CN106309454A - Application of Friedolanostanes in preparation of medicaments for treating ischemic brain injury - Google Patents
Application of Friedolanostanes in preparation of medicaments for treating ischemic brain injury Download PDFInfo
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- CN106309454A CN106309454A CN201610822161.8A CN201610822161A CN106309454A CN 106309454 A CN106309454 A CN 106309454A CN 201610822161 A CN201610822161 A CN 201610822161A CN 106309454 A CN106309454 A CN 106309454A
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- friedolanostanes
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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Abstract
The invention discloses application of Friedolanostanes in the preparation of medicaments for treating ischemic brain injury and belongs to the technical field of new drug use. Friedolanostanes has a therapeutic effect on the ischemic brain injury, so it has a good prospect of development and application. Friedolanostanes is firstly disclosed and effective for the treatment of ischemic brain injury.
Description
Technical field
The present invention relates to the new application of compound Friedolanostanes, particularly relate to Friedolanostanes in system
Application in standby treatment ischemic brain injury medicine.
Background technology
The present inventor by substantial amounts of experiment find, Friedolanostanes have ischemia resisting brain injury, anti-cerebral ischemia/
The pharmacological action of reperfusion injury, has prevention or the medical usage for the treatment of ischemic brain injury.
The compound Friedolanostanes that the present invention relates to be one within 2014, deliver (Saranyoo Klaiklay,
etal.,Friedolanostanes and xanthones from the twigs of Garcinia
Hombroniana.Phytochemistry, 85 (2013) 161 166.) noval chemical compound, this compound has brand-new skeleton
Type, current purposes merely relates to antiinflammatory action (Saranyoo Klaiklay, et al., Friedolanostanes and
xanthones from the twigs of Garcinia hombroniana.Phytochemistry,85(2013)161–
166.), purposes in preparation treatment ischemic brain injury medicine of the Friedolanostanes that the present invention relates to is belonged to
First public, owing to belonging to brand-new structure type, and it must be expected for the therapeutical effect activity of ischemic brain injury is strong
Less than, there is not the possibility being provided any enlightenment by other compounds, possess prominent substantive distinguishing features, be simultaneously used for ischemic
The preventing and treating of brain injury obviously has the most progressive.
Summary of the invention
Do not find that it has treatment ischemic in it is an object of the invention to study according to existing Friedolanostanes
The present situation of the report of brain injury, it is provided that Friedolanostanes application in preparation treatment ischemic brain injury medicine.
Described compound Friedolanostanes structure is as shown in formula I:
The Friedolanostanes that the present invention relates to purposes in preparation treatment ischemic brain injury medicine belongs to first
Secondary disclosure, owing to framework types belongs to brand-new framework types, and it must be expected not for the effect of ischemic brain injury is strong
Arrive, there is not the possibility being provided any enlightenment by other compounds, possess prominent substantive distinguishing features, be simultaneously used for treating ischemia
Property brain injury obviously have significantly progressive.
The present inventor demonstrates Friedolanostanes by the experiment in detailed description of the invention and has treatment or prevention
The effect of ischemic brain injury.
Detailed description of the invention
The preparation method of compound Friedolanostanes involved in the present invention sees document (Saranyoo
Klaiklay, et al., Friedolanostanes and xanthones from the twigs of Garcinia
hombroniana.Phytochemistry,85(2013)161–166.)
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by concrete real
Execute any restriction of example, but be defined in the claims.
Embodiment 1: the preparation of compound Friedolanostanes tablet involved in the present invention:
Take 20 g of compound Friedolanostanes additions and prepare the customary adjuvant 180 grams of tablet, mixing, Conventional compression
Machine makes 1000.
Embodiment 2: the preparation of compound Friedolanostanes capsule involved in the present invention:
Take 20 g of compound Friedolanostanes additions and prepare the customary adjuvant such as starch 180 grams of capsule, mixing,
Encapsulated make 1000.
Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.
The impact that focal cerebral ischemia in rats is damaged by experimental example 1:Friedolanostanes
(1) material is implemented: SD rat, male and female dual-purpose, body weight 190～210g.Positive control drug: taponin, Kang Enbei collection
Pharmaceutical Co. Ltd of group produces, every composition containing ginkgo folic acid extract 40mg.
(2) method and result
1) Friedolanostanes is to rat medium-sized artery thrombosis (MCAO) model test
60 rats are randomly divided into six groups, i.e. Sham-operated control group, MCAO model group, administration group 3 groups, taponin group
(24mg/kg).Gastric infusion before modeling, once-a-day, is administered seven times altogether, Sham-operated control group, MCAT model group, gives equivalent
Drinking water (1ml/100g), after modeling, gastric infusion is once.Rats by intraperitoneal injection 12% chloral hydrate solution (350mg/kg)
Anesthesia, Rat Right lateral position is fixed, and makees a curved incision at paropia and external auditory meatus line midpoint, is about 115cm, pinch off temporo
Bone, does a diameter 215mm bone window by dental burr at cheekbone and temporo squamosum joint at the 1mm of mouth side, clears up residue, exposes big
Brain medium-sized artery (between tractus olfactorius and inferior cerebral vein).The small pieces quantitative filter paper that suction has 50% ferric chloride solution 10ul applies
On this section of middle cerebral artery after 30min, take off filter paper, use normal saline flushing local organization, layer-by-layer suture, steam again and raise.False
Operation group in addition to not dripping ferric chloride solution, the same model group of remaining operating procedure.MCAO rat symptom and infarction size
Evaluation: in operation different time (6h, 24h), by methods such as Bederson and improved, animal is carried out behavior scoring.1.
Put forward rat-tail and leave ground about one chi, observe forelimb flexing situation.As double forelimb symmetries stretch to ground, it is designated as 0 point；Such as offside of performing the operation
Forelimb occur shoulder flexing, time flexing, shoulder inward turning or flexing during existing wrist have again inward turning person, be designated as 1 point.2. animal is placed in flat
On sliding ground, push away both shoulders respectively to side shifting, detection resistance.As bilateral resistance equity and strong person are designated as 0 point；As to operation
Drop in resistance person when offside promotes, is designated as 1 point.3. animal two forelimb is put on a wire netting, observe the muscular tension of two forelimbs.Double
Pleural muscle tension force equity and strong person are 0 point；Operation offside muscle of anterior limb tension force decline is designated as 1 point.4. put forward rat-tail and leave ground about one
Chi, animal have ceaselessly to operation offside be rotating, be designated as 1 point；Otherwise it is designated as 0 point.According to above scale, full marks are 4
Point, the behavior disorder of the highest animal of mark is the most serious.Comparing between behavioral value marking value group, t checks.The results are shown in Table 1.
After animal via last behavior scoring, broken end takes brain.Removing olfactory bulb, cerebellum and low brain stem, remainder is crown at 4 DEG C to be cut into
5.Rapidly brain sheet is placed in TTC dye liquor the (K Han 4%TTC1.5ml, 1M in every 5ml dye liquor2HPO40.1ml), 37 DEG C of lucifuges
Temperature incubates 30min, further takes out to be placed in 10% formalin and keeps in Dark Place.After dyed, non-ischemic region is rose, and infarct is
White.White tissues is carefully dug down and weighs, account for the percentage ratio of right side half brain weight as cerebral infarction model using blocking tissue's weight
Enclose.Comparing between result group, t checks, and the results are shown in Table 2.
Table 1 Friedolanostanes impact (n=10) on MCAO rat cerebral infarction scope and nervous symptoms
Note: * p < 0.05, * * p < 0.01 compared with model group.
Table 2 Friedolanostanes impact (n=10) on photochemical induction cerebral thrombosis rat cerebral infarction
Note: * p < 0.05, * * p < 0.01 compared with model group.
Result shows, except sham-operation has no that dystropy changes, MCAO model group rats 6h, 24h after surgery all occur partially
Paralysis sample symptom.Rat its nervous symptoms of 6h, 24h after surgery of administration group and taponin group all have improvement in various degree (P <
0.01, P < 0.05).Postoperative 24h, in addition to sham operated rats has no cerebral tissue abnormal change, model group compare have significant difference (P <
0.01, P < 0.05).Friedolanostanes can alleviate focus of infarct, and result demonstrates a certain amount effect relationship.
The experimental example 2:Friedolanostanes impact on focal cerebral ischemia in rats/reperfusion injury
(1) experiment material: SD rat, male and female dual-purpose, body weight 190～210g.MDA, SOD, (coomassie is bright for protein quantification
Blue) test kit (Bioengineering Research Institute is built up in Nanjing).
(2) method and result
1) experimental technique: 120 rats are randomly divided into 5 groups, i.e. sham operated rats, model group, 3 administration groups, often group 25.
In addition to sham operated rats not plug wire, remaining 4 groups of modeling (MCAO).Administration group each dosage group ig every day 1 time, continuous 13d.Preoperative 1h
Ig is administered once again.6% chloral hydrate (350mg/kg) intraperitoneal anesthesia, cervical region medisection, separation right carotid (CCA),
External carotid artery (ECA), internal carotid artery (ICA).After ligation common carotid artery proximal part, external carotid artery initiating terminal, at common carotid artery
Cut a " V " shape osculum, along common carotid artery insert line bolt (line bolt use a diameter of 0.235mm fishing line, head end burns till spherical, and
In marking at thread ball 18.5mm) be inserted at middle cerebral artery branching through internal carotid artery to intracranial, insertion depth be 18～
20mm, ligatures line together with internal carotid artery.Art maintains body temperature (37 ± 015) DEG C.When perfusion, external cable makes pommel be back to
ECA, pulls out plug wire, ligatures ECA.Sham operated rats is in addition to not plug wire, and remaining step is ibid.After middle cerebral artery thromboembolism, 2h is extensive
Multiple blood supply, Neurological deficits divides standard processed with reference to ZeaLonga5, and postoperative left fore flexing occur, turns to the left during walking
Circle is i.e. considered as modeling success, and then insulation routine is raised, and draws materials to 24h sacrificed by decapitation.In experimentation, because of anesthetic accident,
MCAO operative failure, modeling be unsuccessful and dead being all discarded in 24h.
The mensuration of brain water content: after rat modeling 24h, broken end takes brain, weighs both sides half cutaneous horn weight.It is placed in baking oven again
In, 100 DEG C of baking 24h, to constant weight, accurate weighing dry weight, calculate water content.Brain water content=(weight in wet base-dry weight)/weight in wet base
× 100%.
Cerebral infarct volume measures: broken end takes brain, brain is made continuous 2mm coronal section, totally 5, is then put into by brain sheet
37 DEG C of constant-temperature incubation 30min in 2%TTC phosphate buffer, normal cerebral tissue's dye is redness, and infarct is in white dead.Filter paper is inhaled
Carefully carve the mass percent taking non-coloured part after removing surface liquid with blade, react Infarction volume ratio with this.Cerebral tissue is even
Slurry SOD vigor, the detection of MDA content: right side half brain adds ice normal saline by 1:10 after weighing and makes homogenate, with reference to SOD,
MDA test kit description, SOD, MDA content in detection cerebral tissue.Data are entered by application SPSS 13.0 for windows software
Row processes；Continuous data represents with x ± s, compares employing one factor analysis of variance between each group.
2) result
Brain water content: left brain water content compares not statistically significant between respectively organizing, the right cerebral tissue of model group is aqueous
Amount is apparently higher than each group (P < 0.05), and higher than sham operated rats (P < 0.05), administration group each dosage group can reduce model cerebral tissue and contain
The water yield (P < 0.05) (table 3).
Table 3 Friedolanostanes is on brain water content, Infarction volume, the impact (n=8) of SOD, MDA content
* p < 0.05, * * p < 0.01 compared with model group
Cerebral infarct volume: model group cerebral tissue cerebral infarct volume is higher than each group (P < 0.05), and administration group each dosage group can drop
Low model cerebral tissue Infarction volume (P < 0.05).
Conclusion: Friedolanostanes can reduce cerebral ischemia tissues following MCAO in rats edema, reduces Infarction volume, improves SOD and lives
Property, reduce MDA content, alleviate the radical reaction infringement to cerebral tissue, ischemic tissue of brain is had significant protective effect.
Friedolanostanes may be used for preparation treatment ischemic brain injury medicine.
Claims (1)
1.Friedolanostanes application in treatment ischemic brain injury medicine, described compound
Friedolanostanes structure is as shown in formula I:
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610822161.8A CN106309454A (en) | 2016-09-14 | 2016-09-14 | Application of Friedolanostanes in preparation of medicaments for treating ischemic brain injury |
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| CN201610822161.8A CN106309454A (en) | 2016-09-14 | 2016-09-14 | Application of Friedolanostanes in preparation of medicaments for treating ischemic brain injury |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107793404A (en) * | 2017-11-07 | 2018-03-13 | 全椒先奇医药科技有限公司 | One kind treats ischemic brain damage pharmaceutical composition and its application |
-
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- 2016-09-14 CN CN201610822161.8A patent/CN106309454A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107793404A (en) * | 2017-11-07 | 2018-03-13 | 全椒先奇医药科技有限公司 | One kind treats ischemic brain damage pharmaceutical composition and its application |
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Application publication date: 20170111 |
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| WD01 | Invention patent application deemed withdrawn after publication |