CN106491614A - A kind of Western medicine for treating spinal cord injury is combined and purposes - Google Patents
A kind of Western medicine for treating spinal cord injury is combined and purposes Download PDFInfo
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- CN106491614A CN106491614A CN201611109100.3A CN201611109100A CN106491614A CN 106491614 A CN106491614 A CN 106491614A CN 201611109100 A CN201611109100 A CN 201611109100A CN 106491614 A CN106491614 A CN 106491614A
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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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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- General Health & Medical Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of Western medicine for treating spinal cord injury is combined and purposes, the Western medicine combination is made up of methotrexate and nitrofurantoin；Wherein, the mass ratio of methotrexate and nitrofurantoin is 0.09 0.13：1；When the treatment of spinal cord injury is applied to, the adult injection dosage of the Western medicine combination is 1.9 2.1mg/kg, and administration time is 6 12h after spinal cord injury.By the test of cure to spinal cord injury modeling animal, it was found that Western medicine combination of the present invention can reduce the apoptosis of cell, promote the survival of neuron, suppress the formation of glial scar, and the BBB of animal scores after significantly improving treatment, the motor function recovery after showing Western medicine combination of the present invention for spinal cord injury has significant facilitation.Compared with being clinically used at present treating the common drug methyl meticortelone of spinal cord injury, the administration window of Western medicine combination of the present invention is wider, and therapeutic effect is more lasting, and long-term effect is more preferable.
Description
Technical field
The present invention relates to technical field of western medicines, specifically a kind of Western medicine combination 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 that organizes caused by the pathophysiological processes such as edema, inflammatory reaction, calcium overload, ischemia-reperfusion, this infringement exists
Continue development several days after primary wound to some months, have reversibility and Modulatory character more, level is controlled to which 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, is created after the Drug therapy purpose after spinal cord injury mainly 1, minimizing spinal cord injury in early days
The illeffectss of wound, inflammation etc.；2nd, to the promotion of spinal cord regeneration and the impact of inhibitive factor is prevented；3rd, support axon regeneration and promote
Enter its contacting with target organ.
Although substantial amounts of research is 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.
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 combination of spinal cord injury and purposes.
For achieving the above object, the present invention provides following technical scheme：
A kind of Western medicine for treating spinal cord injury is combined, and is made up of methotrexate and nitrofurantoin；Wherein, methotrexate
Mass ratio with nitrofurantoin is 0.09-0.13：1.
As further scheme of the invention：The mass ratio of described methotrexate and nitrofurantoin is 0.10-0.12：1.
As further scheme of the invention：The mass ratio of described methotrexate and nitrofurantoin is 0.11：1.
Purposes of the described Western medicine combination in treatment spinal cord injury medicine is prepared.
As further scheme of the invention：The adult injection dosage of described Western medicine combination is 1.9-2.1mg/kg, gives
The medicine time is 6-12h after spinal cord injury.
As further scheme of the invention：The adult injection dosage of described Western medicine combination 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 combination of the present invention can reduce the apoptosis of cell, promote the survival of neuron, the formation of suppression glial scar, and significantly
After improving treatment, the BBB of animal scores, and the motor function recovery after showing Western medicine combination of the present invention for spinal cord injury has aobvious
The facilitation of work.Compared with being clinically used at present treating the common drug methyl meticortelone of spinal cord injury, present invention west
The administration window of medicine combination 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, to the embodiment of the present invention in technical scheme be clearly and completely described,
Obviously, described embodiment is only a part of embodiment of the invention, rather than whole embodiment.In based on the present invention
Embodiment, the every other embodiment obtained under the premise of creative work is not made by those of ordinary skill in the art, all
Belong to the scope of protection of the invention.
Embodiment 1
In the embodiment of the present invention, a kind of Western medicine for treating spinal cord injury is combined, by methotrexate and nitrofurantoin group
Into；Wherein, the mass ratio of methotrexate and nitrofurantoin is 0.09：1.
Embodiment 2
In the embodiment of the present invention, a kind of Western medicine for treating spinal cord injury is combined, by methotrexate and nitrofurantoin group
Into；Wherein, the mass ratio of methotrexate and nitrofurantoin is 0.10：1.
Embodiment 3
In the embodiment of the present invention, a kind of Western medicine for treating spinal cord injury is combined, by methotrexate and nitrofurantoin group
Into；Wherein, the mass ratio of methotrexate and nitrofurantoin is 0.11：1.
Embodiment 4
In the embodiment of the present invention, a kind of Western medicine for treating spinal cord injury is combined, by methotrexate and nitrofurantoin group
Into；Wherein, the mass ratio of methotrexate and nitrofurantoin is 0.12：1.
Embodiment 5
In the embodiment of the present invention, a kind of Western medicine for treating spinal cord injury is combined, by methotrexate and nitrofurantoin group
Into；Wherein, the mass ratio of methotrexate and nitrofurantoin is 0.13：1.
In above-described embodiment, the preparation process that the described Western medicine for treating spinal cord injury is combined is：With methotrexate
It is effective ingredient with nitrofurantoin, using acceptable technique and adjuvant on pharmaceuticss, makes lyophilized injectable powder.
In order to verify therapeutical effect of the Western medicine combination of the present invention to spinal cord injury, the spinal cord injury model of rat is now built,
With the standard drug methyl meticortelone (methylprednisolone, MP) of clinical treatment spinal cord injury as a comparison
Medicine, is studied using the medicine of Western medicine of the present invention combination and drugs compared both types, wherein, if no special instructions,
Test method used is conventional method, and medicinal raw material used, reagent material etc. are commercially available purchase product.
First, therapeutic test of the Western medicine combination of the present invention to spinal cord injury
Using 8w age female Wistar rats, New York University (NYU) standard spinal cord injury beating device (Impactor is applied
ModelII) spinal cord is hit in 10 sections of rat breast, build the animal model of spinal cord injury.8h after damage, respectively by embodiment 1-
With 12.6mg/kg, (dosage is the dose lonvestion coefficient by the dosage × rat of people with people for Western medicine combination obtained in 5
6.3) dosage intraperitoneal injection, 2w after continuing to damage once a day, used as treatment 1-5 groups；8h after damage, by first
Base meticortelone is administered with the dosage tail vein injection of 30mg/kg, 2w after continuing to damage once a day, used as compareing 1 group；Damage
8h after wound, using normal saline as compareing 2 groups.Move after the rat treatment for analyzing 8h administrations after damaging using BBB point systems
The recovery situation of function, dyes the functional rehabilitation of experimental animal, damage after observation each group treatment 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 1 each group of table
| 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 2 each group of table
| 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 combined therapy 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 are substantially less than and compare 1-2 groups, and neuronal quantity is significantly higher than control 1-2 groups, and Western medicine combination of the present invention is described
There is protective effect to local histiocyte after injury, the survival of neuron can be protected after injury, promote neuron again
Raw reparation, while suppress the formation of chronic phase glial scar, the tissue repair and functional rehabilitation after promoting to damage.
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 and reparation of neuron；At a specified future date then reduce glial scar scope, promote rat damage
Functional rehabilitation after wound.It is indicated above that Western medicine combination of the present invention there is the curative effect for determining, wherein embodiment 3 to make spinal cord injury
The Western medicine combined therapy best results for obtaining.
2nd, when different time is administered, Western medicine combination obtained in embodiment 3 is contrasted with the therapeutic effect of methyl meticortelone
When being administered by different time, obtained in embodiment 3, the Comparison of therapeutic of Western medicine combination and methyl meticortelone, determines
Western medicine of the present invention is combined for the effectiveness of spinal cord injury clinical treatment.
8 week old female Wistar rats are divided into three groups (30 per group), New York University (NYU) standard spinal cord injury is applied
Beating device (Impactor ModelII) 10 sections of rat breast hit spinal cord, choose strike after at once (0h), 3h, 6h, 9h,
3 groups of animals are carried out obtained in normal saline, methyl meticortelone and embodiment 3 by 12h, 18h, 24h seven administration times respectively
Western medicine combined therapy of the present invention persistently 2w, observe 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 3 different time of table administration
| Project | Western medicine combined therapy 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 4 different time of table administration
Can be seen that by table 3 and table 4：When after Damage of Rats, 6h is administered, the god of Western medicine combined therapy group rat of the present invention
Through the neuronal quantity that first quantity is significantly higher than methyl meticortelone treatment group rat, and methyl meticortelone treatment was treated in early stage
Effect is more apparent, but declines with postponement its effect is significant of administration time；When after Damage of Rats, 6h is administered, Western medicine group of the present invention
Close treatment group 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, after damage, 6h administrations can preferably play therapeutic effect of the Western medicine combination of the present invention to spinal cord injury.
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 combination 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 realized in other specific forms.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
Contain an independent technical scheme, this narrating mode of description is only that those skilled in the art should for clarity
Using description as an entirety, the technical scheme in each embodiment can also form those skilled in the art through appropriately combined
Understandable other embodiment.
Claims (6)
1. a kind of Western medicine for treating spinal cord injury is combined, it is characterised in that be made up of methotrexate and nitrofurantoin；Its
In, the mass ratio of methotrexate and nitrofurantoin is 0.09-0.13：1.
2. the Western medicine for treating spinal cord injury according to claim 1 is combined, it is characterised in that described methotrexate
Mass ratio with nitrofurantoin is 0.10-0.12：1.
3. the Western medicine for treating spinal cord injury according to claim 2 is combined, it is characterised in that described methotrexate
Mass ratio with nitrofurantoin is 0.11：1.
4. the purposes in treatment spinal cord injury medicine is being prepared according to the arbitrary described Western medicine combination of claim 1-3.
5. Western medicine combination according to claim 4 is preparing the purposes that treats in spinal cord injury medicine, it is characterised in that institute
The adult injection dosage of the Western medicine combination that states is 1.9-2.1mg/kg, and administration time is 6-12h after spinal cord injury.
6. Western medicine combination according to claim 5 is preparing the purposes that treats in spinal cord injury medicine, it is characterised in that institute
The adult injection dosage of the Western medicine combination that states is 2.0mg/kg, and administration time is 6h after spinal cord injury.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611109100.3A CN106491614A (en) | 2016-12-06 | 2016-12-06 | A kind of Western medicine for treating spinal cord injury is combined and purposes |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201611109100.3A CN106491614A (en) | 2016-12-06 | 2016-12-06 | A kind of Western medicine for treating spinal cord injury is combined and purposes |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1758922A (en) * | 2003-01-07 | 2006-04-12 | 耶达研究及发展有限公司 | Eye-drop vaccine containing copolymer 1 for therapeutic immunization |
| WO2016025789A1 (en) * | 2014-08-15 | 2016-02-18 | PixarBio Corporation | Compositions for inhibting inflammation in a subject with a spinal cord injury and methods of using the same |
-
2016
- 2016-12-06 CN CN201611109100.3A patent/CN106491614A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1758922A (en) * | 2003-01-07 | 2006-04-12 | 耶达研究及发展有限公司 | Eye-drop vaccine containing copolymer 1 for therapeutic immunization |
| WO2016025789A1 (en) * | 2014-08-15 | 2016-02-18 | PixarBio Corporation | Compositions for inhibting inflammation in a subject with a spinal cord injury and methods of using the same |
Non-Patent Citations (2)
| Title |
|---|
| 方超等: "不同时间点应用甲氨蝶呤对大鼠脊髓损伤后神经细胞凋亡的影响", 《中国修复重建外科杂志》 * |
| 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: 20170315 |