CN106511359A - Western medicine mixture for treating spinal cord injury, and application thereof - Google Patents

Western medicine mixture for treating spinal cord injury, and application thereof Download PDF

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Publication number
CN106511359A
CN106511359A CN201611108700.8A CN201611108700A CN106511359A CN 106511359 A CN106511359 A CN 106511359A CN 201611108700 A CN201611108700 A CN 201611108700A CN 106511359 A CN106511359 A CN 106511359A
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China
Prior art keywords
spinal cord
cord injury
western medicine
medicine mixture
sulbactam
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CN201611108700.8A
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Chinese (zh)
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不公告发明人
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Zhengzhou Zhengxian Pharmaceutical Technology Co Ltd
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Zhengzhou Zhengxian Pharmaceutical Technology Co Ltd
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Priority to CN201611108700.8A priority Critical patent/CN106511359A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7032Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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
    • A61K31/425Thiazoles
    • A61K31/429Thiazoles condensed with heterocyclic ring systems
    • A61K31/43Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a western medicine mixture for treating spinal cord injury, and an application thereof. The western medicine mixture comprises monosialotetrahexosyl ganglioside sodium and sulbactam, wherein a mass ratio of the monosialotetrahexosyl ganglioside sodium to the sulbactam is (0.17-0.22):1, the mixture injection dose for an adult in the spinal cord injury treatment process is 0.95-1.00 mg/kg, and the administration time is 6-24 h after the spinal cord injury. Test treatment of the spinal cord injury model animals shows that the western medicine mixture can reduce cell apoptosis, promote the viability of neurons and inhibit formation of colloidal scars, and also can substantially improve the BBB score of treated animals, so the western medicine mixture has a substantial promotion effect on motor function recovery after the spinal cord injury. Compared with a common medicine methylprednisolone which is clinically used for treating the spinal cord injury at present, the western medicine mixture has the advantages of wide window, lasting treatment effect and good long-term effect.

Description

A kind of Western medicine mixture for treating spinal cord injury and its application
Technical field
The present invention relates to technical field of western medicines, specifically a kind of Western medicine mixture for treating spinal cord injury and its application.
Background technology
With the development of countries in the world economic level, spinal cord injury incidence is presented the trend for increasing year by year.Spinal cord injury Refer to and cause spinal cord injury due to extraneous directly or indirectly factor various motions occur in the corresponding sections of infringement, feel and include The about corresponding change of muscular function obstacle, 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 have 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:Primary is damaged Wound (infringement, bleeding etc.) and secondary lesion (inflammatory reaction, ischemia-reperfusion, cell factor 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 invertibity and can be adjusted.
At present, it is the medicine of representative in clinic with methylprednisolone (methylprednisolone, abbreviation methylprednisolone) Certain curative effect is achieved using in, but the bad reaction of medicine and its promptness for using cause people 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 mixture and its application of spinal cord injury.
For achieving the above object, the present invention provides following technical scheme:
A kind of Western medicine mixture for treating spinal cord injury, is made up of GM1 and Sulbactam; Wherein, the mass ratio of GM1 and Sulbactam is 0.17~0.22:1.
As further scheme of the invention:The quality of described GM1 and Sulbactam Than for 0.18~0.20:1.
As further scheme of the invention:The quality of described GM1 and Sulbactam Than for 0.19:1.
Application of the described Western medicine mixture in treatment spinal cord injury medicine is prepared.
As further scheme of the invention:The adult injection dosage of described Western medicine mixture 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 mixture is 0.98mg/kg, during administration Between for 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 mixture 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 shows that Western medicine mixture 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 for treating the common drug methylprednisolone of spinal cord injury at present, Western medicine mixture of the present invention Administration window it is wider, 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 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 mixture for treating spinal cord injury, by Monostalotetrahexosylgangliside Sodium and Sulbactam composition;Wherein, the mass ratio of GM1 and Sulbactam is 0.17:1.
Embodiment 2
In the embodiment of the present invention, a kind of Western medicine mixture for treating spinal cord injury, by Monostalotetrahexosylgangliside Sodium and Sulbactam composition;Wherein, the mass ratio of GM1 and Sulbactam is 0.22:1.
Embodiment 3
In the embodiment of the present invention, a kind of Western medicine mixture for treating spinal cord injury, by Monostalotetrahexosylgangliside Sodium and Sulbactam composition;Wherein, the mass ratio of GM1 and Sulbactam is 0.18:1.
Embodiment 4
In the embodiment of the present invention, a kind of Western medicine mixture for treating spinal cord injury, by Monostalotetrahexosylgangliside Sodium and Sulbactam composition;Wherein, the mass ratio of GM1 and Sulbactam is 0.20:1.
Embodiment 5
In the embodiment of the present invention, a kind of Western medicine mixture for treating spinal cord injury, by Monostalotetrahexosylgangliside Sodium and Sulbactam composition;Wherein, the mass ratio of GM1 and Sulbactam is 0.19:1.
In above-described embodiment, the preparation process of the Western medicine mixture of described treatment spinal cord injury is:With single sialic acid four oneself Sugar ganglioside sodium and Sulbactam are active ingredient, using acceptable technique and auxiliary material in pharmacy, make various medicaments Acceptable peroral dosage form on.
In order to verify therapeutic action of the Western medicine mixture of the present invention to spinal cord injury, now enter using the spinal cord injury model of rat Row research, with the standard drug methylprednisolone of clinical treatment spinal cord injury medicine as a comparison, wherein, such as without special theory Bright, 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 mixture 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 10 sections of rat chest, build the animal model of spinal cord injury.8 hours after damage, will implement respectively With 6.174mg/kg, (dosage is the dose lonvestion by the dosage × rat of people with people to Western medicine mixture obtained in example 1~5 Coefficient dosage intraperitoneal injection 6.3), continues to damage 2 weeks once a day, used as 1~5 group for the treatment of;8 after damage Hour, methylprednisolone is administered with the dosage tail vein injection of 30mg/kg, continues to damage 2 weeks once a day, as control 1 Group;8 hours after damage, using physiological saline as compareing 2 groups.The rat of administration in 8 hours after damaging is analyzed using BBB point systems The recovery situation of motor function after treatment, dyes the work(of experimental animal after observation each group treatment using TUNEL, NF-200 and GFAP The size of Apoptosis, neuronal survival quantity and glial scar after energy recovery, damage, result of the test is as shown in table 1~2.
The BBB appraisal results of 1 each group of table
Project 1d 3d 1 week 2 weeks 3 weeks 4 weeks 5 weeks 6 weeks 7 weeks 8 weeks
Treat 1 group 0.4 1.6 3.6 5.6 7.7 9.5 10.4 10.7 11.5 11.5
Treat 2 groups 0.4 1.7 3.6 5.8 7.7 9.6 10.4 10.8 11.5 11.5
Treat 3 groups 0.5 1.7 3.8 5.9 7.9 9.8 10.6 11.0 11.6 11.6
Treat 4 groups 0.5 1.8 3.8 6.0 7.8 9.8 10.6 11.0 11.6 11.6
Treat 5 groups 0.5 1.8 3.9 6.2 8.0 9.9 10.7 11.1 11.8 11.8
Compare 1 group 0.0 0.0 0.7 1.4 2.1 2.7 4.3 4.5 4.7 4.8
Compare 2 groups 0.0 0.0 0.2 1.3 2.0 2.4 4.0 4.0 4.0 3.9
TUNEL, NF-200 and GFAP dyeing observation result of 2 each group of table
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 mixture 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 Mixture has protective effect to local histocyte after injury, can protect the survival of neuron after injury, promotes neuron Regeneration and Repair, while suppress chronic phase glial scar formation, promote damage after tissue repair and functional rehabilitation.
Above-mentioned result of the test shows, compared with 1~2 group of control, after 1~5 group for the treatment of significantly reduces damage, acute stage is thin 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 mixture of the present invention has the curative effect for determining, wherein embodiment 5 to spinal cord injury Obtained Western medicine mixture therapeutic effect is optimal.
2nd, when different time is administered, Western medicine mixture obtained in embodiment 5 is contrasted with the therapeutic effect of methylprednisolone
When being administered by different time, the Comparison of therapeutic of Western medicine mixture obtained in embodiment 5 and methylprednisolone, it is determined that of the invention Western medicine mixture is for the validity 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) 10 sections of rat chest hit spinal cord, choose strike after at once (0 hour), 3 hours, 6 3 groups of animals are carried out physiological saline, methylprednisolone by hour, 9 hours, 12 hours, 18 hours, 24 hours seven administration times respectively Treat with Western medicine mixture of the present invention obtained in embodiment 5 and continue 2 weeks, 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 3 different time of table administration
Project Western medicine mixture treatment group of the present invention Methylprednisolone 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 4 different time of table administration
Can be seen that by table 3 and table 4:After Damage of Rats during administration in 9 hours, Western medicine mixture treatment group rat of the present invention Neuronal quantity is significantly higher than the neuronal quantity of methylprednisolone treatment group rat, and methylprednisolone treatment is more apparent in early efficacy, But its effect is significant declines with the postponement of administration time;After Damage of Rats during administration in 9 hours, Western medicine mixture treatment of the present invention Group is most notable to the inhibitory action of glial scar, and its inhibition to glial scar is significantly higher than methylprednisolone group.To sum up, damage Administration in 9 hours after wound can preferably play therapeutic effect of the Western medicine mixture of the present invention to spinal cord injury.
To sum up, methylprednisolone 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 mixture of the present invention is more lasting, the administration window phase is wider, 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 Containing an independent technical scheme, this narrating mode of specification is only that those skilled in the art should for clarity Using specification 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 mixture for treating spinal cord injury, it is characterised in that by GM1 and relax Batan is constituted;Wherein, the mass ratio of GM1 and Sulbactam is 0.17~0.22:1.
2. it is according to claim 1 treatment spinal cord injury Western medicine mixture, it is characterised in that described single sialic acid four oneself The mass ratio of sugar ganglioside sodium and Sulbactam is 0.18~0.20:1.
3. it is according to claim 2 treatment spinal cord injury Western medicine mixture, it is characterised in that described single sialic acid four oneself The mass ratio of sugar ganglioside sodium and Sulbactam is 0.19:1.
4. the application according to the arbitrary described Western medicine mixture of claims 1 to 3 in treatment spinal cord injury medicine is prepared.
5. application of the Western medicine mixture according to claim 4 in treatment spinal cord injury medicine is prepared, it is characterised in that institute The adult injection dosage of the Western medicine mixture stated is 0.95~1.00mg/kg, and administration time is 6~24 hours after spinal cord injury.
6. application of the Western medicine mixture according to claim 5 in treatment spinal cord injury medicine is prepared, it is characterised in that institute The adult injection dosage of the Western medicine mixture stated is 0.98mg/kg, and administration time is 9 hours after spinal cord injury.
CN201611108700.8A 2016-12-06 2016-12-06 Western medicine mixture for treating spinal cord injury, and application thereof Pending CN106511359A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006065234A1 (en) * 2004-12-10 2006-06-22 University Of Pittsburgh Use of lipid and hydrogel vehicles for treatment and drug delivery
CN102641281A (en) * 2011-02-19 2012-08-22 山东新时代药业有限公司 Monosialotetrahexosyl ganglioside sodium for injection and preparation method thereof
CN103961309A (en) * 2013-02-01 2014-08-06 北京旭泽医药科技有限公司 Monosialotetrahexosylganglioside sodium preparation and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006065234A1 (en) * 2004-12-10 2006-06-22 University Of Pittsburgh Use of lipid and hydrogel vehicles for treatment and drug delivery
CN102641281A (en) * 2011-02-19 2012-08-22 山东新时代药业有限公司 Monosialotetrahexosyl ganglioside sodium for injection and preparation method thereof
CN103961309A (en) * 2013-02-01 2014-08-06 北京旭泽医药科技有限公司 Monosialotetrahexosylganglioside sodium preparation and preparation method thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
崔鑫: "舒巴坦通过上调 GLT-1 的表达发挥抗大鼠缺血性脑损伤作用", 《河北医科大学博士毕业论文》 *
陶恒沂 等 主编: "《高压氧的临床应用》", 30 March 2015, 第二军医大学出版社 *

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Application publication date: 20170322

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