CN106511987A - Western medicine compound for treating fracture - Google Patents
Western medicine compound for treating fracture Download PDFInfo
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- CN106511987A CN106511987A CN201611234387.2A CN201611234387A CN106511987A CN 106511987 A CN106511987 A CN 106511987A CN 201611234387 A CN201611234387 A CN 201611234387A CN 106511987 A CN106511987 A CN 106511987A
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- western medicine
- fracture
- medicine compound
- ulinastatin
- levofloxacin
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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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
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- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
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- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Gastroenterology & Hepatology (AREA)
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- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a western medicine compound for treating fracture. The western medicine compound consists of ulinastatin and levofloxacin, wherein the mass ratio of the ulinastatin to the levofloxacin is 0.09-0.13: 1; when the western medicine compound is used for treating the fracture, the injected dose of the western medicine compound for adults is 1.9-2.1 mg/kg, and the drug administration time is the time of 6-12 hours after fracture. Through testing therapy to fracture molding animals, the western medicine compound can reduce cell apoptosis, promote survival of nerve cells and inhibit formation of glial scar; BBB grade of treated animals is increased remarkably; and the western medicine has remarkable promotion effect on functional recovery of locomotion after fracture. Compared with methylprednisolone as a common drug for treating fracture, the western medicine compound is wider in administration window, is lasting in treatment effect and better in long-term effect.
Description
Technical field
The present invention relates to technical field of western medicines, specifically a kind of Western medicine compound for treating fracture.
Background technology
Fracture is the severe complication of spinal fracture, due to vertebral body displacement or bone cipses protrude from intraspinal tube, make fracture
Or cauda equina nerve produces different degrees of damage.Can occur together in cervical vertebra, thoracic vertebra, breast waist, lumbar vertebra, sacral fracture, cause limbs to be transported
Dynamic obstacle, sensory disturbance, defecation obstacle.Person between twenty and fifty are more common in, male is in the majority, modal damage location low neck marrow in being,
Next to that breast waist intersection.
Fracture is made up of primary injury and secondary injury, and primary injury is by machines such as shock, cutting, bleeding compressings
Tissue injury caused by tool external force, generally irreversible damage；Secondary injury be fracture primary injury on the basis of by
The infringement of tissue caused by the pathophysiological processes such as edema, inflammatory reaction, calcium overload, ischemia-reperfusion, this infringement is primary
Continue development several days after wound to some months, have reversibility and Modulatory character more, the level that controls to which directly influences final bone
Folding functional rehabilitation degree.
For fracture patient, in addition to timely and effectively stablizing spinal column, releasing the treatments such as fracture compressing, give in early days effectively
Drug therapy it is also very important, the Drug therapy purpose after fracture mainly 1, reduce early trauma, inflammation etc. after fracture
Illeffectss；2nd, the promotion for fracture being regenerated the impact for preventing inhibitive factor；3rd, support axon regeneration and promote which with target device
Contact of official etc..
Although the pathophysiological mechanism to fracturing has carried out substantial amounts of research 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 of fracture.
For achieving the above object, the present invention provides following technical scheme：
A kind of Western medicine compound for treating fracture, is made up of ulinastatin and Levofloxacin；Wherein, ulinastatin and
The mass ratio of Levofloxacin is 0.09-0.13：1.
As further scheme of the invention：The mass ratio of described ulinastatin and Levofloxacin is 0.10-0.12：
1。
As further scheme of the invention：The mass ratio of described ulinastatin and Levofloxacin is 0.11：1.
Purposes of the described Western medicine compound in treatment fracture 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 fracture.
As further scheme of the invention：The adult injection dosage of described Western medicine compound is 2.0mg/kg, during administration
Between for fracture after 6h.
Compared with prior art, the invention has the beneficial effects as follows：By the test of cure to the modeling animal that fractures, this is found
Invention Western medicine compound can reduce the apoptosis of cell, promote the survival of neuron, suppress the formation of glial scar, and significantly improve
The BBB scorings of animal after treatment, show Western medicine compound of the present invention significant promotion for the motor function recovery after fracture has
Effect.Compared with being clinically used for treating the common drug methyl meticortelone of fracture at present, the administration of Western medicine compound of the present invention
Window 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 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 compound for treating fracture is made up of ulinastatin and Levofloxacin；
Wherein, the mass ratio of ulinastatin and Levofloxacin is 0.09：1.
Embodiment 2
In the embodiment of the present invention, a kind of Western medicine compound for treating fracture is made up of ulinastatin and Levofloxacin；
Wherein, the mass ratio of ulinastatin and Levofloxacin is 0.10：1.
Embodiment 3
In the embodiment of the present invention, a kind of Western medicine compound for treating fracture is made up of ulinastatin and Levofloxacin；
Wherein, the mass ratio of ulinastatin and Levofloxacin is 0.11：1.
Embodiment 4
In the embodiment of the present invention, a kind of Western medicine compound for treating fracture is made up of ulinastatin and Levofloxacin；
Wherein, the mass ratio of ulinastatin and Levofloxacin is 0.12：1.
Embodiment 5
In the embodiment of the present invention, a kind of Western medicine compound for treating fracture is made up of ulinastatin and Levofloxacin；
Wherein, the mass ratio of ulinastatin and Levofloxacin is 0.13：1.
In above-described embodiment, the described preparation process for treating the Western medicine compound of fracture is：With ulinastatin and a left side
Ofloxacin is effective ingredient, using acceptable technique and adjuvant on pharmaceuticss, makes lyophilized injectable powder.
In order to verify that Western medicine compound of the present invention, to the therapeutical effect fractured, now builds the fracture model of rat, with clinically
The standard drug methyl meticortelone (methylprednisolone, MP) fractured medicine as a comparison is treated, using this
The medicine of invention Western medicine compound and drugs compared both types is studied, wherein, if no special instructions, test side used
Method is conventional method, and medicinal raw material used, reagent material etc. are commercially available purchase product.
First, therapeutic test of the Western medicine compound of the present invention to fracturing
Using 8w age female Wistar rats, using New York University (NYU) standard fracture beating device (Impactor
ModelII) fracture in the strike of 10 sections of rat breast, build the animal model of fracture.8h after damage, respectively by embodiment 1-5 system
Western medicine compound with 12.6mg/kg (dosage be the dose lonvestion coefficient 6.3 by the dosage × rat of people and people and
Come) dosage intraperitoneal injection, continue the 2w to damage once a day, as treatment 1-5 groups；8h after damage is strong by methyl
Pine dragon be administered with the dosage tail vein injection of 30mg/kg, continue the 2w to damage once a day, as compareing 1 group；After damage
8h, using normal saline as compareing 2 groups.Motor function after the rat treatment of 8h administrations after damaging is analyzed using BBB point systems
Recovery situation, using TUNEL, NF-200 and GFAP dye observation each group treatment after experimental animal functional rehabilitation, damage after
The size of apoptosis, neuronal survival quantity and glial scar, 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 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
There is protective effect to local histiocyte after injury, the survival of neuron can be protected after injury, promote neuron again
It is raw to repair, 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 scope that reduce glial scar, promote rat damage
Functional rehabilitation after wound.It is indicated above that Western medicine compound of the present invention is to curative effect of the fracture with determination, wherein obtained in embodiment 3
Western medicine compound therapeutic effect 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 fracture clinical treatment.
8 week old female Wistar rats are divided into into three groups (30 per group), are hit using New York University (NYU) standard fracture
Device (Impactor ModelII) 10 sections of rat breast strike fracture, choose strike after at once (0h), 3h, 6h, 9h, 12h,
Seven administration times of 18h, 24h, 3 groups of animals are carried out respectively normal saline, methyl meticortelone and embodiment 3 it is obtained this
2w is treated and continued to bright Western medicine compound, 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 3 different time of table 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 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 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 was treated in early stage
Effect is more apparent, but as postponement its effect is significant of administration time declines；When after Damage of Rats, 6h is administered, Western medicine of the present invention is multiple
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, after damage, 6h administrations can preferably play therapeutic effect of the Western medicine compound of the present invention to fracture.
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 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 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 Jing it is appropriately combined, form those skilled in the art
Understandable other embodiment.
Claims (6)
1. it is a kind of for treat fracture Western medicine compound, it is characterised in that be made up of ulinastatin and Levofloxacin；Wherein,
The mass ratio of ulinastatin and Levofloxacin is 0.09-0.13：1.
2. it is according to claim 1 for treat fracture Western medicine compound, it is characterised in that described ulinastatin and a left side
The mass ratio of Ofloxacin is 0.10-0.12：1.
3. it is according to claim 2 for treat fracture Western medicine compound, it is characterised in that described ulinastatin and a left side
The mass ratio of Ofloxacin is 0.11：1.
4. the purposes in treatment fracture 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 that treatment is fractured in medicine, it is characterised in that described
The adult injection dosage of Western medicine compound is 1.9-2.1mg/kg, and administration time is 6-12h after fracture.
6. Western medicine compound according to claim 5 is preparing the purposes that treatment is fractured in medicine, it is characterised in that described
The adult injection dosage of Western medicine compound is 2.0mg/kg, and administration time is 6h after fracture.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611234387.2A CN106511987A (en) | 2016-12-28 | 2016-12-28 | Western medicine compound for treating fracture |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611234387.2A CN106511987A (en) | 2016-12-28 | 2016-12-28 | Western medicine compound for treating fracture |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106511987A true CN106511987A (en) | 2017-03-22 |
Family
ID=58339074
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611234387.2A Pending CN106511987A (en) | 2016-12-28 | 2016-12-28 | Western medicine compound for treating fracture |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106511987A (en) |
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2016
- 2016-12-28 CN CN201611234387.2A patent/CN106511987A/en active Pending
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170322 |
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| WD01 | Invention patent application deemed withdrawn after publication |