CN106176715A - A kind of neuropathic pain medicine for treatment compositions and application thereof - Google Patents
A kind of neuropathic pain medicine for treatment compositions and application thereof Download PDFInfo
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- CN106176715A CN106176715A CN201610496810.XA CN201610496810A CN106176715A CN 106176715 A CN106176715 A CN 106176715A CN 201610496810 A CN201610496810 A CN 201610496810A CN 106176715 A CN106176715 A CN 106176715A
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- retigabine
- ginkalide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
Abstract
The invention discloses a kind of pharmaceutical composition treating the neuropathic pain that neuropathic pain particularly diabetes cause, this pharmaceutical composition is with ginkalide B and retigabine as active constituents of medicine, in pharmaceutical composition, the weight ratio of ginkalide B and retigabine is 1:0.01 500, it is preferably 1:0.2 300, more preferably 1:1.5 24.Pharmaceutical composition is preferably oral administration when diabetes nerve pathologic pain, and in pharmaceutical composition, ginkalide B and retigabine embody significant synergism to the treatment of neuropathic pain.This pharmaceutical composition definite ingredients, therapeutic effect is definite, and ill effect is little, has good medical value.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of neuropathic pain medicine for treatment compositions and application thereof, tool
Body relates to a kind of containing ginkalide B with the medical composition and its use of retigabine.
Background technology
Neuropathic pain is one of two kinds of main Types of chronic pain.Generation chronic nociceptive/struvite
During pain, body tissue sustains damage, and forms the chronic of pain signal by the nervous pathway of conduction nociception sexual stimulus
Transmission.And neuropathic pain usually not tissue injury, or occur after peripheral nerve injury, pain transduction path merit
Can be disorderly, cause the chronic transmission of exception of pain signal.In some cases (such as cancer), can have both pain classes simultaneously
Type.
When forming neuropathic pain, can there is obvious nerve injury, it is also possible to do not have.Do not involve nervus motorius fine
The nerve injury of dimension is generally difficult to diagnosis.Damage is it may happen that around or any water of maincenter nociception nervous pathway
Flat, but due to the reason of distributing position, perineural damage is the most common.The generation mechanism of neuropathic pain is also at present
The not clearest and the most definite, but the research of this aspect is the most active.The participation of number of mechanisms may be had in this case in many patients,
This situation is similar with the chronic disease of some other complexity, such as asthma or chronic heart failure, it is thus possible to be required for each
The different pharmaceutical planting mechanism is treated.
Retigabine is a kind of new antiepileptic medicine, GlaxoSmithKline PLC and Valeant company develop cooperatively, be simultaneously
Opener and the reinforcing agent of γ-aminobutyric acid (GABA) as potassium-channel.The double action mechanism of retigabine, permissible
From different mechanisms, control the outbreak of epilepsy, alleviate the state of an illness.For neuron potassium channel openers.Neuron potassium channel openers is auspicious
Good therapeutic effect is had for the epilepsy partial seizure adding shore (retigabine) treatment intractable epilepsy patient.Anti-on international market at present
The Hot spots for development of AED is concentrated mainly on efficiently, in low-risk and low side effect.The appearance of retigabine, is to be interrupted outbreak
Property epilepsy therapy a potential major progress, give be interrupted ictal epileptic bring new hope.
Ginkalide B is that the active physiological activity of ginkalide B (BN52021) is the strongest in bilobalide, is to send out so far
The strongest existing platelet activating factor antagonist, can be used clinically for treating thrombosis, acute pancreatitis and cardiovascular disease,
Can be additionally used in the treatment of metastatic cancer, effect the most protected to injured neuron, there is antioxidation simultaneously, the work of slow down aging
With.Bilobalide b injectable liquefied composition is single clearly, evident in efficacy, and safety is good, and market acceptance is high, in recent years can not be many
The new medicine intravenous form obtained.Bilobalide b injection function cures mainly dissipating phlegm and removing blood stasis, TONGMAI SHULUO.Scarce for treating
The phlegm-stasis in channels of courageous and upright apoplexy.In the medicine of existing treatment neuropathic pain, there is no with retigabine and Semen Ginkgo
Lactone B is the pharmaceutical composition of active component.
Summary of the invention
In order to overcome existing neuropathic pain treatment medication effect undesirable, the defect that side effect is big, the present invention carries
For a kind of new neuropathic pain treatment pharmaceutical composition, the advantage of this pharmaceutical composition is that component is clear and definite, and definite effect is controlled
Therapeutic effect is notable, and toxic and side effects is low.
Pharmaceutical composition of the present invention contains active constituents of medicine ginkalide B and retigabine, and the present inventor is by a large amount of
Pharmacological evaluation finds that this pharmaceutical composition shows significant therapeutic effect when treating neuropathic pain.The embodiment of the present invention 7
Prove that ginkalide B retigabine pharmaceutical composition is significantly better than each single medicine group to the therapeutic effect of various neuropathic pain
Therapeutic effect to neuropathic pain, two kinds of medicines embody the most collaborative work to the treatment of neuropathic pain
With.After the embodiment of the present invention 8 shows ginkalide B and retigabine composition compound recipe, no matter compared with ginkalide B list medicine group,
Or compared with retigabine list medicine group, diabetes nerve pathologic pain rat model is all shown and significantly treats work by it
With, and this therapeutic effect is obviously enhanced along with the prolongation for the treatment of time.Ginkalide B and retigabine draw in treatment diabetes
The neuropathic pain aspect sent out shows significant synergism.
In the present invention after ginkalide B and retigabine use in conjunction composition compound recipe, ingredient clearly, stable in properties,
Influencing each other less, it is simple to the foundation of pharmaceutical preparation quality control, when being conducive to producing preparation, the control of quality, is especially suitable for work
The big production of industryization.
Pharmaceutical composition of the present invention comprises two kinds of active constituents of medicine:
1) ginkalide B；
2) retigabine.
In pharmaceutical composition as above, the weight ratio of ginkalide B and retigabine is 1:0.01-500, preferably
Ground, the weight ratio of ginkalide B and retigabine is 1:0.2-300；It is further preferred that ginkalide B and retigabine
Weight ratio is 1:1.5-24.
Drug regimen species of the present invention can also be prepared as suitably containing acceptable auxiliary material excipient on preparation process
Drug formulation.The medicine composition dosage form of the present invention is preferably oral Pharmaceutical dosage forms.Oral Pharmaceutical dosage forms can be tablet, slow control
Release tablet formulations, capsule, oral liquid, granule etc..Described tablet contains one or more following adjuvants: starch, dextrin, low replacement
Hydroxypropyl cellulose, magnesium stearate, microcrystalline Cellulose, hydroxypropyl cellulose, starch slurry lactose, mannitol, micropowder silica gel, crosslinking
Sodium carboxymethyl cellulose, crospolyvinylpyrrolidone.Described capsule or granule contain one or more following adjuvants: can
Pressure property starch, lactose, low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, micropowder silica gel.Described slow releasing agent or controlled release agent contain one
Plant or multiple following adjuvant: amylum pregelatinisatum, lactose, low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, micropowder silica gel, card ripple
Nurse, sodium alginate, calcium alginate, chitin.
According in the pharmaceutical dosage form that pharmaceutical composition provided by the present invention is prepared as, each preparation unit in described preparation
Effective dose containing retigabine is 10mg-500mg, and the effective dose containing ginkalide B is 10mg-250mg.
It is another object of the present invention to open pharmaceutical composition purposes in preparation treatment neuropathic pain medicine.
Pharmaceutical composition of the present invention achieves good therapeutic effect, the god especially caused in treatment diabetes to neuropathic pain
Obvious synergism is achieved, controlling when being significantly better than retigabine and the independent medication of ginkalide B when pathological pain
Therapeutic effect.The nerve pathological pain that medicine composite for curing neuropathic pain of the present invention, especially diabetes cause
Time, preferably oral administration.In pharmaceutical composition, the dosage of retigabine is 5mg/kg.d-40mg/kg.d, is preferably
10mg/kg.d-40mg/kg.d；The dosage of ginkalide B is 1mg/kg.d-3mg/kg.d, preferably 1.5mg/kg.d-
2.5mg/kg.d。
The advantage of this pharmaceutical composition is embodied in following aspect:
(1) in pharmaceutical composition of the present invention, ginkalide B and retigabine are the most sugared at treatment neuropathic pain
During the neuropathic pain that urine disease causes, it is significantly better than each single therapy group, embodies the strongest synergism.It addition, this
Invention pharmaceutical composition embodies effect build-up effect during long-term prescription, therefore it is desired that long-term prescription can be notable
Improve neuropathic pain, and may thoroughly reach the purpose cured.
(2) over the course for the treatment of, merge the medicine using mechanism of action different can strengthen neuropathic pain
Therapeutic effect, makes Other Risk Factors or cohesive disease be optimally controlled, and is conducive to the neural system structure and function of protection, enters
One step reduces toxic and side effects incidence rate.
(3) owing to when forming immobilised compound, each single pharmaceutical quantities has reduced, and makes side effects of pharmaceutical drugs reduce, and controls
Treatment expense but greatly reduces, and therefore immobilised compound is administered and the benefit/expense ratio for the treatment of is significantly improved, so that patient's controls
Treatment compliance is greatly improved.
(4) neuropathic pain that diabetes are especially caused by pharmaceutical composition of the present invention is effective, and effectively alleviating should
The pain of class patient, and diabetes itself are also functioned to certain and mitigation, so that the quality of life of patient is substantially improved.
Detailed description of the invention
Now being further illustrated by the following examples present disclosure, wherein embodiment 1～6 is formulation embodiment,
Embodiment 7～8 is pharmacodynamics embodiment, but the range of application of the present invention is not limited only to the following example.
The preparation of embodiment 1 retigabine ginkalide B compound tablet
Preparation technology: retigabine and cyclodextrin are first put into ground and mixed in mortar uniform, is sequentially added into carboxymethyl and forms sediment
Powder sodium, amylum pregelatinisatum mix homogeneously, be eventually adding ginkalide B mixing, make binding agent with the ethanol solution of 5%PVP
Pelletizing, 40 DEG C are dried, granulate, add magnesium stearate mixing, tabletting, to obtain final product.
The preparation of embodiment 2 retigabine ginkalide B compound tablet
Preparation technology: retigabine and cyclodextrin are first put into ground and mixed in mortar uniform, is sequentially added into carboxymethyl and forms sediment
Powder sodium, amylum pregelatinisatum mix homogeneously, be eventually adding ginkalide B mixing, make binding agent with the ethanol solution of 5%PVP
Pelletizing, 40 DEG C are dried, granulate, add magnesium stearate mixing, tabletting, to obtain final product.
The preparation of embodiment 3 retigabine ginkalide B compound tablet
Preparation technology: first retigabine and beta-schardinger dextrin-are put into ground and mixed in mortar uniform, be sequentially added into carboxymethyl
Starch Sodium, microcrystalline Cellulose, micropowder silica gel mix homogeneously, be eventually adding ginkalide B mixing, direct powder compression, to obtain final product.
The preparation of embodiment 4 retigabine ginkalide B capsule
Preparation technology: first retigabine and beta-schardinger dextrin-are put into ground and mixed in mortar uniform, be sequentially added into crystallite fine
Dimension element, micropowder silica gel mix homogeneously, be eventually adding ginkalide B mixing, load capsule shells, to obtain final product.
The preparation of embodiment 5 retigabine ginkalide B granule
Preparation technology: first retigabine is mixed homogeneously with beta-schardinger dextrin-, be subsequently adding ginkalide B, microcrystalline Cellulose,
Cross-linking sodium carboxymethyl cellulose, methylcellulose, sodium lauryl sulphate are crossed and are mixed after 16 mesh sieves, after again with orange flavor, Ah
This Ba Tian mix homogeneously.Mixture is pelletized with 5% polyvidone ethanol, is dried, granulate, subpackage, to obtain final product.
The preparation of embodiment 6 retigabine ginkalide B slow releasing tablet
Preparation technology: weigh the retigabine of recipe quantity, ginkalide B, carbomer, hydroxypropyl cellulose, beta-schardinger dextrin-
Mix homogeneously.Separately taking 8% starch slurry solution of Sq, add in mixed-powder, soft material processed after mix homogeneously, by 16 mesh sieves
Pelletizing, less than 60 DEG C are dried.Carry out granulate with 18 mesh sieves after completing after drying, sift out the fine powder in dry granular, with the tristearin sieved
Acid magnesium mixing, is mixed evenly with dry granule, tabletting the most again, to obtain final product.
The embodiment 7 retigabine ginkalide B pharmaceutical composition therapeutical effect to neuropathic pain
1. experiment modeling and administration
(1) the retigabine ginkalide B pharmaceutical composition impact on rat formaldehyde induced pain
50 SD rats are randomly divided into 5 groups, often group 10, and male and female half and half, before modeling, 1h gavage gives each group of medicine
(10ml/kg) (as shown in table 1), model group gavage is to pure water.With l00L microsyringe at the left sufficient plantar subcutaneous injection 2% of rat
Formaldehyde 100 μ L, after injection of formaldehyde, observe immediately each group of rat behavioristics change, every 5min record 1 time, continue lh, observe
Person does not knows the packet situation (double blinding) of experiment.Experimentation is avoided high light, keeps environment quiet.
It is that two hind paws lie in ground that rat pain is divided into 4 grades: 0 grade, movable without exception；L level is light for injection sole
, there is limping on micro-contact ground time movable；2 grades are lifted for injection sole, not in contact with the ground；Lick for rat for 3 grades and sting or shake injection
Sole.
The computational methods of level (pain intensity scoring, PIS): PIS=(Tl+2 × T2+3 × T3) bitterly/(5 ×
60), wherein Tl, T2, T3 are l occur in 5min respectively, the time of 2,3 grades.
The packet of table 1 experimental rat and dosage
(2) the retigabine ginkalide B pharmaceutical composition impact on rat hotplate induced pain
Female sd inbred rats 50, is divided into 5 groups immediately, and each treated animal presses table 2 gastric infusion (10ml/kg), and model group fills pure
Water, twice daily, the 3rd afternoon is administered half an hour after and is measured, and controls room temperature 18 DEG C～21 DEG C during experiment.Rat is put
On hot-plate instrument (hot plate temperature controls at 55 DEG C), with stopwatch record rat, being placed on hot plate up to occurs that licking metapedes is taken certainly
Between, as the pain threshold of this Mus.Every rat measures 3 pain thresholds, and every rat measures time interval 40min 2 times.
The packet of table 2 experimental rat and dosage
(3) the retigabine ginkalide B impact on rat hot water induced pain
50 SD rats divide 5 groups at random, often group 10, male and female half and half, and gavage gives each group of medicine (10ml/kg) 1h afterwards and surveys
Analgesic therapy threshold value (such as table 2), model group gavage gives pure water.First leica is spread out sheet machine temperature and is set in 48 DEG C, exist in advance before mensuration
Making a labelling with oil pen on the tail of all rats, this labelling is about 5cm, then by rat with the distance of rat tail tip
Wrap with Mus bag, expose tail, and the tail of rat is put into stand sheet machine water so that liquid level and the labelling weight on rat tail
Close, clock with stopwatch at once when rat tail and hot water contacts, the time that record rat tail shrinks for the first time from hot water, often
Rat measures 3 induced pain times (it is 10min that every rat measures time intervals for 2 times, otherwise easily by burned rats), takes 3
The threshold of pain that mean is this rat of secondary induced pain time.
(4) retigabine ginkalide B causes the impact of mouse writhing test to glacial acetic acid
Mouse peritoneal injection acetic acid, causes abdominal cavity large area and more lasting pain stimulation, causes mice to produce and turns round
Precursor reactant, 1h, i.p 0.6% acetic acid normal saline solution 0.1ml/10g after administration, record after injection acetic acid induced pain every little
The time of the writhing response that Mus occurs in 20min and number of times.
The packet of table 3 experimental rat and dosage
2 statistical analysis
All data all input SPSS l1.5 and carry out t inspection, and each Sets of Measurement data all use scholar s to represent.
3 experimental results
The impact on rat formaldehyde induced pain of the 3.1 retigabine ginkalide B
After 2% formaldehyde 0.1mL is injected in experimental group Rats With Unilateral vola, injection part is the redst and the most swollen, and after administration, animal stands
Contracting foot i.e. occur and licks the behaviors such as foot, in 1h, showing obvious biphasic reaction, test result indicate that each group of medicine all can not
Alleviating the scoring of rat the first phase, compound recipe low dose group is 15-20 minute period of the second phase, 25-30 minute period and the
The scoring of 40-50 minute period alleviates (P ＜ 0.05 or P ＜ 0.01) compared with model group, and compound recipe high dose group 20-60 minute is marked
Being below model group (P ＜ 0.05 or P ＜ 0.01), retigabine group is the lowest the 25-35 minute and section scoring in 40-50 minute
In model group (P ＜ 0.01), ginkalide B group is divided at 25-30 and is significantly alleviated (P ＜ with the scoring of 40-50 minutes section
0.05).Result shows that compound recipe group presents dose-dependent effect, high dose group scoring less than low dose group, wherein 5-10 minute,
Within 30-35 minute, with 50-60 minute difference, there is significant.The scoring of retigabine group is higher than compound recipe high dose group, at 55-60
Time period difference is statistically significant.Ginkalide B group was marked also above compound recipe high dose group, the 25-40 minute section difference
There is statistical significance, and the time that the peak value being administered each group of scoring occurs all postpones than model group.
The impact on rat hotplate induced pain of the 3.2 retigabine ginkalide B
Experimental result (such as table 4) shows: compound recipe low dose group with compound recipe high dose group upon administration compared with model group pain
Threshold value significantly raised (P ＜ 0.01), pain threshold is also compared with retigabine list medicine a large amount group and ginkalide B list medicine a large amount group
There is rising (P ＜ 0.05), show that retigabine and ginkalide B also exist obvious synergism in terms of raising pain threshold.
After wherein compound recipe group is administered after 30min, 70min and 110min, pain threshold persistently raises and shows that compound recipe group shows in terms for the treatment of
Go out and persistently obtain effect build-up effect.Low group of compound recipe is better than retigabine list medicine a large amount group and bilobalide in terms of raising pain threshold
B mono-medicine high group, shows significant synergism.
The impact on rat hotplate induced pain effect of the table 4 retigabine ginkalide B
Compared with model group*P ＜ 0.05,**P ＜ 0.01；With retigabine group ratio#P ＜ 0.05,##P ＜ 0.01
Compared with ginkalide B group,&P ＜ 0.05,&&P ＜ 0.01；
The impact on rat hot water induced pain of the 3.3 retigabine ginkalide B
Experimental result (such as table 5) shows: after administration, 1h surveys the Rat Tall Flick time as pain threshold, compound recipe low dose group,
Compound recipe high dose group, retigabine group whipping time compare the most substantially shortening (P ＜ 0.01, P ＜ 0.001, P ＜ with matched group
0.01)。
The impact on rat hot water induced pain pain threshold of the table 5 retigabine ginkalide B
Compared with model group,*P ＜ 0.05,**P〈0.01；
Diabetes are caused the treatment of neuropathic pain by embodiment 8 retigabine ginkalide B pharmaceutical composition
1.1 laboratory animals and experimental article
Healthy male SD rat 120, body weight 180～220g, SPF level, Shandong New Times Pharmaceutical new drug An Ping center carries
Supply.Room temperature 20～25 DEG C, room ventilation is good, and ammonia density is less than 20 × 10-6mL/m3, and relative humidity is 40%～70%, shines
Bright cycle 12h, rat feeding in rustless steel mouse cage, 4, every cage, freely ingest, drink water.
Streptozotocin (STZ, sigma company produces, the U.S.)；ZH LUO/B type rat-tail photo-thermal dolorimeter, YLS 3E type
Electronics tenderness instrument is purchased from Northern Huaihe River Anhui Zheng Hua biological Instrument and equipments company limited.
1.2 modelings and screening
120 rats are left and taken 10 at random and are only used as Normal group, press 75mg kg-after remaining 110 Rat Fast 12h
1 disposable celiac injection STZ solution (STZ solution is prepared: be dissolved in by STZ in pH 4.2,0.1m mol/L citrate buffer solution,
Solution matching while using, concentration is 3.75% (W/V) i.e. 0.5mL/100g).
Blood sugar detection: surveying tail vein sugar after modeling 7d, blood glucose >=16m mol/L is then diabetes rat, has in experiment
47 rats successfully build up DM model (model group).STZ injection before and injection after the 7th, 21,35,49d detect blood glucose, blood glucose is low
Then abandon in 16m mol/L.
Machinery Determination of Pain Threshold: in STZ inject before (base state), injection after 21,35,49d measure machinery the threshold of pain.By rat
It is placed in the transparent organic glass equipped with audio frequency amplifier and fixes in cylinder, outside rat-tail dew cylinder, at labelling at tail point 5cm.Rat is fitted
Answer environment 15min, after rat combing and inquiry activity disappear, rat-tail mark is placed at electronics tenderness instrument pressure head, to Mus
Tail pressure (increase 10g per second), when rat occurs that pain reaction then stops pressing as whinnied, struggling, record pressure data (g),
METHOD FOR CONTINUOUS DETERMINATION 5 times, every minor tick 10min, averages as machinery pain threshold.If force value is more than 500g, reject.
Hot Determination of Pain Threshold: minute point, preparation method are with the machinery threshold of pain.The heating temperature of ZH LUO/B type rat-tail dolorimeter
Degree is set as 49 DEG C, is directed at tail point 4cm by radiating light source after reaching setting value, records and starts to rat-tail tilting from illumination
Time (s).If light application time tilts not yet more than 15s rat-tail, reject, measure 5 times, every minor tick 10min, take average conduct
Burning pain threshold value.
Modeling result: the rat of injection streptozotocin is surplus after blood sugar detection screening, the machinery threshold of pain and the screening of burning pain threshold
Remaining rat is modeling successful diabetes nerve pathologic pain rat, and rat modeling success 96, modeling success rate is
87.2%.
1.3 animal packet and administrations
Choosing successfully the diabetes nerve pathologic rat 60 of modeling, be randomly divided into six groups, often group ten, gives respectively
Agents, separately increases Normal group.
Normal group: gavage gives isopyknic distilled water
Model group: gavage gives isopyknic distilled water
Retigabine high group: gavage gives the retigabine of 300mg/kg
Low group of retigabine: gavage gives the retigabine of 10mg/kg
Hexanone high group: gavage gives the ginkalide B of 50mg/kg
Low group of hexanone: gavage gives the ginkalide B of 1mg/kg
Compound recipe one group: gavage gives the retigabine of 10mg/kg and the pharmaceutical composition of the ginkalide B of 50mg/kg
Compound recipe two groups: gavage gives retigabine and the pharmaceutical composition of 1mg/kg ginkalide B of 10mg/kg
Compound recipe three groups: gavage gives retigabine and the 1mg/kg ginkalide B pharmaceutical composition of 300mg/kg
Compound recipe four groups: gavage gives retigabine and the 50mg/kg ginkalide B pharmaceutical composition of 300mg/kg
Each administration group medicine dissolves with appropriate distilled water, and gastric infusion is administered once a day.After being administered 7d, 14d, 21d,
Measure mechanical pain threshold and the burning pain threshold value of each administration group rat.It is as shown in the table for each administration group measurement result.
Table 6 compound recipe therapeutical effect to diabetes nerve pathologic rat
Compared with normal group,**P〈0.01；Compared with model group,#P ＜ 0.05,##P〈0.01；
Compared with retigabine high group,$P ＜ 0.05,$$P〈0.01；Compared with in the of low with retigabine group,&P ＜ 0.05,&&P
〈0.01；
Compared with ginkalide B high group,@P ＜ 0.05,@@P〈0.01；Compared with in the of low with ginkalide B group,%P ＜ 0.05,%%P
〈0.01；
As can be seen from the above table, model group is compared with normal group, and the machinery threshold of pain and burning pain threshold decline notable (P ＜ 0.01), table
Bright employing injects streptozotocin gained diabetes nerve pathologic pain rat model ideal, meets experiment needs.Auspicious for adding
Shore only has certain rising effect when high dose group to the diabetes nerve pathologic pain rat machinery threshold of pain and burning pain threshold, and
Its therapeutic effect does not extend with treatment time and strengthens.The high dose group of ginkalide B and low dose group the most do not cause glycosuria
The mechanical threshold of pain of sick rat models of neuropathic pain and the change of burning pain threshold.But when ginkalide B and retigabine composition compound recipe,
The neuropathic pain then caused diabetes shows significant therapeutic effect, and along with the prolongation of administration time, glycosuria
The mechanical threshold of pain and the burning pain threshold of sick rat models of neuropathic pain move closer to normal rat group.Compound recipe group (compound recipe one, two, three,
Four groups) compared with ginkalide B list medicine group, or in the neuropathy that diabetes are caused compared with retigabine list medicine group
The god that the notable significant therapeutic effect of the equal table of rationality pain aspect, i.e. ginkalide B and retigabine cause in treatment diabetes
Significant synergism is there is through pathological pain aspect.
Claims (9)
1. a neuropathic pain medicine for treatment compositions, it is characterised in that its active constituents of medicine is ginkalide B
And retigabine.
2. pharmaceutical composition as claimed in claim 1, it is characterised in that ginkalide B and retigabine in pharmaceutical composition
Weight ratio is 1:0.01-500.
3. pharmaceutical composition as claimed in claim 2, it is characterised in that ginkalide B and retigabine in pharmaceutical composition
Weight ratio is 1:0.2-300.
4. pharmaceutical composition as claimed in claim 3, it is characterised in that ginkalide B and retigabine in pharmaceutical composition
Weight ratio is 1:1.5-24.
5. pharmaceutical composition as claimed in claim 1, it is characterised in that pharmaceutical composition is oral drug preparation.
6. pharmaceutical composition as claimed in claim 5, it is characterised in that described oral drug preparation is tablet, capsule, delays
Release tablet formulations, granule.
7. the pharmaceutical composition as described in claim 1-5, it is characterised in that in each preparation unit of described oral drug preparation
Effective dose containing retigabine is 10mg-500mg, and the effective dose containing ginkalide B is 10mg-250mg.
8. the purposes in preparation treatment neuropathic pain medicine of the pharmaceutical composition described in claim 1.
9. pharmaceutical composition purposes as claimed in claim 8, it is characterised in that described neuropathic pain is that diabetes are drawn
The neuropathic pain sent out.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020207398A1 (en) * | 2019-04-10 | 2020-10-15 | 成都百裕制药股份有限公司 | Use of ginkgo terpene lactone in preparing drug for preventing and/or treating guillain-barré-strohl syndrome |
| CN111803487A (en) * | 2019-04-10 | 2020-10-23 | 成都百裕制药股份有限公司 | Application of ginkgolide in preparation of medicine for preventing and/or treating Guillain-Barre syndrome |
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| WO2020207398A1 (en) * | 2019-04-10 | 2020-10-15 | 成都百裕制药股份有限公司 | Use of ginkgo terpene lactone in preparing drug for preventing and/or treating guillain-barré-strohl syndrome |
| CN111803487A (en) * | 2019-04-10 | 2020-10-23 | 成都百裕制药股份有限公司 | Application of ginkgolide in preparation of medicine for preventing and/or treating Guillain-Barre syndrome |
| CN111803487B (en) * | 2019-04-10 | 2022-12-02 | 成都百裕制药股份有限公司 | Application of ginkgolide in preparation of medicine for preventing and/or treating Guillain-Barre syndrome |
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