WO2002017931A1 - Utilisation d'un ou de plusieurs extraits de tripterygium wilfordii hook.f pour la preparation de medicaments destines a prevenir et a traiter des troubles du systeme nerveux - Google Patents

Utilisation d'un ou de plusieurs extraits de tripterygium wilfordii hook.f pour la preparation de medicaments destines a prevenir et a traiter des troubles du systeme nerveux Download PDF

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WO2002017931A1
WO2002017931A1 PCT/CN2000/000258 CN0000258W WO0217931A1 WO 2002017931 A1 WO2002017931 A1 WO 2002017931A1 CN 0000258 W CN0000258 W CN 0000258W WO 0217931 A1 WO0217931 A1 WO 0217931A1
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triptolide
disease
cells
neurons
extracts
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PCT/CN2000/000258
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English (en)
Chinese (zh)
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Xiaomin Wang
Jisheng Han
Fengqiao Li
Duanduan Ma
Yanwen Jiang
Rujin Tian
Xiaodong Wu
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Xiaomin Wang
Jisheng Han
Fengqiao Li
Xiaodong Wu
Duanduan Ma
Yanwen Jiang
Rujin Tian
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Priority to PCT/CN2000/000258 priority Critical patent/WO2002017931A1/fr
Publication of WO2002017931A1 publication Critical patent/WO2002017931A1/fr

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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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/37—Celastraceae (Staff-tree or Bittersweet family), e.g. tripterygium or spindletree

Definitions

  • tripterygium plant extract in prevention and treatment of nervous system diseases
  • the present invention relates to the use of tripterygium plant extracts in the preparation of a medicament for the prevention and treatment of neurological diseases.
  • the neurological diseases include Alzheimer's disease, Parkinson's disease, and Huntington's neurodegenerative disease.
  • the invention also relates to a medicament for the prevention and treatment of neurological diseases.
  • Senile neurodegenerative diseases are a type of neurological diseases that appear with age and are characterized by progressive necrosis of certain neurons in a specific region of the brain parenchyma, with learning and memory disorders or motor, behavioral, and psychological disorders as the main manifestations.
  • AD Alzheimer's disease
  • PD Parkinson's disease
  • the PD is a common extrapyramidal degenerative disease of the nervous system that occurs frequently in the middle and old age, and patients often experience symptoms such as tremor, muscle stiffness, and bradykinesia.
  • the main pathological change of PD is dopamine (DA) in the mesencephalic and substantia nigra striatum pathways, which can cause neuronal degeneration and necrosis, leading to a significant reduction in striatum DA content. Therefore, supplementation with DA precursor L-DOPA (L-DOPA) can alleviate the symptoms of PD.
  • L-DOPA itself cannot delay the further necrosis of dopaminergic neurons and has other side effects. Therefore, people have been trying to find a drug that can delay the degeneration and necrosis of DA neurons and have nutritional protective effects on DA neurons.
  • Neurotrophic factors are a class of specific peptides or proteins that maintain and promote the normal survival, growth and differentiation of nerve cells and promote their regeneration in the case of nerve damage. Including nerve growth factor (NCF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophic Factor-3 (neuro'trophic-3, NT-3) and so on.
  • NVF nerve growth factor
  • BDNF brain-derived neurotrophic factor
  • GDNF glial cell line-derived neurotrophic factor
  • neurotrophic Factor-3 neurotrophic Factor-3
  • NT-3 neurotrophic Factor-3
  • GDNF can be more specific-nutritionally and protect DA neurons, and can promote the regeneration of DA neurons, which has become a hot spot in the current prevention and treatment of PD.
  • NGF, GDNF, BDNF, etc. are macromolecular proteins that cannot penetrate the blood-brain barrier and should not be administered peripherally.
  • the foreign GDNF gene is introduced into the brain by vectors such as engineered cells and adenovirus, so that it can express and secrete GDNF protein for a long time, and play a role in nutrition, protection and repair; 2. Look for small molecules that have neurotrophic effects or promote the expression of endogenous neurotrophic factors.
  • Alzheimer's disease also known as senile dementia
  • senile dementia is a primary cerebral degenerative disease that occurs in middle-aged and elderly people.
  • the main clinical manifestations are cognitive and learning and memory dysfunction, and even emotional or personality defects.
  • the main pathological changes of AD are senile plaques (also known as amyloid plaques), nerve fiber tangles, and selective cholinergic neurons and synaptic loss.
  • Pathological anatomy showed that neurons in the neocortex, hippocampus, Menet basal nucleus, and blue nucleus of AD patients had a large number of neurons, especially the reduction of acetylcholinergic nerves in the cortex and hippocampus.
  • acetylcholine is a neurotransmitter that promotes learning and memory, and M-cholinergic synapses are the basis of memory. Degeneration of cholinergic neurons is considered to be an important pathological factor causing dementia. Therefore, drugs that can prevent cholinergic neurodegeneration are the first choice for future AD treatment. NGF has been shown to be effective in preventing degeneration and death of basal forebrain cholinergic neurons in animals that mimic AD disease. However, due to the large molecular weight of NGF, it is difficult to reach the brain by oral or injection. Some people tried to repeatedly inject NGF into the brain with lateral ventricle intubation, and received positive results.
  • NGF administration In order to solve the problems caused by repeated intracerebral administration, in recent years, researchers have been trying to find alternative routes for NGF administration. These pathways include: 1. Transplantation of genetically engineered NGF-producing cells in the brain; 2. Drugs that promote NGF biosynthesis in the brain.
  • CsA can slow the degeneration of DA neurons induced by 6-hydroxydopamine (6-HDA) in the mouse brain.
  • FK506 and CsA can also protect against DA depletion in MP57-induced C57 / BLACK Parkinson's disease mice. Both CsA and FK506 can significantly increase the content of DA and D0PAC in the striatum, which is of significant significance. Of the two, FK506 is particularly important. CsA 'also protects against lack of brain tissue' after repeated blood perfusion injury.
  • CsA corresponds to Cyclophilin (Cyp)
  • FK506 and RAPA correspond to FK506 binding proteins.
  • FK506 binding protein, FKBP FK506 binding protein
  • the immunosuppressant specifically forms a complex with FKBP and Cyp, and then binds to phospholipase 2B (Calcineurin, CaN), which inhibits the activity of this enzyme to catalyze protein dephosphorylation.
  • CaN phospholipase 2B
  • Nitric oxide synthase N0S
  • the phosphorylated form of N0S will inhibit its catalytic activity, and immunosuppressants can increase NOS by
  • the degree of phosphorylation inhibits the generation of NO to block the neurotoxic effects of excessive glutamate; 2.
  • Growth-associated protein GAP-43
  • GAP-43 is involved in the growth of neurons and its phosphorylated form can enhance this growth-promoting effect.
  • Axon elongation can occur in PC12 cells under NGF stimulation.
  • Very low concentration (nmol level) of FK506 can increase the sensitivity of cells to NGF, induce axonal growth effect of PC12 cells, and increase the effect of NGF by 100 times. Therefore, drugs that selectively inhibit certain substrates of CaN, such as inhibitors of GAP-43 dephosphorylation, may have significant potential therapeutic value in the treatment of neurodegenerative diseases.
  • Tripterygium is a plant belonging to the genus Celastraceae (Tripterygium Wilfordii Hook, f). Tripterygium also includes T. Hypoglacum (Levi) Hutch and T. Regelli Sprague et Tak. , Have medicinal value. Tripterygium wilfordii contains alkaloids, diterpenes, triterpenes, and sesquiterpenes. Among them, diterpenes are the main active ingredients, and triterpenes and alkaloids are also active.
  • tripterygium Currently known monomeric constituents of tripterygium include triptolide, triptolide, triptolide, tripdiolide, and tripteride compounds such as triptolide and tripterylide Triterpenes such as tripterine are shown in Figure 1.
  • the extract of Tripterygium wilfordii has various pharmacological activities such as immunosuppressive, anti-inflammatory, anti-tumor and anti-fertility, especially the immunosuppressive effect is its main pharmacological activity. 06mg / kg ⁇ The strongest immunosuppressive activity of the monomer component extracted from tripterygium wilfordii is triptolide, and its immunosuppressed ED 50 3 ⁇ 4 0. 06mg / kg.
  • Tripterygium decoction, triptolide "total glycosides" (TII) or triptolide and triptolide have significantly inhibited the effects of concanavallin A (ConA) -induced mouse spleen cell secretion of IL-2 effect.
  • triptolide chlorolactone one of the main active ingredients of tripterygium wilfordii, has a dose-dependent two-way regulation effect on mouse spleen NK cell activity, indicating that tripterygium wilfordii is not only immunosuppressive.
  • the total extract of Tripterygium wilfordii was used clinically to treat rheumatoid arthritis and nephropathy such as chronic glomerulonephritis, nephrotic syndrome, and allergic purpura nephritis. In addition, it has certain effects on connective tissue diseases such as systemic lupus erythematosus, polymyositis, dermatitis, and some skin diseases.
  • the total extract of tripterygium wilfordii or its single body component has been used as a neuron protective agent for the prevention and treatment of senile neurodegenerative diseases, and there have been no reports so far. Summary of invention
  • An object of the present invention is to provide use of a tripterygium plant extract in the manufacture of a medicament for preventing and treating a nervous system disease.
  • Another object of the present invention is to provide a medicament for preventing and treating a nervous system disease.
  • the present invention provides a kind selected from triptolide, triptolide, triptolide, Triptolide triol, 16-hydroxy triptolide, triptolide, triptolide, and one or more of triptolide and triptolide are used in the preparation Application in medicine for preventing and treating neurological diseases.
  • the neurological disease may be Alzheimer's disease, Parkinson's disease, Huntington's neurodegenerative disease and spinal cord injury, or lateral spinal cord sclerosis disease.
  • the present invention also provides a medicament for the prevention and treatment of neurological diseases, which contains a drug selected from the group consisting of triptolide, triptolide, triptolide glycol, triptolide triol, 16-hydroxy triptolide Extracts of triptolide, triptolide, triptolide, and one or more of triptolide and triptolide.
  • a drug selected from the group consisting of triptolide, triptolide, triptolide glycol, triptolide triol, 16-hydroxy triptolide Extracts of triptolide, triptolide, triptolide, and one or more of triptolide and triptolide.
  • the above-mentioned medicine of the present invention may further contain a neurotrophic factor, so as to achieve a better therapeutic effect.
  • the neurotrophic factor may be a nerve growth factor, a glial-derived neurotrophic factor, a brain-derived neurotrophic factor, and / or a ciliary neurotrophic factor.
  • triptolide lactone (hereinafter referred to as 968) has a significant nutritional effect on cultured DA energy neurons.
  • 968 was cultured in DMEM containing 10% fetal bovine serum for 4 days at a lower concentration (0.01 ng / ml) and a higher concentration (0.1 ng / ml). surviving DA neurons than the control group were 87% and 29% lower than the additional 10- 13 mol / L to 968 can promote the growth of nerve cells, neurite length compared with the control group the 113% Gao.
  • the neurotrophic effect of 968 does not seem to be confined to DA energy neurons. At a very low concentration, 968 can promote the elongation of the primary cultured cortical neurons. This axonal growth-promoting effect of 968 is of great significance for the reconstruction of synapses between nerve cells in diseases such as PD, AD and spinal cord injury.
  • triptolide Another important feature of triptolide is its ability to antagonize the damage to nerve cells caused by some neurotoxins.
  • Environmental toxins, endogenous toxins, and excitatory neurotoxins are one of the important mechanisms for the pathogenesis of neurodegenerative diseases such as PD and AD.
  • Figure 1 shows the chemical structure of the main active monomer in the extract of Tripterygium wilfordii. Among them, (1) is triptolide, (2) is triptolide, (3) is triptolide triol, (4) is triptolide, (5) is triptolide diol, (6) is 16-hydroxytriptolide, and (7) is triptolide.
  • Figure 2 shows the effect of different concentrations of 968 on the survival of dopaminergic neurons in the brain of primary cultured rats. Counted dopaminergic neurons are TH immunohistochemically positive cells. Each point of data is the average count of three parallel experiments.
  • Figure 3 shows the effect of different concentrations of 968 on the survival percentage of rat dopaminergic neurons in the primary culture.
  • Figure 4 shows the effects of pretreatment with different doses of 968 on DA content in striatum of C57BL / 6J mice damaged by MPTP.
  • Figure 5 shows the effect of pretreatment with different doses of 968 on DA metabolic rate (DOPAC + HVA / DA) in the striatum of C57BL I 6J mice damaged by MPTP.
  • Experiment 1 In vitro Study of Triptolide on Protecting Dopaminergic Neurons
  • MPTP is a toxin that specifically damages DA neurons.
  • Peripheral injection can specifically penetrate the blood-brain barrier and specifically destroy nigrostriatal dopaminergic neurons.
  • C57BL I 6J mice, ip MFTP 30mg I kg body weight per day, for three consecutive days, can reduce the DA content in the striatum by more than 80%.
  • Inject 968 or saline once a day before MPTP damage after that, inject 968 or normal saline every morning, and then inject MPTP or normal saline for three days in the afternoon; continue to inject 968 or normal saline once a day until the day before the animal is sacrificed, and inject lld .
  • the HPLC method was used to detect the contents of DA and its metabolites HVA (vanillin) and D0PAC (dihydroxyphenylacetic acid) in the striatum of mice, and the ratio of DA, (HVA + DOPAC) / DA Calculations and statistical analysis were performed.
  • HVA and DOPAC are the final metabolites of DA in the brain.
  • (HVA + DOPAC) / DA ratio increases, indicating that the metabolic rate of DA is increased, and the production of metabolites is increased. It is more common when DA neurons are incompletely damaged.
  • 968 can reduce the ratio of (HVA + DOPAC) / DA, indicating that it can slow the DA metabolism renewal rate in DA neurons in MPTP-injured mice, thereby effectively protecting the survival of neurons. It has a certain protection for the damage of DA neurons in the midbrain of Parkinson mice caused by MPTP. ⁇ ⁇ Protective effect.
  • 968 does have a certain neurotrophic effect. According to the difference of the role of 968 in serum-free medium and serum-free medium, it is speculated that the mechanism may be to increase the susceptibility of neurons to serum nerve growth factor (NGF) and so on, thereby exerting neurotrophic effects. Effect of Experiment 3 968 on the synaptic length of mesencephalic neurons in primary cultured fetal rats.
  • NGF serum nerve growth factor
  • SD pregnant rats with fetal fetuses for 16 days Take the fetal rat midbrain for primary neuron culture.
  • the midbrain tissue is chopped, digested, and blown out to make it a single cell. It is planted at a density of 3 ⁇ 10 5 cells / well in 24 wells.
  • a culture plate First add 10% fetal bovine serum medium with DMEM, incubate at 37 ° C, 5% ⁇ 2 for 24 hours, then change to DMEM / F-12 (1: 1) medium, add! ⁇
  • the method of primary culture of fetal rat midbrain was the same as that in Example 3, except that the medium was changed to DMEM / F-12 + 1% [ ⁇ medium, and then treated with 968 for 7 days, and the culture solution was aspirated on the 8th day, and used Rinse in PBS. Add 0.01% pyridine orange staining, observe under a fluorescence microscope (100X), the nucleus shows green fluorescence, take three fields per well, and count with a manual counter.
  • AN0VA data were analyzed, and by Dunnet multiple comparison test, was found 10_ 12 -10- "mol / L 968 treated group was significantly higher number of viable cells, contribute to the survival of nerve cells 968 described in Table 4: treatment with different concentrations 968 Effect on Fetal Rat Midbrain Primary Cultured Neuronal Cell Survival ( ⁇ SF)
  • PC12 cells were cultured with RPMI 1640 + 10% newborn bovine serum, and then uniformly at a density of 1.5 ⁇ 10 5 Plant in a 96-well plate. After the cells adhere well, add 968 or ⁇ . After pretreatment for 2 hours, PCI2 cells were injured by adding dopaminergic neurotoxin MPP + 60 ⁇ 1 / L to the experimental group. We have demonstrated in other experiments that the median lethal concentration (LC 5 ) of MPP + injured PC12 cells is 60 ⁇ 1 / L. After 72 hours, the medium was aspirated, and 0.5 mg / ml of thiazole blue (MTT) 100 ⁇ l was added to each well, and incubated at 37 ° C for 4 hours.
  • MPP + 60 ⁇ 1 / L thiazole blue
  • the original yellow-green TT was catalyzed by the succinase enzyme in living cells.
  • An ELISA plate reader detects the absorbance of each well at a wavelength of 490 nm. Under the same conditions, the absorbance is directly proportional to the number of cells in each well. The ratio of the absorbance of the experimental group (including the control group and the 968 and. Treatment groups) to the MPP + uninjured group is the percentage of cell survival.
  • Table 5 lists the mean ⁇ standard deviation of the cell viability of 8 wells per group. * Indicates that after a fine OVA analysis, followed by Dunnet multiple comparison test, the difference with the control group is significant, * P ⁇ 0.05, * P ⁇ 0.01. The results showed that: 1CT 9 - l (T 7 mol / L and 968 have an antagonistic 7. Processing of MPP + toxicity in PC12 cells, so that cell viability was improved by about 30%.
  • DMEM / F-12 medium Isolate the cerebral cortex of 16-18d fetal rats under sterile conditions in pre-chilled DMEM / F-12 medium, carefully remove the pia mater and blood vessels, and transfer the brain tissue to another ice-containing DMEM / F-12 ( In a small beaker containing a volume fraction of 10% fetal bovine serum and 10% horse serum), gently blow 20-30 times with a pointed polished glass tube until all brain tissue is dispersed into a cell suspension and passed through a 200 mesh nylon sieve Filter to remove undigested tissue pieces, and use DMEM / F-12 medium for the filtrate (10% fetal bovine serum, 10% horse serum, 100kU. L- 1 streptomycin, pH 7. 2-7.
  • Taiwan After Pan-Ilan staining 500 cells were counted under an inverted phase-contrast microscope, and the stained cells were dead cells, and the density was adjusted to 1 ⁇ 10 9 cells.
  • 0.5 cell suspension was inoculated into 12.5 ⁇ ⁇ 1 ml overnight cultured 6-well culture plate, cultured in 37 ° C, 5% C0 2 incubator, after 24 hours, the cells were adhered to the wall to change the solution once to remove Dead cells were changed every 3 to 4 days thereafter, and 5-fluorouracil (final concentration 10 ⁇ m ⁇ . ⁇ ) was added on day 3 for 24 hours to inhibit non-neuronal proliferation. Continue to culture until the 5th day and start the experiment.
  • 968 has a significant nutritional effect on primary cortical neurons cultured in vitro in a medium with serum.
  • Use different concentrations of 968 (1 (T 13 — 10_ 7 mol / L) in serum (10% fetal bovine serum). + 10% horse serum)
  • DMEM / F1-12 incubated primary cortical neurons cultured in vitro (5d, Wistar suckling rat 14-16d), solidified after 24h
  • the number of cells, the length of the protrusions and the area of the cell body were determined and analyzed by microscopic images. The results show that the number of cells
  • apoptosis is the main form of death of a large number of neurons in neurodegenerative diseases such as PD and AD, and high-dose Glu treatment can induce apoptosis of neural cells.
  • Glu 25 ( ⁇ mol / L was added and incubated for 30rain to induce apoptosis.
  • Cells were collected and subjected to propidium iodide (PI) fluorescence staining. The percentage of apoptotic cells was detected and analyzed by flow cytometry.
  • PI propidium iodide
  • Glu was found at a given concentration and Under the action time, 38.9% of the nerve cells can undergo apoptosis, while only 22.5% of the cells in the l (T 1Q mol IL 968 treatment group undergo apoptosis, which is equivalent to the effect of 100ng / ml NGF (21.9 %).
  • Table 9 Effects of different concentrations of 968 treatment on glutamate-induced apoptosis of fetal rat cortical neurons in primary culture 3 ⁇ 4 ⁇ SE)
  • NGF 968 concentration (log mol / L) Normal group Control group

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Abstract

L'invention concerne l'utilisation d'un ou de plusieurs extraits de Tripterygium wilfordii Hook.f pour la préparation de médicaments destinés à prévenir et à traiter des troubles du système nerveux. Les dits extraits de Tripterygium wilfordii Hook.f sont sélectionnés parmi le triptolide, le tripchlorolide, le tripdiolide, le triptriolide, le 16-hydroxytriptolide, le triptolidémol, le triptolidénol, la triptérine et la wilfortrine. Ces extraits de Tripterygium wilfordii présentent une activité immunosuppressive et possèdent également un important effet nutritionnel sur le neurone dopaminergique (DA). Les extraits peuvent stimuler la croissance de cellules nerveuses mésencéphaliques et stimuler l'élongation du processus de cellules nerveuses corticales primaires cultivées. Ils peuvent antagoniser l'effet nocif de la toxine exogène, de la toxine endogène et de la toxine nerveuse excitatoire sur les cellules nerveuses, et permettent une protection remarquable de la survie cellulaire.
PCT/CN2000/000258 2000-09-01 2000-09-01 Utilisation d'un ou de plusieurs extraits de tripterygium wilfordii hook.f pour la preparation de medicaments destines a prevenir et a traiter des troubles du systeme nerveux WO2002017931A1 (fr)

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Cited By (6)

* Cited by examiner, † Cited by third party
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WO2010091193A2 (fr) 2009-02-05 2010-08-12 Pharmagenesis, Inc. Dérivés de triptolide à cycle c modifié en tant qu'agents anticancéreux et modulateurs immunitaires
US8426616B2 (en) 2004-03-02 2013-04-23 Pharmagenesis, Inc. Triptolide lactone ring derivatives as immunomodulators and anticancer agents
US8617906B2 (en) 2004-10-13 2013-12-31 Pharmagenesis, Inc. Identification and screening of triptolide target molecules
CN104398526A (zh) * 2014-10-31 2015-03-11 暨南大学 雷公藤甲素和雷公藤红素在制备抗肿瘤药物中的应用
CN107603870A (zh) * 2017-11-10 2018-01-19 上海保兴生物设备工程有限公司 一种用于微载体细胞培养的消化过滤装置
CN115400133A (zh) * 2022-09-01 2022-11-29 扬州市职业大学(扬州开放大学) 一种山海棠素在心肌肥厚病症药物制备中的用途

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WO1996018395A1 (fr) * 1994-12-15 1996-06-20 Pharmacia & Upjohn Company Utilisation de pramipexole en tant qu'agent neuroprotecteur
US5972998A (en) * 1997-05-23 1999-10-26 Hoechst Marion Roussel, Inc. Triptolide derivatives useful in the treatment of autoimmune diseases
US6004999A (en) * 1997-05-23 1999-12-21 Hoechst Marion Roussel, Inc. Triptolide derivatives useful in the treatment of autoimmune diseases

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8426616B2 (en) 2004-03-02 2013-04-23 Pharmagenesis, Inc. Triptolide lactone ring derivatives as immunomodulators and anticancer agents
US8617906B2 (en) 2004-10-13 2013-12-31 Pharmagenesis, Inc. Identification and screening of triptolide target molecules
WO2010091193A2 (fr) 2009-02-05 2010-08-12 Pharmagenesis, Inc. Dérivés de triptolide à cycle c modifié en tant qu'agents anticancéreux et modulateurs immunitaires
US8268882B2 (en) 2009-02-05 2012-09-18 Pharmagenesis, Inc. Triptolide C-ring derivatives as anticancer agents and immune modulators
CN104398526A (zh) * 2014-10-31 2015-03-11 暨南大学 雷公藤甲素和雷公藤红素在制备抗肿瘤药物中的应用
CN107603870A (zh) * 2017-11-10 2018-01-19 上海保兴生物设备工程有限公司 一种用于微载体细胞培养的消化过滤装置
CN107603870B (zh) * 2017-11-10 2023-06-02 上海保兴生物设备工程有限公司 一种用于微载体细胞培养的消化过滤装置
CN115400133A (zh) * 2022-09-01 2022-11-29 扬州市职业大学(扬州开放大学) 一种山海棠素在心肌肥厚病症药物制备中的用途
CN115400133B (zh) * 2022-09-01 2024-02-06 扬州市职业大学(扬州开放大学) 一种山海棠素在心肌肥厚病症药物制备中的用途

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