the neuron membrane of damaged, as having repaired damaged electric wire " leather sheath ", improve the degree of polarization of neuron membrane, reduce the irritability of neurocyte, eliminate producing the focus that unusual transmembrane potential signal is provided, eliminate or alleviating pain.
Find that through screening the polysaccharose substance that contains in Herba Asari, Radix Notoginseng, Radix Panacis Quinquefolii, Tremella, Radix Codonopsis or the cattle lacquer has this function, becomes the source of extracting effective analgesic composition.Through extracting, concentrate and dried polysaccharose substance can being deposited separately, get wherein two or more extraction composition arbitrarily when needing preparation, be mixed with analgesic according to the ratio that differs that is equivalent between the crude drug at the scope water of 1 to 6 gram.Compare with Chinese medicine compound preparation, this analgesic has following advantage:
1. do not contain depressor of nerve centre, including effective ingredient is the pure natural polysaccharose substance that only acts on peripheral nervous system.Especially the athlete who is fit to child and participation international tournament takes.
2. be the Chinese medicine that can use modern biomedical theory and experiment to illustrate and verify pharmacological mechanism.This analgesic at the indication pathomechanism clear and definite, the source of medicine and chemical composition part is clear and definite, pharmacology and drug effect are clear and definite, drug toxicology is clear.
As the plant extract raw material of analgesic forgiven with high content of technology, added value is high, the industrialization Maturity is higher, be the medical kind that the great market development potentiality is arranged.
4. the analgesic action mechanism of Zu Chenging is to be capped by the neuron membrane bag with damaged, fundamentally eliminates the root that the exception throw transmembrane potential is provided.So for due to illness rational injured nerve cell membrane or teleneuron and cause that it is a kind of analgesic for the treatment of both the principal and secondary aspects of a disease that paradoxical discharge causes pain.The indication of medication is clear and definite, and is rapid-action, do not have toxic and side effects.
5. the analgesic of the composition of the polysaccharide effective ingredient through extracting has been removed most of and the incoherent material of curative effect, enrichment effective ingredient, the oral liquid color and luster of therefore making is limpid transparent, the thick profit of mouthfeel, do not have abnormal flavour, need not add any correctives or chemical addition agent.Compare with the present outward appearance of existing Chinese medicine antalgica and to be as far apart as heaven and earth.
6. owing to be the preparation that the herbal polysaccharide effective constituents through extracting is formed, thus preparation not only without any toxicity, side effect, become more dynamic after opposite animal is taken, hair color is smooth and shining, shows body is also had tonic effect.
7. low with the Chinese medicine wide cost of originating, the extraction process simple and stable, compound method is simple.
8. constituent is polysaccharose substance, and affiliated chemical property is stable, and is heat-resisting.Preparation keeps never degenerating more than 2 years under normal temperature condition through behind the high temperature sterilize, does not lose drug effect.Therefore composition that extracts and the preparation long shelf-life that is mixed with are convenient to store and transportation.
The preparation finished of preparation and the various polysaccharose substance that extracts all can set up separately quality standard and finger printing for evaluation.
10. Pei Zhi analgesic pain that the damage that is subjected to because of peripheral nervous system is caused has significant therapeutical effect.Through extensively inquiry, at present at international and the domestic report that similar theory and application are also never arranged, mechanism that proposes with the present invention and mode prepare analgesic and at home and abroad all belong to and initiating.
11. extract is a polysaccharose substance, the preparation that is mixed with and each extract all can be set up its specific evaluation finger printing and quality standard, meet clinical medicine inspection application standard on the U.S. FDA, therefore can be to declaring new drug abroad and to the refining raw extract of state's outer vent.
12. the unique distinction of this analgesic is to explain from the angle of molecular cytology, cell electrophysiology and preclinical medicine the pharmacological mechanism of effective ingredient, and the modernization and the developing internationalization market of Chinese medicine is had great importance.Used plant: Herba Asari, Radix Notoginseng, Radix Panacis Quinquefolii, Tremella, Radix Codonopsis or cattle lacquer extraction process: above-mentioned Chinese medicine can extract polysaccharose substance according to following usual manner respectively.
1. the Chinese medicine powder that will extract is broken into the 2-4 millimeter-sized particles or thinly slices.
2. the purpose of step is to remove the liposoluble substance that contains in the crude drug.Can adopt but be not limited to modes such as ultrasonic extractions, hot cooking method.With 59～95% soak with ethanol Chinese medicine of 2-20 times of volume and be heated to 90-100 ℃ 2～12 hours, filter clean solution then and keep filtering residue.
3. the purpose of this step is for extracting polysaccharose substance the medicinal residues from previous step is removed liposoluble substance through extracting after.Available but be not limited to use supercritical CO
2Extraction and water-boiling method.Water logging bubble with 2-20 times of filtering residue volume has been removed fat
Medicinal residues behind the soluble substance and be heated to 90-100 ℃ 2～12 hours, collect extracting solution.This process can repeat to extract 2～4 times.Ultrafiltration, filtration or centrifugal removal filtering residue or precipitation, merge extractive liquid.
5. concentrate the polysaccharide extraction liquid that obtains.
6. add ethanol and in polysaccharide extraction liquid, reach 80-85% to be settled out polysaccharose substance until concentration.
7. with the polysaccharose substance absolute ethanol washing twice that is settled out, make unformed Powdered polyoses extract through low pressure drying or spray drying then.
Listed Herba Asari, Radix Notoginseng, Radix Panacis Quinquefolii, Tremella, Radix Codonopsis or the cattle lacquer of this paper all can adopt the said extracted mode to extract polysaccharose substance respectively, comprises Radix Notoginseng polysaccharide, Radix Panacis Quinquefolii polysaccharide, tremella polysaccharide, Radix Codonopsis polysaccharide, Herba Asari polysaccharide or the application of cattle urushipolysaccharide in analgesic of no matter adopting which kind of extracting method to obtain simultaneously.
According to the ratio that is equivalent to crude drug 1 gram, with wherein arbitrarily two or more polyoses extract water be hybridly prepared into the oral dose that is used for once.Suitably add granule, pill, capsule or tablet auxilliary, that batching can be made into the treatment chronic pain according to this proportioning.The pain-relieving oral liquid color made from this method is light brown, the thick profit of mouthfeel, does not have abnormal flavour, and curative effect is clear and definite, rapid-action, do not have toxic and side effects, preserve easily.
The specific embodiment
The present invention is described further for embodiment below, but be not limited thereto explanation:
Embodiment 1:
1. Herba Asari is ground into the 2-4 millimeter-sized particles for 1 kilogram.
2.5 rise 60% soak with ethanol and boil to little boiling and keep 4 hours, filter clean solution and collect filtering residue.
With filtering residue with 15 times decocting in water 4 hours, collect solution and discard dregs, repeat to extract centrifugal merge extractive liquid, 1 time.
4. add 95% ethanol and to extracting solution, reach 80%, 4 ℃ of standing over night until concentration of alcohol.
5. centrifugal with precipitate washing with alcohol twice, be drying to obtain Powdered Herba Asari polyoses extract through low pressure.
Listed raw material Herba Asari, Radix Notoginseng, Radix Panacis Quinquefolii, Tremella, Radix Codonopsis or the cattle lacquer of claim 1 all can extract polysaccharose substance with reference to the method.Get the Herba Asari, Radix Notoginseng and the tremella polysaccharide extract that are equivalent to crude drug 1 gram respectively and merge, promptly be mixed with the antalgica of the treatment chronic pain that is used for an oral dose with 20 milliliters water dissolutioies.Take every day 3 times, each 20 milliliters, body weight reduces by half the child below 20 kilograms.
Embodiment 2:
1. 60% the ethanol of getting 5 times of volumes of 1 kilogram of usefulness of Radix Codonopsis thin slice boils to little and boiled 4 hours, filters clean solution and collects filtering residue.
With filtering residue with 15 times decocting in water 4 hours, collect extracting solution, repeat to extract 2 times.Merge extractive liquid, after the ultrafiltration.
3. concentrating under reduced pressure extracting solution to 1 liter.
4. the ethanol mixing that adds 4 times of volumes 95%, 4 ℃ of standing over night.
5. twice of washing with alcohol of the filtering residue of ultrafiltration gained
6. filtering residue uses water dissolution after spray drying promptly gets Powdered Radix Codonopsis polysaccharide extract.
Listed raw material Herba Asari, Radix Notoginseng, Radix Panacis Quinquefolii, Tremella, Radix Codonopsis or the cattle lacquer of claim 1 all can extract polysaccharose substance with reference to the method.Get the Radix Codonopsis, cattle lacquer, Radix Panacis Quinquefolii and the tremella polysaccharide extract that are equivalent to crude drug 1 gram respectively and promptly make the antalgica of the treatment chronic pain of oral dose with 20 milliliters water dissolution.Take every day 3 times, each 20 milliliters, body weight reduces by half the child below 20 kilograms.
Pharmacological action
The animal pharmacodynamics test is to adopt the CCI standard heat radiation pain model of international endorsement to measure the drug effect of polysaccharide analgesic (with reference to Gary J.Bennett and Y.-K.Xie " A peripheral mononeuropathy in rat that producesdisorders of pain sensation like those seen in man " Pain 1988,33:87-107 and " herbal pharmacology research methodology " Qi Chen chief editor, the People's Health Publisher publishes, the 1st edition the 4th printing July in 2000, the 380-381 page or leaf).The effect of pain sensation model (CCI model) testing drug of this nerve damage is all adopted in each laboratory of the whole world and pharmaceutical factory.The analgesia preparation that the preparation method of employing embodiment 2 is made is done pharmacodynamics test.[experimental principle]
Rat is placed in the cage at the bottom of the glass, the vola of the light beam irradiates rat of the constant intensity that produces with spotlight, the radiation temperature of spotlight will make rat feel pain and produce the withdrawal reflex sexual act that lifts foot, and record is unit from beginning to shine the time of lifting foot with the second.[experimental evaluation]
This method device is simple, and is easy to operate, reacts constant, can determine pain threshold and stimulus intensity sensitive and accurately.Stimulus intensity also can be controlled by regulating adjustable transformer, therefore becomes and uses maximum methods, is applicable to the screening study of narcoticness and non-narcotic analgesics.[experimental technique]
Select the rat of body weight between the 200-300 gram for use, male and female are regardless of totally 12.Tested preceding 15 days, the nerve tract ligation of control rats with left forward and backward limb is set up neural chronic injury model and done contrast with self forward and backward normal limb in right side.Measure the animal vola to thermal-radiating pain sensation sensitivity.This experiment is to do normal limbs and the nerve injury limbs mensuration to pain sensation sensitivity on one's body same animal.[experiment 1]
Rat is normally raised after damaging the left limb nerve artificially, the vola of normal limb of measuring the damage limb of rats with left and right side every day is to thermal-radiating pain sensation sensitivity, determine there not being filling to raise under the situation of medicine, show the heat radiation sensitivity in the natural repair process of animal after nerve injury.Experimental result is listed in table 1.Table 1.
[experimental result] table 1 is classified the controlled trial result as.Evidence not administration according to the nerve of its damaged limbs of rat of normal raising in the week after injured, promptly by the 7th day, the sensitivity that the vola of right side damage side limbs stimulates heat radiation does not all have notable difference when just sustaining damage, average reflection time left fore is 8.3 seconds, and left hind is 8.5 seconds.And the vola of the normal limb in right side is respectively thermal-radiating tolerance meansigma methods: right fore is 12.27 and right hind 12.4 seconds.The damaged value of forelimb is deducted the normal value of forelimb, and average is-3.97, and the hind leg average is-3.8.Negative value is represented heat radiation is stimulated responsive.Illustrate that the rat nerve that sustains damage did not all have the sign of recovery by the 7th day under natural situation.[experiment 2]
| Water is raised in filling | Left limb before the damage | The left limb in damage back | Right limb before normal | The right limb in normal back | The forelimb difference | The hind leg difference |
| Before | 8.0 second | Second | 12.2 second | Second | ????-4.3 | |
| The 1st day | ????7.6 | ????8.6 | ????12.0 | ????12.0 | ????-4.4 | ????-3.4 |
| The 2nd day | ????8.2 | ????8.2 | ????11.6 | ????11.2 | ????-3.4 | ????-3.0 |
| The 3rd day | ????8.4 | ????8.5 | ????12.4 | ????13.9 | ????-4.0 | ????-5.4 |
| The 4th day | ????9.0 | ????9.0 | ????12.2 | ????12.6 | ????-3.2 | ????-3.5 |
| The 5th day | ????8.7 | ????8.6 | ????13.2 | ????12.3 | ????-4.5 | ????-3.7 |
| The 6th day | ????8.2 | ????12.3 | ????-4.1 | |||
| The 7th day | ????8.1 | ????11.9 | ????-3.8 | |||
| Meansigma methods | ????8.2 | ????8.58 | ????12.27 | ????12.2 | ????-3.96 | ????-3.8 |
Tried 24 of rats, test the preceding nerve tract ligation that will control the forward and backward limb of rats with left in 15 days artificially and cause the forward and backward normal limb of neural chronic injury and the right side of self to do contrast, the pain sensation sensitivity that the heat radiation that mensuration rat sole produces the spotlight bundle causes.Animal every day irritates and raises the polysaccharide analgesic 2 times, measures the rat sole every day to thermal-radiating pain sensation sensitivity 1 milliliter of every day, contrasts nerve injury side (left side) sole and normal side (right side) the sole difference to pain sensation sensitivity on one's body same animal.The responsive difference of being tried the forward and backward limb of rat is the measured value that is deducted normal forelimb sole by the measured value of the forelimb sole of damaged, the measured value of the hind leg sole of damaged deducts the measured value of normal hind leg sole, the result shows that for negative value null value is and normal zero difference to stimulating sensitivity.Table 2.
Result in [experimental result] table 2 proves that the nerve injury side of being tried rat stimulates the reflex latency that produces short to hyperpathia to heat radiation.Non-damage side is to pain sensation relative insensitivity, and is long to the incubation period of thermostimulation reflection.Along with the increase of day number of drug administration, the sole of rat nerve injury side is significantly improved at the 2nd day that takes medicine to thermal-radiating toleration.By the 3rd day, damage side limbs were to the approaching substantially normal limbs of the responsive tolerance degree of the thermal-radiating pain sensation.And the control animals of administration not yet there are no obvious improvement at the 7th day, showed that the polysaccharide analgesic makes rat damage side acra stimulate the toleration of the pain that causes to be significantly improved to heat radiation, and the neurocyte and the function thereof of damaged had repair fast.[experiment 3] sets up neural chronic injury (CCI) model of rat.Separate the sciatic nerve of rat and use chromic suture (chromic gute) ligation sew up wound then at microscopically.The model (Pain 33 (1988) 87-107) that myelin degraded after 15 days on the nerve fiber comes off and promptly forms neural chronic injury.Cut muscle and expose sciatic nerve and make the muscle groove, contain polysaccharide analgesic (the 1ml normal saline adds 0.1ml polysaccharide analgesic) at nerve injury position drop.Measure the spontaneous discharge activity of record C class nerve fiber with the silvery detecting head at sciatic nearly proximal end.The chronic pain model that the injury of sciatic nerve of [experimental result] rat was set up after 15 days shows that the nerve injury position produces irregular spontaneous discharge continuously.When add at the nerve injury position contain polysaccharide analgesic 25 minutes after, unusual spontaneous discharge phenomenon promptly disappears, the neuropotential activity returns to normal condition and promptly is a straight line, shows the generation that does not have spontaneous discharge.Write down (referring to Figure of description 1) as oscillograph, vertical moulding is represented the activity of spontaneous discharge, and high-frequency spontaneous discharge then forms the black rectangle part on recorder chart.The nerve injury position can send irregular spontaneous discharge signal by the neurad proximal end.Polysac is the abbreviation of English polysaccharide, is illustrated in the nerve injury position and begins to add the polysaccharide analgesic.Horizontal line is represented time coordinate, and numeral 10 ' is represented 10 minutes.[clinical experiment result]
| The polysaccharide analgesia is raised in filling | Left limb before the damage | The left limb in damage back | Right limb before normal | The right limb in normal back | The forelimb difference | The hind leg difference |
| Before the administration | 6.0 second | 11.0 second | -5.0 seconds | |||
| The 1st day | ????6.6 | ????9.9 | ????11.3 | ????12.2 | ????-4.7 | ????-2.3 |
| The 2nd day | ????8.9 | ????9.3 | ????11.6 | ????10.5 | ????-2.7 | ????-1.3 |
| The 3rd day | ????10.4 | ????10.7 | ????12.3 | ????10.8 | ????-1.9 | ????-0.1 |
| The 4th day | ????10.3 | ????10.7 | ????11.7 | ????10.3 | ????-1.4 | ????0.4 |
| The 5th day | ????10.0 | ????11.8 | ????11.6 | ????11.9 | ????-1.6 | ????-0.1 |
Clinical trial is to volunteer requirement by the patient who suffers from chronic pain to take the polysaccharide analgesic, and through testing in the crowd, the result shows that the chronic pain that this polysaccharide analgesic causes peripheral nerve injury has the therapeutic effect of highly significant.To the pain that diabetic syndrome causes by late period, the lasting calcination sample pain that the damage location of paralyses patient produces, trigeminal neuralgia, is had a toothache and the pain of cancer patient has and relieves the pain significantly and mitigation at muscle injury pain, nervus motorius damage.Many patients are taking under the invalid situation of other antalgica, and aspiration requires to take this medicine, state through patient master, after taking one day pain condition be improved significantly.
Animal experiment and human trial all prove, this polysaccharide analgesic is different from the analgesic that contains depressor of nerve centre (codeine, Semen Papaveris, caffeine, morphine etc.) type, analgesia mechanism between the two is different fully, the effect that contains the analgesic of depressor of nerve centre is to cure the symptoms, not the disease, and only is that the blocking-up nociceptive reflex is to central nervous system's conduction rather than go to eliminate the root that produces nociceptive reflex.The pharmacological mechanism of this polysaccharide analgesic is to repair the C class epilemma sheath and the tip of leading nociceptive reflex, reduce the granting of the unusual transmembrane potential at damage location place, fundamentally eliminating the neural reflex that causes pain, is a kind of analgesia new drug for the treatment of both the principal and secondary aspects of a disease therefore.Animal test results and further confirmed design theory and the research and development mode of this new drug invention institute foundation to suffering from because of peripheral nerve injury causes the patient's of chronic pain efficacy result.
Claims (4)
1. the medicine of the chronic pain that causes because of peripheral nerve injury of a treatment, its feature are the application of extracting from Chinese medicine Herba Asari, Radix Notoginseng, Radix Panacis Quinquefolii, Tremella, Radix Codonopsis or cattle lacquer aspect the medicine that polysaccharose substance is used for the chronic pain that causes because of peripheral nerve injury in preparation.
2. the method for extracting polysaccharose substance from raw material of Chinese medicine as herein described is meant the method with any extraction polysaccharose substance.Its feature comprises and will remove liposoluble substance with the ethanol extracting after the raw material pulverizing that the reuse boiling water extraction goes out polysaccharose substance.Polysaccharose substance ethanol precipitation in the extracting solution promptly gets polysaccharose substance after drying.
3. the concrete grammar that extracts polysaccharose substance from raw material of Chinese medicine is that the Chinese medicine powder that will extract is broken into granule or thinly slices.Can adopt but be not limited to modes such as ultrasonic extraction or hot cooking method will handle in medicinal 2-20 times volume 59～95% soak with ethanol and be heated to 60-100 ℃ 2～24 hours, filter clean solution then.Filtering residue can with but be not limited to use supercritical CO
2Extraction or water-boiling method.With the water logging of 2-20 times of filtering residue volume bubble and be heated to 60-100 ℃ 2～24 hours, collect extracting solution.Remove filtering residue or precipitation through ultrafiltration, filtration or method such as centrifugal, collect extracting solution.Adding ethanol after concentrating makes the ethanol ultimate density surpass 70% to be settled out the polysaccharose substance of extraction to extracting solution.The polysaccharose substance drying that is settled out is promptly made unformed Powdered polyoses extract.
4. the liquid of the Herba Asari polysaccharide, Radix Notoginseng polysaccharide, Radix Panacis Quinquefolii polysaccharide, tremella polysaccharide, Radix Codonopsis polysaccharide or the cattle urushipolysaccharide that extract respectively or dry powder are used for the application aspect oral liquid, granule, tablet, pill and the capsule of the chronic pain that causes because of peripheral nerve injury in the preparation treatment.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104800236A (en) * | 2014-03-25 | 2015-07-29 | 广州医科大学附属第一医院 | Asarum total polysaccharides extract with cough relieving activity as well as extraction method and application thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104800236A (en) * | 2014-03-25 | 2015-07-29 | 广州医科大学附属第一医院 | Asarum total polysaccharides extract with cough relieving activity as well as extraction method and application thereof |
| WO2015144059A1 (en) * | 2014-03-25 | 2015-10-01 | 广州医科大学附属第一医院 | Asarum total polysaccharides extract having antitussive activity and extraction method and use thereof |
| CN104800236B (en) * | 2014-03-25 | 2019-06-21 | 广州医科大学附属第一医院 | Asarum total polysaccharide extractive and its extracting method and application with antitussive activity |
| US10744152B2 (en) | 2014-03-25 | 2020-08-18 | The First Affiliatted Hospital Of Guangzhou Medical University | Application of Asarum total polysaccharides in preparation of medicine for treating cough |
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