CN107501381A - It is a kind of that there is compound for promoting motor neuron growth and its production and use - Google Patents
It is a kind of that there is compound for promoting motor neuron growth and its production and use Download PDFInfo
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- CN107501381A CN107501381A CN201710590389.3A CN201710590389A CN107501381A CN 107501381 A CN107501381 A CN 107501381A CN 201710590389 A CN201710590389 A CN 201710590389A CN 107501381 A CN107501381 A CN 107501381A
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- motor neuron
- neuron growth
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- pyridine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to natural drug and drug therapy field, discloses a kind of compound for having and promoting motor neuron growth and its production and use.The compound is formed by oleanolic acid and nicotinic acid coupling, structural formula such as formula (I).Preparation includes step：Oleanolic acid and nicotinic acid are dissolved in anhydrous methylene chloride, under the catalysis of pyridine and 4 dimethylamino naphthyridines, room temperature reaction overnight, filtering, crosses silica gel chromatographic column, rotates, and dries, you can obtains target compound.By horizontal in isolated cells, the compound can be with the promotion motor neuron enation of conspicuousness；Horizontal in whole animal, such compound can be with the functional rehabilitation for promoting injured sciatic nerves and femoral nerve of conspicuousness.Can be as the drug development for carrying out ALS and relative motion neural disorder.
Description
Technical field
It is more particularly to a kind of that there is promotion motor neuron growth to make the invention belongs to natural drug and drug therapy field
Compound and its production and use.
Background technology
Motor neuron disease there is no the side cured at present as a kind of nervous system chronic lethal degenerative disease
Method.But since finding over more than 100 years of motor neuron disease, people just struggle with it always, have attempted nearly hundred kinds of medicines and have controlled
Treat.As the development of Neuscience, the deep understanding of the cause of disease and Pathological Physiology to motor neuron disease, people are difficult to this
A series of achievements to attract people's attention are achieved in the challenge of the property controlled disease.Current primary treatment includes etiological treatment, controls to the ill
Treat the supportive treatment with a variety of non-drug.The developing direction of Therapy study includes neuroprotective agent, anti-exitotoxicity medicine at this stage
Thing, neurotrophic factor, anti-oxidant and free radical scavenger, stem cell and gene therapy etc..
Using the myoneural diseases such as traditional Chinese medical science pure Chinese medicine prescription treatment motor neuron disease, impotence card, good control can be obtained
Treat effect.Because suitable Chinese herbal medicine is as chelating agent, can with it is being deposited in tissue, organ, excessive, harmful from
By the material such as base, calcareous, lipid, collagen, mucopolysaccharide, lead, mercury, arsenic, aluminium, copper chelate, drain accumulate in vivo it is a variety of
Virulence factor, antibody in patients blood plasma, the pathogenic factor such as immune complex are removed, eliminates illness；Meanwhile pass through chelating agent
Chelation, drained internal big quantity of material, caused these harmful or harmless materials in body drastically to reduce, lead to
The material for crossing these falls sharply, and stimulates the maincenter systems such as the nerve of body, endocrine, immune, digestion, circulation, breathing, uropoiesis, reproduction
System, stress reaction is carried out, a series of endogenous materials such as neurotransmitter, hormone, immune factor etc. is generated, body " is pushed away old
Go out new ", the effect such as " remoulding oneself thoroughly ", detoxify for whole human body, recovered the metabolic balance of body, so as to dispel in body
A variety of hidden danger and focus, have been finally reached the purpose prevented and cured diseases.The effective Chinese medicinal formulae of clinical report includes at present plus taste is good for
Walk Huqian Wan, beneficial marrow soup, more class Buyang Huanwu Tang, impotence soup etc..
The content of the invention
In order to overcome shortcoming and defect present in prior art, primary and foremost purpose of the invention is that providing one kind has rush
Enter the compound of motor neuron growth；The compound passes through linkage by oleanolic acid and nicotinic acid.
Another object of the present invention is to provide a kind of preparation method of above-claimed cpd.
It is still another object of the present invention to provide a kind of purposes of above-claimed cpd.
The purpose of the present invention is achieved through the following technical solutions：
A kind of to have the compound for promoting motor neuron growth, the compound is by oleanolic acid and nicotinic acid coupling
Form, there is the structural formula as shown in following formula (I)：
The compound passes through linkage by oleanolic acid and nicotinic acid.
A kind of above-mentioned preparation method with the compound for promoting motor neuron growth, comprises the following steps：
Oleanolic acid and nicotinic acid are dissolved in anhydrous methylene chloride, under the catalysis of pyridine and DMAP (DMAP), room
Temperature reaction overnight, filtering, crosses silica gel chromatographic column, rotates, and dries, you can obtains target compound.
The room temperature is 25-30 DEG C；
The mol ratio of the pyridine and DMAP is (1~3):1.
Eluting solvent used in the silica gel chromatographic column is ethyl acetate and petroleum ether, and solvent volume ratio is (2~10):7.
Above-mentioned a kind of compound and its pharmaceutically acceptable salt with promotion motor neuron growth is being made
The standby purposes promoted in motor neuron growth medicine.
Above-mentioned a kind of compound and its pharmaceutically acceptable salt with promotion motor neuron growth is being made
Purposes in standby repairing of neural injury medicine.The repairing of neural injury medicine is treatment by wound, disorder, sudden disease
Disease, motion sickness, the medicine of demyelinating disease or nerve injury disease caused by nerve retrograde affection.
A kind of pharmaceutical composition, wherein above-mentioned the having containing therapeutically effective amount promotes motor neuron growth
Compound or its pharmaceutically acceptable salt and carrier.
A kind of above-mentioned pharmaceutical composition is preparing the purposes in promoting motor neuron growth medicine.
The present invention has the advantages of following prominent and beneficial effect compared with prior art：
The compounds of this invention has the function of promoting motor neuron growth, and horizontal in isolated cells, such compound can
With the promotion motor neuron enation of conspicuousness；It is horizontal in whole animal, such compound can with the promotion of conspicuousness by
Damage the functional rehabilitation of sciatic nerve and femoral nerve.
Brief description of the drawings
Fig. 1 is that growth of the medicine for cell axon has obvious facilitation figure, the ★ P ＜ 0.05 compared with PBS groups；
★ ★ P ＜ 0.01；The Δ P ＜ 0.01 compared with proto-drug group.
Fig. 2 is different pharmaceutical to the influence figure of SFI (sciatic nerve function index) value, S.O：ShamOperated (does evil through another person
Art)；The ★ P ＜ 0.05 compared with model group；★ ★ P ＜ 0.01；The Δ P ＜ 0.01 compared with former medicine group.
Fig. 3 is influence figure of the different pharmaceutical to sufficient caudal horn, S.O：Sham Operated (sham-operation)；Compared with model group
★ P ＜ 0.05；★ ★ P ＜ 0.01；The Δ P ＜ 0.01 compared with former medicine group.
Fig. 4 is influence figure of the different pharmaceutical to sufficient caudal horn, S.O：Sham Operated (sham-operation)；Compared with model group
★ P ＜ 0.05；★ ★ P ＜ 0.01；The Δ P ＜ 0.01 compared with former medicine group.
Fig. 5 is influence figure of the different pharmaceutical to length ratio of stretching one's legs, S.O：Sham Operated (sham-operation).With model
Group compares ★ P ＜ 0.05；★ ★ P ＜ 0.01；The Δ P ＜ 0.01 compared with former medicine group.
Embodiment
With reference to embodiment, the present invention is described in further detail, but the implementation of the present invention is not limited to this.
Embodiment 1：Compound synthesis
Oleanolic acid (1.1mmole) and nicotinic acid (1.3eq) are dissolved in anhydrous methylene chloride (30ml), in pyridine
Reacted under the catalysis of (0.5g) and DMAP (0.5g), at 25-30 DEG C of room temperature overnight, filtering, cross silica gel chromatographic column
(eluting solvent used is volume ratio (3~9):7 ethyl acetate and petroleum ether), rotate, dry, you can obtain white solid
Target compound.Analyzed through liquid chromatography mass and nuclear magnetic resonance technique, the freshly prepd white solid target compound of institute is tool
There is the conjugate of structure shown in formula (I)：
Embodiment 2：Cellular level carries out pharmic function checking
Medicine (PSB, nicotinic acid, oleanolic acid and the gained target compound of embodiment 1) is respectively acting on original cuiture
After motor neuron 24h, with neuron axon growing state is observed under inverted microscope, every group of 3 holes, randomly selected per hole some
The visual field is taken pictures, and statistics projection length is measured with IPP softwares, and each class value is compared with PBS control group, and evaluation medicine is to kinesitherapy nerve
The influence of first projection length.Next, counting respectively in various concentrations lower motor neuron axon length, as a result find, this five
Kind medicine can promote the growth of neurite under finite concentration, there is significant difference (Fig. 1) compared with PBS.
The animal of embodiment 3 is horizontal to carry out pharmic function checking
To Wistar rats carry out sciatic nerve and femoral nerve clamp operation, Post operation by medicine (nicotinic acid, oleanolic acid and
The gained target compound of embodiment 1) it is administered respectively in a manner of being injected intraperitoneally 28 days.Before detecting administration, it is administered 14 days, administration
The locomitivity and histological change of experimental animal at 28 days, the help that evaluation medicine recovers to experimental animal locomitivity are made
With.The experimental animal of different groups has been counted respectively in behaviouristics detection：SFI values (Fig. 2), sufficient caudal horn (Fig. 3), vola angle
Testing index such as (Fig. 4), length ratio of stretching one's legs (Fig. 5), it was demonstrated that medicine can promote experimental animal to move energy under finite concentration
The recovery of power, there is significant difference compared with physiological saline group.Confirm that medicine can promote impaired sciatic nerve and stock
The functional rehabilitation of nerve.
Above-described embodiment is the preferable embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any Spirit Essences without departing from the present invention with made under principle change, modification, replacement, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
Claims (10)
1. a kind of have the compound for promoting motor neuron growth, it is characterised in that：The compound is by oleanolic acid
Formed with nicotinic acid coupling, there is the structural formula as shown in following formula (I)：
A kind of 2. compound with promotion motor neuron growth according to claim 1, it is characterised in that：Institute
State compound and linkage is passed through by oleanolic acid and nicotinic acid.
3. a kind of preparation method with the compound for promoting motor neuron growth according to claim 1, its
It is characterised by：Comprise the following steps：Oleanolic acid and nicotinic acid are dissolved in anhydrous methylene chloride, in pyridine and 4- dimethylaminos
Under the catalysis of pyridine, room temperature reaction overnight, filtering, crosses silica gel chromatographic column, rotates, and dries, you can obtains target compound.
4. preparation method according to claim 3, it is characterised in that：The room temperature is 25-30 DEG C；The pyridine and 4- bis-
The mol ratio of methylamino pyridine is (1~3):1.
5. preparation method according to claim 3, it is characterised in that：Eluting solvent used in the silica gel chromatographic column is second
Acetoacetic ester and petroleum ether, solvent volume ratio are (2~10):7.
6. it is according to claim 1 it is a kind of have promote motor neuron growth compound and its can pharmaceutically connect
The salt received is preparing the purposes in promoting motor neuron growth medicine.
7. it is according to claim 1 it is a kind of have promote motor neuron growth compound and its can pharmaceutically connect
Purposes of the salt received in repairing of neural injury medicine is prepared.
8. purposes according to claim 7, it is characterised in that：The repairing of neural injury medicine is treatment by wound, machine
Can disorder, sudden illness, motion sickness, the medicine of nerve injury disease caused by demyelinating disease or nerve retrograde affection
Thing.
A kind of 9. pharmaceutical composition, wherein having described in the claim 1 containing therapeutically effective amount promotes motor neuron life
The compound or its pharmaceutically acceptable salt and carrier of long effect.
10. a kind of pharmaceutical composition according to claim 9 is preparing the purposes in promoting motor neuron growth medicine.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710590389.3A CN107501381A (en) | 2017-07-19 | 2017-07-19 | It is a kind of that there is compound for promoting motor neuron growth and its production and use |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710590389.3A CN107501381A (en) | 2017-07-19 | 2017-07-19 | It is a kind of that there is compound for promoting motor neuron growth and its production and use |
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| CN107501381A true CN107501381A (en) | 2017-12-22 |
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| CN201710590389.3A Pending CN107501381A (en) | 2017-07-19 | 2017-07-19 | It is a kind of that there is compound for promoting motor neuron growth and its production and use |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024078517A1 (en) * | 2022-10-13 | 2024-04-18 | Hong Kong Baptist University | Identification of oleanolic acid and plant extract for glucose-6-phosphate dehydrogenase-related disorders including bag3opathy |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101690814A (en) * | 2009-10-09 | 2010-04-07 | 中国药科大学 | Traditional Chinese medicine monomer having function of promoting growth of motoneuron |
-
2017
- 2017-07-19 CN CN201710590389.3A patent/CN107501381A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101690814A (en) * | 2009-10-09 | 2010-04-07 | 中国药科大学 | Traditional Chinese medicine monomer having function of promoting growth of motoneuron |
Non-Patent Citations (4)
| Title |
|---|
| 俞卫锋: "《肝胆麻醉和围术期处理》", 31 August 2016 * |
| 宋善俊: "《现代内科治疗学》", 31 October 1999 * |
| 宋小丹等: "齐墩果酸对谷氨酸诱导神经细胞损伤的影响", 《哈尔滨医科大学学报》 * |
| 杨元德: "《养生食疗方 疾病一扫光》", 31 March 2013 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024078517A1 (en) * | 2022-10-13 | 2024-04-18 | Hong Kong Baptist University | Identification of oleanolic acid and plant extract for glucose-6-phosphate dehydrogenase-related disorders including bag3opathy |
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Application publication date: 20171222 |