CN104706648B - Purposes of the albiflorin in anti-laryngocarcinoma medicament is prepared - Google Patents
Purposes of the albiflorin in anti-laryngocarcinoma medicament is prepared Download PDFInfo
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- CN104706648B CN104706648B CN201510043906.6A CN201510043906A CN104706648B CN 104706648 B CN104706648 B CN 104706648B CN 201510043906 A CN201510043906 A CN 201510043906A CN 104706648 B CN104706648 B CN 104706648B
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
The invention discloses the purposes of albiflorin or its pharmaceutically acceptable salt, enantiomer or racemic mixture in the medicine for preparing prevention and/or treatment laryngocarcinoma.Inside and outside is expected to develop anti-cancer agent, new selection is provided for clinical treatment tumour it is demonstrated experimentally that the albiflorin has definite antitumor activity.
Description
The application is Application No. 201310180327.7, and the applying date is on May 15th, 2013, entitled " Chinese herbaceous peony
The divisional application of the Chinese invention patent application of purposes of the glycosides compound in antineoplastic is prepared ".
Technical field
The invention belongs to field of antineoplastic medicaments, is related to purposes of the paeoniflorin compound in antineoplastic is prepared,
More particularly to purposes of the albiflorin in antineoplastic is prepared.
Background technology
Tumour is body under the effect of various carcinogenic factors, and cell loses the normal tune grown to it on gene level
Control, the neoformation for causing its clonal abnormality hyperplasia and being formed, shows as lump.Tumour cell is in formalness, metabolism and work(
Energy aspect is different from normal cell, and continuous multiplication is presented more.Counted according to valid data, tumour is the current threat whole world mankind
First of three big factors of life and health, so the research and development of antineoplastic turn into focus in recent years.
According to the traditional classification and progress of antineoplastic, conventional antineoplastic can be divided into following several big
Class：First, cell toxicity medicament, including destroy the medicine (such as endoxan, Irinotecan) of DNA structure and function, influence nucleic acid life
The medicine (such as 5 FU 5 fluorouracil, cytarabine, methopterin) of thing synthesis；2nd, the medicine of hormonal balance is influenceed, including it is anti-female
Hormone medicine (such as Toremifene), antiandrogens (such as Bicalutamide) and arimedex (such as Letrozole)
Deng；3rd, other and ancillary drug, including body's immunity conditioning agent (such as interleukin, interferon), BRM
(such as Erlotinib, Gefitinib), cell-differentiation inducers (such as vitamin A acid, arsenious acid), folic acid resisting preparation (Alimta), Dan Ke
Grand antibody (such as Arastin) and auxiliary analgesia, antiemetic, leucocyte rise medicine.But above medicine is more or less present
Side effect, the middle severe digestive system of patient can be triggered to react (such as pernicious vomiting, stomatitis), bone as cell toxicity medicament
Marrow suppresses (such as Neuroleptic Leukocytopenia, decrease of platelet) and organ toxicity's (such as neurotoxicity, liver renal toxicity), hormonal balance interference medicine
Thing can then cause the light moderate gastrointestinal reaction of patient, reproductive system damage even mental depression symptom, most conditioning agents and lure
The different degrees of dermoreaction of patient and liver and kidney dysfunction can also be triggered by leading agent etc..Such as Irinotecan (Irinotecan
Hydrochloride) be usually used in being grown up the treatment of Metastatic Colorectal Cancer, effect is than more significant, but after medication, 20% patient
There is gastrointestinal side effect --- severe diarrhea, neutrophilic granulocytopenia, 9% patient occurred in 78.7% patient
Occur of short duration serious cholinergic syndrome (.Science such as Bret Wallace, 330,2010.；Traditional Chinese medicines in the such as grandson's Yi
Room, 18 (35), 2007.；The such as Wu Yuhong Anhui medicine, 14 (10), 2010.)；Alimta (Pemetrexed disodium,
Alimta) it is first anti-pleural mesothelium tumor medicine, it can cause the bone marrow suppression of patient, including Neutrophilic granulocytopenia, blood
Platelet is reduced, anaemia or pancytopenia, the infull person of Liver and kidney function avoid use (such as Zheng Hang treatment and prevention of tumour is studied, 34 (4),
2007.；The healthy digest in the such as Wang Jianying China and foreign countries, 12,2011.)；Arastin (Bevacizumab, Avastin) is blood vessel endothelium
The monoclonal antibody of growth factor VEGF, by combining VEGF and preventing it from being combined with the acceptor of endothelial cell surface, reduce
The generation of capilary simultaneously inhibits metastatic lesion to be in progress.But its side effect is it is obvious that comprehensive including gastric-intestinal perforation, wound dehiscence
Close (the .Clinical such as Eric O.Gamboa such as disease, bleeding, hypertensive crisis, nephrotic syndrome and congestive heart failure
Colorectal Cancer,9(1),2010；The .British Journal of such as A Mailliez Cancer, 103,2010；
The .Oncology such as Sanjaykumar Hapani, 79,2010).
By contrast, infringement of the anti-tumor Chinese medicine to body is then smaller, and the mechanism of action of anti-tumor Chinese medicine relates generally to carefully
Cytotoxicity, improve immunity of organisms, inducing apoptosis of tumour cell and differentiation and suppress neonate tumour blood vessel etc..In
The effect of medicine and action character, anti-tumor Chinese medicine can be divided into following a few major classes：First, antipyretic and antidotal type, such as radix scutellariae, folium isatidis；
2nd, blood-activating stasis-removing kind, such as rheum officinale, the red sage root；3rd, righting reinforcing class, such as ginseng, the Radix Astragali, asparagus fern；4th, reducing phlegm and resolving masses class, such as half
Summer, Snakegourd Fruit, rhizoma arisaematis；5th, promoting diuresis to clear away damp pathogen class, such as Poria cocos, plantain seed, Zhai Mai；6th, external application type medicine, such as realgar, vomiting nut.
Part active ingredient in above-mentioned anti-tumor Chinese medicine, as the normal quilt of the taxol (taxol) in Japanese yew (Taxus brevifolia)
People are used for antitumor research, and achieve the effect of preferable (the Chinese Clinical rehabilitations such as sunshine Tang Dynasty, 27,2006.；Jiang Zhiwu
Deng Heilungkiang scientific and technological information, 7,2010；The .Cancer such as Pluznik, DH Research, 54 (15), 1994).Accordingly, with respect to
The further investigation of anti-tumor Chinese medicine active ingredient has important theoretical significance and Clinical significance of MG.
However, because the chemical composition in most of Chinese medicines is complicated, separating-purifying is difficult, and quality control is limited and drug effect
It is still unintelligible with the mechanism of action, magnanimity screening antineoplastic effective composition be not easy very much, so on anti-tumor Chinese medicine effectively into
The research divided is in the prevalence of many deficiencies and limitation.Such as the taxol extracted from Japanese yew is the specificity stabilization of micro-pipe
Agent, the assembling of micro-pipe can be promoted and keep microtubule stabilization, the accumulation of these micro-pipes disturbs the various functions of cell, particularly made
Cell division stops at m period, so as to block the proper splitting of cell, has played the effect of anticancer.But taxol
Side effect to patient is larger, and common adverse reactions have allergic reaction (incidence is up to 39%), bone marrow suppression (serious neutral grain
Cell incidence is 47%, serious blood platelet reduce incidence for 5%), (peripheral neuropathy incidence is neurotoxicity
62%), (nausea, vomiting, diarrhoea and mucositis incidence are respectively for Cardiovascular Toxicity (incidence 55%), gastrointestinal reaction
59%, 43% and 39%) and alopecia (incidence is up to more than 80%) etc. (the China Dispensaries such as Ye Dongmei, 29,2011.；Ma Lian
The medicine world such as suitable, 3,2009；The .Cancer such as Derry, WB Research, 58 (6), 1998.).
Therefore, study of pharmacy personnel still are being directed to developing new anti-tumor Chinese medicine active ingredient.
The root of herbaceous peony be ranunculaceae plant Chinese herbaceous peony (Paeonia albiflora Pall) root, it is known that pharmacological action include town
Bitterly, calm, anticonvulsion, anti-inflammatory, resisting pathogenic microbes and protect liver, also there is effect to immune system, smooth muscle, can clinically apply
In anti-epileptic, analgesia, only drug rehabilitation, dizziness, treatment rheumatoid arthritis, bacillary dysentery and enteritis, virus hepatitis and
Geriatric disease, also there is the flocculation of sulfuric-resisting barium and dissolving mucus.One of active component of the root of herbaceous peony is Chinese herbaceous peony glycoside
Compound, with albiflorin (the entitled Albiflorin of English；English alias Paeonilactone C；Abbreviation AL) and Paeoniflorin
(the entitled Paeoniflorin of English) is representative.It is an object of the invention to provide the new therapeutic uses of paeoniflorin compound,
New selection is provided for the prevention and treatment of clinical tumor.
The content of the invention
It is an object of the invention to provide the new anti-tumor medical application of albiflorin.
In order to realize foregoing invention purpose, present invention employs following technical scheme：
Structural formula I albiflorin or its pharmaceutically acceptable salt, enantiomer or racemic mixture are being prepared in advance
Purposes in anti-and/or treatment tumour medicine, the tumour is laryngocarcinoma,
In purposes of the present invention, the pre- preventing tumor refers to treat precancerous lesion.
In purposes of the present invention, the medicine is clinically acceptable any formulation.Preferably, the formulation includes
Through gastrointestinal administration preparation and non-through gastrointestinal administration preparation.It is furthermore preferred that described be selected from powder, piece through gastrointestinal administration preparation
Agent, granule, capsule, dripping pill, emulsion or supensoid agent；It is described it is non-through gastrointestinal administration preparation be selected from injection, spray, bolt
Agent, filling agent, patch or ointment.
In purposes of the present invention, albiflorin can as it is described prevention and/or tumor it is unique
Active component；The prevention and/or tumor can also be prepared together with other materials.
Experiment in vitro shows that albiflorin can significantly inhibit intestinal cancer, breast cancer, cervical carcinoma, rhabdomyosarcoma, nasopharynx
The kinds of tumors such as cancer, cancer of pancreas, laryngocarcinoma, prostate cancer, lung cancer, neuroblastoma, kidney and adrenocortical tumor, have wide
The anti-tumor function of spectrum；Albiflorin enables in particular to significantly inhibit intestinal cancer, cancer of pancreas, laryngocarcinoma, cervical carcinoma, breast cancer and forefront
Gland cancer.Specifically,
1st, albiflorin suppresses tumor cell proliferation experiment
MTT testing results show that albiflorin is to colon-cancer cell HT29, colon-cancer cell CT26, human rhabdomyosarcoma cells
A204, nasopharyngeal carcinoma cell CNE-2Z, laryngeal cancer cell Hep2, pancreatic cancer cell PANC1, prostate gland cancer cell DU145, cervical carcinoma are thin
Born of the same parents Hela, breast cancer cell MDA231, the propagation of breast cancer cell T47D and breast cancer cell MCF7, which have, significantly inhibits effect.
Wherein, colon-cancer cell HT29, pancreatic cancer cell PANC1, laryngeal cancer cell Hep2, cervical cancer cell Hela, breast cancer cell
MDA231 and prostate gland cancer cell DU145 are particularly sensitive to albiflorin.
2nd, albiflorin suppresses tumor cell migration experiment
Tumor cell migration test experience result shows, albiflorin to colon-cancer cell CT26, cervical cancer cell Hela,
Neuroblastoma cell SY5Y, breast cancer cell MDA231, breast cancer cell T47D, breast cancer cell MCF7, band muscle
Oncocyte A204, kidney Wilms cells G401, nasopharyngeal carcinoma cell CNE2Z, prostate gland cancer cell DU145, laryngeal cancer cell Hep2,
Lung cell A549, lung carcinoma cell LLC, pancreatic cancer cell PANC1 and adrenal cortex oncocyte SW13 etc. migration have aobvious
Write inhibitory action.Wherein, albiflorin is to cervical cancer cell Hela, colon-cancer cell CT26, breast cancer cell MDA231, nasopharynx
The inhibitory action of cancer cell CNE2Z and pancreatic cancer cell PANC1 migrations is especially notable.
3rd, tumorigenic effect is prevented
Gene mutation agent oxidized azoethane (AOM) inducing mouse enteritis is handled using albiflorin to primary intestinal cancer to turn
The experimental result of change shows that albiflorin turns in treatment intestinal cancer precancerous lesion, prevention and blocking from hyperenteritis to intestinal cancer
Obvious action is played during change.
Brief description of the drawings
Fig. 1：Influence (Transwell detection) of the albiflorin to tumor cell migration ability.
Fig. 2：Influence (Scratch Analysis detection) of the albiflorin to tumor cell migration ability.
Fig. 3：The influence of albiflorin and TGP to tumor cell migration is compared (Transwell detections).
Fig. 4：The blocking effect experimental result that albiflorin converts to enteritis to intestinal cancer：Wherein,
4A：The colon photo of three groups of mouse；4B：Colon's HE coloration results of three groups of mouse.
Embodiment
Illustrate the present invention referring to specific embodiment.It will be appreciated by those skilled in the art that these embodiments are only
For illustrating the present invention, its scope not limiting the invention in any way.
In following embodiments albiflorin used purchased from Shanghai Ding Rui Chemical Co., Ltd.s (purity be 98% with
On), peony root total glycosides capsules (Pa Fulin) are purchased from Ningbo LiHua Pharmaceutical Co., Ltd.
Influence of the albiflorin of embodiment 1 to tumor cell proliferation
Experimental program：It is real using tetrazolium bromide (3- (4,5- dimethylthiazole -2) -2,5- diphenyltetrazolium bromide bromides, MTT)
Test, it is thin that albiflorin handles human rhabdomyosarcoma cells A204, nasopharyngeal carcinoma cell CNE-2Z, colon-cancer cell CT26, intestinal cancer respectively
Born of the same parents HT29, neuroblastoma cell SY5Y, laryngeal cancer cell Hep2, pancreatic cancer cell PANC1, cervical cancer cell Hela, mammary gland
Cancer cell MDA231, breast cancer cell T47D, breast cancer cell MCF7, Skin Squamous Cell Carcinoma cell A431, kidney Wilms cells
G401, prostate gland cancer cell DU145 about 24 hours；MTT is dyed 4 hours afterwards, dimethyl sulfoxide (DMSO) (DMSO) dissolving, ELIASA
Absorption photometric value is surveyed under 570nm.
Experimental result：It was found that albiflorin is to pancreatic cancer cell PANC1, colon-cancer cell CT26, colon-cancer cell HT29, larynx
Cancer cell Hep2, cervical cancer cell Hela, breast cancer cell MDA231, prostate gland cancer cell DU145, nasopharyngeal carcinoma cell CNE2Z,
All there is human rhabdomyosarcoma cells A204, breast cancer cell T47D and breast cancer cell MCF7 cell propagation significant suppression to make
With.Wherein, albiflorin to colon-cancer cell HT29, pancreatic cancer cell PANC1, laryngeal cancer cell Hep2, cervical cancer cell Hela,
Breast cancer cell MDA231 and prostate gland cancer cell DU145 effect are most sensitive, and concrete outcome is shown in Table 1.
Influence (IC of the albiflorin of table 1 to tumor cell proliferation50)
(Transwell is detected and Scratch Analysis for influence of the albiflorin of embodiment 2 to tumor cell migration
Detection)
Experimental program：1) using cell migration detection (Transwell) experiment, to A549, LLC, Hela, SY5Y, CT26,
T47D, MCF7, MDA231, A204, G401, CNE-2Z, DU145, Hep2, PANC1 and SW13 tumour cell dosing peony lactone
Glycosides (selects the μ g/ml of safe dose 20) after 24 hours, and no water-ice methanol fixes 20 minutes, violet staining 15 minutes, 100 times of light
Mirror is taken pictures, and detects the number of cell migration.
2) use cell migration test experience (Scratch Analysis), to Hela, LLC, A549, SY5Y, CT26,
MCF7, MDA231 and T47D cell add albiflorin 6 hours and 24 hours (selecting the μ g/ml of safe dose 20), 40 times of light microscopics
Take pictures, detection iuntercellular away from.
Experimental result：1) Transwell experimental results are shown, albiflorin (AL) can significantly inhibit lung carcinoma cell
A549, lung carcinoma cell LLC, cervical cancer cell Hela, neuroblastoma cell SY5Y, colon-cancer cell CT26, breast cancer T47D,
Breast cancer MCF7, breast cancer MDA231, human rhabdomyosarcoma cells A204, kidney Wilms cells G401, nasopharyngeal carcinoma cell CNE-
2Z, prostate gland cancer cell DU145, laryngeal cancer cell Hep2, pancreatic cancer cell PANC1 and adrenal cortex oncocyte SW13 cells
Migration, shows as cell number in administration group and is substantially reduced relative to control group, wherein, albiflorin is to cervical cancer cell
Hela, colon-cancer cell CT26, breast cancer cell MDA231, nasopharyngeal carcinoma cell CNE2Z and pancreatic cancer cell PANC1 tumour cells move
The inhibitory action of shifting is especially notable.It is specifically shown in Fig. 1.
2) Scratch Analysis experimental results are shown, for control group, albiflorin administration group is drawn
Trace width significantly increases with respect to Normal group, it was demonstrated that albiflorin can suppress the migration of surveyed tumour cell.Specifically
See Fig. 2.
In summary, migration of the experimental result prompting albiflorin to tumour cell has extensive, significant suppress
Effect.
The albiflorin of embodiment 3 is compared with the effect that TGP suppresses tumour
1st, the influence of albiflorin and TGP to tumor cell proliferation is compared (MTT)
Experimental program：It is real using tetrazolium bromide (3- (4,5- dimethylthiazole -2) -2,5- diphenyltetrazolium bromide bromides, MTT)
To test, albiflorin and TGP handle A204, CNE-2Z, CT26, Hep2 and PANC1 tumour cell 24 hours respectively, it
MTT is dyed 4 hours afterwards, dimethyl sulfoxide (DMSO) (DMSO) dissolving, and absorption photometric value is surveyed under ELIASA 570nm.
Experimental result：It was found that albiflorin and TGP are to human rhabdomyosarcoma cells A204, nasopharyngeal carcinoma cell CNE-
2Z, colon-cancer cell CT26, laryngeal cancer cell Hep2 and pancreatic cancer cell PANC1 propagation are all inhibited, but in Chinese herbaceous peony
IC of the ester glycosides to these tumours50(half inhibiting rate) value is entirely below TGP, illustrates albiflorin to rhabdomyosarcoma
Cell A204, nasopharyngeal carcinoma cell CNE-2Z, colon cancer cell CT26, laryngeal cancer cell Hep2 and pancreatic cancer cell PANC1 tumours are thin
The inhibitory action of born of the same parents' propagation is better than TGP.Concrete outcome is shown in Table 2.
Influence (the IC of the albiflorin of table 2 and TGP to tumor cell proliferation50)
2nd, the influence of albiflorin and TGP to tumor cell migration is compared (Transwell)
Experimental program：Using cell migration detect (Transwell) experiment, to A204, CNE-2Z, CT26, DU145,
Hep2, PANC1 and SW13 tumour cell are separately added into albiflorin and TGP acts on 24 hours and (selects safe dose 10
μM), no water-ice methanol fixes 20 minutes, violet staining 15 minutes, and 100 times of light microscopics are taken pictures and detect the number of migrating cell.
Experimental result：Albiflorin and TGP can be significantly inhibited to human rhabdomyosarcoma cells A204, nasopharynx
Cancer cell CNE-2Z, colon-cancer cell CT26, prostate gland cancer cell DU145, laryngeal cancer cell Hep2, pancreatic cancer cell PANC1 and kidney
Upper gland cortical tumor SW13 tumor cell migrations, show as cell number in administration group and are substantially reduced relative to control group；But Chinese herbaceous peony
Lactone glycoside is to human rhabdomyosarcoma cells A204, nasopharyngeal carcinoma cell CNE-2Z, colon-cancer cell CT26, prostate gland cancer cell DU145, larynx
The inhibitory action of cancer cell Hep2, pancreatic cancer cell PANC1 and adrenocortical tumor SW13 tumor cell migrations is all strong excessively white
The total glycosides of Chinese herbaceous peony.It is specifically shown in Fig. 3.
Therapeutic action of the albiflorin of embodiment 4 to intestinal cancer precancerous lesion
Experimental program：BALB/C mice is divided into 3 groups：Normal group, model group and albiflorin intervention group, every group 5.Mould
Type group and intervention group mouse peritoneal injection gene mutation agent oxidized azoethane (AOM, 20mg/Kg).Albiflorin intervention group
In the 2nd day intraperitoneal injection (100mg/Kg) of AOM injections, once two days, totally 3 times.Model group is without any drug-treated.
AOM is continuously drunk 7 days after being administered one week with 3% sodium dextran sulfate (DSS) substitution normal drinking water, mouse；Gain afterwards just
Normal drinking water, mouse are continuously drunk 14 days.From AOM injections, drink DSS water and be repeated 3 times altogether to the normal water cycle of 14 days is drunk,
The all normal administration in 3 cycles of albiflorin intervention group.Normal group mouse diet and drinking-water, it is not added with any processing.
During 3 end cycle, mouse is put to death, cuts intestinal tissue, prepare pathological section, carry out HE dyeing.
Experimental result：Outward appearance shows that the colon even thickness of normal mouse, mucous membrane is without hyperemia.Relative to normal mouse,
Model group mouse Colon mucous membrane is congested obvious, and enteron aisle thickness is uneven, and has generated several tumours；And albiflorin intervention
Group mouse Colon thickness is more uniform, without obvious blutpunkte, also has no that tumour generates, is specifically shown in accompanying drawing 4A.
Pathological section HE coloration results show that normal mouse intestinal tissue gland structure is complete and is evenly distributed, without obvious scorching
Property cellular infiltration, no mucous membrane bleed bottom and ulcerative phenomena.There is mucosa ulcer in model group mouse intestinal tissue, and multiple bodies of gland lack companion
Inflammatory cell infiltration, cancer cell infiltrate the characteristic feature that intestinal cancer in situ to intestinal mucosa layer and submucosa, is presented.And peony lactone
Though there is stove inflammatory cell infiltration in glycosides intervention group mouse intestinal tissue, indivedual bodies of gland missings, without obvious cancer cell infiltration phenomenon,
The characteristic feature of enteritis is shown, is specifically shown in accompanying drawing 4B.
As a result show, albiflorin is played in conversion process of the mouse from hyperenteritis to intestinal cancer and is effectively blocked
Effect, play an important roll to treatment precancerous lesion.
Summarize, albiflorin can effectively suppress intestinal cancer, lung cancer, cancer of pancreas, laryngocarcinoma, cervical carcinoma, breast cancer, prostate
The growth and transfer of cancer, nasopharyngeal carcinoma, rhabdomyosarcoma, lung cancer, neuroblastoma, kidney and adrenocortical tumor, special energy
Enough growths and transfer for effectively suppressing intestinal cancer, cancer of pancreas, laryngocarcinoma, cervical carcinoma, breast cancer and prostate cancer.Albiflorin can also
Intestinal cancer precancerous lesion is enough treated, blocks conversion of the hyperenteritis to intestinal cancer.
Claims (6)
1. the albiflorin of structural formula 1 or its pharmaceutically acceptable salt, enantiomer or racemic mixture are preparing prevention
And/or the purposes in the medicine for the treatment of laryngocarcinoma,
2. purposes according to claim 1, it is characterised in that：The prevention laryngocarcinoma refers to treat precancerous lesion.
3. purposes according to claim 1, it is characterised in that：The medicine is clinically acceptable any formulation, is wrapped
Include through gastrointestinal administration preparation and non-through gastrointestinal administration preparation.
4. purposes according to claim 3, it is characterised in that：It is described through gastrointestinal administration preparation optionally from powder, tablet,
Granule, capsule, dripping pill, emulsion or supensoid agent.
5. purposes according to claim 3, it is characterised in that：It is described it is non-through gastrointestinal administration preparation optionally from injection,
Spray, suppository, filling agent, patch or ointment.
6. according to the purposes described in any one of claim 1 to 5, it is characterised in that：Albiflorin as it is described prevention and/or
The sole active agent of laryngeal cancer medicine is treated, or the medicine of prevention and/or the treatment laryngocarcinoma is prepared together with other materials.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510043906.6A CN104706648B (en) | 2012-05-15 | 2013-05-15 | Purposes of the albiflorin in anti-laryngocarcinoma medicament is prepared |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210151425 | 2012-05-15 | ||
| CN2012101514253 | 2012-05-15 | ||
| CN201510043906.6A CN104706648B (en) | 2012-05-15 | 2013-05-15 | Purposes of the albiflorin in anti-laryngocarcinoma medicament is prepared |
| CN201310180327.7A CN103417561B (en) | 2012-05-15 | 2013-05-15 | Paeoniflorin compound is preparing the purposes in antitumor drug |
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| CN201310180327.7A Division CN103417561B (en) | 2012-05-15 | 2013-05-15 | Paeoniflorin compound is preparing the purposes in antitumor drug |
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| CN201510043906.6A Expired - Fee Related CN104706648B (en) | 2012-05-15 | 2013-05-15 | Purposes of the albiflorin in anti-laryngocarcinoma medicament is prepared |
| CN201310180327.7A Expired - Fee Related CN103417561B (en) | 2012-05-15 | 2013-05-15 | Paeoniflorin compound is preparing the purposes in antitumor drug |
| CN201510043887.7A Expired - Fee Related CN104706647B (en) | 2012-05-15 | 2013-05-15 | Purposes of the albiflorin in anti-pancreatic cancer medicament is prepared |
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| CN201510043887.7A Expired - Fee Related CN104706647B (en) | 2012-05-15 | 2013-05-15 | Purposes of the albiflorin in anti-pancreatic cancer medicament is prepared |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105273015B (en) * | 2015-11-18 | 2018-11-30 | 上海同田生物技术股份有限公司 | A kind of preparation method of high-purity Paeoniflorin and albiflorin |
| CN107397752A (en) * | 2016-10-11 | 2017-11-28 | 张作光 | Purposes of the albiflorin in the product for improving gut flora systemic-function is prepared |
| EP3566707A4 (en) * | 2017-01-06 | 2020-08-19 | Zuoguang Zhang | Application of albiflorin as indoleamine 2,3-dioxygenase (ido) inhibitor |
| CN108823157B (en) * | 2018-07-05 | 2020-06-05 | 浙江大学 | Application of crocin II and albiflorin in promoting proliferation of mesenchymal stem cells cultured in vitro and inhibiting replicative senescence |
| WO2020020343A1 (en) * | 2018-07-26 | 2020-01-30 | 张作光 | Use of total glucosides of paeony as potentiating agent for immunological checkpoint inhibitor for tumor treatment |
| CN109481453A (en) * | 2019-01-07 | 2019-03-19 | 安徽医科大学 | A kind of purposes of paeoniflorins CP-25 |
| CN109481452A (en) * | 2019-01-07 | 2019-03-19 | 安徽医科大学 | A kind of purposes of Paeoniflorin -6-O '-benzene sulfonate |
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|---|---|---|---|---|
| US20030166583A1 (en) * | 2002-02-22 | 2003-09-04 | Oliver Yoa-Pu Hu | Dermal cytochrome P450 1A inhibitors and enhancers |
| CN101601737A (en) * | 2009-02-10 | 2009-12-16 | 魏伟 | A kind of Radix Paeoniae Alba total glucosides and effective ingredient microemulsion thereof |
| CN102319302A (en) * | 2011-09-27 | 2012-01-18 | 辽宁大学 | Total paeony glucoside self-microemulsifying soft capsules and preparation method thereof |
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| US7930673B2 (en) * | 2007-05-29 | 2011-04-19 | Magma Design Automation, Inc. | Method for automatic clock gating to save power |
| CN101156863B (en) * | 2007-09-30 | 2010-09-08 | 广州艾格生物科技有限公司 | A medicine composition for treating cardiac and cerebral vascular disease and its medical usage |
| CN101385736A (en) * | 2008-10-24 | 2009-03-18 | 南方医科大学 | Use of penoniflorin in preparing medicine for preventing and treating depression and medicine composition thereof |
| CN101940583A (en) * | 2009-07-10 | 2011-01-12 | 张作光 | Antidepressant application of composition of paeoniflorin and albiflorin and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030166583A1 (en) * | 2002-02-22 | 2003-09-04 | Oliver Yoa-Pu Hu | Dermal cytochrome P450 1A inhibitors and enhancers |
| CN101601737A (en) * | 2009-02-10 | 2009-12-16 | 魏伟 | A kind of Radix Paeoniae Alba total glucosides and effective ingredient microemulsion thereof |
| CN102319302A (en) * | 2011-09-27 | 2012-01-18 | 辽宁大学 | Total paeony glucoside self-microemulsifying soft capsules and preparation method thereof |
Non-Patent Citations (2)
| Title |
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| 芍药苷和芍药内酯的微生物转化;刘鑫鑫等;《中国中药杂志》;20100430;第35卷(第7期);第872-875页 * |
| 赤芍总苷抗S180和K562肿瘤细胞作用机制的实验研究;许惠玉;《中国博士学位论文全文数据库 医药卫生科技辑》;20081215;第40-41，44页 * |
Also Published As
| Publication number | Publication date |
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| CN103417561A (en) | 2013-12-04 |
| CN103417561B (en) | 2015-10-28 |
| CN104706647B (en) | 2017-12-12 |
| CN104706648A (en) | 2015-06-17 |
| CN104706647A (en) | 2015-06-17 |
| HK1191868A1 (en) | 2014-08-08 |
| WO2013170637A1 (en) | 2013-11-21 |
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