CN106580969A - Western medicine compound for treatment of spinal cord injury and use thereof - Google Patents
Western medicine compound for treatment of spinal cord injury and use thereof Download PDFInfo
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- CN106580969A CN106580969A CN201611107177.7A CN201611107177A CN106580969A CN 106580969 A CN106580969 A CN 106580969A CN 201611107177 A CN201611107177 A CN 201611107177A CN 106580969 A CN106580969 A CN 106580969A
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- spinal cord
- western medicine
- cord injury
- medicine compound
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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
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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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
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
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- Pharmacology & Pharmacy (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a Western medicine compound for treatment of spinal cord injury and a use thereof. The Western medicine compound is composed of gabexate mesylate and nitrofurantoin, wherein the mass ratio of gabexate mesilate to nitrofurantoin is (0.09-0.13) to 1. When the Western medicine compound is applied to the treatment of spinal cord injury, the adult injection dosage of the Western medicine compound is 1.9-2.1 mg/kg, and the drug administration is performed 6-12 h later after spinal cord injury. Through test treatment of a spinal cord injury modeling animal, the Western medicine compound is found out to reduce cell apoptosis, promote nerve cell survival, inhibit formation of glial scar and significantly improve BBB scores of the animal after treatment, and the Western medicine compound is indicated to have a significant effect on promoting motion function recovery after spinal cord injury. Compared with a commonly used drug methylprednisolone for treating spinal cord injury in clinic at current, the Western medicine compound has the advantages of wider drug administration window, more lasting treatment effect and better long-term effect.
Description
Technical field
The present invention relates to technical field of western medicines, specifically a kind of Western medicine compound and purposes for treating spinal cord injury.
Background technology
Spinal cord injury is the severe complication of spinal fracture, due to vertebral body displacement or bone cipses protrude from intraspinal tube, make
Spinal cord or cauda equina nerve produce different degrees of damage.Can occur together in cervical vertebra, thoracic vertebra, breast waist, lumbar vertebra, sacral fracture, cause limb
The body dyskinesia, sensory disturbance, defecation obstacle.Person between twenty and fifty are more common in, male is in the majority, modal damage location low neck in being
Marrow, next to that breast waist intersection.
Spinal cord injury is made up of primary injury and secondary injury, and primary injury is by shock, cutting, bleeding compressing
Deng tissue injury caused by mechanical external force, generally irreversible damage；Secondary injury is on the basis of spinal cord primary injury
On by the infringement organized caused by the pathophysiological processes such as edema, inflammatory reaction, calcium overload, ischemia-reperfusion, this infringement exists
Continue to develop several days after primary wound to some months, have reversibility and Modulatory character more, level is controlled to it and is directly influenced most
Whole spinal function recovery extent.
For Patients of Spinal, in addition to timely and effectively stablizing spinal column, releasing the treatment such as spinal compression, give in early days
Effectively Drug therapy is also very important, and the Drug therapy purpose after spinal cord injury is mainly 1, reduces and created in early days after spinal cord injury
The illeffectss of wound, inflammation etc.；2nd, to spinal cord regeneration promotion simultaneously prevents the impact of inhibitive factor；3rd, support axon regeneration and promote
Enter its contacting with target organ.
Although substantial amounts of research has been carried out to the pathophysiological mechanism of spinal cord injury in recent years, with methyl meticortelone
(methylprednisolone, MP) is that the medicine of representative also achieves certain curative effect in clinical practice, but medicine is not
Good reaction and its administration limitation cause people still continuing to look for effective medicine.
The content of the invention
It is an object of the invention to provide a kind of administration window width, effect are persistently, without obvious adverse reaction for treating
The Western medicine compound and purposes 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 gabexate mesilate and nitrofurantoin；Wherein, first sulphur
The mass ratio of sour gabexate and nitrofurantoin is 0.09-0.13：1.
As further scheme of the invention：Described gabexate mesilate and the mass ratio of nitrofurantoin is 0.10-
0.12：1.
As further scheme of the invention：Described gabexate mesilate and the mass ratio of nitrofurantoin is 0.11：1.
Purposes 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 1.9-2.1mg/kg, is given
The medicine time is 6-12h after spinal cord injury.
As further scheme of the invention：The adult injection dosage of described Western medicine compound is 2.0mg/kg, during administration
Between for 6h 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, the formation of suppression glial scar, and significantly
The BBB scorings of animal after treatment are improved, shows that Western medicine compound of the present invention is aobvious for the motor function recovery after spinal cord injury has
The facilitation of work.Compared with being clinically used to treat the common drug methyl meticortelone of spinal cord injury at present, present invention west
The administration window of recurrence due to taking drug side 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 appropriate by gabexate mesilate and furan
Because of composition；Wherein, the mass ratio of gabexate mesilate and nitrofurantoin is 0.09：1.
Embodiment 2
In the embodiment of the present invention, a kind of Western medicine compound for treating spinal cord injury is appropriate by gabexate mesilate and furan
Because of composition；Wherein, the mass ratio of gabexate mesilate and nitrofurantoin is 0.10：1.
Embodiment 3
In the embodiment of the present invention, a kind of Western medicine compound for treating spinal cord injury is appropriate by gabexate mesilate and furan
Because of composition；Wherein, the mass ratio of gabexate mesilate and nitrofurantoin is 0.11：1.
Embodiment 4
In the embodiment of the present invention, a kind of Western medicine compound for treating spinal cord injury is appropriate by gabexate mesilate and furan
Because of composition；Wherein, the mass ratio of gabexate mesilate and nitrofurantoin is 0.12：1.
Embodiment 5
In the embodiment of the present invention, a kind of Western medicine compound for treating spinal cord injury is appropriate by gabexate mesilate and furan
Because of composition；Wherein, the mass ratio of gabexate mesilate and nitrofurantoin is 0.13：1.
In above-described embodiment, the preparation process of the described Western medicine compound for treating spinal cord injury is：With added methanesulfonic acid
Shellfish ester and nitrofurantoin are effective ingredient, using acceptable technique and adjuvant on pharmaceuticss, make lyophilized injectable powder.
In order to verify therapeutical effect of the Western medicine compound of the present invention to spinal cord injury, the spinal cord injury model of rat is now built,
With the standard drug of clinical treatment spinal cord injury --- methyl meticortelone (methylprednisolone, MP) is as a comparison
Medicine, is studied using the medicine of Western medicine compound of the present invention and drugs compared both types, wherein, if no special instructions,
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 8w age 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.8h after damage, respectively by embodiment 1-
With 12.6mg/kg, (dosage is the dose lonvestion coefficient of the dosage × rat by people and people to Western medicine compound obtained in 5
6.3) dosage intraperitoneal injection, continues once a day the 2w to damage, used as treatment 1-5 groups；8h after damage, by first
Base meticortelone is administered with the dosage tail vein injection of 30mg/kg, and the 2w to damage is continued once a day, used as compareing 1 group；Damage
8h after wound, using normal saline as compareing 2 groups.Move after the rat treatment that 8h administrations after damaging are analyzed using BBB point systems
The recovery situation of function, is dyeed the functional rehabilitation of experimental animal after observation each group treatment, is damaged using TUNEL, NF-200 and GFAP
The size of apoptosis, neuronal survival quantity and glial scar after wound, result of the test is as shown in table 1-2.
The BBB appraisal results of each group of table 1
| Project | 1d | 3d | 1w | 2w | 3w | 4w | 5w | 6w | 7w | 8w |
| Treat 1 group | 0.5 | 1.5 | 3.5 | 5.7 | 7.7 | 9.6 | 10.5 | 10.9 | 11.6 | 11.6 |
| Treat 2 groups | 0.5 | 1.6 | 3.7 | 5.8 | 7.8 | 9.7 | 10.7 | 11.0 | 11.6 | 11.6 |
| Treat 3 groups | 0.6 | 1.7 | 3.8 | 6.1 | 7.9 | 9.8 | 10.8 | 11.1 | 11.7 | 11.7 |
| Treat 4 groups | 0.6 | 1.7 | 3.7 | 5.9 | 7.8 | 9.7 | 10.7 | 11.1 | 11.7 | 11.7 |
| Treat 5 groups | 0.5 | 1.6 | 3.5 | 5.8 | 7.6 | 9.6 | 10.6 | 10.9 | 11.6 | 11.6 |
| Compare 1 group | 0.0 | 0.0 | 0.8 | 1.5 | 2.0 | 2.7 | 4.2 | 4.5 | 4.8 | 4.7 |
| Compare 2 groups | 0.0 | 0.0 | 0.2 | 1.2 | 2.0 | 2.5 | 3.9 | 4.0 | 3.9 | 3.9 |
TUNEL, NF-200 and GFAP dyeing observation result of each group of table 2
| Project | TUNEL | NF-200 | GFAP |
| Treat 1 group | 31000 | 65000 | 54000 |
| Treat 2 groups | 31000 | 66000 | 53000 |
| Treat 3 groups | 30000 | 67000 | 51000 |
| Treat 4 groups | 30000 | 65000 | 53000 |
| Treat 5 groups | 31000 | 65000 | 54000 |
| Compare 1 group | 43000 | 39000 | 73000 |
| Compare 2 groups | 45000 | 36000 | 79000 |
By Tables 1 and 2 it can be seen that：The BBB scorings for the treatment of 1-5 groups are significantly higher than control 1-2 groups, show using the present invention
Western medicine compound treatment can remarkably promote the functional rehabilitation after Damage of Rats；The apoptosis quantity of the rat for the treatment of 1-5 groups,
GFAP expressions substantially less than compare 1-2 groups, and neuronal quantity is significantly higher than control 1-2 groups, illustrates Western medicine compound of the present invention
After injury there is protective effect to local histiocyte, can after injury protect the survival of neuron, promote neuron again
It is raw to repair, while suppressing the formation of chronic phase glial scar, promote the tissue repair after damaging and functional rehabilitation.
Above-mentioned result of the test shows, compared with control 1-2 groups, treatment 1-5 groups significantly reduce acute stage cell after damage
Necrosis and apoptosis, promote the survival of neuron and repair；At a specified future date then scope that reduce glial scar, promote rat damage
Functional rehabilitation after wound.It is indicated above that Western medicine compound of the present invention has the curative effect for determining to spinal cord injury, wherein embodiment 3 is made
The Western medicine compound therapeutic effect for obtaining is optimal.
2nd, when different time is administered, Western medicine compound obtained in embodiment 3 is contrasted with the therapeutic effect of methyl meticortelone
When being administered by different time, the Comparison of therapeutic of Western medicine compound obtained in embodiment 3 and methyl meticortelone, it is determined that
Western medicine compound of the present invention 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 (0h), 3h, 6h, 9h,
3 groups of animals are carried out respectively obtained in normal saline, methyl meticortelone and embodiment 3 by seven administration times of 12h, 18h, 24h
2w is treated and continued to Western medicine compound of the present invention, observes the recovery situation of rat, and result of the test is as shown in table 3-4.
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 | Methyl meticortelone treatment group | Saline control group |
| 0h | 22 | 118 | 1.1 |
| 3h | 67 | 40 | / |
| 6h | 145 | 31 | / |
| 9h | 129 | 28 | / |
| 12h | 108 | 20 | / |
| 18h | 46 | 14 | / |
| 24h | 18 | 8 | / |
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：When 6h after Damage of Rats is administered, the god of Western medicine compound treatment group of the present invention rat
Jing units quantity is significantly higher than the neuronal quantity of methyl meticortelone treatment group rat, and methyl meticortelone treatment is treated in early stage
Effect is more apparent, but its effect is significant declines with the postponement of administration time；When 6h after Damage of Rats is administered, Western medicine of the present invention is answered
Square treatment group is most notable to the inhibitory action of glial scar, and its inhibition to glial scar is significantly higher than methyl prednisone
Imperial group.To sum up, 6h administrations can preferably play therapeutic effect of the Western medicine compound of the present invention to spinal cord injury after damage.
To sum up, methyl meticortelone is more significant in the therapeutic effect for damaging early stage, but its curative effect is with the postponement of administration time
And reduce, 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, administration window
Phase is wider, and 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 gabexate mesilate and nitrofurantoin；
Wherein, the mass ratio of gabexate mesilate and nitrofurantoin is 0.09-0.13：1.
2. the Western medicine compound for treating spinal cord injury according to claim 1, it is characterised in that described added methanesulfonic acid
The mass ratio of shellfish ester and nitrofurantoin is 0.10-0.12：1.
3. the Western medicine compound for treating spinal cord injury according to claim 2, it is characterised in that described added methanesulfonic acid
The mass ratio of shellfish ester and nitrofurantoin is 0.11：1.
4. the purposes treated in spinal cord injury medicine is being prepared according to the arbitrary described Western medicine compound of claim 1-3.
5. Western medicine compound according to claim 4 is preparing the purposes treated in spinal cord injury medicine, it is characterised in that institute
The adult injection dosage of the Western medicine compound stated is 1.9-2.1mg/kg, and administration time is 6-12h after spinal cord injury.
6. Western medicine compound according to claim 5 is preparing the purposes treated in spinal cord injury medicine, it is characterised in that institute
The adult injection dosage of the Western medicine compound stated is 2.0mg/kg, and administration time is 6h after spinal cord injury.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611107177.7A CN106580969A (en) | 2016-12-06 | 2016-12-06 | Western medicine compound for treatment of spinal cord injury and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611107177.7A CN106580969A (en) | 2016-12-06 | 2016-12-06 | Western medicine compound for treatment of spinal cord injury and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106580969A true CN106580969A (en) | 2017-04-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611107177.7A Withdrawn CN106580969A (en) | 2016-12-06 | 2016-12-06 | Western medicine compound for treatment of spinal cord injury and use thereof |
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| Country | Link |
|---|---|
| CN (1) | CN106580969A (en) |
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2016
- 2016-12-06 CN CN201611107177.7A patent/CN106580969A/en not_active Withdrawn
Non-Patent Citations (2)
| Title |
|---|
| 关云艳等: "甲磺酸加贝酯药理作用的分子机制及应用概况", 《中国药房》 * |
| 朱佳琪等: "脊髓损伤患者泌尿系感染研究进展", 《中国康复理论与实践》 * |
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Application publication date: 20170426 |