CN102648915B - Medicinal composition for treating or preventing neuropathic pain - Google Patents

Medicinal composition for treating or preventing neuropathic pain Download PDF

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CN102648915B
CN102648915B CN201110056964.4A CN201110056964A CN102648915B CN 102648915 B CN102648915 B CN 102648915B CN 201110056964 A CN201110056964 A CN 201110056964A CN 102648915 B CN102648915 B CN 102648915B
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pentoxifylline
lyrica
neuropathic pain
group
pain
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CN201110056964.4A
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CN102648915A (en
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张贵民
胡守艳
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鲁南制药集团股份有限公司
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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

The pharmaceutical composition of a kind for the treatment of or prevention neuropathic pain

Technical field

The invention belongs to field of medicaments, be specifically related to the pharmaceutical composition of a kind for the treatment of or prevention neuropathic pain.

Background technology

Neuropathic pain is the major disease of serious threat human life health, sickness rate up to 1%, especially in diabetics sickness rate up to 50%.Neuropathic pain refers to the pain because nervous system sustains damage or produces pathological changes and cause, and comprises the intractable pain of oncothlipsis, the polyneuritis pain (neuropathic pain that diabetes cause) etc. of trigeminal neuralgia, postherpetic neuralgia, spinal disease patient oppress spinal cord or nerve root causes pain and diabetics.For the acute pain caused due to tissue injury, neuropathic pain is often long-term and chronic, sustainable several days or several months.The pain continued has a strong impact on the quality of life of people.The clinical origin of neuropathic pain is extensive, and symptom is various, and pathomechanism is complicated, and conventional analgesic such as opiates potent narcotic analgesics and NSAID (non-steroidal anti-inflammatory drug) all do not have obvious curative effect to it, thus one of difficult point becoming clinical treatment.

The chemical name of lyrica (pregabalin) is (3S)-3-aminomethyl-5-methylhexanoic acid, and research shows that lyrica can reduce rat motor spinal reflex; Reduce diabetes, nervus peripheralis damage or the corelation behaviour of chemotherapy nerve animal pain models; Can suppress or reduce spine gives pain that stimulus object causes relevant behavior.Lyrica is a kind of novel γ-aminobutyric acid (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 the excitatory neurotransmitters such as glutamate, Glu, norepinephrine, Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 thereupon, but be not very desirable to neuropathic pain therapeutic effect.

Li Aihong is at " status quo and future of glycosuria slight illness neurotherapy " (Inpharm research magazine, in October, 2007,34th volume the 5th phase 377-379 page) one to the article pointed out, although discuss a large amount of glycosuria slight illness neuropathy (DPN) curatives at present, not yet find the cause of disease or all fully effective medicine of symptom.Find the work that the minimum single medicine of effective side effect or combination are difficulty efforts, but will continue.

Summary of the invention

In view of current neuropathic pain there is no effective Drug therapy, the invention provides a kind of pharmaceutical composition for the treatment of neuropathic pain, 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-dimethylxanthine, is clinically mainly used in thromboangiitis obliterans, cerebrovascular disorders, vascular headache etc.Pentoxifylline can increase erythrocytic morphotropism, improves leukocytic lectin from hemolymph feature, suppresses sticking and activating of neutrophil cell, and expansion blood capillary, reduces blood viscosity, increases PtO2, has antiinflammatory action, can eliminate free radical etc.Pentoxifylline is creatively combined with lyrica and is used for the treatment of neuropathic pain by the present invention, achieves collaborative therapeutic effect.Show through a large amount of animal experiment studies, the form of lyrica and Combined Pentoxifylline medication is for treating neuropathic pain determined curative effect, therefore, the invention provides the fixed Combination form of lyrica and pentoxifylline, namely contain the pharmaceutical composition of lyrica and pentoxifylline.

Be used for the treatment of the curative effect of neuropathic pain according to lyrica and pentoxifylline pharmaceutical composition, the weight ratio of the present invention to lyrica in pharmaceutical composition and pentoxifylline is carried out preferably.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 in the pharmaceutical composition of neuropathic pain and also contains the third active component: diclofenac or its officinal salt.Diclofenac is non-steroid compound, and it plays its pharmacological action by suppressing prostate synthesis.There is rheumatism, antiinflammatory, analgesia and refrigeration function.Be characterized in alleviating clinical sign and symptom significantly, as multiple pain, arthroncus, wound and post-operation inflammatory etc.Pharmaceutical composition of the present invention combines the third active component diclofenac or its officinal salt on the basis of pentoxifylline and lyrica, and 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 carries out preferably the weight ratio of diclofenac, lyrica and pentoxifylline in pharmaceutical composition.Preferably, in pharmaceutical composition of the present invention, the weight ratio of diclofenac and lyrica, pentoxifylline is (0.02 ~ 2): 1: (0.01 ~ 50), further preferably, the weight ratio of diclofenac and lyrica, pentoxifylline is (0.02 ~ 2): 1: (0.1 ~ 3).

In order to better express pharmaceutical composition of the present invention, pharmaceutical composition of the present invention can be prepared into oral formulations conventional clinically, as conventional tablet, capsule, granule, slow releasing tablet or enteric coated tablet.Preferably, in the unit dose of these drug composition oral preparations, diclofenac 25 ~ 300mg, pentoxifylline 50 ~ 1800mg, lyrica 150 ~ 600mg is contained.

Excipient in aforementioned pharmaceutical compositions oral formulations can be selected from diluent, wetting agent, binding agent, disintegrating agent and lubricant one or more; Wherein diluent is selected from one or more in starch, dextrin, lactose and microcrystalline Cellulose; Wetting agent and binding agent be selected from water, ethanol, hydroxypropyl methylcellulose, ethyl cellulose and polyvinylpyrrolidone one or more; Disintegrating agent be selected from carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose and polyvinylpolypyrrolidone one or more; Lubricant be selected from magnesium stearate, zinc stearate and micropowder silica gel one or more.Above-mentioned oral formulations all conveniently preparation technique is prepared, such as dry granulation, wet granulation etc.

Present invention also offers a kind of method for the treatment of neuropathic pain, namely give pharmaceutical composition of the present invention.The effective dose that pharmaceutical composition of the present invention is used for the treatment of neuropathic pain is diclofenac 25 ~ 300mg/d, pentoxifylline 50 ~ 1800mg/d, lyrica 150 ~ 600mg/d.

The pain that neuropathic pain of the present invention comprises the intractable pain of oncothlipsis, trigeminal neuralgia, postherpetic neuralgia, spinal disease patient oppress spinal cord or nerve root causes and the neuropathic pain that diabetes cause.

Surprisingly, the neuropathic pain effect that causes diabetes of pharmaceutical composition of the present invention is particularly remarkable.The effective dose that pharmaceutical composition of the present invention is used for the treatment of the neuropathic pain that diabetes cause is diclofenac 25 ~ 300mg/d, pentoxifylline 50 ~ 1800mg/d, lyrica 150 ~ 600mg/d.

The present invention also passes through the impact of pharmaceutical composition of the present invention on neuropathic pain of pharmacodynamics test high spot reviews.Experimental result shows, the pharmaceutical composition that the present invention contains lyrica and pentoxifylline has good therapeutical effect to neuropathic pain model rat, and compared with individually dosed lyrica or pentoxifylline, show good synergism.Especially the neuropathic pain caused for treatment diabetes has more outstanding therapeutical effect.Therefore, the pharmaceutical composition containing lyrica and pentoxifylline can be used in treating neuropathic pain, especially may be used for the treatment of the neuropathic pain disease that diabetes cause.

In addition, the present inventor is surprised to find, the present invention creatively introduces diclofenac on the basis of the pharmaceutical composition containing lyrica and pentoxifylline, at treatment neuropathic pain, especially diabetes cause neuropathic pain time, show more efficiently therapeutic outcome.And compared with individually dosed pentoxifylline, lyrica or diclofenac, achieve collaborative therapeutic effect.Therefore, the pharmaceutical composition containing pentoxifylline, lyrica and diclofenac may be used for the neuropathic pain that treatment neuropathic pain is particularly useful for treating diabetes initiation.Meanwhile, the present invention has also investigated the pharmaceutical composition of lyrica, pentoxifylline and diclofenac containing Different Weight ratio to the therapeutic effect of the neuropathic pain that diabetes cause, result display weight ratio is (0.02 ~ 2): 1: the pharmaceutical composition of (0.01 ~ 50) achieves 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) compared with individually dosed lyrica or pentoxifylline, the pharmaceutical composition that the present invention contains lyrica and pentoxifylline has good therapeutical effect to neuropathic pain model rat, and shows good synergism.Especially the neuropathic pain caused for treatment diabetes has more outstanding therapeutical effect.

(2) compared with individually dosed pentoxifylline, lyrica or diclofenac, the present invention contains the pharmaceutical composition of lyrica, pentoxifylline and diclofenac at treatment neuropathic pain, especially the neuropathic pain of diabetes initiation, show more efficiently therapeutic outcome, and achieve collaborative therapeutic effect.

(3) compared with individually dosed or administering drug combinations, pharmaceutical composition of the present invention, with the form of therapy neuropathic pain of fixed Combination, improves compliance and the compliance of patient.

Detailed description of the invention

Further describe the present invention below by way of specific 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, to replacement and/or the combination of the technology of the present invention feature, will be readily apparent to persons skilled in the art, and be included among the present invention.

Part I drug combination preparation of the present invention and preparation method thereof

Embodiment 1-6 tablet

Table 1 tablet formulation

Embodiment 1 preparation technology: first lyrica and cyclodextrin are put into mortar ground and mixed even, add carboxymethyl starch sodium, amylum pregelatinisatum mix homogeneously successively, finally add pentoxifylline mixing, make binding agent with the ethanol solution of appropriate 5%PVP to granulate, 40 DEG C of dryings, granulate, adds magnesium stearate mixing, tabletting, to obtain final product.

Embodiment 2-6 preparation technology is with embodiment 1.

Embodiment 7-12 tablet

Table 2 tablet formulation

Embodiment 7 preparation technology: first lyrica and cyclodextrin are put into mortar ground and mixed even, add carboxymethyl starch sodium, amylum pregelatinisatum mix homogeneously successively, finally add pentoxifylline, diclofenac mixing, make binding agent with the ethanol solution of appropriate 5%PVP to granulate, 40 DEG C of dryings, granulate, adds magnesium stearate mixing, tabletting, to obtain final product.

Embodiment 8-12 preparation technology is with embodiment 7.

Embodiment 13 capsule

Preparation technology: first lyrica and beta-schardinger dextrin-are put into mortar ground and mixed even, add microcrystalline Cellulose, micropowder silica gel mix homogeneously successively, finally add pentoxifylline, diclofenac mixing, filling capsule shell, to obtain final product.

Embodiment 14 capsule

Preparation technology: first lyrica and beta-schardinger dextrin-are put into mortar ground and mixed even, add microcrystalline Cellulose, micropowder silica gel mix homogeneously successively, finally add pentoxifylline, diclofenac mixing, filling capsule shell, to obtain final product.

Embodiment 15 capsule

Preparation technology: first lyrica and beta-schardinger dextrin-are put into mortar ground and mixed even, add microcrystalline Cellulose, micropowder silica gel mix homogeneously successively, finally add pentoxifylline, diclofenac mixing, filling capsule shell, to obtain final product.

Embodiment 16 granule

Preparation technology: first lyrica is mixed homogeneously with beta-schardinger dextrin-, then add pentoxifylline, diclofenac, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, methylcellulose, sodium lauryl sulphate mix after crossing 16 mesh sieves, after mix homogeneously with orange flavor, aspartame again.Mixture 5% polyvidone ethanol is granulated, and dry, granulate, subpackage, to obtain final product.

Embodiment 17 slow releasing tablet

Preparation technology: take the lyrica of recipe quantity, pentoxifylline and diclofenac, carbomer, hydroxypropyl cellulose, beta-schardinger dextrin-mix homogeneously.Separately get 8% starch slurry solution of Sq, add in mixed-powder, soft material processed after mix homogeneously, granulated by 16 mesh sieves, less than 60 DEG C dry.After completing after drying, use 18 mesh sieve carries out granulate, sifts out the fine powder in dry granular, mixes with the magnesium stearate of sieving, and then is mixed evenly with dry granule, tabletting, to obtain final product.

Embodiment 18 capsule

Preparation technology: first lyrica and beta-schardinger dextrin-are put into mortar ground and mixed even, add microcrystalline Cellulose, micropowder silica gel mix homogeneously successively, finally add pentoxifylline mixing, filling capsule shell, to obtain final product.

Embodiment 19 granule

Preparation technology: first lyrica is mixed homogeneously with beta-schardinger dextrin-, then add pentoxifylline, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, methylcellulose, sodium lauryl sulphate mix after crossing 16 mesh sieves, after mix homogeneously with orange flavor, aspartame again.Mixture 5% polyvidone ethanol is granulated, and dry, granulate, subpackage, to obtain final product.

Embodiment 20 slow releasing tablet

Preparation technology: take the lyrica of recipe quantity, pentoxifylline, carbomer, hydroxypropyl cellulose, beta-schardinger dextrin-mix homogeneously.Separately get 8% starch slurry solution of Sq, add in mixed-powder, soft material processed after mix homogeneously, granulated by 16 mesh sieves, less than 60 DEG C dry.After completing after drying, use 18 mesh sieve carries out granulate, sifts out the fine powder in dry granular, mixes with the magnesium stearate of sieving, and then is mixed evenly with dry granule, tabletting, to obtain final product.

Part II pharmaceutical composition pharmacodynamic study of the present invention

Test example 1 pharmaceutical composition of the present invention is on the impact of rat hotplate induced pain

1, test method

Male SD rat 96, is divided into 8 groups immediately, often organizes 12.Each treated animal is with 10ml/kg gastric infusion, and model group fills with pure water, and every day sooner or later respectively once.After 3rd afternoon administration, half an hour measures, and controls room temperature 18 DEG C ~ 21 DEG C during experiment.Be placed in by rat (hot plate temperature controls at 55 DEG C) on hot-plate instrument, with stopwatch record rat, from being placed on hot plate, to occurring licking metapedes required time, (unit: s), as the pain threshold (unit: s) of this Mus.Every rat measures 3 pain thresholds (every minor tick 40min), averages, is the pain threshold (unit: s) of this Mus.To each group of pain threshold, (unit: s) carry out t check analysis calculates 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 pair of group: gastric infusion lyrica 60mg/kg+ diclofenac 20mg/kg;

Own two group: gastric infusion pentoxifylline 40mg/kg+ diclofenac 20mg/kg;

General own group: gastric infusion lyrica 60mg/kg+ pentoxifylline 40mg/kg;

General own two group: gastric infusion lyrica 60mg/kg+ pentoxifylline 40mg/kg+ diclofenac 20mg/kg.

2, result of the test

Experimental result shows (see table 3):

(1) compared with model group, each experimental group pain threshold obviously raises, and has significance or pole significant difference;

(2) compared with lyrica group, pentoxifylline group, oneself group pain threshold general obviously raises, and has significant difference, and is surprised to find lyrica and Combined Pentoxifylline medication and serves the collaborative effect raising pain threshold.

(3) compared with lyrica group, pentoxifylline group, diclofenac group, oneself two group pain threshold general obviously raises, there is significant difference, and be surprised to find lyrica, pentoxifylline, diclofenac drug combination serve the collaborative effect raising pain threshold.

(4) compared with general own group, general pair group, oneself two group, oneself two group pain threshold general obviously raises, and has significant difference.Pain threshold continues to raise and shows that compound recipe group shows lasting effect build-up effect in treatment.

Table 3 present composition is on the impact of rat hotplate induced pain effect

Note: compare with model group *p < 0.05, *p < 0.01;

With lyrica group ratio #p < 0.05, ##p < 0.01;

Compare with pentoxifylline group, aMP.AMp.Ampp < 0.05, aMP.AMp.Amp &p < 0.01;

Compare with diclofenac group, p < 0.05, ▲ ▲p < 0.01;

Compare with oneself two group, p < 0.05;

Compare with general pair of group, p < 0.05;

Compare with general own group, p < 0.05.

Test example 2 pharmaceutical composition of the present invention surveys the impact of pain model rat to whipping

1, test method

96 SD rats divide 8 groups at random, and often organize 12, male and female half and half, give each group of medicine with the amount gavage of 10ml/kg, measure pain threshold after 1h, model group gavage gives pure water.First LEICA is spread out sheet machine temperature and be set in 48 DEG C, on the tail of all rats, a labelling is made with oil pen in advance before mensuration, the distance of this labelling and rat tail tip is about 5cm, then rat Mus bag is wrapped, expose tail, and the tail of rat is put into stand sheet machine water, liquid level is overlapped with the labelling on rat tail, clock with stopwatch at once when rat tail and hot water contacts, the time that record rat tail first time shrinks from hot water, every rat measures 3 induced pain time (every minor tick 10min, otherwise easily by burned rats), the mean getting 3 induced pain 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 pair of group: gastric infusion lyrica 60mg/kg+ diclofenac 20mg/kg;

Own two group: gastric infusion pentoxifylline 40mg/kg+ diclofenac 20mg/kg;

General own group: gastric infusion lyrica 60mg/kg+ pentoxifylline 40mg/kg;

General own two group: gastric infusion lyrica 60mg/kg+ pentoxifylline 40mg/kg+ diclofenac 20mg/kg.

2, result of the test

Experimental result shows (see table 4):

(1) compared with model group, each experimental group pain threshold obviously raises, and has significance or pole significant difference;

(2) compared with lyrica group, pentoxifylline group, oneself group pain threshold general obviously raises, and has significant difference, and is surprised to find lyrica and Combined Pentoxifylline medication and serves the collaborative effect raising pain threshold.

(3) compared with lyrica group, pentoxifylline group, diclofenac group, oneself two group pain threshold general obviously raises, there is significant difference, and be surprised to find lyrica, pentoxifylline, diclofenac drug combination serve the collaborative effect raising pain threshold.

(4) compared with general own group, general pair group, oneself two group, oneself two group pain threshold general obviously raises, and has significant difference.Pain threshold continues rising and shows that compound recipe group shows lasting effect build-up effect in treatment.

Table 4 pharmaceutical composition of the present invention surveys the impact of pain model Pain Regulation In The Rat value to whipping

Note: compare with model group *p < 0.05, *p < 0.01;

With lyrica group ratio #p < 0.05, ##p < 0.01;

Compare with pentoxifylline group, aMP.AMp.Ampp < 0.05, aMP.AMp.Amp &p < 0.01;

Compare with diclofenac group, p < 0.05, ▲ ▲p < 0.01;

Compare with oneself two group, p < 0.05;

Compare with general pair of group, p < 0.05;

Compare with general own group, p < 0.05.

Test example 3 pharmaceutical composition of the present invention causes the impact of neuropathic pain model rat to diabetes

1, test material

1.1 laboratory animals and experimental article

Healthy male SD rat 150, body weight 180 ~ 220g, SPF level, Shandong New Times Pharmaceutical new drug An Ping center provides.Room temperature 20 ~ 25 DEG C, room ventilation is good, and ammonia density is less than 20 × 10 -6ml/m 3, relative humidity is 40% ~ 70%, illumination period 12h, and rat feeding is in rustless steel mouse cage, and 4, every cage, freely ingests, drinks water.

Streptozotocin (STZ, sigma company produces, the U.S.); ZHLUO/B type Mus tail photo-thermal dolorimeter, YLS 3E type electronics tenderness instrument are all purchased from Northern Huaihe River Anhui Zheng Hua biological Instrument and equipments company limited.

STZ solution preparation: be dissolved in by STZ in pH 4.2,0.1mmol/L citrate buffer solution, solution matching while using, concentration is 3.75% (W/V), i.e. 0.5ml/100g.

The foundation of 1.2 test models

150 rats leave and take 10 at random as Normal group, press 75mgkg after all the other 140 Rat Fast 12h -1disposable celiac injection STZ solution.

Blood sugar detection: survey tail vein sugar after modeling 7d, blood glucose >=16mmol/L is then diabetes rat, has 47 rats successfully to build up DM model (model group) in experiment.Before STZ injection and after injection the 7th, 21,35,49d detects blood glucose, blood glucose is then abandoned lower than 16mmol/L.

Machinery Determination of Pain Threshold: before STZ injection, after injection 21,35,49d measures the mechanical threshold of pain.Rat is placed in and is equipped with in the transparent organic glass stationary magazine creel of audio frequency amplifier, outside Mus tail dew cylinder, at distance tail point 5cm place labelling.Rat conforms 15min, after rat combing and inquiry activity disappear, Mus tail tag note is disposed in electronics tenderness instrument pressure head place, (increase 10g per second) is exerted pressure to Mus tail, when rat occurs that pain reaction then stops exerting pressure as whinnied, struggling, record data (g) of exerting pressure, METHOD FOR CONTINUOUS DETERMINATION 5 times, every minor tick 10min, averages as mechanical pain threshold.If force value is more than 500g, reject.

Hot Determination of Pain Threshold: minute point, preparation method are with the mechanical threshold of pain.The heating-up temperature of ZHLUO/B type Mus tail dolorimeter is set as 49 DEG C, is aimed at by radiating light source apart from tail point 4cm place, record from illumination to the time (s) that Mus tail tilts after reaching setting value.If light application time tilts not yet more than 15s Mus tail, reject, measure 5 times, every minor tick 10min, get average as burning pain threshold value.

Modeling result: the rat of injection streptozotocin remains rat and is modeling successful diabetes nerve pathologic pain rat, rat modeling success 120 after blood sugar detection screening, the mechanical threshold of pain and the screening of burning pain threshold.

1.3 animal grouping and administrations

Choose successfully the diabetes nerve pathologic rat 100 of modeling, be divided into 10 groups at random, often organize 10, give agents respectively, another increase by 1 Normal group.

Normal group: gavage gives isopyknic distilled water;

Model group: gavage gives isopyknic distilled water;

General group: gavage gives the lyrica of 30mg/kg;

Hexanone A group: gavage gives the pentoxifylline of 90mg/kg;

Hexanone B group: gavage gives the pentoxifylline of 0.3mg/kg;

Two chlorine A group: gavage gives the diclofenac of 6mg/kg;

Two chlorine B group: gavage gives the diclofenac of 60mg/kg;

General own A group: gavage gives the pentoxifylline of the lyrica+90mg/kg of 30mg/kg;

General own B group: gavage gives the pentoxifylline of the lyrica+0.3mg/kg of 30mg/kg;

General own two A group: gavage gives the diclofenac of the pentoxifylline+6mg/kg of the lyrica+90mg/kg of 30mg/kg;

General own two B group: gavage gives the diclofenac of the pentoxifylline+60mg/kg of the lyrica+0.3mg/kg of 30mg/kg;

The appropriate distilled water of each administration group medicine dissolves, and gastric infusion, every day is administered once.After administration 10d, 20d, measure mechanical pain threshold and the burning pain threshold value of each administration group rat.Each administration group measurement result is as shown in table 5.

1.4 date processing

Above obtained experimental data is carried out statistical procedures in accordance with the following methods:

Adopt SPSS13.0 statistical software, calculate data with mean ± standard deviation represent, many groups data compares employing variance analysis, compares and adopt t inspection in group.With p < 0.05 for there being statistical significance.

2, result of the test

Result of the test shows (see table 5):

(1) model group is compared with normal group, and the mechanical threshold of pain and burning pain threshold decline significantly (p < 0.01), shows to adopt injection streptozotocin gained diabetes nerve pathologic pain rat model desirable, meets 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, but do not have significant difference compared with model group;

(3) lyrica has certain rising effect to the diabetes nerve pathologic pain rat machinery threshold of pain and burning pain threshold, and has statistical significance compared with model group.But its therapeutic effect does not extend with treatment time and strengthens.

(4) compared 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 normal rat group.With general group, hexanone A group, compared with hexanone B group, general own A group and general own B group show significant therapeutical effect to the neuropathic pain that diabetes cause, and have synergism;

(5) compared with model group, general own two A group and oneself two B group general 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 normal rat group.

(6) with general group, hexanone A group, two chlorine A group, compared with general own A group, oneself two A group general shows significant therapeutical effect to the neuropathic pain that diabetes cause, and have synergism, this shows that the neuropathic pain that the medicine composite for curing diabetes containing lyrica, pentoxifylline and diclofenac cause has good synergism.Oneself two B group general also shows similar result.

Table 5 compound recipe is to the therapeutical effect of diabetes nerve pathologic rat

Note: compare with model group #p < 0.05, ##p < 0.01; Compare with general group *p < 0.05, *p < 0.01;

Compare with hexanone A group, aMP.AMp.Ampp < 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 group, ▲ ▲p < 0.05; Compare with two chlorine B group, p < 0.05.

Due to by embodiment above describes product of the present invention, preparation method and its usage.Any equivalent replacement for this area technology people be apparent, and to be included within the scope of the present invention.And not departing from spirit and scope of the invention, product as herein described and method being changed and/or being combined and implements the technology of the present invention, for this area technology people be apparent, and to be included within the scope of the present invention.

Claims (8)

1. treat a pharmaceutical composition for neuropathic pain, it is characterized in that it is made up of pentoxifylline and lyrica two kinds of active component, described pentoxifylline and the weight ratio of lyrica are 0.01 ~ 3: 1.
2. treat the pharmaceutical composition of neuropathic pain for one kind, it is characterized in that it is made up of with lyrica, pentoxifylline three kinds of active component diclofenac or its officinal salt, the weight ratio of described diclofenac and lyrica, pentoxifylline is (0.2 ~ 2): 1: (0.01 ~ 3).
3. the pharmaceutical composition as described in as arbitrary in claim 1 ~ 2, is characterized in that it is conventional tablet, capsule, granule, slow releasing tablet or enteric coated tablet.
4. the pharmaceutical composition as described in claim 2, is characterized in that in described pharmaceutical composition containing diclofenac 25 ~ 300mg, pentoxifylline 50 ~ 1800mg, lyrica 150 ~ 600mg.
5. the purposes of the pharmaceutical composition as described in as arbitrary in claim 1 ~ 2 in the medicine of preparation treatment neuropathic pain.
6. the purposes as described in claim 5, is characterized in that in described pharmaceutical composition containing diclofenac 25 ~ 300mg, pentoxifylline 50 ~ 1800mg, lyrica 150 ~ 600mg.
7. purposes as claimed in claim 5, is characterized in that described neuropathic pain is the intractable pain of oncothlipsis, trigeminal neuralgia, postherpetic neuralgia, spinal disease patient oppress spinal cord or nerve root causes pain and the neuropathic pain that diabetes cause.
8. purposes as claimed in claim 7, is characterized in that described neuropathic pain is the neuropathic pain that diabetes cause.
CN201110056964.4A 2011-02-28 2011-02-28 Medicinal composition for treating or preventing neuropathic pain CN102648915B (en)

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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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CN101600458A (en) * 2006-12-22 2009-12-09 瑞蔻达蒂爱尔兰有限公司 Combination therapy of lower urinary tract disorders with a2d ligands and nsaids
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CN101679445A (en) * 2007-04-13 2010-03-24 先灵公司 Pyrimidinedione derivatives and methods of use thereof
CN101898977A (en) * 2009-05-31 2010-12-01 徐锋 GABA (Gamma-Aminobutyric Acid) conjugates and using method thereof
CN101919860A (en) * 2009-06-12 2010-12-22 鲁南制药集团股份有限公司 Medicine composite containing pentoxifyllinum and diclofenac and application thereof

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CN101648941A (en) * 2002-11-18 2010-02-17 欧洲凯尔特公司 4-tetrazolyl-4phenylpiperidine derivatives for treating pain
CN101600458A (en) * 2006-12-22 2009-12-09 瑞蔻达蒂爱尔兰有限公司 Combination therapy of lower urinary tract disorders with a2d ligands and nsaids
CN101679445A (en) * 2007-04-13 2010-03-24 先灵公司 Pyrimidinedione derivatives and methods of use thereof
CN101898977A (en) * 2009-05-31 2010-12-01 徐锋 GABA (Gamma-Aminobutyric Acid) conjugates and using method thereof
CN101919860A (en) * 2009-06-12 2010-12-22 鲁南制药集团股份有限公司 Medicine composite containing pentoxifyllinum and diclofenac and application thereof

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