CN104478822B - One is treated osteoporotic pharmaceutical composition - Google Patents
One is treated osteoporotic pharmaceutical composition Download PDFInfo
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- CN104478822B CN104478822B CN201410696604.4A CN201410696604A CN104478822B CN 104478822 B CN104478822 B CN 104478822B CN 201410696604 A CN201410696604 A CN 201410696604A CN 104478822 B CN104478822 B CN 104478822B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
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- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
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Abstract
The present invention relates to one and treat osteoporotic pharmaceutical composition, the compound that described pharmaceutical composition comprises effective dose and pharmaceutically acceptable carrier, described compound has lower array structure:
Description
Technical field
The present invention relates to field of medicaments, relate in particular to one and treat osteoporotic medicine groupCompound.
Background technology
Osteoporosis is that a health worldwide, that more and more attract people's attention is askedTopic. The whole world approximately 200,000,000 people suffer from osteoporosis at present, and its incidence of disease has leapt to common disease, manyMorbidity the 7th. Estimate that ill total number of persons has exceeded 200,000,000. Osteoporosis is that the elderly is the most normalThe disease of seeing. In the U.S. and western countries, exceed in 55 years old postclimacteric women at the age,There is the people of half to suffer from the osteoporosis that degree is different, and suffer from the elderly of over-65sOsteoporosis person is up to more than 95%. Along with the reach of science and the mankind's progress, per capita longevityLife constantly extends, and elderly population increase sharply, and the osteoporotic incidence of disease is also along with occurring rapidlyIncrease. Estimate to the year two thousand fifty whole world over-65s the elderly will be by current 3.23 hundred millionBe increased to 15.55 hundred million, osteoporosis causes hip fracture generation number also by by current when the time comes1660000 are increased to 6,260,000, wherein the patient of Asia, Latin America, the Middle East and African countryTo account for more than 70%. According to official statistics, the U.S. every year for osteoporosis aspect directlyReach 10,000,000,000 dollars with indirect cost; The health of Britain and social security institution are every year for sclerotin is dredgedThe fund that pine provides exceedes 500,000,000 pounds; France only pays 30,000 fractures of neck of femur every year on averagePatient's hospitalization cost approximately 13.5 hundred million French Francs. The like this huge society that osteoporosis causesAnd financial burden, form a serious global problem, cause the utmost point of countries in the worldLarge concern. The arrival of aging society is increased osteoporotic incidence increasingly, serious threatPeople's quality of life.
China is the country that world population is maximum, and wherein elderly population account for Asia elderly population1/2 and world population 1/5. The osteoporosis epidemiology in Beijing, Shanghai and 3 cities, Chengdu is adjustedThe fruit that comes to an end shows, 60-69 year osteoporotic incidence women of age bracket and the male sex are respectively 60% and 30% left and right. China's large population base, sufferers of osteoporosis face has reached 6,000 ten thousand～8000Ten thousand examples, this brings serious burden to family and society. According to another adding up 2000 national 65 years oldAbove people has 1.3 hundred million, accounts for 10.7% of national population, has become typical veteran form country.And the patient who suffers from osteoporosis accounts for 90% in these crowds, and the disease of hip fracturePeople will have 12%～40% to die from various complication in 1 year. In survivor, also have 50%Human action inconvenience. This has not only caused serious body and mind to wreck to patient, also gives family simultaneouslyHuge manpower and financial resources burden are increased with society. Therefore, it is anti-ageing preventing and treating osteoporosis,Life-extending, a very urgent research topic of the guarantee people's quality of life.
Summary of the invention
The object of this invention is to provide one and treat osteoporotic pharmaceutical composition.
In order to realize object of the present invention, the invention provides one and treat osteoporotic chemical combinationThing, this compound has lower array structure:
The present invention also provides one to treat osteoporotic pharmaceutical composition, described pharmaceutical compositionThe compound that comprises effective dose and pharmaceutically acceptable carrier, described compound has following knotStructure:
Preferably, described pharmaceutically acceptable carrier be diluent, disintegrant, adhesive,Lubricant, stabilizing agent or corrigent.
Preferably, described diluent is sugar derivatives, starch derivatives or cellulose derivative.
Preferably, described diluent is lactose.
Preferably, described pharmaceutical composition is powder, fine granule, granule, capsule or sheetAgent.
The present invention also provides the purposes of compound in the osteoporotic medicine of preparation treatment, this changeCompound has lower array structure:
Term used herein " pharmaceutically acceptable " refers to not eliminate compound as herein describedBA or the material of character, as carrier or diluent. This class material is applied to individualBody does not cause undesirable biological action or not to be harmful to mode and the composition that comprises itIn any component interaction.
Term " pharmaceutically acceptable carrier " comprises any and all molten as used hereinAgent, decentralized medium, coating material, surfactant, antioxidant, anticorrisive agent (for example resistMicrobial inoculum, antifungal agent), isotonic agent, absorption delay agent, salt, anticorrisive agent, medicine stabilizing agent,Adhesive, excipient, disintegrant, lubricant, sweetener, flavouring, dyestuff etc. and its groupClose, this is well-known to those skilled in the art (for example, referring to Remington'sPharmaceuticalSciences,18thEd.MackPrintingCompany, 1990, pp.1289-1329). Except with the inconsistent carrier of active component,In treatment or pharmaceutical composition, consider to use any conventional carrier.
The propagation of compound of the present invention to rat kind skeletonization UMR106 cell and/or pointChange and all show certain facilitation.
Detailed description of the invention
Further illustrate the present invention below by embodiment. It should be understood that reality of the present inventionExecuting example is for the present invention instead of limitation of the present invention are described. According to essence pair of the present inventionThe simple modifications that the present invention carries out all belongs to the scope of protection of present invention. Unless separately hadBright, otherwise percentage in the present invention is percetage by weight.
Experimental example
Material: α-MEM culture medium is Gibco company product, and Hepes trypsase isSigma company product, UMR106 cell line is purchased from Peking University's oral surgery laboratory, sourceIn masschusetts, u.s.a hospital general. Hyclone is purchased from blood disease research institute of the Chinese Academy of Medical Sciences.
Method: taking rat human osteosarcoma cell be UMR106 as target cell, adopt contrast seeThe method of examining, with the positive contrast of estradiol, establish Normal group (not dosing only adds simultaneouslyEquivalent cell suspension and culture medium) and blank group (not dosing and cell suspension only add etc.Amount culture medium). Preparation compound is 1 × 10-8、1×10-7、1×10-6Mol/L3 concentration group,Totally 6 groups. Preparation positive control and compound use DMSO.
UMR106 cell is cultivated and morphological observation: UMR106 cell is incubated at containing 150ML/L hyclone, 25mmol/LHepes, 100kU/L penicillin, 100mg/L strepto-In α-MEM culture medium of element, put in 37 DEG C, 50mL/L CO2gas incubator and trainSupport. Get the cell that growth conditions is good, use 2.5g/L Trypsin Induced, add α-MEM trainingFoster base is made cell suspension, and adjusting cell concentration is 4 × 107L-1, be inoculated in 4 12 hole trainingsSupport on plate, in culture plate, place 1.5 × 1.5cm slide. Blank group, the estradiol positive are rightAccording to group, 1 × 10-8、1×10-7、1×10-6Mol/L3 concentration group respectively established 8 multiple holes, every holeAdd cell suspension 2.7mL, corresponding liquid 0.3mL. After 48h, under inverted microscope, seeExamining cellular morphology changes.
The impact of the compounds of this invention on UMR106 cell proliferation: adjusting cell concentration is2×107L-1, being inoculated in 96 well culture plates, every hole adds cell suspension 180 μ L, treats 24hAfter, adding the compound of above-mentioned 3 concentration, every hole 20 μ L, separately establish blank group (noAdd compound, only add equivalent cell suspension). Establish 8 multiple holes for every group, continue to cultivate after 48h,Adopt tetrazolium salts method taking 490nm as measuring wavelength, 655nm is reference wavelength, measures each holeAbsorbance A value. Calculate the average rate of increase.
The impact of the compounds of this invention on the inside and outside alkaline phosphatase activities of UMR106 cell:Adjusting cell concentration is 2 × 107L-1, be inoculated on 2 24 well culture plates, establish normal controlGroup, estradiol 1 × 10-8L-1Positive controls and compound 1 × 10-8、1×10-7、1×10-6mol/L3 concentration groups, totally 5 groups, establish 8 multiple holes, according to the method for JohaAP, add for every groupAfter medicine 72h, adopt phosphoric acid p-nitrophenyl matrix KINETIC METHOD to measure cell interior and culture mediumAlkaline phosphatase activities.
MAIN OUTCOME MEASURES: the compounds of this invention 1 × 10-8、1×10-7、1×10-63 of mol/LThe impact of individual concentration group on UMR106 cell proliferation and inside and outside alkaline phosphatase activities.
Statistical analysis: completed by SPSS statistical software. Data are usedRepresent, between organizingT inspection, P < 0.05 thinks to have significant difference.
Result
The impact that the compound of variable concentrations changes UMR106 cellular morphology
In culture medium, add compound to cultivate after 48h, cell quantity is obvious compared with control groupIncrease, karyokinetic phase, is common. Normal group is being cultivated after 48h, control group UMR106Cell proliferation is slow, has no matrix and piles up. Add compound 1 × 10-8Mol/L cultivates after 48h,Obviously, cell number increases UMR106 propagation, and a small amount of matrix is piled up. Add compound 1 × 10-7Mol/L cultivates after 48h, and cell number obviously increases, overlapping growth, and matrix is piled up obviously. AddEnter compound 1 × 10-6Mol/L cultivates after 48h, and cell is bred in a large number, connects in flakes matrixBulk deposition, overlapping growth.
The compounds of this invention sees the following form to the proliferation of UMR106 cell
Cell, after compound treatment 48h, detects through tetrazolium salts method, with respect to control group, and 3Individual administration group all has significant difference compared with control group.
The impact of compound on alkaline phosphatase activities in UMR106 cell
Cell is after compound treatment when 24h, 48h, through phosphoric acid p-nitrophenyl matrix dynamicsMethod detects, and in cellular control unit, alkaline phosphatase activities is respectively 713.12 ± 12.15,2281.32± 7.62 μ kat/g, compound 1 × 10-6In mol/L group cell, alkaline phosphatase activities is respectively823.12 ± 12.31,2415.41 ± 15.86 μ kat/g, difference has conspicuousness compared with control groupMeaning. Estradiol 1 × 10-8Mol/L group is 24h, 48h after processing, alkaline phosphatase in cellActivity is respectively 275.19 ± 18.63,2355.48 ± 15.62 μ kat/g, with control group phase ratioDifferent have a significant. 72h after processing, the each concentration group of compound and estradiol 1 × 10-8mol/LGroup group is compared with control group, and in cell, alkaline phosphatase activities has the trend of enhancing, but without statisticsLearn difference.
The impact of compound on UMR106 extracellular alkaline phosphatase activities
After 24h, control group culture medium activity change of Alkaline phosphatase is 652.83 ± 11.31μ kat/g, compound 1 × 10-6Mol/L group is 781.62 ± 11.58 μ kat/g, with control group phaseThan there being significant difference. Estradiol 1 × 10-8Mol/L group and compound 1 × 10-7Mol/L componentBe not 728.85 ± 9.87 μ kat/g and 733.18 ± 15.32 μ kat/g, have aobvious compared with control groupWork property difference. Compound 1 × 10-8Mol/L group is 671.32 ± 14.27 μ kat/g, with control groupIndifference. 48h and 72h after processing, the each concentration group of compound and estradiol 1 × 10-8mol/LGroup is compared with control group, and extracellular alkaline phosphatase activities has the trend of enhancing, but without statisticsDifference.
Claims (1)
1. the purposes of compound in the osteoporotic medicine of preparation treatment, is characterized in that,This compound has lower array structure:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410696604.4A CN104478822B (en) | 2014-11-26 | 2014-11-26 | One is treated osteoporotic pharmaceutical composition |
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| CN201410696604.4A CN104478822B (en) | 2014-11-26 | 2014-11-26 | One is treated osteoporotic pharmaceutical composition |
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| CN104478822A CN104478822A (en) | 2015-04-01 |
| CN104478822B true CN104478822B (en) | 2016-05-11 |
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| CN201410696604.4A Expired - Fee Related CN104478822B (en) | 2014-11-26 | 2014-11-26 | One is treated osteoporotic pharmaceutical composition |
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| CN105218465A (en) * | 2015-11-14 | 2016-01-06 | 刘杰 | A kind of pharmaceutical composition for the treatment of mammary cancer |
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| DK1753417T3 (en) * | 2004-06-07 | 2012-07-23 | Univ Tennessee Res Foundation | SELECTIVE ANDROGEN RECEPTOR MODULATOR AND MEDICAL APPLICATIONS THEREOF |
| EP2286808A1 (en) * | 2009-08-18 | 2011-02-23 | Rheinische Friedrich-Wilhelms Universität | Cytohesin inhibitors |
| DE102010013716A1 (en) * | 2010-03-31 | 2011-10-06 | Rheinische Friedrich-Wilhelms-Universität Bonn Körperschaft des öffentlichen Rechts | Use of amide compounds in combination with epidermal growth factor receptor inhibitor comprising gefitinib and/or erlotinib for the treatment of cancer e.g. lung cancer, colon cancer, bladder cancer, breast cancer and/or ovarian cancer |
| AU2011337004A1 (en) * | 2010-12-03 | 2013-07-11 | Allergan, Inc. | Novel phenyl oxadiazole derivatives as sphingosine 1-phosphate (S1P) receptor modulators |
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| C41 | Transfer of patent application or patent right or utility model | ||
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Inventor after: Wang Tao Inventor before: Zhang Huan |
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Effective date of registration: 20160224 Address after: 273200 Surabaya County Chinese medicine hospital, 092 Si Si Road, Si county, Jining, Shandong, Surabaya Applicant after: Wang Tao Address before: 200062 East China Normal University, Putuo District, Zhongshan North Road, 3663, Shanghai Applicant before: Zhang Huan |
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