CN110151753A - Morin or its hydrate are preparing the application in osteosporosis resistant medicament - Google Patents
Morin or its hydrate are preparing the application in osteosporosis resistant medicament Download PDFInfo
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- CN110151753A CN110151753A CN201910514115.5A CN201910514115A CN110151753A CN 110151753 A CN110151753 A CN 110151753A CN 201910514115 A CN201910514115 A CN 201910514115A CN 110151753 A CN110151753 A CN 110151753A
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- Prior art keywords
- morin
- hydrate
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- compound
- zebra fish
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- Health & Medical Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Steroid Compounds (AREA)
Abstract
The invention discloses a kind of natural products to prepare the application in osteosporosis resistant medicament.The compound involved in the present invention arrived is morin or its hydrate, molecular formula are as follows: C15H10O7·xH2O.Cell assay in vitro shows that the compound can inhibit the formation of osteoclast, and animal experiment shows that the compound has significant therapeutic effect to the zebra fish osteoporosis that prednisone induces in vivo.
Description
Technical field
The present invention relates to a kind of natural products, are to be related to morin or its hydrate to prepare anti-sclerotin more specifically
Application in loose drug.
Background technique
Osteoporosis is one kind caused by many reasons with the reduction of bone tissue content, and the microstructure degeneration of bone is spy
Sign causes the brittleness of bone to increase, strength reduction and causing is prone to a kind of systemic skeletal disease fractured.With mankind society
Aging can be progressed into, the illness rate of osteoporosis increases year by year.Osteoporosis not only seriously threatens people's health,
Thus bring fracture has also brought heavy burden.
Bone remodeling is a complicated biological process, and in this course, osteoclast completes the absorption function of bone, at
Osteocyte dominates the formation function of bone, and the two generates and active coordination is that bone remodeling process maintains skeletal structure completely to close
Key.Healthy bone is in the state of bon e formation and bone resorption dynamic equilibrium, this balance once be broken can lead to osteoporosis,
A variety of bone metabolic diseases such as osteopetrosis.
More and more researches show that there are many active materials to have function of resisting osteoporosis, such as flavones in traditional Chinese medicine
Class, saponins, alkaloids, Coumarins, phenylpropionic acid compound etc., therefore finding in traditional Chinese medicine, there is anti-sclerotin to dredge
The active active principle of pine is the important channel for developing osteosporosis resistant medicament.Morin or its hydrate are that moraceae plants are worked as
Contained in flavone compound, research shows that the compound have the effects that it is antitumor, anti-inflammatory, anti-oxidant, moreover it is possible to prevention is swollen
Muscular atrophy caused by tumor cachexia, but have no that the research in terms of its anti-osteoporosis is reported.
Summary of the invention
The purpose of the present invention is: discovery morin or its hydrate are preparing the application in osteosporosis resistant medicament.
The present invention is implemented as follows: morin or its hydrate are preparing the application in osteosporosis resistant medicament, molecule
Formula are as follows: C15H10O7·xH2O, the compound specific structure such as following formula.
For clear morin or the anti-osteoporosis activity of its hydrate, inventor has carried out following experiment:
Osteoclast and bone marrow cell are isolated from newborn rabbit shin bone and femur, with 1 α, 25- (OH)2VitD3It is thin to marrow
Born of the same parents induce, and using the osteoclast model of this primary separation building, it is living to osteoclast to study morin or its hydrate
The effect of property, the results showed that the compound is inhibited to the formation of osteoclast.
3dpf wild type AB strain zebra fish is randomly selected in 6 orifice plates, prednisone processing is given and establishes osteoporosis
Model.After 28 DEG C of incubators are handled 5 days, zebra fish is dyed with 0.2% calcein, takes pictures after dyeing and acquires number
According to zebra fish, first three fluorescence intensity for saving vertebrae evaluates therapeutic effect of the compound to zebra fish osteoporosis.Knot
Fruit shows that the compound can dramatically increase the bone density of zebra fish, has to the osteoporosis of prednisone induction and significantly controls
Treatment effect.
Present invention firstly discloses the compounds to the active function of osteoclast, and controls zebra fish osteoporosis
Treatment effect is studied, and illustrates that this compound can be used for preventing and treating the bone loss disease such as osteoporosis.
Specific embodiment
The present invention is further described by the following examples, but embodiment is not delimit the scope of the invention.
Embodiment 1: the research that morin acts on osteoclast activity
By be born 48h within newborn rabbit break neck put to death, 75% alcohol disinfecting, in aseptic operating platform remove hind leg femur and
Shin bone is placed in PBS.It strips soft tissue to be placed in the α-MEM culture medium containing 10% fetal calf serum, cuts off backbone, gently scrape
Cell, whirlpool concussion, is sieved with 200 mesh cell sieves, is diluted to 2 × 106The cell suspension of a/mL is inoculated in 48 well culture plates
On, it is placed in incubator and cultivates.It is rinsed, is changed to containing 1 α, 25- (OH) with PBS afterwards for 24 hours2VitD3Pastille culture medium, then often
Change within 3 days a subculture, culture is aobvious to being dyed after the 8th day by Tartrate resistant acid phosphatase (TRAP) staining kit
To TRAP Positive Cell Counts under micro mirror.The result shows that 1 μm of ol/L and 10 μm of ol/L morin is compared with blank control group,
TRAP positive cell number significantly reduces, and difference has statistical significance (p < 0.01), shows that high concentration morin is able to suppress
Osteoclast formation.
1 morin of table is to TRAP+The influence of osteoclast number
Compared with blank group, p < 0.01 * *
Embodiment 2: morin is to zebra fish osteoporosis therapy evaluation of effect
3dpf wild type AB strain zebra fish is randomly selected in 6 orifice plates, it is water-soluble to give prednisone processing to establish zebra
Fish Osteoporotic Model.It is water-soluble respectively to osteoporosis model zebra fish to give 0.4,1.1,3.3,10 μM of morin, the positive
300 μ g/mL concentration of comparison medicine disodium etidronate, while Normal group (the normal zebra fish of fish culture water processing) and mould are set
Type control group.After 28 DEG C of incubators are handled 5 days, zebra fish is dyed with 0.2% calcein, is taken pictures simultaneously after dyeing
First three section vertebrae of analysis statistics zebra fish accumulates optical density, and statistical procedures result is indicated with mean ± SE.
The result shows that the zebra fish vertebrae of model control group accumulates optical density p < 0.01 compared with Normal group, mention
Representation model constructs successfully;Positive control drug disodium etidronate group zebra fish vertebrae accumulation optical density (49438 pixel) with
Model control group (30162 pixel) compares p < 0.01, and positive drug is prompted to have the zebra fish osteoporosis that prednisone induces
Significant therapeutic effect.The zebra fish vertebrae of 1.1,3.3,10 μM of groups of morin accumulates optical density, compared with model control group
There is significant difference (p < 0.01 or p < 0.01), it is significant to illustrate that morin has the zebra fish osteoporosis that prednisone induces
Therapeutic effect.See Table 2 for details.
Therapeutic effect (n=10) of 2 morin of table to zebra fish osteoporosis
Compared with model control group, p < 0.01 * p < 0.05, * *
In addition, inventor explain, the research of the compound of the application be inventor in the true of experimentation the study found that
The application is with another patent application submitted on the same day " mulberrin is preparing the application in osteosporosis resistant medicament " although seeing
Get up similar, and in experimental method use identical experimental method, but to the research of both compounds all, experiment
And the data that experiment generates all are true, rather than the false application that data are made up is carried out for patent numbers.It is all
The progress of experiment has the formalities such as contract, the documentary evidence of commission experimental unit, needs, can be provided at any time if examined.
Claims (1)
1. a kind of natural products is preparing the application in osteosporosis resistant medicament, it is characterised in that: the compound be morin or
Its hydrate, molecular formula are as follows: C15H10O7·xH2O。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN201910514115.5A CN110151753A (en) | 2019-06-14 | 2019-06-14 | Morin or its hydrate are preparing the application in osteosporosis resistant medicament |
Applications Claiming Priority (1)
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CN201910514115.5A CN110151753A (en) | 2019-06-14 | 2019-06-14 | Morin or its hydrate are preparing the application in osteosporosis resistant medicament |
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CN201910514115.5A Pending CN110151753A (en) | 2019-06-14 | 2019-06-14 | Morin or its hydrate are preparing the application in osteosporosis resistant medicament |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002076241A1 (en) * | 2001-03-23 | 2002-10-03 | N.V. Nutricia | Preparation for the prevention and/or treatment of altered bone metabolism |
CN104523677A (en) * | 2015-01-21 | 2015-04-22 | 广东省农业科学院动物卫生研究所 | Novel application of morin in pharmacy |
CN104523722A (en) * | 2014-11-11 | 2015-04-22 | 济南星懿医药技术有限公司 | Medicine composition for treating neuropathic pains |
-
2019
- 2019-06-14 CN CN201910514115.5A patent/CN110151753A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002076241A1 (en) * | 2001-03-23 | 2002-10-03 | N.V. Nutricia | Preparation for the prevention and/or treatment of altered bone metabolism |
CN104523722A (en) * | 2014-11-11 | 2015-04-22 | 济南星懿医药技术有限公司 | Medicine composition for treating neuropathic pains |
CN104523677A (en) * | 2015-01-21 | 2015-04-22 | 广东省农业科学院动物卫生研究所 | Novel application of morin in pharmacy |
Non-Patent Citations (1)
Title |
---|
CHENGUANG WANG ET AL.: "Morin protects glucocorticoid‑induced osteoporosis through regulating the mitogen‑activated protein kinase signaling pathway", 《JOURNAL OF NATURAL MEDICINES》 * |
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Application publication date: 20190823 |