CN102648915A - Medicinal composition for treating or preventing neuropathic pain - Google Patents
Medicinal composition for treating or preventing neuropathic pain Download PDFInfo
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- CN102648915A CN102648915A CN2011100569644A CN201110056964A CN102648915A CN 102648915 A CN102648915 A CN 102648915A CN 2011100569644 A CN2011100569644 A CN 2011100569644A CN 201110056964 A CN201110056964 A CN 201110056964A CN 102648915 A CN102648915 A CN 102648915A
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Abstract
The invention belongs to the field of medicine, and particularly relates to a medicinal composition for treating or preventing neuropathic pain. At present, an effective medicament for treating neuropathic pain is unavailable. The invention provides a medicinal composition for treating neuropathic pain. The medicinal composition contains pregabalin and pentoxifylline, and can further contain diclofenac or a pharmaceutical salt thereof. Compared with separate application of pentoxifylline, pregabalin or diclofenac, the medicinal composition which contains pregabalin and pentoxifylline and further contains diclofenac has a synergistic action on the aspect of treatment of neuropathic pain and a particularly better effect on neuropathic pain caused by diabetes mellitus.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to the pharmaceutical composition of a kind of treatment or prevention neuropathic pain.
Background technology
Neuropathic pain is the healthy major disease of serious threat human life, and sickness rate is up to 1%, especially in diabetics sickness rate up to 50%.Neuropathic pain is meant owing to nervous system sustains damage or produces the pain that pathological changes causes, and intractable pain, trigeminal neuralgia, postherpetic neuralgia, the spinal disease patient who comprises oncothlipsis oppresses the pain that spinal cord or nerve root cause and the polyneuritis pain (neuropathic pain that diabetes cause) of diabetics etc.For the acute pain that causes owing to tissue injury, neuropathic pain often is long-term and chronic, sustainable several days or several months.The pain that continues has a strong impact on people's quality of life.The clinical cause of neuropathic pain is extensive, and symptom is various, and pathomechanism is complicated, conventional analgesic such as opiates is imitated opioid analgesics by force and NSAID does not all have tangible curative effect to it, thereby become one of difficult point of clinical treatment.
The chemical name of lyrica (pregabalin) is (3S)-3-aminomethyl-5-methylhexanoic acid, and research shows that lyrica can reduce the rat motor spinal reflex; Reduce the corelation behaviour of diabetes, nervus peripheralis damage or chemotherapy nerve animal pain model; Can suppress or reduce spine and give the relevant behavior of pain that stimulus object causes.Lyrica is a kind of novel GABA (GABA) receptor stimulating agent, can suppress the α of central nervous system's voltage dependent channel
2-δ subunit reduces flow of calcium ions, reduces the release of excitatory neurotransmitters such as glutamate, Glu, norepinephrine, P material thereupon, is not very desirable to the neuropathic pain therapeutic effect still.
Li Aihong is at " present situation and the future of glycosuria slight illness property neurotherapy " (Inpharm research magazine; In October, 2007; The 34th volume the 5th phase 377-379 page or leaf) points out in the literary composition; Though a large amount of glycosuria slight illness property neuropathy (DPN) curatives has been discussed at present, has not been found as yet to the cause of disease or symptom medicine all in full force and effect.Seek the work that minimum single medicine of effective side effect or combination are difficulty efforts, but will continue.
Summary of the invention
In view of present neuropathic pain does not still have effective Drug therapy, the present invention provides a kind of pharmaceutical composition of treating neuropathic pain, and it contains lyrica and pentoxifylline.Lyrica is the common drug of clinical treatment neuropathic pain; Pentoxifylline is a kind of non-selective phosphodiesterase inhibitor; Chemical name is 3,7-dimethyl xanthine, clinical thromboangiitis obliterans, cerebrovascular disorders, the vascular headache etc. of being mainly used in.Pentoxifylline can increase erythrocytic morphotropism, improves leukocytic hemorheology characteristic, suppresses sticking and activating of neutrophil cell, and the expansion blood capillary reduces blood viscosity, and there is antiinflammatory action in increase PtO2, can eliminate free radical etc.The invention property ground is united pentoxifylline and lyrica and is used to treat neuropathic pain, has obtained the therapeutic effect of working in coordination with.Show through a large amount of animal experiment studies; The form of lyrica and pentoxifylline drug combination is for treatment neuropathic pain determined curative effect; Therefore; The invention provides the fixed combination form of lyrica and pentoxifylline, promptly contain the pharmaceutical composition of lyrica and pentoxifylline.
Be used to treat the curative effect of neuropathic pain according to lyrica and pentoxifylline pharmaceutical composition, the present invention has carried out preferably the weight ratio of lyrica in the pharmaceutical composition and pentoxifylline.Preferably; The weight ratio of pentoxifylline and lyrica is 0.01～50: 1, and further preferably, the weight ratio of pentoxifylline and lyrica is 0.05～12: 1; Again further preferably, the weight ratio of pentoxifylline and lyrica is 0.1～3: 1.
Preferably, the present invention treats and also contains the third active component in the pharmaceutical composition of neuropathic pain: diclofenac or its officinal salt.Diclofenac is a non-steroid compound, and prostate is synthetic brings into play its pharmacological action through suppressing for it.Have rheumatism, antiinflammatory, analgesia and refrigeration function.Be characterized in alleviating significantly clinical sign and symptom, like multiple pain, arthroncus, wound and post-operation inflammatory etc.Pharmaceutical composition of the present invention is united the third active component diclofenac or its officinal salt on the basis of pentoxifylline and lyrica, treatment neuropathic pain effect is better.The officinal salt of diclofenac is physiologically acceptable pharmaceutical salts, preferred potassium salt and sodium salt.
The present invention has carried out preferably the weight ratio of diclofenac, lyrica and pentoxifylline in the pharmaceutical composition.Preferably; The weight ratio of diclofenac and lyrica, pentoxifylline is (0.02～2) in the pharmaceutical composition of the present invention: 1: (0.01～50); Further preferably, the weight ratio of diclofenac and lyrica, pentoxifylline is (0.02～2): 1: (0.1～3).
In order better to express pharmaceutical composition of the present invention, pharmaceutical composition of the present invention can be prepared into oral formulations commonly used clinically, like conventional tablet, capsule, granule, slow releasing tablet or enteric coated tablet.Preferably, in the UD of these drug composition oral preparations, contain diclofenac 25～300mg, pentoxifylline 50～1800mg, lyrica 150～600mg.
Excipient in the aforementioned pharmaceutical compositions oral formulations can be selected from one or more in diluent, wetting agent, binding agent, disintegrating agent and the lubricant; Wherein diluent is selected from one or more in starch, dextrin, lactose and the microcrystalline Cellulose; Wetting agent and binding agent are selected from one or more in water, ethanol, hydroxypropyl methylcellulose, ethyl cellulose and the polyvinylpyrrolidone; Disintegrating agent is selected from one or more in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose and the polyvinylpolypyrrolidone; Lubricant is selected from one or more in magnesium stearate, zinc stearate and the micropowder silica gel.Above-mentioned oral formulations all prepares according to the conventional formulation technology, such as dry granulation, wet granulation etc.
The present invention also provides a kind of method of treating neuropathic pain, promptly gives pharmaceutical composition of the present invention.The effective dose that pharmaceutical composition of the present invention is used to treat neuropathic pain is diclofenac 25～300mg/d, pentoxifylline 50～1800mg/d, lyrica 150～600mg/d.
Neuropathic pain of the present invention comprises that intractable pain, trigeminal neuralgia, postherpetic neuralgia, the spinal disease patient of oncothlipsis oppress the neuropathic pain that pain that spinal cord or nerve root cause and diabetes cause.
Surprisingly, pharmaceutical composition of the present invention is particularly remarkable to the neuropathic pain effect that diabetes cause.The effective dose of the neuropathic pain that the diabetes that are used to pharmaceutical composition of the present invention to treat cause is diclofenac 25～300mg/d, pentoxifylline 50～1800mg/d, lyrica 150～600mg/d.
The influence of pharmaceutical composition of the present invention that the present invention has also passed through the pharmacodynamics test high spot reviews to neuropathic pain.Experimental result shows; The pharmaceutical composition that the present invention contains lyrica and pentoxifylline has good therapeutical effect to the neuropathic pain rat model; And compare with individually dosed lyrica or pentoxifylline, shown good synergism.Especially the neuropathic pain that causes for the treatment diabetes has more outstanding therapeutical effect.Therefore, the pharmaceutical composition that contains lyrica and pentoxifylline can be used in the treatment neuropathic pain, especially can be used for the neuropathic pain treatment of diseases that diabetes cause.
In addition; The inventor is surprised to find; The present invention creatively introduces diclofenac on the basis of the pharmaceutical composition that contains lyrica and pentoxifylline; During the neuropathic pain that causes in treatment neuropathic pain, especially diabetes, shown more efficiently therapeutic outcome.And compare with individually dosed pentoxifylline, lyrica or diclofenac, obtained collaborative therapeutic effect.Therefore, the pharmaceutical composition that contains pentoxifylline, lyrica and diclofenac can be used to treat neuropathic pain and be particularly useful for treating the neuropathic pain that diabetes cause.Meanwhile; The present invention has also investigated the therapeutic effect of the pharmaceutical composition of the lyrica, pentoxifylline and the diclofenac that contain the Different Weight ratio to the neuropathic pain of diabetes initiation; The result shows that weight ratio is (0.02～2): 1: the pharmaceutical composition of (0.01～50) has been obtained good therapeutic effect, and especially weight ratio is (0.2～2): 1: the medicine composite for curing effect of (0.1～3) is better.
In a word, the present invention compared with prior art has following outstanding advantage:
(1) compare with individually dosed lyrica or pentoxifylline, the pharmaceutical composition that the present invention contains lyrica and pentoxifylline has good therapeutical effect to the neuropathic pain rat model, and has shown good synergism.Especially the neuropathic pain that causes for the treatment diabetes has more outstanding therapeutical effect.
(2) compare with individually dosed pentoxifylline, lyrica or diclofenac; The present invention contains the pharmaceutical composition of lyrica, pentoxifylline and diclofenac at the treatment neuropathic pain; Especially the neuropathic pain that causes of diabetes; Show more efficiently therapeutic outcome, and obtained collaborative therapeutic effect.
(3) compare with individually dosed or administering drug combinations, pharmaceutical composition of the present invention has improved patient's compliance and compliance with the form of therapy neuropathic pain of fixed combination.
The specific embodiment
Below further describe the present invention through the practical implementation method, but range of application of the present invention is not limited only to the following example.In content of the present invention, spirit and/or scope, replacement and/or combination to technical characterictic of the present invention will be readily apparent to persons skilled in the art, and be included among the present invention.
First's drug combination preparation of the present invention and preparation method thereof
Embodiment 1-6 tablet
Table 1 tablet formulation
Embodiment 1 preparation technology: it is even earlier lyrica and cyclodextrin to be put into the mortar ground and mixed, adds carboxymethyl starch sodium, amylum pregelatinisatum mix homogeneously successively, adds the pentoxifylline mixing at last; Making binding agent with the ethanol solution of an amount of 5%PVP granulates; 40 ℃ of dryings, granulate adds the magnesium stearate mixing; Tabletting promptly gets.
Embodiment 2-6 preparation technology is with embodiment 1.
Embodiment 7-12 tablet
Table 2 tablet formulation
Embodiment 7 preparation technologies: it is even earlier lyrica and cyclodextrin to be put into the mortar ground and mixed, adds carboxymethyl starch sodium, amylum pregelatinisatum mix homogeneously successively, adds pentoxifylline, diclofenac mixing at last; Making binding agent with the ethanol solution of an amount of 5%PVP granulates; 40 ℃ of dryings, granulate adds the magnesium stearate mixing; Tabletting promptly gets.
Embodiment 8-12 preparation technology is with embodiment 7.
Embodiment 13 capsules
Preparation technology: it is even earlier lyrica and beta-schardinger dextrin-to be put into the mortar ground and mixed, adds microcrystalline Cellulose, micropowder silica gel mix homogeneously successively, adds pentoxifylline, diclofenac mixing at last, and the filling capsule shell promptly gets.
Embodiment 14 capsules
Preparation technology: it is even earlier lyrica and beta-schardinger dextrin-to be put into the mortar ground and mixed, adds microcrystalline Cellulose, micropowder silica gel mix homogeneously successively, adds pentoxifylline, diclofenac mixing at last, and the filling capsule shell promptly gets.
Embodiment 15 capsules
Preparation technology: it is even earlier lyrica and beta-schardinger dextrin-to be put into the mortar ground and mixed, adds microcrystalline Cellulose, micropowder silica gel mix homogeneously successively, adds pentoxifylline, diclofenac mixing at last, and the filling capsule shell promptly gets.
Embodiment 16 granules
Preparation technology: earlier with lyrica and beta-schardinger dextrin-mix homogeneously; Add pentoxifylline, diclofenac, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, methylcellulose, sodium lauryl sulphate then and mix after crossing 16 mesh sieves, after again with orange flavor, aspartame mix homogeneously.Mixture is granulated with 5% polyvidone ethanol liquid, drying, and granulate, packing promptly gets.
Embodiment 17 slow releasing tablet
Preparation technology: take by weighing lyrica, pentoxifylline and the diclofenac of recipe quantity, carbomer, hydroxypropyl cellulose, beta-schardinger dextrin-mix homogeneously.Other gets 8% starch slurry solution of Sq, adds in the mixed-powder, makes soft material behind the mix homogeneously, granulates through 16 mesh sieves, and is dry below 60 ℃.Carry out granulate with 18 mesh sieves after accomplish dry back, sift out the fine powder in the dry granular, with the magnesium stearate mixing that sieves, and then evenly mixed with dried granule, tabletting promptly gets.
Embodiment 18 capsules
Preparation technology: it is even earlier lyrica and beta-schardinger dextrin-to be put into the mortar ground and mixed, adds microcrystalline Cellulose, micropowder silica gel mix homogeneously successively, adds the pentoxifylline mixing at last, and the filling capsule shell promptly gets.
Embodiment 19 granules
Preparation technology: earlier with lyrica and beta-schardinger dextrin-mix homogeneously; Add pentoxifylline, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, methylcellulose, sodium lauryl sulphate then and mix after crossing 16 mesh sieves, after again with orange flavor, aspartame mix homogeneously.Mixture is granulated with 5% polyvidone ethanol liquid, drying, and granulate, packing promptly gets.
Embodiment 20 slow releasing tablet
Preparation technology: take by weighing lyrica, pentoxifylline, the carbomer of recipe quantity, hydroxypropyl cellulose, beta-schardinger dextrin-mix homogeneously.Other gets 8% starch slurry solution of Sq, adds in the mixed-powder, makes soft material behind the mix homogeneously, granulates through 16 mesh sieves, and is dry below 60 ℃.Carry out granulate with 18 mesh sieves after accomplish dry back, sift out the fine powder in the dry granular, with the magnesium stearate mixing that sieves, and then evenly mixed with dried granule, tabletting promptly gets.
Second portion pharmaceutical composition pharmacodynamic study of the present invention
Test Example 1 pharmaceutical composition of the present invention causes the influence of pain to the rat hot plate
1, test method
96 of male SD rats are divided into 8 groups immediately, 12 every group.Each treated animal is with the 10ml/kg gastric infusion, and model group is irritated pure water, and every day sooner or later respectively once.Measure half an hour after the administration in afternoon in the 3rd day, and the control room temperature is 18 ℃～21 ℃ during experiment.Rat is placed (hot plate temperature is controlled at 55 ℃) on the hot-plate instrument, with stopwatch record rat from be placed on the hot plate to occur licking the metapedes required time (unit: s), as the pain threshold (unit: s) of this Mus.Every rat is measured 3 pain thresholds (each 40min at interval), averages, and is the pain threshold (unit: s) of this Mus.To each group pain threshold (unit: s) carry out the t check analysis, calculate the p value.
Model control group: gastric infusion equal-volume pure water;
Diclofenac group: gastric infusion diclofenac 20mg/kg;
Pentoxifylline group: gastric infusion pentoxifylline 40mg/kg;
Lyrica group: gastric infusion lyrica 60mg/kg;
General two group: gastric infusion lyrica 60mg/kg+ diclofenac 20mg/kg;
Oneself is two to organize: gastric infusion pentoxifylline 40mg/kg+ diclofenac 20mg/kg;
It is general that oneself organizes: gastric infusion lyrica 60mg/kg+ pentoxifylline 40mg/kg;
General own two groups: gastric infusion lyrica 60mg/kg+ pentoxifylline 40mg/kg+ diclofenac 20mg/kg.
2, result of the test
Experimental result shows (seeing table 3):
(1) compare with model group, each experimental group pain threshold obviously raises, and has significance or utmost point significant difference;
(2) compare with lyrica group, pentoxifylline group, general oneself group pain threshold obviously raises, and has significant difference, and is surprised to find the effect that lyrica and pentoxifylline drug combination have played collaborative rising pain threshold.
(3) compare with lyrica group, pentoxifylline group, diclofenac group; General oneself two group pain thresholds obviously raise; Have significant difference, and be surprised to find the effect that lyrica, pentoxifylline, diclofenac drug combination have played collaborative rising pain threshold.
(4) compare with general own group, general two groups, own pair of group, general oneself two pain thresholds of organizing obviously raise, and have significant difference.Pain threshold continues to raise and shows that the compound recipe group shows lasting effect build-up effect aspect treatment.
Table 3 present composition causes the influence of pain effect to the rat hot plate
Annotate: compare with model group
*P＜0.05,
*P＜0.01;
With lyrica group ratio
#P＜0.05,
##P＜0.01;
Compare with the pentoxifylline group,
&P＜0.05,
& &P＜0.01;
Compare with the diclofenac group,
▲P＜0.05,
▲ ▲P＜0.01;
Compare with oneself two groups,
△P＜0.05;
Compare with general two groups,
★P＜0.05;
Compare with general oneself group,
■P＜0.05.
Test Example 2 pharmaceutical compositions of the present invention are surveyed the influence of pain model rat to whipping
1, test method
96 SD rats are divided 8 groups at random, and 12 every group, male and female half and half are irritated stomach with the amount of 10ml/kg and given respectively to organize medicine, measure pain threshold behind the 1h, and model group is irritated stomach and given pure water.Earlier LEICA is spread out sheet machine temperature and be set in 48 ℃, on the tail of all rats, make a labelling with the oil pen in advance before the mensuration, the distance of this labelling and rat tail tip is about 5cm; Then rat is wrapped with the Mus bag, expose tail, and the tail of rat is put into stand sheet machine water; Make liquid level overlap with labelling on the rat tail; Clock with stopwatch at once when the rat tail contacts with hot water, the time that record rat tail contracts from hot water for the first time, every rat is measured the pain time that causes for 3 times (each 10min at interval; Otherwise easily with burned rats), getting the mean that causes the pain time for 3 times is the pain threshold of this rat.
Model control group: gastric infusion equal-volume pure water;
Diclofenac group: gastric infusion diclofenac 20mg/kg;
Pentoxifylline group: gastric infusion pentoxifylline 40mg/kg;
Lyrica group: gastric infusion lyrica 60mg/kg;
General two group: gastric infusion lyrica 60mg/kg+ diclofenac 20mg/kg;
Oneself is two to organize: gastric infusion pentoxifylline 40mg/kg+ diclofenac 20mg/kg;
It is general that oneself organizes: gastric infusion lyrica 60mg/kg+ pentoxifylline 40mg/kg;
General own two groups: gastric infusion lyrica 60mg/kg+ pentoxifylline 40mg/kg+ diclofenac 20mg/kg.
2, result of the test
Experimental result shows (seeing table 4):
(1) compare with model group, each experimental group pain threshold obviously raises, and has significance or utmost point significant difference;
(2) compare with lyrica group, pentoxifylline group, general oneself group pain threshold obviously raises, and has significant difference, and is surprised to find the effect that lyrica and pentoxifylline drug combination have played collaborative rising pain threshold.
(3) compare with lyrica group, pentoxifylline group, diclofenac group; General oneself two group pain thresholds obviously raise; Have significant difference, and be surprised to find the effect that lyrica, pentoxifylline, diclofenac drug combination have played collaborative rising pain threshold.
(4) compare with general own group, general two groups, own pair of group, general oneself two pain thresholds of organizing obviously raise, and have significant difference.Pain threshold continue to raise and to show that the compound recipe group shows lasting effect build-up effect aspect treatment.
Table 4 pharmaceutical composition of the present invention is surveyed the influence of pain model rat pain threshold to whipping
Annotate: compare with model group
*P＜0.05,
*P＜0.01;
With lyrica group ratio
#P＜0.05,
##P＜0.01;
Compare with the pentoxifylline group,
&P＜0.05,
& &P＜0.01;
Compare with the diclofenac group,
▲P＜0.05,
▲ ▲P＜0.01;
Compare with oneself two groups,
△P＜0.05;
Compare with general two groups,
★P＜0.05;
Compare with general oneself group,
■P＜0.05.
Test Example 3 pharmaceutical compositions of the present invention cause the influence of neuropathic pain rat model to diabetes
1, test material
1.1 laboratory animal and experimental article
150 of healthy male SD rats, body weight 180～220g, the SPF level, the Shandong New Times Pharmaceutical new drug peace center of commenting provides.20～25 ℃ of room temperatures, room ventilation is good, and ammonia concentration is less than 20 * 10
-6Ml/m
3, relative humidity is 40%～70%, and illumination period 12h, rat feeding are in the rustless steel mouse cage, and 4 in every cage is freely ingested, is drunk water.
Streptozotocin (STZ, sigma company produces, the U.S.); ZHLUO/B type Mus tail photo-thermal dolorimeter, YLS 3E type electronics tenderness appearance are all available from Anhui Huaibei Zhenghua Biological Instrument Co., Ltd..
The preparation of STZ solution: STZ is dissolved in pH 4.2, the 0.1mmol/L citrate buffer solution, and with join at present, concentration is 3.75% (W/V), i.e. 0.5ml/100g to solution at present.
1.2 the foundation of test model
150 rats are left and taken 10 at random as the normal control group, press 75mgkg behind all the other 140 rat fasting 12h
-1Disposable celiac injection STZ solution.
Blood sugar detection: survey tail vein sugar behind the modeling 7d, blood glucose >=16mmol/L is a diabetes rat then, has 47 rats successfully to build up DM model (model group) in the experiment.Detect blood glucose with injection back the 7th, 21,35,49d before the STZ injection, blood glucose is lower than 16mmol/L and then abandons.
The machinery threshold of pain is measured: before the STZ injection, after the injection 21,35,49d measures the mechanical threshold of pain.Rat is placed in the transparent organic glass stationary magazine creel that audio frequency amplifier is housed, and the Mus tail reveals outside the tube, at the labelling apart from tail point 5cm place.The rat 15min that conforms, treat that rat combing and inquiry activity disappear after, Mus tail tag note is disposed in electronics tenderness appearance pressure head place; To Mus tail exert pressure (per second increase 10g); Then stop to exert pressure as whinnying, struggling when pain reaction appears in rat, write down the data (g) of exerting pressure, METHOD FOR CONTINUOUS DETERMINATION 5 times; Each 10min at interval averages as mechanical pain threshold.If surpassing 500g, force value then rejects.
The burning pain threshold is measured: minute point, preparation method are with the mechanical threshold of pain.The heating-up temperature of ZHLUO/B type Mus tail dolorimeter is set at 49 ℃, reaches after the setting value radiating light source is aimed at apart from tail point 4cm place, writes down to begin the time (s) to the perk of Mus tail from illumination.If light application time surpass 15s Mus tail not yet perk then reject, measures 5 times, each interval 10min gets average as the burning pain threshold value.
The modeling result: the rat of injection streptozotocin residue rat after blood sugar detection screening, the mechanical threshold of pain and the screening of burning pain threshold is the successful diabetes nerve pathologic pain rat of modeling, 120 of rat modeling successes.
1.3 animal divides into groups and administration
Choose successfully 100 of the diabetes nerve pathologic rats of modeling, be divided into 10 groups at random, 10 every group, give following medicine respectively, other increases by 1 normal control group.
Normal group: irritate stomach and give isopyknic distilled water;
Model group: irritate stomach and give isopyknic distilled water;
General group: irritate the lyrica that stomach gives 30mg/kg;
Hexanone A group: irritate the pentoxifylline that stomach gives 90mg/kg;
Hexanone B group: irritate the pentoxifylline that stomach gives 0.3mg/kg;
Two chlorine A groups: irritate the diclofenac that stomach gives 6mg/kg;
Two chlorine B groups: irritate the diclofenac that stomach gives 60mg/kg;
General own A group: irritate the pentoxifylline that stomach gives lyrica+90mg/kg of 30mg/kg;
General own B group: irritate the pentoxifylline that stomach gives lyrica+0.3mg/kg of 30mg/kg;
General oneself two A groups: irritate the diclofenac of pentoxifylline+6mg/kg that stomach gives lyrica+90mg/kg of 30mg/kg;
General oneself two B groups: irritate the diclofenac of pentoxifylline+60mg/kg that stomach gives lyrica+0.3mg/kg of 30mg/kg;
Each administration group medicine is used an amount of dissolved in distilled water, gastric infusion, and be administered once every day.Behind administration 10d, the 20d, measure mechanical pain threshold and the burning pain threshold value of each administration group rat.It is as shown in table 5 that each administration group is measured the result.
1.4 date processing
Above gained experimental data is carried out statistical procedures according to following method:
Adopt the SPSS13.0 statistical software; Calculating data is represented with mean ± standard deviation
; Many groups data relatively adopts variance analysis, relatively adopts the t check in the group.With p＜0.05 for statistical significance is arranged.
2, result of the test
Result of the test shows (seeing table 5):
(1) model group and compared with normal, the mechanical threshold of pain and burning pain threshold descend significantly (p＜0.01), show to adopt injection streptozotocin gained diabetes nerve pathologic pain rat model ideal, meet the experiment needs;
(2) hexanone A group, hexanone B group, two chlorine A group and two chlorine B group can cause the mechanical threshold of pain of diabetes nerve pathologic pain rat and the change of burning pain threshold, still compare with model group not have significant difference;
(3) lyrica has certain rising effect to the diabetes nerve pathologic pain rat machinery threshold of pain and burning pain threshold, and compares with model group and to have statistical significance.But its therapeutic effect does not prolong with treatment time and strengthens.
(4) compare with model group; General own A group and general own B group show significant therapeutical effect to the neuropathic pain that diabetes cause; And along with the prolongation of administration time, the mechanical threshold of pain and the burning pain threshold of diabetes nerve pathologic pain rat move closer to the normal rat group.Compare with general group, hexanone A group, hexanone B group, general own A group and general own B group show significant therapeutical effect to the neuropathic pain of diabetes initiation, and have synergism;
(5) compare with model group; General oneself two A organize and general oneself two B groups show significant therapeutical effect to the neuropathic pain that diabetes cause; And along with the prolongation of administration time, the mechanical threshold of pain and the burning pain threshold of diabetes nerve pathologic pain rat move closer to the normal rat group.
(6) compare with general group, hexanone A group, two chlorine A group, general own A group; General oneself two A groups show significant therapeutical effect to the neuropathic pain that diabetes cause; And have synergism, this neuropathic pain that shows the medicine composite for curing diabetes initiation that contains lyrica, pentoxifylline and diclofenac has good synergism.General oneself two B groups also show similar result.
Table 5 compound recipe is to the therapeutical effect of diabetes nerve pathologic rat
Annotate: compare with model group
#P＜0.05,
##P＜0.01; With general group of comparison
*P＜0.05,
*P＜0.01;
Compare with hexanone A group,
&P＜0.05; Compare with hexanone B group,
△P＜0.05;
Compare with general own A group,
★P＜0.05; Compare with general own B group,
■P＜0.05;
Compare with two chlorine A groups,
▲ ▲P＜0.05; Compare with two chlorine B groups,
P＜0.05.
Owing to described product of the present invention, preparation method and its usage through above embodiment.Any to be equal to replacement be conspicuous for the technological people of this area, and be included within the scope of the present invention.And do not breaking away from the spirit and scope of the invention, the embodiment of the present invention technology is being changed and/or made up to product as herein described and method, be conspicuous for the technological people of this area, and be included within the scope of the present invention.
Claims (13)
1. pharmaceutical composition of treating neuropathic pain is characterized in that it contains following active component: pentoxifylline and lyrica.
2. pharmaceutical composition as claimed in claim 1, the weight ratio that it is characterized in that described pentoxifylline and lyrica is 0.01～50: 1.
3. pharmaceutical composition as claimed in claim 2, the weight ratio that it is characterized in that described pentoxifylline and lyrica is 0.05～12: 1.
4. pharmaceutical composition as claimed in claim 3, the weight ratio that it is characterized in that described pentoxifylline and lyrica is 0.1～3: 1.
5. pharmaceutical composition as claimed in claim 1 is characterized in that it also contains following active component: diclofenac or its officinal salt.
6. pharmaceutical composition as claimed in claim 5 is characterized in that the weight ratio of described diclofenac and lyrica, pentoxifylline is (0.02～2): 1: (0.01～50).
7. pharmaceutical composition as claimed in claim 6 is characterized in that the weight ratio of described diclofenac and lyrica, pentoxifylline is (0.2～2): 1: (0.1～3).
8. like the arbitrary described pharmaceutical composition of claim 1～7, it is characterized in that it is conventional tablet, capsule, granule, slow releasing tablet or enteric coated tablet.
9. pharmaceutical composition as claimed in claim 5 is characterized in that containing in the described pharmaceutical composition diclofenac 25～300mg, pentoxifylline 50～1800mg, lyrica 150～600mg.
10. like the purposes of the arbitrary described pharmaceutical composition of claim 1～7 in the medicine of preparation treatment neuropathic pain.
11. purposes as claimed in claim 10 is characterized in that containing in the described pharmaceutical composition diclofenac 25～300mg, pentoxifylline 50～1800mg, lyrica 150～600mg.
12. purposes as claimed in claim 10 is characterized in that described neuropathic pain is that intractable pain, trigeminal neuralgia, postherpetic neuralgia, the spinal disease patient of oncothlipsis oppresses the neuropathic pain that pain that spinal cord or nerve root cause and diabetes cause.
13. purposes as claimed in claim 12 is characterized in that described neuropathic pain is the neuropathic pain that diabetes cause.
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| CN201110056964.4A CN102648915B (en) | 2011-02-28 | 2011-02-28 | Medicinal composition for treating or preventing neuropathic pain |
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| CN201110056964.4A CN102648915B (en) | 2011-02-28 | 2011-02-28 | Medicinal composition for treating or preventing neuropathic pain |
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| WO2023274117A1 (en) * | 2021-07-01 | 2023-01-05 | 南京宁丹新药技术有限公司 | Pharmaceutical composition and use thereof |
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