CN106580974A - Western medicine composition for treating spinal cord injury, and application of composition - Google Patents
Western medicine composition for treating spinal cord injury, and application of composition Download PDFInfo
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- CN106580974A CN106580974A CN201611107176.2A CN201611107176A CN106580974A CN 106580974 A CN106580974 A CN 106580974A CN 201611107176 A CN201611107176 A CN 201611107176A CN 106580974 A CN106580974 A CN 106580974A
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- spinal cord
- cord injury
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
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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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
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Abstract
The invention discloses a western medicine composition for treating spinal cord injury, and an application of the composition. The western medicine composition consists of hexoprenaline and sulbactam, wherein a mass ratio of hexoprenaline to sulbactam is (0.17-0.22) : 1; and when the western medicine composition is used for treating the spinal cord injury, an injection dose for adults is 0.95-1.00mg/kg, and the administration time is 6-24 hours after the spinal cord injury. Through test treatment of a model of an animal with spinal cord injury, it is discovered that the western medicine composition can reduce cell apoptosis, facilitate neuronal survival, inhibit glial scar formation and remarkably improve a BBB score of the treated animal, so that the western medicine composition has a remarkable promotion effect for motor function recovery after the spinal cord injury. Compared with an existing common medicine-methylprednisolone used for treating the spinal cord injury in clinic, the western medicine composition has the advantages that an administration window is wider, the treatment effect is more lasting, and the long-term effect is better.
Description
Technical field
The present invention relates to technical field of western medicines, specifically a kind of Western medicine compound for treating spinal cord injury and its application.
Background technology
With the development of countries in the world economic level, spinal cord injury incidence rate is presented the trend for increasing year by year.Spinal cord injury
Refer to because extraneous directly or indirectly factor causes spinal cord injury various motions occur in the corresponding sections of infringement, feel and include
About muscular function obstacle, the corresponding change of dystonia and pathologic reflex etc..Spinal cord injury is the concurrent of spinal injury most serious
Disease, often leads to damage sections with the serious dysfunction of lower limb body.Spinal cord injury not only can to sufferers themselves bring body and
The grievous injury of psychology, can also cause huge financial burden to entire society.Due to social economy caused by spinal cord injury institute
Loss, the prevention, treatment and rehabilitation for spinal cord injury has become a big problem of current medical circle.
Research to the pathogenesis of spinal cord injury shows that spinal cord injury is mainly caused by two kinds of mechanism:Constitutional is damaged
Wound (infringement, bleeding etc.) and secondary injury (inflammatory reaction, ischemia-reperfusion, cytokine etc.).Primary injury is passively
Occur after injury (it is generally acknowledged that in 4 hours) in the short time, and the nervous lesion for producing is irreversible, and spinal cord Secondary cases
Damage is that a kind of cell and molecular level actively adjust process, with reversibility and can be adjusted.
At present, it is the medicine of representative in clinic with methyl meticortelone (methylprednisolone, abbreviation Solu-Medrol)
Achieve certain curative effect using in, but the untoward reaction of medicine and its promptness that uses are so that people are still continuing to look for
The medicine of effect.
The content of the invention
It is an object of the invention to provide a kind of administration window width, consumption are few, effect is lasting, controlling without obvious adverse reaction
Treat Western medicine compound and its application of spinal cord injury.
For achieving the above object, the present invention provides following technical scheme:
A kind of Western medicine compound for treating spinal cord injury, is made up of hexoprenaline and sulbactam;Wherein, hexoprenaline and relax
The mass ratio of Batan is 0.17~0.22:1.
As further scheme of the invention:Described hexoprenaline and the mass ratio of sulbactam is 0.18~0.20:1.
As further scheme of the invention:Described hexoprenaline and the mass ratio of sulbactam is 0.19:1.
Application of the described Western medicine compound in treatment spinal cord injury medicine is prepared.
As further scheme of the invention:The adult injection dosage of described Western medicine compound is 0.95~1.00mg/
Kg, administration time is 6~24 hours after spinal cord injury.
As further scheme of the invention:The adult injection dosage of described Western medicine compound is 0.98mg/kg, is administered
Time is 9 hours after spinal cord injury.
Compared with prior art, the invention has the beneficial effects as follows:By the test of cure to spinal cord injury modeling animal, send out
Existing Western medicine compound of the present invention can reduce the apoptosis of cell, promote the survival of neuron, suppress the formation of glial scar, and show
The BBB scorings for improving animal after treatment are write, shows that Western medicine compound of the present invention has for the motor function recovery after spinal cord injury
There is significant facilitation.Compared with being clinically used to treat the common drug Solu-Medrol of spinal cord injury at present, Western medicine of the present invention
The administration window of compositionss is wider, and therapeutic effect is more lasting, and long-term effect is more preferable.
Specific embodiment
Below in conjunction with the embodiment of the present invention, the technical scheme in the embodiment of the present invention is clearly and completely described,
Obviously, described embodiment is only a part of embodiment of the invention, rather than the embodiment of whole.Based in the present invention
Embodiment, the every other embodiment that those of ordinary skill in the art are obtained under the premise of creative work is not made, all
Belong to the scope of protection of the invention.
Embodiment 1
In the embodiment of the present invention, a kind of Western medicine compound for treating spinal cord injury is made up of hexoprenaline and sulbactam;Its
In, the mass ratio of hexoprenaline and sulbactam is 0.17:1.
Embodiment 2
In the embodiment of the present invention, a kind of Western medicine compound for treating spinal cord injury is made up of hexoprenaline and sulbactam;Its
In, the mass ratio of hexoprenaline and sulbactam is 0.22:1.
Embodiment 3
In the embodiment of the present invention, a kind of Western medicine compound for treating spinal cord injury is made up of hexoprenaline and sulbactam;Its
In, the mass ratio of hexoprenaline and sulbactam is 0.18:1.
Embodiment 4
In the embodiment of the present invention, a kind of Western medicine compound for treating spinal cord injury is made up of hexoprenaline and sulbactam;Its
In, the mass ratio of hexoprenaline and sulbactam is 0.20:1.
Embodiment 5
In the embodiment of the present invention, a kind of Western medicine compound for treating spinal cord injury is made up of hexoprenaline and sulbactam;Its
In, the mass ratio of hexoprenaline and sulbactam is 0.19:1.
In above-described embodiment, the preparation process of the Western medicine compound of described treatment spinal cord injury is:With hexoprenaline and
Sulbactam is effective ingredient, using acceptable technique and adjuvant on pharmaceuticss, is made acceptable oral on various pharmaceuticss
Dosage form.
In order to verify therapeutical effect of the Western medicine compound of the present invention to spinal cord injury, now using the spinal cord injury model of rat
Studied, with the standard drug of clinical treatment spinal cord injury --- Solu-Medrol medicine as a comparison, wherein, such as without special theory
Bright, test method used is conventional method, medicinal raw material, reagent material used etc. and is commercially available purchase product.
First, therapeutic test of the Western medicine compound of the present invention to spinal cord injury
Using 8 week old female Wistar rats, using New York University (NYU) standard spinal cord injury beating device (Impactor
ModelII) spinal cord is hit in the sections of rat breast 10, builds the animal model of spinal cord injury.8 hours after damage, will implement respectively
With 6.174mg/kg, (dosage is changed by the dosage × rat of people and the dosage of people to Western medicine compound obtained in example 1~5
Calculate coefficient 6.3) dosage intraperitoneal injection, 2 weeks are continued to damage once a day, as treat 1~5 group;Damage
8 hours afterwards, Solu-Medrol is administered with the dosage tail vein injection of 30mg/kg, 2 weeks is continued to damage once a day, as right
According to 1 group;8 hours after damage, using normal saline as compareing 2 groups.Administration in 8 hours after damaging is analyzed using BBB point systems
The recovery situation of motor function after rat treatment, using experimental animal after TUNEL, NF-200 and GFAP dyeing observation each group treatment
Functional rehabilitation, damage after apoptosis, neuronal survival quantity and glial scar size, the result of the test such as institute of table 1~2
Show.
The BBB appraisal results of each group of table 1
TUNEL, NF-200 and GFAP dyeing observation result of each group of table 2
Project | TUNEL | NF-200 | GFAP |
Treat 1 group | 32000 | 64000 | 55000 |
Treat 2 groups | 32000 | 65000 | 54000 |
Treat 3 groups | 31000 | 65000 | 53000 |
Treat 4 groups | 30000 | 65000 | 52000 |
Treat 5 groups | 29000 | 66000 | 52000 |
Compare 1 group | 42000 | 41000 | 72000 |
Compare 2 groups | 44000 | 37000 | 78000 |
By Tables 1 and 2 it can be seen that:The BBB scorings of 1~5 group for the treatment of are significantly higher than 1~2 group of control, show using this
Bright Western medicine compound treatment can remarkably promote the functional rehabilitation after Damage of Rats;The apoptosis number of the rat of 1~5 group for the treatment of
Amount, GFAP expressions substantially less than compare 1~2 group, and neuronal quantity is significantly higher than 1~2 group of control, illustrates Western medicine of the present invention
Compositionss have protective effect to local histiocyte after injury, can after injury protect the survival of neuron, promote nerve
The Regeneration and Repair of unit, while suppressing the formation of chronic phase glial scar, promotes the tissue repair after damaging and functional rehabilitation.
Above-mentioned result of the test shows, compared with 1~2 group of control, it is thin that 1~5 group for the treatment of significantly reduces acute stage after damage
The necrosis of born of the same parents and apoptosis, promote the survival of neuron and repair;At a specified future date then scope that reduce glial scar, promote rat
Functional rehabilitation after damage.It is indicated above that Western medicine compound of the present invention has the curative effect for determining, wherein embodiment to spinal cord injury
Western medicine compound therapeutic effect is optimal obtained in 5.
2nd, when different time is administered, Western medicine compound obtained in embodiment 5 is contrasted with the therapeutic effect of Solu-Medrol
When being administered by different time, the Comparison of therapeutic of Western medicine compound obtained in embodiment 5 and Solu-Medrol determines this
Bright Western medicine compound is for the effectiveness of spinal cord injury clinical treatment.
8 week old female Wistar rats are divided into into three groups (30 per group), using New York University (NYU) standard spinal cord injury
Beating device (Impactor ModelII) the sections of rat breast 10 hit spinal cord, choose strike after at once (0 hour), 3 hours, 6
3 groups of animals are carried out respectively normal saline, Solu-Medrol by hour, 9 hours, 12 hours, 18 hours, 24 hours seven administration times
2 weeks are treated and continued with Western medicine compound of the present invention obtained in embodiment 5, observe the recovery situation of rat, result of the test such as table 3
Shown in~4.
The each group NF200 dyeing observation result of the different time of table 3 administration
Project | Western medicine compound treatment group of the present invention | Solu-Medrol treatment group | Saline control group |
0 hour | 17 | 116 | 1.1 |
3 hours | 40 | 39 | / |
6 hours | 119 | 32 | / |
9 hours | 142 | 29 | / |
12 hours | 130 | 20 | / |
18 hours | 56 | 12 | / |
24 hours | 22 | 7 | / |
The each group GFAP dyeing observation result of the different time of table 4 administration
Can be seen that by table 3 and table 4:In administration in 9 hours after Damage of Rats, Western medicine compound treatment group of the present invention rat
Neuronal quantity be significantly higher than the neuronal quantity of Solu-Medrol treatment group rat, and Solu-Medrol treatment is brighter in early efficacy
It is aobvious, but with the postponement of administration time, its effect is significant declines;In administration in 9 hours after Damage of Rats, Western medicine combination of the present invention
Thing treatment group is most notable to the inhibitory action of glial scar, and its inhibition to glial scar is significantly higher than Solu-Medrol group.
To sum up, administration in 9 hours can preferably play therapeutic effect of the Western medicine compound of the present invention to spinal cord injury after damage.
To sum up, Solu-Medrol is more significant in the therapeutic effect for damaging early stage, but its curative effect is reduced with the postponement of administration time,
Administration window is narrower, and long-term effect is limited;And the therapeutic effect of Western medicine compound of the present invention is more lasting, the administration window phase is more
Width, late result is notable.
It is obvious to a person skilled in the art that the invention is not restricted to the details of above-mentioned one exemplary embodiment, Er Qie
In the case of spirit or essential attributes without departing substantially from the present invention, the present invention can be in other specific forms realized.Therefore, no matter
From the point of view of which point, embodiment all should be regarded as exemplary, and be nonrestrictive, the scope of the present invention is by appended power
Profit is required rather than described above is limited, it is intended that all in the implication and scope of the equivalency of claim by falling
Change is included in the present invention.
Moreover, it will be appreciated that although this specification is been described by according to embodiment, not each embodiment is only wrapped
Containing an independent technical scheme, this narrating mode of description is only that for clarity those skilled in the art should
Using description as an entirety, the technical scheme in each embodiment can also Jing it is appropriately combined, form those skilled in the art
Understandable other embodiment.
Claims (6)
1. a kind of Western medicine compound for treating spinal cord injury, it is characterised in that be made up of hexoprenaline and sulbactam;Wherein, sea
The mass ratio of Suo Nalin and sulbactam is 0.17~0.22:1.
2. the Western medicine compound for the treatment of spinal cord injury according to claim 1, it is characterised in that described hexoprenaline and
The mass ratio of sulbactam is 0.18~0.20:1.
3. the Western medicine compound for the treatment of spinal cord injury according to claim 2, it is characterised in that described hexoprenaline and
The mass ratio of sulbactam is 0.19:1.
4. the application according to the arbitrary described Western medicine compound of claims 1 to 3 in treatment spinal cord injury medicine is prepared.
5. application of the Western medicine compound according to claim 4 in treatment spinal cord injury medicine is prepared, it is characterised in that
The adult injection dosage of described Western medicine compound is 0.95~1.00mg/kg, and administration time is little for after spinal cord injury 6~24
When.
6. application of the Western medicine compound according to claim 5 in treatment spinal cord injury medicine is prepared, it is characterised in that
The adult injection dosage of described Western medicine compound is 0.98mg/kg, and administration time is 9 hours after spinal cord injury.
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CN201611107176.2A CN106580974A (en) | 2016-12-06 | 2016-12-06 | Western medicine composition for treating spinal cord injury, and application of composition |
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CN201611107176.2A CN106580974A (en) | 2016-12-06 | 2016-12-06 | Western medicine composition for treating spinal cord injury, and application of composition |
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Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN103492389A (en) * | 2011-04-21 | 2014-01-01 | 原真股份有限公司 | Pyrazolo [4, 3-d] pyrimidines useful as kinase inhibitors |
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Publication number | Priority date | Publication date | Assignee | Title |
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CN103492389A (en) * | 2011-04-21 | 2014-01-01 | 原真股份有限公司 | Pyrazolo [4, 3-d] pyrimidines useful as kinase inhibitors |
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Application publication date: 20170426 |