CN103127092A - Application of Aphanamixoid A to medicine for treating osteoporosis caused by antiestrogen insufficiency - Google Patents
Application of Aphanamixoid A to medicine for treating osteoporosis caused by antiestrogen insufficiency Download PDFInfo
- Publication number
- CN103127092A CN103127092A CN 201210414596 CN201210414596A CN103127092A CN 103127092 A CN103127092 A CN 103127092A CN 201210414596 CN201210414596 CN 201210414596 CN 201210414596 A CN201210414596 A CN 201210414596A CN 103127092 A CN103127092 A CN 103127092A
- Authority
- CN
- China
- Prior art keywords
- aphanamixoid
- osteoporosis
- bone
- medicine
- treating
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses novel application of Aphanamixoid A to prevention and treatment of osteoporosis. The osteoporosis is one of key diseases endangering human health, with aging of population, the number of patients suffering from the osteoporosis is gradually increased, and the situation brings huge social, medical and economic burden to the whole world. Effective medicine for treating the disease is still absent even though domestic and foreign relevant experts and scholars pay great attention to prevention and treatment of the disease. In-vivo tests show that the Aphanamixoid A has significant anti-osteoporosis functions. Test results show that the Aphanamixoid A can inhibit bone conversion percent improvement caused by ovariectomization, reduce bone destruction, improve blood calcium concentration and be beneficial for bone deposition. The Aphanamixoid A has the function of treating the osteoporosis caused by antiestrogen insufficiency and is free of estrogen-like side effects.
Description
Technical field
The present invention relates to the relevant drug world of osteoporosis, relate in particular to Aphanamixoid A and be used for preventing and treating osteoporotic new purposes.
Background technology
Osteoporosis is the osteopathia of a kind of general, metabolic, it is characterized in that the bone amount reduces and loses, and bone fragility and fracture risk increase.Along with the aging of population, osteoporotic sickness rate has become the important diseases of harm humans health also along with increasing sharply, and has brought huge society and financial burden to the whole world.Although relevant experts and scholars attach great importance to the control of this disease, should disease still lack effective medicine both at home and abroad.
The osteoporotic medicine of control of commonly using clinically at present comprises the estrogen replacement medicine, bisphosphonates, selective estrogen receptor modulators, vitamin D, parathyroid hormone and people's recombined parathyroid hormone (1-34) etc.Although the bisphosphonates effect is pretty good, can cause the serious adverse reactions such as jawbone necrosis, musculoskeletal pain and renal failure; Although Hormone Replacement Therapy is the important method of control postmenopausal osteoporosis, life-time service has the potential danger that causes breast carcinoma, carcinoma of endometrium and the risk that thrombosis occurs also to increase; And selective estrogen receptor modulators can make thrombotic episodes obviously increase.Other drug or expensive, or late result is imprecise, all not ideal enough.Because osteoporosis is a kind of chronic disease, need Long-term taking medicine, so low price, the Chinese herbal medicine that toxic and side effects is little has become one of osteoporotic focus of research treatment.
the compd A phanamixoid A that the present invention relates to is one and delivered (Cai in 2012, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.) New skeleton compound, this compound has brand-new framework types, present purposes only relates to insect antifeedant activity (Cai, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.), belong to open first for the purposes of the Aphanamixoid A that the present invention relates in the preparation estrogen antagonist lacks the medicine for treating osteoporosis that causes, because framework types belongs to brand-new framework types, and the osteoporosis activity that its estrogen antagonist shortage causes is unexpectedly strong, there is not the possibility that is provided any enlightenment by other compounds, possesses outstanding substantive distinguishing features, be used for simultaneously osteoporotic control and obviously have significant progress.
Summary of the invention
The invention provides the new purposes of osteoporosis of Aphanamixoid A.
The present invention finds the application of Aphanamixoid A in the preparation osteosporosis resistant medicament by experiment in body.
Further, described osteoporosis is because estrogen deficiency causes.
The present invention finds that by in vivo test Aphanamixoid A has the effect of significant prevention of osteoporosis.Aphanamixoid A can suppress the enhancing of bone conversion ratio and the bone destruction that removal ovary causes, can improve blood calcium concentration simultaneously, is conducive to the deposition of bone.It is the osteoporotic medicine of a kind of desirable control.
Described compd A phanamixoid A structure is as shown in formula I:
The purposes of the Aphanamixoid A that the present invention relates in the preparation estrogen antagonist lacks the medicine for treating osteoporosis that causes belongs to open first, because framework types belongs to brand-new framework types, and the osteoporosis activity that its estrogen antagonist shortage causes is unexpectedly strong, there is not the possibility that is provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, be used for simultaneously osteoporotic control and obviously have significant progress.
The specific embodiment
The preparation method of compd A phanamixoid A involved in the present invention is referring to document (Cai, J. Y. et al., 2012. Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya. Organic Letters 14 (10), 2524 – 2527.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subjected to any restriction of specific embodiment, but limited by claim.
Embodiment 1: the preparation of compd A phanamixoid A tablet involved in the present invention:
Get 20 and digest compound Aphanamixoid A, add conventional adjuvant 180 grams that prepare tablet, mixing, conventional tablet machine are made 1000.
Embodiment 2: the preparation of compd A phanamixoid A capsule involved in the present invention:
Get 20 and digest compound Aphanamixoid A, add the conventional adjuvant such as starch 180 grams that prepare capsule, mixing is encapsulatedly made 1000.
Further illustrate its pharmaceutically active below by pharmacodynamic experiment.
1, materials and methods
The ten week female Mus of healthy SD in age (18, Jiangsu Province's animal center) are divided into 3 groups, 6 every group at random: sham operated rats (Sham), oophorectomize model group (OVX), Aphanamixoid A group.The raising condition: temperature is (23 ± 2) ℃, and illumination: dark is 12: 12.Allow and respectively organize rat and conform and begin osteoporosis modeling operation after 2 weeks: each organizes rat all through lumbar injection 20% urethane anesthesia (6ml/ kg body weight), closes abdomen, all the other two groups of row bilateral oophorectomies after the Sham group is opened abdomen.The 4th week of postoperative rises, and Sham group and OVX organize take food every day standard feed and deionized water, and Aphanamixoid A organizes take food every day standard feed and deionized water, and gavage is given and Aphanamixoid A 10 mg/kg simultaneously, continuous 3 months, claims weekly body weight one time.After experiment finishes, with urethane anesthesia, win the eyeball blood sampling, 2000r/min is centrifugal, draws supernatant (being serum).Extract rat uterus, weigh rapidly.Take out rats with bilateral femur and bilateral tibial, reject soft tissue.Two tibias are ashing 8 h in 800 ℃ of high temperature furnaces (being provided by chemical institute of Nanjing University), and cooling rear title ash is heavy.Pulverize into grey shape with mortar, get the 0.1g bone ash and be dissolved in 1 ml, in 6 mol/l hydrochloric acid, get 0.2 ml when surveying bone calcium and bone phosphorus and be diluted to 1ml with ultra-pure water, detect bone calcium and bone phosphorus content with automatic clinical chemistry analyzer.Fl is measured bone density (BMD) with borne densitometers (Jiangsu Prov. People's Hospital Nuclear Medicine Department provides).Biochemical Indices In Serum is measured: get serum 0.5 ml, detect serum alkaline phosphatase (ALP), calcium (Ca) and phosphorus (P) with automatic clinical chemistry analyzer (department of general surgery of Nanjing General Hospital, Nanjing Military Area Command, PLA provides).Experimental result represents with x ± S.
2, result
(1) Aphanamixoid A on Bilateral oophorectomy rat body weight and uterus coefficient impact
Table 1 shows respectively organizes rat body weight without significant difference, and the obvious atrophy in uterus of Ovariectomy model group rat gave Aphanamixoid A after 3 months, did not cause the obvious increase of uterus weight, illustrated that Aphanamixoid A has no stimulation to uterine growth.
Table 1 Aphanamixoid A on Bilateral oophorectomy rat body weight and uterus coefficient impact
| The experiment group | Body weight (g) | Uterus index (mg/g) |
| Sham | 347.7±54.4 | 1.894±0.95 |
| OVX | 346.0±41.9 | 0.141±0.59 |
| Aphanamixoid A | 345.1±18.8 | 0.266±1.11 |
(2) Aphanamixoid A is to Bilateral oophorectomy rat blood serum ALP, serum Ca and blood-serum P impact
After table 2 can be found out removal ovary, model group rat blood serum alkaline phosphatase activities increased.After removal ovary, the body inner estrogen lacks, and causes the bone conversion ratio to increase, and is consistent with postmenopausal women's high transformant osteoporosis.Give Aphanamixoid A after 3 months, alkaline phosphatase activities significantly descends, and visible Aphanamixoid A can suppress the increase of the bone conversion ratio that removal ovary causes, the destruction of reducing sclerotin.Also show with sham operated rats in table and compare, model group rat blood serum calcium obviously descends, and Aphanamixoid A can significantly promote serum calcium cancentration.Serum calcium is osteoplastic important marker, illustrates that Aphanamixoid A can effectively reverse the reduction of the serum calcium that causes due to oophorectomize, is conducive to the formation of bone.
Table 2 Aphanamixoid A is to Bilateral oophorectomy rat blood serum ALP, serum Ca and blood-serum P impact
* P＜0.05vs OVX organizes
(3) Aphanamixoid A on Bilateral oophorectomy rat fl BMD impact
After table 3 can be found out removal ovary, model group rat fl bone density significantly descends than sham operated rats, gives Aphanamixoid A after 3 months, and bone density increases to some extent.
Table 3 Aphanamixoid A on Bilateral oophorectomy rat fl BMD impact
| The experiment group | Fl BMD (g/cm 2) |
| sham | 0.332±0.027 |
| OVX | 0.215±0.037 |
| Aphanamixoid A | 0.285±0.025 * |
* P＜0.05vs OVX organizes
(4) impact of Aphanamixoid A on Bilateral oophorectomy rats with bilateral tibia parameters
Table 4 can find out with sham operated rats and compare, and the two tibias ash of model group rat representation work reduces, and Aphanamixoid A raises to some extent than model group.Each organizes bone calcium and the bone phosphorus content does not have significant difference.
The impact of table 4 Aphanamixoid A on Bilateral oophorectomy rats with bilateral tibia parameters
* P＜0.05vs OVX organizes
Conclusion: Aphanamixoid A can suppress the enhancing of bone conversion ratio and the bone destruction that removal ovary causes, can improve blood calcium concentration simultaneously, is conducive to the deposition of bone.Have preventive and therapeutic effect for the osteoporosis that causes due to estrogen deficiency, and the side effect of no estrogen sample.Aphanamixoid A can be used for osteoporotic control.
Claims (1)
1.Aphanamixoid the application of A in the medicine for treating osteoporosis that the estrogen antagonist shortage causes, described compd A phanamixoid A structure is as shown in formula I:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210414596 CN103127092A (en) | 2012-10-25 | 2012-10-25 | Application of Aphanamixoid A to medicine for treating osteoporosis caused by antiestrogen insufficiency |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210414596 CN103127092A (en) | 2012-10-25 | 2012-10-25 | Application of Aphanamixoid A to medicine for treating osteoporosis caused by antiestrogen insufficiency |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103127092A true CN103127092A (en) | 2013-06-05 |
Family
ID=48487967
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210414596 Withdrawn CN103127092A (en) | 2012-10-25 | 2012-10-25 | Application of Aphanamixoid A to medicine for treating osteoporosis caused by antiestrogen insufficiency |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103127092A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104887671A (en) * | 2015-05-27 | 2015-09-09 | 南京大学 | Application of O-(diethylin) ethyl derivative of daphmalenine A in preparation of anti-osteoporosis medicines |
-
2012
- 2012-10-25 CN CN 201210414596 patent/CN103127092A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104887671A (en) * | 2015-05-27 | 2015-09-09 | 南京大学 | Application of O-(diethylin) ethyl derivative of daphmalenine A in preparation of anti-osteoporosis medicines |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NZ585408A (en) | Formulas comprising calcium, magnesium, zinc, and vitamin d3 for the prevention and amelioration of osteoporosis | |
| CN102670657A (en) | Percutaneous absorption preparation for treating bone joint disease | |
| CN103349674B (en) | Tortoise shell rana japonica oil composition for increasing bone density and preventing osteoporosis | |
| CN102920713B (en) | Application of Gypensapogenin B in medicament for treating osteoporosis caused by anti-estrogenic deficiency | |
| CN103127092A (en) | Application of Aphanamixoid A to medicine for treating osteoporosis caused by antiestrogen insufficiency | |
| CN102988385B (en) | Application of Houttuynoid A to preparation of medicine for treating osteoporosis caused by lack of antiestrogen | |
| CN103127066A (en) | Application of Eryngiolide A in medicines curing rarefaction of bone caused by lack of antiestrogen | |
| US6797285B1 (en) | Leaves of Cajanus Cajan(L.) Millsp and extract, formulation and uses thereof | |
| CN103356602B (en) | Application of Chukrasone B in medicines for resisting osteoporosis caused by estrogen deficiency | |
| CN102626463A (en) | Natural medicine compound for increasing bone mineral density and preventing and treating osteoporosis | |
| CN102895237B (en) | Application of Gypensapogenin A in drugs for resisting osteoporosis caused by estrogen deficiency | |
| CN108938989A (en) | It is a kind of treat osteoporosis cover fennel essence bone-building up powder | |
| CN102114195A (en) | Anti-drug capsule prepared from pure traditional Chinese medicines | |
| CN102988391A (en) | Application of Houttuynoid E to preparation of medicine for treating osteoporosis caused by lack of antiestrogen | |
| CN103356660A (en) | Application of Chukrasone A in medicines for resisting osteoporosis caused by estrogen deficiency | |
| CN103393650A (en) | Application of Sarcaboside A to medicament for resisting osteoporosis caused by estrogen deficiency | |
| CN102772421B (en) | New application of triptolide against osteoporosis | |
| CN101804075B (en) | Application of starfishes to preparation of medicament for treating osteoporosis | |
| CN103356572A (en) | Application of Sarcaboside B in preparation of medicines for treating osteoporosis caused by antiestrogen deficiency | |
| CN102772401A (en) | Novel osteoporosis resistant use of carnosol | |
| CN102961518B (en) | Application for ginseng-rhizoma curculiginis combined medicine for preparation for medicine used for treating osteoporosis | |
| CN101352480B (en) | Chinese medicinal composition for treating osteoporosis and preparation method thereof | |
| Kim et al. | Effects of Yuhyangjeongtong-san on Fracture Healing in Rats | |
| US8765188B2 (en) | Composition for treating and/or preventing osteoporosis | |
| CN109674799B (en) | Application of betulinic acid in body lead elimination and preparation of lead elimination food, health-care product and medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C04 | Withdrawal of patent application after publication (patent law 2001) | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20130605 |