CN101014370A - Gingko extract for curing neurotoxicity induced by therapeutic agent - Google Patents
Gingko extract for curing neurotoxicity induced by therapeutic agent Download PDFInfo
- Publication number
- CN101014370A CN101014370A CN200480011775.3A CN200480011775A CN101014370A CN 101014370 A CN101014370 A CN 101014370A CN 200480011775 A CN200480011775 A CN 200480011775A CN 101014370 A CN101014370 A CN 101014370A
- Authority
- CN
- China
- Prior art keywords
- medicine
- therapeutic agent
- combination
- agent
- neurotrophic factor
- 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.)
- Pending
Links
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention features methods for treating neurotoxicity associated with therapeutic agents, e.g., chemotherapeutic agents, and compositions and kits for use therein. The methods employ an extract of Ginkgo biloba to mitigate the neurotoxic effects of the therapeutic agents.
Description
Background of invention
The present invention relates to neurovirulent treatment and relevant pharmaceutical composition.
For example treat a lot that the treatment of diseases agent meeting of cancer causes the undesirable neurological side effect of people, thereby the application of this type of therapeutic agent is restricted.Usually, do not have what Therapeutic Method, and after arriving the treatment threshold value, the patient who is treating has to interrupt using certain medicine or interrupting using whole medicines in a period of time for these side effect.This interruption might produce adverse influence to patient's treatment, for example, but needs to use the relatively poor medicine of the less therapeutic effect of side effect.
In an example, oxaliplatin is the important agent of carrying out property of a kind of treatment colon cancer, and this disease influences 50,000 patients every year in the U.S..The use of oxaliplatin can extend to wideer scope, comprises that other suffer from the patient of human primary gastrointestinal cancers and ovarian cancer.In a word, this medicine is a kind of medicine with good tolerability, but but has significant neurotoxicity.Described neurotoxicity is to cause this chemical compound to use one of limited major side effects, and also is to cause the patient to interrupt the common cause of Drug therapy when medicine still has therapeutic effect to tumor.Now, only there is 5-6 week the time of the Drug therapy accepted before neurotoxicity take place to worsen and is forced to therapy discontinued of patient.
A kind of neurovirulent method that reverses oxaliplatin relates to vein infusion of electrolytes method a kind of complexity and consuming time.Though data show that this method is effective, the patient of 10-20% is benefited, and cause patient's treatment time and cost significantly to increase.
Correspondingly, people need a kind of quality of life and survival rate to patient (for example patient of progressive carcinoma disease) that positive effect is arranged, and can treat the neurovirulent Therapeutic Method relevant with therapeutic agent.
Summary of the invention
The present invention relates to treat the neurovirulent method relevant with therapeutic agent such as chemotherapeutics, and employed compositions of the method and medicine box.This method is used the neurotoxic effect of Semen Ginkgo (Ginkgo biloba) extract with the remissive treatment agent.
On the one hand, the present invention relates among a kind of patient of treatment neurovirulent method by therapeutic-induced, this method comprises the Semen Ginkgo extrac (for example, EGb 761, IPS200, LI1379, LI1370, BN 52063, PN246, Geriaforceg or ZGE) that gives effective dose to the patient.Also put down in writing other Semen Ginkgo extrac herein.In a specific embodiment, before giving Semen Ginkgo extrac, the patient need carry out the neurovirulent diagnosis of therapeutic-induced earlier.This method has significantly alleviated the neurotoxicity of therapeutic-induced.Neurotoxicity is inductive by therapeutic agent described herein.This method can further comprise antioxidant (alpha-lipoic acid for example, sodium thiosulfate, diethyldithiocarbamate, 4-methyl thiobenzoate, L-and D-methionine, Salicylate or glutathion), neurotrophic factor (nerve growth factor for example, neurotrophic factor-3, neurotrophic factor-4/5, Brain Derived Neurotrophic Factor and glial cell derived neurotrophic factor), melanocortin (thyroliberin (ACTH) for example, α-?plain cytositimulation hormone, β-?plain cytositimulation hormone and γ-?plain cytositimulation hormone, or Org2766), glutamate, Glu, calcium-magnesium infusion agent, Anti-epileptics (for example carbamazepine or gabapentin), insulin-like growth factor I, perhaps above two kinds, three kinds, four kinds or multiple combination.When comprising one or more compounds for treating neurotoxicityes, the combination of one or more chemical compounds and Semen Ginkgo extrac is with its treatment effective dose administration ideally.
In a specific embodiment, the patient that said method is used for the treatment of can suffer from breast carcinoma, colon cancer, Hodgkin, kaposi's sarcoma, Lai-Sai Er Shi (Letterer-Siwe) disease, leukemia, pulmonary carcinoma, lymphoma, the plain tumor of ?, ovarian cancer, nonsmall-cell lung cancer, cancer of pancreas, gastric cancer or uterus carcinoma.
Semen Ginkgo extrac can, for example, before giving the patient treatment agent and/or during and/or give Semen Ginkgo extrac afterwards.The administration of Semen Ginkgo extrac can be adjusted according to the administration of therapeutic agent.
This method can well treat comprise that pain, activeness disappearance, ataxia, numbness, numb, myasthenia of limbs, nystagmus, dizziness, dysmetria, dysphonia, dysdiadochokinesia, drowsiness, epilepsy, personality changes, areflexia, constipation, hoarse, orthostatic hypotension, gait disorder, paralysis, stupor, lethargy are unable, chaotic, depressed, hallucination, myoclonus, vibrations decreased sensation, deep are trodden on hyporeflexia, temperature (for example heat or cold) anaphylaxis, paraesthesia or the neurotoxicity of its combination.
The invention still further relates to and contain for example pharmaceutical composition of oxaliplatin of Semen Ginkgo extrac (for example, EGb 761, IPS200, LI1379, LI1370, BN52063, PN246, Geriaforce or ZGE) and therapeutic agent.Other exemplary extract and therapeutic agent all are recorded in this.This combination can be used for for example treating cancer.Said composition also (for example can contain antioxidant, amifostine, alpha-lipoic acid, sodium thiosulfate, diethyldithiocarbamate, 4-methyl thiobenzoate, L-and D-methionine, Salicylate or glutathion), neurotrophic factor (for example, nerve growth factor, neurotrophic factor-3, neurotrophic factor-4/5, Brain Derived Neurotrophic Factor and glial cell derived neurotrophic factor), melanocortin (for example, thyroliberin (ACTH), α, β, with γ-?plain cell-stimulation-hormone or Org2766), glutamate, Glu, calcium-magnesium infusion agent, Anti-epileptics (for example, carbamazepine or gabapentin), insulin-like growth factor I, or its combination.In addition, compositions also can contain pharmaceutically acceptable carrier.In every specific embodiments, there be (for example, cancer, infection, arrhythmia, hyperlipidemia or excessive immune response) in therapeutic agent with the effective dose for the treatment of following disease.Being used for the treatment of neurovirulent Semen Ginkgo extrac and equally also need existing separately or with other chemical compounds are combined of this place record can effectively treat the neurovirulent amount that causes by therapeutic agent.
On the other hand, the present invention relates to contain the medicine box of therapeutic agent (for example oxaliplatin and Semen Ginkgo extrac for example EGb761, IPS200, LI1379, LI1370, BN 52063, PN246, Geriaforce or ZGE).Medicine box also can comprise the label that is used for the treatment of the inductive neurotoxicity treatment of agent about this medicine box.Exemplary Semen Ginkgo extrac and therapeutic agent have been put down in writing herein.Medicine box also can comprise antioxidant (amifostine for example, alpha-lipoic acid, sodium thiosulfate, diethyldithiocarbamate, 4-methyl thiobenzoate, L-and D-methionine, Salicylate or glutathion), neurotrophic factor (for example, nerve growth factor, neurotrophic factor-3, neurotrophic factor-4/5, Brain Derived Neurotrophic Factor and glial cell derived neurotrophic factor), melanocortin (thyroliberin (ACTH) for example, α-?plain cytositimulation hormone, β-?plain cytositimulation hormone and γ-?plain cytositimulation hormone or Org2766), glutamate, Glu, calcium-magnesium infusion agent, Anti-epileptics (for example carbamazepine or gabapentin), insulin-like growth factor I or their combination.In every specific embodiments, therapeutic agent exists with the treatment effective dose that can effectively treat following disease (for example cancer, infection, arrhythmia, hyperlipidemia or over-drastic immunoreation).Separately or therewith described in the literary composition other be used for the treatment of the Semen Ginkgo extrac that neurovirulent therapeutic agent is used in combination, equally also exist can effectively treat the neurovirulent treatment effective dose that causes by therapeutic agent.
In every specific embodiments of above-mentioned various aspects, described therapeutic agent is immunosuppressant, antibiotic, arrhythmia medicine, antilipemic medicine, chemotherapeutics, perhaps their combination.Antibiotic involved in the present invention includes but not limited to sulfonamides, Tetracyclines, aminoglycoside, tetracycline evil class, polymyxins, beta-lactam, carbapenems, cephalosporins, monobactam class medicine, fluoroquinolones medicine, and the combination of these materials.Exemplary therapeutic agent comprises cyclosporin, tacrolimus, chloromycetin, chloroquine, isoniazid, metronidazole, nitrofurantoin, caprolactam, rifampicin, ethionamide, cycloserine, erythromycin, polymyxin E, vancomycin, ethambutol, lincomycin, clindamycin, penicillin, imipenum, cefepime, ceftazidime, cefazolin sodium, cefmetazole, benzylpcnicillin, trovafloxacin, ciprofloxacin, levofloxacin, ofloxacin, amiodarone, vitamin B6, bezafibrate, clofibrate, almitrine bimesylate, Thalidomide, colchicine, disulfiram, phenytoin, dapsone, sodium aurothiomalate, and, their combination.Chemotherapeutics can be for example alkylating agent, antimetabolite, anti-microtubule agent, antimitotic agent, antitumor antibiotics, perhaps their combination.The example of chemotherapeutics comprises amycin, the altheine enzyme, BBR3464, carboplatin, chlorambucil, cisplatin, cytosine arabinoside, doxetacel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, altretamine, ifosfamide, IL-2, interferon, JM216, lorazepam, misonidazole, mitotane, nedaplatin, oxaliplatin, pamldronate, pentostatin, plicamycin, procarbazine, SPI-77, suramin, taxanes (for example, paclitaxel), hycamtin, vinblastine, vincristine, vindesine, vinorelbine, xeloda, ZD0473, and their combination.
Therapeutic agent required for the present invention comprises cyclosporin, tacrolimus, chloromycetin, chloroquine, isoniazid, metronidazole, nitrofurantoin, caprolactam, rifampicin, ethionamide, cycloserine, erythromycin, polymyxin E, vancomycin, ethambutol, lincomycin, clindamycin, penicillin, imipenum, cefepime, ceftazidime, cefazolin sodium, cefmetazole, benzylpcnicillin, trovafloxacin, ciprofloxacin, levofloxacin, ofloxacin, amiodarone, vitamin B6, bezafibrate, clofibrate, almitrine bimesylate, Thalidomide, colchicine, disulfiram, phenytoin, dapsone, sodium aurothiomalate, the altheine enzyme, carboplatin, chlorambucil, cytosine arabinoside, etoposide, altretamine, ifosfamide, IL-2, interferon, lorazepam, misonidazole, mitotane, oxaliplatin, pamldronate, pentostatin, plicamycin, procarbazine, suramin, hycamtin, vinblastine, vincristine, vindesine, vinorelbine, xeloda, JM216, ZD0473, BBR3464, SPI-77, nedaplatin and their combination.
" chemotherapeutics " refer to separately or with the medicine of other combinations of substances treatment cancers.Exemplary chemotherapeutics comprises alkylating agent, antimetabolite, antimitotic agent and antitumor antibiotics.The example of chemotherapeutics includes but not limited to amycin, altheine enzyme, carboplatin, chlorambucil, cisplatin, cytosine arabinoside, doxetacel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, altretamine, ifosfamide, IL-2, interferon, lorazepam, misonidazole, mitotane, oxaliplatin, paclitaxel, pamldronate, pentostatin, plicamycin, procarbazine, suramin, hycamtin, vinblastine, vincristine, vindesine, vinorelbine, and xeloda.
" Semen Ginkgo extrac " refers to and contains at least a extraction obtains from ginkgo independent chemical compound, particularly chromocor compound or the compositions of terpenoid such as ginkgolide or bilobalide or its combination.Semen Ginkgo extrac required among the present invention can effectively be treated neurotoxicity.EGb 761, IPS200, LI1379, LI1370, BN52063, PN246, Geriaforce and ZGE are exemplary Semen Ginkgo extrac.Other Semen Ginkgo extrac is recorded in such as U.S. Patent number 4,981, and 688,5,322,688,5,389,370,5,399,348,5,512,286,5,637,302,5,972,952,6,030,621,6,086,883,6,221,356,6,274,621,6,328,999,6,447,819 and 6,475,534, and international publication number WO97/17068, WO99/64028, WO01/12208 and WO01/75181, every piece of article is hereby incorporated by.
" neurotoxicity " refers to the damage to central nervous system or peripheral nervous system.Reflection that the example of neurotoxic effect includes but not limited to that pain, activeness disappearance, ataxia, numbness, numb, myasthenia of limbs, nystagmus, dizziness, dysmetria, dysphonia, dysdiadochokinesia, drowsiness, epilepsy, personality changes, areflexia, constipation, hoarse, orthostatic hypotension, gait disorder, paralysis, stupor, lethargy are unable, chaotic, depressed, hallucination, myoclonus, vibrations sensation reduce, tread in the deep reduces, to temperature (for example heat or cold) tetchiness, and paraesthesia.
Neurovirulent " reduction " refers to and alleviates or the elimination neurotoxicity.Neurovirulent reduction can be measured, and for example carries out by body constitution inspection, the inspection of patient medical history or by the nervous function test.
The patient's condition of " by therapeutic-induced " refer to use certain therapeutic agent for example chemotherapeutics treat and the situation that causes neurotoxicity for example.
" treatment effective dose " refer to the pharmaceutical composition that contains one or more reactive compounds in treatment disease or patient's condition process, for example treating is enough to produce prevention, healing, treatment, stablizes or the amount of mitigation in the neurovirulent process.
" treatment " refers to the Medical Treatment mode for the patient, is intended to prevent, cures, stablizes or alleviates the symptom that is caused.This term comprises: the active disposal, also promptly at the disposal of directly determining of the improvement of disease; Conservative treatment also is the disposal of relief of symptoms rather than treatment disease; Preventive disposal also is direct prophylactic disposal; And supportive treatment, also, as the specific direct disposal that replenishes that improves the therapy of disease of another kind.Term " treatment " also comprises symptomatic treatment, that is, and directly at the method for disposal of the general symptom of disease.
According to following detailed Description Of The Invention and claims, other feature and advantage of the present invention are conspicuous.
Detailed Description Of The Invention
The present invention relates to be used for the treatment of the neurovirulent Treatment and composition for relevant with pharmacotherapy.
Neurotoxicity by therapeutic-induced
Neurotoxicity is cause a kind of deleterious of therapeutic agent and is dosage-dependent side effect.Can cause the common treatment agent of neurotoxic side effects comprise chemotherapeutics and other such as immunosuppressant (for example cyclosporin and tacrolimus), antibiotic (chloromycetin for example, chloroquine, isoniazid, metronidazole, nitrofurantoin, caprolactam, rifampicin, ethionamide, cycloserine, erythromycin, sulfonamides, Tetracyclines, polymyxin E, aminoglycoside, vancomycin, ethambutol, Tetracyclines, polymyxins, lincomycin, clindamycin, beta-lactam (for example, carbapenems, cephalosporins, monobactam, penicillin, imipenum, cefepime, ceftazidime, cefazolin sodium, cefmetazole and benzylpcnicillin) and fluoroquinolones medicine (trovafloxacin for example, ciprofloxacin, levofloxacin and ofloxacin)), antiarrhythmics (for example amiodarone), antilipemic medicine (for example bezafibrate and clofibrate), and other drug (for example, almitrine bimesylate, Thalidomide, colchicine, disulfiram, phenytoin, vitamin B6, dapsone and sodium aurothiomalate) medicine.
The example of chemotherapeutics includes but not limited to: contain platinum compounds (such as carboplatin, cisplatin, oxaliplatin, JM216, ZD0473, BBR3464, SPI-77 and nedaplatin), taxanes (such as paclitaxel), vinca alkaloids is (such as vincristine, vinblastine, vindesine and vinorelbine), amycin, the altheine enzyme, chlorambucil, cytosine arabinoside, doxetacel, doxorubicin, etoposide, 5-fluorouracil, altretamine, ifosfamide, IL-2, interferon, lorazepam, misonidazole, mitotane, pamldronate, pentostatin, plicamycin, procarbazine, suramin, hycamtin and xeloda.These chemotherapeutics are used for the treatment of various cancers, such as breast carcinoma, colon cancer, Hodgkin, kaposi's sarcoma, letteres-Siwe disease, leukemia, pulmonary carcinoma, lymphoma, ?plain tumor, nonsmall-cell lung cancer, ovarian cancer, cancer of pancreas, gastric cancer, tumor and uterus carcinoma.
The standard dose of therapeutic agent is well known in the art described in this literary composition, for example, Merck diagnosis and treatment handbook (17 editions, MH Beers etc., Merck ﹠ Co., Inc.) and doctor's handbook (Physicians ' Desk Reference) 2003 (people such as 57thEd.Medical Economics Staff, Medical Economics Co., 2002).Those skilled in the art can wait to determine each suitable therapeutic dose according to patient's the various situations such as type and degree, the general health of particular patient, the formulation conditions and the route of administration of chemical compound of disease.Can use the clinical trial of standard to optimize the dosage and the administration frequency of any particular therapeutic agent.
In order to make these medicines obtain maximum therapeutic effect, the patient must stand any side effect that treatment brings.Yet the neurotoxic side effects of these therapeutic agents can limit the consumption of the therapeutic agent that gives particular patient.Can reduce the effect of treatment like this, thus the extended treatment time or cause the treatment prove an abortion.In addition, both certain treatment of box lunch was to certain disease or the patient's condition, and for example cancer is effective, and neurotoxic side effects also can be ended the back continuity in treatment.The alleviation that some this type of side effect meeting is spontaneous in time, some then is nonvolatil or can continues several months or several years after treatment.Thus, the Therapeutic Method that can reduce side effect can increase survival rate by the treatment time that prolongs particular therapeutic agent, and, improve the quality of life of patient before and after treatment by alleviating side effect.
In order to realize this purpose, we find that Semen Ginkgo extrac can be used for treating the neurotoxic side effects of therapeutic agent.
Semen Ginkgo extrac
Identify." Semen Ginkgo extrac " is described to a kind of mixture that contains other materials that exist in flavonoid glycoside and some ginkgo leaf at first.The fundamental difference of medical herbs and chemistry-definition medicine is that the former always contains the mixture that some are formed by the active substance of inferring basically, and quality and effect have very big fluctuation.The quality of Folium Ginkgo extract is very important for the preparation standard Semen Ginkgo extrac.
Maximum Semen Ginkgo extrac EGb 761 of research is defined as follows by the German FederalHealth Authority of Bundesgesundheitsamt: " a kind of exsiccant extract that extracts from ginkgo leaf; preparation process is used acetone and follow-up purification step; do not have additional mixture to concentrate or the separation of active component (DeFeudis FV 1998 Semen Ginkgo extrac (EGb 761): from chemistry to clinical .Ullstein Medical; Wisbaden, Germany).EGb 761 can be commercially available in Europe, and name is called Tanakan
TM, Ginkgo
TM, Rokan
TM, Tebonin
TM, but must under medical supervision (needing prescription), just can obtain.In the U.S., are tonic product of OTC Semen Ginkgo of EGb 761 by a lot of main components, such as Ginkgo
TM, GinkgoGold
TMAnd Quater
TMEGb 761 quality and activity can be controlled (european patent number 0431535B1 and U.S. Patent number 5,399,348 are incorporated herein by reference) by preparation method clear and definite, license herein.Medical herbs: the ratio average out to of extract 50: 1.
EGb 761 extracts are characterised in that and contain 24% ginkgetin glycosides and 6% terpene three lactones (terpene tri lactones) (3.1% ginkgolide and 2.9% bilobalide).In addition, EGb 761 contains other materials (such as proanthocyanidins, carboxylic acids, non--flavonoid glycoside, and some high molecular weight component), and its concentration also is decided by preparation method, and its viscosity also is to guarantee its high-quality key factor.EGb 761 does not contain ginkgoic acid.Various studies show that, some component of EGb 761 has independently biologic activity, and is playing the part of important role in pharmacology and therapeutics activity.Yet; the effect compensatory between these components, synergitic makes Semen Ginkgo extrac have regulating action and protective effect; thereby make it become a kind of equilibrated " totum " (Drieu K; Jaggy H 1999 History; development and constituents ofEGb 76 1.In:Ginkgo biloba.Van Beek T (ed) .Medicinal and Aromatic Plants andIndustrial Profiles Series; Harwood Academic Publishers, 267-277).Other Semen Ginkgo extrac, for example, IPS200 (a kind of EGb 761 goods that do not contain proanthocyanidins), LI1379, LI1370, BN52063 (ginkgolide C that contains 40% ginkgolide A, 40% ginkgolide B and 20%), PN246 (contain the terpene lactones of 7mg and the flavonoid glycoside of 24mg/each coated tablet; Bio-Biloba, PharmaNord, Vejle, Denmark), Geriaforce (water/alcohol extract of Folium Ginkgo (70%v/v), 1: 4 extract; 0.34mg/mL total ginkgolide and 0.20 mg/mL total flavonoid glycoside; Biohorma B.V.) and ZGE all be well known in the art, and can be used in the method described herein.Other extract can, for example, contain at least 5%, 10%, 15%, 20%, 24%, 30%, 35%, 40%, 45%, 50%, 75%, 85% or 95% ginkgetin glycosides.
Therapeutic activity.Numerous researchs have been described the Semen Ginkgo extrac couple patient that Vigilance, memory and the cognitive function relevant with aging are interfered and have been had useful effect, and various types of dementias, anxious state of mind, the patient that can't tackle pressure every day had useful effect (DeFeudis FV1998 Ginkgo bilobaextract (EGb 761): from chemistry to clinic.Ullstein Medical, Wisbaden, Germany; LeBars PL, Katz MM, Berman N, Itil TM, Freedman AM Schatzberg AF 1997, Semen Ginkgo extrac for the dull-witted placebo of treatment, double blinding, random experiment JAMA 278:1327-1332, Lemay M, Kergoat M-J, Lupien S 1999 Ginkgo biloba:what good is it? Mat.Medicine Canada 2:34-37).In addition, people also attempt using the effect of Semen Ginkgo extrac with improvement use such as the treatment of cancer of the chemotherapeutics of 5-fluorouracil, doxetacel, doxorubicin and amycin.In most this type of research, all used standardized Folium Ginkgo extract, EGb761.In addition, EGb 761 also shows to have the Cardioprotective effect.Most important active component is three kinds of main flavone among the EGb 761, and its chemical constitution is similar to nucleoside, isoalloxazine and folic acid; And two kinds of terpenoid: sesquiterpene, bilobalide; And diterpene, i.e. ginkgolide.
Anti-neurotoxicity activity.We find, give the neurotoxic side effects that Semen Ginkgo extrac can effectively be treated therapeutic agent.The described exemplary Semen Ginkgo extrac that is used for the treatment of of this literary composition is EGb 761.And other Semen Ginkgo extrac is as known in the art.Neurotoxic side effects, the method of record according to the present invention, the neurotoxic side effects of being treated includes but not limited to, pain, the activeness disappearance, ataxia, numb, numb, myasthenia of limbs, nystagmus, dizzy, dysmetria, dysphonia, dysdiadochokinesia, drowsiness, epilepsy, personality changes, areflexia, constipation, hoarse, orthostatic hypotension, gait disorder, paralysis, stupor, lethargy is unable, chaotic, depressed, hallucination, myoclonus, the vibrations decreased sensation, the deep hyporeflexia of treading on, temperature (for example heat or cold) anaphylaxis, paraesthesia.
Semen Ginkgo extrac can give before giving therapeutic agent and/or simultaneously, is used to reduce or prevents any and the relevant neurotoxicity of therapeutic agent treatment.In addition, Semen Ginkgo extrac gives after can stopping in the treatment of therapeutic agent again, is used for the treatment of the neurotoxic effect that is caused by therapeutic agent.Can adjust with the method that Semen Ginkgo extrac and therapeutic agent are treated.
Semen Ginkgo extrac also can with other chemical compound together administration with the treatment neurotoxicity, described chemical compound such as antioxidant (for example, amifostine, alpha-lipoic acid, sodium thiosulfate, diethyldithiocarbamate, 4-methyl thiobenzoate, L-and D-methionine, Salicylate, or glutathion), neurotrophic factor (for example, nerve growth factor, neurotrophic factor-3, neurotrophic factor-4/5, Brain Derived Neurotrophic Factor, and glial cell derived neurotrophic factor), melanocortin (for example, thyroliberin (ACTH), α, β, with γ-?plain cell-stimulation-hormone, or Org2766), glutamate, Glu, calcium-magnesium infusion agent, Anti-epileptics (for example, carbamazepine or gabapentin), insulin-like growth factor I, perhaps their combination.The standard dose of these other chemical compounds is known in the art, for example, is found in Merck diagnosis and treatment handbook (people such as 17th Ed.MH Beers, Merck﹠amp; Co.) and Physicians ' Desk Reference 2003 (people Medical Econornics Co. such as 57th Ed.Medical Econornics Staff, 2002).In addition, those skilled in the art can wait to determine each suitable therapeutic dose according to patient's the various situations such as type and degree, the general health of particular patient, the formulation conditions and the route of administration of chemical compound of disease.Can use the clinical trial of standard to optimize the dosage and the administration frequency of any particular therapeutic agent.
Semen Ginkgo extrac preferably can oral administration, and still, administering mode can be adjusted according to the disease of treatment or the therapeutic agent of use.Other route of administration comprises in part, parenteral route, vein, tremulous pulse, subcutaneous, intramuscular, intracranial, the socket of the eye, in the ophthalmic, ventricle, in the capsule, in the spinal column, in the brain pond, intraperitoneal, intranasal, spraying, suppository form administration, perhaps by other administration path administrations that suit.
Semen Ginkgo extrac also can be identical dosage unit form, for example be used to the bolus injection agent of injecting or the form of piller, optional with together administration of therapeutic agent (for example oxaliplatin), can be with together administration of neurovirulent other treatment agent described herein.Whole required preparation will contain a certain amount ofly can effectively treat the treatment of diseases agent, and, a certain amount of Semen Ginkgo extrac, optional, also contain other and can effectively treat the neurovirulent chemical compound that causes by therapeutic agent.The method for preparing preparation is well known in the art, for example, and can be referring to Remington:The Scienceand Practice of Pharmacy (20th ed., A.R. Gennaro ed., Lilppincott:Philadelphia, 2000).The pharmacy acceptable auxiliary that is used for preparation also is known in the field.
Semen Ginkgo extrac can be treated effective dose and be given human patients, to provide for neurovirulent treatment.Representational dosage range is 0.1 μ g/kg to 1,5 or the 10mg/kg body weight/day, for example, and 0.5mg/kg.Exemplary dosage is, twice of 761 every day of EGb of 120mg.Can be according to type and degree, the general health of particular patient, the formulation conditions of chemical compound and the dosage that route of administration waits to determine Semen Ginkgo extrac of patient's various situations such as disease.Can use the clinical trial of standard to optimize the dosage and the administration frequency of any particular therapeutic agent.
The patient suffers from neurovirulent degree, can record in the illness history of carrying out Semen Ginkgo extrac treatment front and back by the physical examinations of standard or by comparing the patient.For example, the patient can be required to finish before and after the treatment and during about the question and answer of its body constitution and mental status.In addition, the patient can carry out the test of standard cognitive or sense organ to determine its level of neurotoxicity.
Following examples only are elaboration the present invention, rather than limit the present invention by any way.
Embodiment 1
We measured commercial can get contain standardized EGb 761 Semen Ginkgo extrac (Ginkgoba
TM) the OTC preparation to the patient's that accepts oxaliplatin influence.Before beginning to take Semen Ginkgo extrac, all patients have accepted oxaliplatin and neurotoxicity occurred.According to our data and reading report, the Ginkgoba that we recommend
TMDosage is 120mg, one day twice, and take continuously (every day).(preceding chemotherapy treatment several times) measures patient's acute neurotoxicity according to ill history before accepting Semen Ginkgo extrac, and with used Semen Ginkgo extrac after the situation of (the follow-up course of treatment of chemotherapy) compare.We treat 8 patients, the remarkable neurotoxicity that they have occurred being caused by treatment, but the anticarcinogen oxaliplatin that is to use still has antitumaous effect in vivo.These patients are in using oxaliplatin and interrupt after the oxaliplatin Ginkgoba of successive every day of twice use 120mg in 1 to 2 months
TM, take the several months.There are 7 patients to report that its neurotoxicity weakens in 8, and improved quality of life.Neurotoxicity is determined by ill history and body constitution inspection.5 patients are the male, and 3 patients are the women.All patients suffer from the property of carrying out colon cancer, and all suffer from neurotoxicity to a certain degree.Patient's mean age is about 55 years old.
Other specific embodiments
Modification of the method for the invention and variation all are conspicuous to those skilled in the art, and do not deviate from the scope and spirit of the present invention.Although the present invention has got in touch some necessary specific embodiments when describing, can not think that the present invention is limited only within these specific specific embodiments.In fact, the various changes of described mode also can be implemented the present invention, and these are changed to a new form still within the scope of the present invention.
The publication of all introducings that the present invention mentions, patent and patent application all are used for reference, as each independent publication, patent or patent application clear and definite and independently be introduced into as a reference.
Other specific embodiments is included in claims.
Claims (60)
1. treat among the patient by the neurovirulent method of therapeutic-induced for one kind, described method comprises the Semen Ginkgo extrac for the treatment of effective dose to described patient.
2. the method for claim 1, described neurotoxicity are inductive by the therapeutic agent institute that is selected from immunosuppressant, antibiotic, arrhythmia medicine, antilipemic medicine, chemotherapeutics or its combination.
3. the method for claim 2, described therapeutic agent is cyclosporin, tacrolimus, chloromycetin, chloroquine, isoniazid, metronidazole, nitrofurantoin, caprolactam, rifampicin, ethionamide, cycloserine, erythromycin, polymyxin E, vancomycin, ethambutol, lincomycin, clindamycin, penicillin, imipenum, cefepime, ceftazidime, cefazolin sodium, cefmetazole, benzylpcnicillin, trovafloxacin, ciprofloxacin, levofloxacin, ofloxacin, amiodarone, bezafibrate, clofibrate or its combination.
4. the method for claim 2, wherein said therapeutic agent is sulfonamides, Tetracyclines medicine, aminoglycoside medicine, Tetracyclines medicine, polymyxins medicine, beta-lactam medicine, carbapenems medicine, cephalosporins medicine, monobactam class medicine, fluoroquinolones medicine or its combination.
5. the method for claim 2, wherein said chemotherapeutics is alkylating agent, antimetabolite, anti-microtubule agent, antimitotic agent, antitumor antibiotics or its combination.
6. the method for claim 2, wherein said chemotherapeutics is altheine enzyme, carboplatin, chlorambucil, cytosine arabinoside, etoposide, altretamine, ifosfamide, IL-2, interferon, lorazepam, misonidazole, mitotane, oxaliplatin, pamldronate, pentostatin, plicamycin, procarbazine, suramin, hycamtin, vinblastine, vincristine, vindesine, vinorelbine, xeloda, JM216, ZD0473, BBR3464, SPI-77, nedaplatin or its combination.
7. the method for claim 2, wherein said chemotherapeutics is an oxaliplatin.
8. the process of claim 1 wherein that described neurotoxicity is inductive by almitrine bimesylate, Thalidomide, colchicine, disulfiram, phenytoin, dapsone, vitamin B6, sodium aurothiomalate or its combination.
9. the process of claim 1 wherein that described extract comprises EGb 761, IPS200, LI1379, LI1370, BN 52063, PN246, Geriaforce or ZGE.
10. the process of claim 1 wherein that described patient suffers from breast carcinoma, colon cancer, Hodgkin, kaposi's sarcoma, letteres-Siwe disease, leukemia, pulmonary carcinoma, lymphoma, melanoma, ovarian cancer, nonsmall-cell lung cancer, cancer of pancreas, gastric cancer or uterus carcinoma.
11. the method for claim 10, wherein said patient suffers from colon cancer.
12. the process of claim 1 wherein and also comprise and give antioxidant, neurotrophic factor, melanocortin, glutamate, Glu, calcium-magnesium infusion agent, antuepileptic, insulin-like growth factor I or its combination.
13. the method for claim 12, wherein said antioxidant are amifostine, alpha-lipoic acid, sodium thiosulfate, diethyldithiocarbamate, 4-methyl thiobenzoate, L-and D-methionine, Salicylate or glutathion.
14. the method for claim 12, wherein said antuepileptic are carbamazepine or gabapentin.
15. the method for claim 12, wherein said melanocortin are thyroliberin (ACTH), α-Hei Suxibaocijijisu, β-melanotropin, γ-melanotropin or Org2766.
16. the method for claim 12, wherein said neurotrophic factor are nerve growth factor, neurotrophic factor-3, neurotrophic factor-4/5, Brain Derived Neurotrophic Factor or glial cell derived neurotrophic factor.
17. the process of claim 1 wherein the administration of described extract with respect to for the agent of patient's drug treatment, can be before it, during, afterwards or the combination of these modes.
18. the method for claim 17, the administration simultaneously of wherein said extract and described therapeutic agent.
19. the method for claim 17, the administration before described therapeutic agent of wherein said extract.
20. the method for claim 17, the administration after described therapeutic agent of wherein said extract.
21. the process of claim 1 wherein that the administration of described extract and the administration of therapeutic agent hocket.
22. the process of claim 1 wherein that the administration of described extract can alleviate the neurotoxicity of described therapeutic-induced.
23. the method for claim 1, wherein said neurotoxicity comprises that pain, activeness disappearance, ataxia, numbness, numb, myasthenia of limbs, nystagmus, dizziness, dysmetria, dysphonia, dysdiadochokinesia, drowsiness, epilepsy, personality changes, areflexia, constipation, hoarse, orthostatic hypotension, gait disorder, paralysis, stupor, lethargy are unable, chaotic, depressed, hallucination, myoclonus, vibrations decreased sensation, deep are trodden on hyporeflexia, temperature anaphylaxis, paraesthesia, the perhaps combination of these types.
24. the process of claim 1 wherein before giving the described extract of patient, described patient carried out neurovirulent diagnosis by therapeutic-induced.
25. pharmaceutical composition that contains therapeutic agent and Semen Ginkgo extrac.
26. the pharmaceutical composition of claim 25, wherein said extract comprise EGb 761, IPS200, LI1379, LI1370, BN 52063, PN246, Geriaforec or ZGE.
27. the pharmaceutical composition of claim 25, wherein said therapeutic agent are immunosuppressant, antibiotic, arrhythmia medicine, antilipemic medicine, chemotherapeutics or its combination.
28. the pharmaceutical composition of claim 27, wherein said therapeutic agent are cyclosporin, tacrolimus, chloromycetin, chloroquine, isoniazid, metronidazole, nitrofurantoin, caprolactam, rifampicin, ethionamide, cycloserine, erythromycin, polymyxin E, vancomycin, ethambutol, lincomycin, clindamycin, penicillin, imipenum, cefepime, ceftazidime, cefazolin sodium, cefmetazole, benzylpcnicillin, trovafloxacin, ciprofloxacin, levofloxacin, ofloxacin, amiodarone, bezafibrate, clofibrate or its combination.
29. the pharmaceutical composition of claim 27, wherein said therapeutic agent are sulfonamides, Tetracyclines medicine, aminoglycoside medicine, Tetracyclines medicine, polymyxins medicine, beta-lactam medicine, carbapenems medicine, cephalosporins medicine, monobactam class medicine, fluoroquinolones medicine or its combination.
30. the pharmaceutical composition of claim 27, wherein said chemotherapeutics are alkylating agent, antimetabolite, anti-microtubule agent, antimitotic agent, antitumor antibiotics or its combination.
31. the pharmaceutical composition of claim 27, wherein said chemotherapeutics are altheine enzyme, carboplatin, chlorambucil, cytosine arabinoside, etoposide, altretamine, ifosfamide, IL-2, interferon, lorazepam, misonidazole, mitotane, oxaliplatin, pamldronate, pentostatin, plicamycin, procarbazine, suramin, hycamtin, vinblastine, vincristine, vindesine, vinorelbine, xeloda, JM216, ZD0473, BBR3464, SPI-77, nedaplatin or its combination.
32. the pharmaceutical composition of claim 27, wherein said chemotherapeutics is an oxaliplatin.
33. the pharmaceutical composition of claim 25, wherein said therapeutic agent are almitrine bimesylate, Thalidomide, colchicine, disulfiram, phenytoin, dapsone, vitamin B6, sodium aurothiomalate or its combination.
34. the pharmaceutical composition of claim 25, it also comprises antioxidant, neurotrophic factor, melanocortin, glutamate, Glu, calcium-magnesium infusion agent, antuepileptic, insulin-like growth factor I or its combination.
35. the pharmaceutical composition of claim 34, wherein said antioxidant are amifostine, alpha-lipoic acid, sodium thiosulfate, diethyldithiocarbamate, 4-methyl thiobenzoate, L-and D-methionine, Salicylate or glutathion.
36. the pharmaceutical composition of claim 34, wherein said antuepileptic are carbamazepine or gabapentin.
37. the pharmaceutical composition of claim 34, wherein said melanocortin are thyroliberin (ACTH), α-Hei Suxibaocijijisu, β-melanotropin, γ-melanotropin or Org2766.
38. the pharmaceutical composition of claim 34, wherein said neurotrophic factor are nerve growth factor, neurotrophic factor-3, neurotrophic factor-4/5, Brain Derived Neurotrophic Factor or glial cell derived neurotrophic factor.
39. the pharmaceutical composition of claim 25, it also contains pharmaceutically acceptable carrier.
40. the pharmaceutical composition of claim 25, wherein said therapeutic agent exists with the treatment effective dose.
41. the pharmaceutical composition of claim 25, wherein said Semen Ginkgo extrac exists with the neurovirulent treatment effective dose that treatment is caused by described therapeutic agent.
42. the pharmaceutical composition of claim 34, wherein said Semen Ginkgo extrac and described antioxidant, neurotrophic factor, melanocortin, glutamate, Glu, calcium-magnesium infusion agent, antuepileptic, insulin-like growth factor I or its combine the neurovirulent treatment effective dose that is caused by described therapeutic agent with treatment and exist.
43. medicine box that contains therapeutic agent and Semen Ginkgo extrac.
44. the medicine box of claim 43, it also comprises about medicine box being used for the treatment of the neurovirulent label by therapeutic-induced.
45. the medicine box of claim 43, wherein said extract comprise EGb 761, IPS200, LI1379, LI1370, BN 52063, PN246, Geriaforce or ZGE.
46. the medicine box of claim 43, wherein said therapeutic agent are immunosuppressant, antibiotic, arrhythmia medicine, antilipemic medicine, chemotherapeutics or its combination.
47. the medicine box of claim 46, wherein said therapeutic agent are cyclosporin, tacrolimus, chloromycetin, chloroquine, isoniazid, metronidazole, nitrofurantoin, caprolactam, rifampicin, ethionamide, cycloserine, erythromycin, polymyxin E, vancomycin, ethambutol, lincomycin, clindamycin, penicillin, imipenum, cefepime, ceftazidime, cefazolin sodium, cefmetazole, benzylpcnicillin, trovafloxacin, ciprofloxacin, levofloxacin, ofloxacin, amiodarone, bezafibrate, clofibrate or its combination.
48. the medicine box of claim 46, wherein said therapeutic agent are sulfonamides, Tetracyclines medicine, aminoglycoside medicine, Tetracyclines medicine, polymyxins medicine, beta-lactam medicine, carbapenems medicine, cephalosporins medicine, monobactam class medicine, fluoroquinolones medicine or its combination.
49. the medicine box of claim 46, wherein said chemotherapeutics are alkylating agent, antimetabolite, anti-microtubule agent, antimitotic agent, antitumor antibiotics or its combination.
50. the medicine box of claim 46, wherein said chemotherapeutics are altheine enzyme, carboplatin, chlorambucil, cytosine arabinoside, etoposide, altretamine, ifosfamide, IL-2, interferon, lorazepam, misonidazole, mitotane, oxaliplatin, pamldronate, pentostatin, plicamycin, procarbazine, suramin, hycamtin, vinblastine, vincristine, vindesine, vinorelbine, xeloda, JM216, ZD0473, BBR3464, SPI-77, nedaplatin or its combination.
51. the medicine box of claim 46, wherein said chemotherapeutics is an oxaliplatin.
52. the medicine box of claim 43, wherein said therapeutic agent are almitrine bimesylate, Thalidomide, colchicine, disulfiram, phenytoin, dapsone, vitamin B6, sodium aurothiomalate or its combination.
53. the medicine box of claim 43 will also comprise antioxidant, melanocortin, glutamate, Glu, calcium-magnesium infusion agent, antuepileptic, insulin-like growth factor I or its combination.
54. the medicine box of claim 53, wherein said antioxidant are amifostine, alpha-lipoic acid, sodium thiosulfate, diethyldithiocarbamate, 4-methyl thiobenzoate, L-and D-methionine, Salicylate or glutathion.
55. the medicine box of claim 53, wherein said antuepileptic are carbamazepine or gabapentin.
56. the medicine box of claim 53, wherein said melanocortin are thyroliberin (ACTH), α-Hei Suxibaocijijisu, β-melanotropin, γ-melanotropin or Org2766.
57. the medicine box of claim 53, wherein said neurotrophic factor are nerve growth factor, neurotrophic factor-3, neurotrophic factor-4/5, Brain Derived Neurotrophic Factor or glial cell derived neurotrophic factor.
58. the medicine box of claim 43, wherein said therapeutic agent exists with the treatment effective dose.
59. the medicine box of claim 43, wherein said Semen Ginkgo extrac exists with the neurovirulent treatment effective dose that treatment is caused by described therapeutic agent.
60. the medicine box of claim 53, wherein said Semen Ginkgo extrac and described antioxidant, neurotrophic factor, melanocortin, glutamate, Glu, calcium-magnesium infusion agent, antuepileptic, insulin-like growth factor I or its combine the neurovirulent treatment effective dose that is caused by described therapeutic agent with treatment and exist.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2004/013609 WO2004098519A2 (en) | 2003-05-02 | 2004-05-03 | Ginkgo biloba extract as a treatment for therapeutic induced neurotoxicity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101014370A true CN101014370A (en) | 2007-08-08 |
Family
ID=38701477
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200480011775.3A Pending CN101014370A (en) | 2004-05-03 | 2004-05-03 | Gingko extract for curing neurotoxicity induced by therapeutic agent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101014370A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109596818A (en) * | 2018-12-13 | 2019-04-09 | 丁蓉 | A kind of research method based on electrophysiology analysis danggui sini decoction prevented oxaliplatin induced neurotoxicity |
| WO2019223787A1 (en) * | 2018-05-25 | 2019-11-28 | 成都百裕制药股份有限公司 | Use of ginkgo biloba terpene lactone in preparation of drugs for prevention and/or treatment of tremors and healthcare products |
| CN114432325A (en) * | 2022-01-21 | 2022-05-06 | 贵州医科大学附属医院 | Antitumor drug for reducing adriamycin cardiotoxicity |
-
2004
- 2004-05-03 CN CN200480011775.3A patent/CN101014370A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019223787A1 (en) * | 2018-05-25 | 2019-11-28 | 成都百裕制药股份有限公司 | Use of ginkgo biloba terpene lactone in preparation of drugs for prevention and/or treatment of tremors and healthcare products |
| CN110522748A (en) * | 2018-05-25 | 2019-12-03 | 成都百裕制药股份有限公司 | Purposes of the ginkgoterpene lactone in the drug that preparation prevention and/or treatment are trembled, health care product |
| CN110522748B (en) * | 2018-05-25 | 2023-08-15 | 成都百裕制药股份有限公司 | Application of ginkgolide in preparing medicament and health-care product for preventing and/or treating tremors |
| CN109596818A (en) * | 2018-12-13 | 2019-04-09 | 丁蓉 | A kind of research method based on electrophysiology analysis danggui sini decoction prevented oxaliplatin induced neurotoxicity |
| CN109596818B (en) * | 2018-12-13 | 2024-03-19 | 丁蓉 | Research method for preventing oxaliplatin neurotoxicity mechanism based on electrophysiology analysis of angelica sinensis four-reverse decoction |
| CN114432325A (en) * | 2022-01-21 | 2022-05-06 | 贵州医科大学附属医院 | Antitumor drug for reducing adriamycin cardiotoxicity |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2020090507A5 (en) | ||
| Zubenko et al. | Use of clonidine in treating neuroleptic-induced akathisia | |
| Wheless | Use of the mTOR inhibitor everolimus in a patient with multiple manifestations of tuberous sclerosis complex including epilepsy | |
| AU2012340840A1 (en) | Method for treating hepatitis C virus infection using quercetin-containing compositions | |
| US20210085638A1 (en) | Terpene Control in Scaleable Cannabinoid Medicinal Formulations | |
| US20070269539A1 (en) | Ginkgo Biloba Extract as a Treatment for Therapeutic-Induced Neurotoxicity | |
| Frye et al. | Drug–induced thrombocytosis | |
| CN101014370A (en) | Gingko extract for curing neurotoxicity induced by therapeutic agent | |
| NO20001717L (en) | Serotonin-containing formulation for oral administration and use of the same | |
| ZA200305967B (en) | Method of cancer therapy | |
| Mason et al. | Flavopiridol increases therapeutic ratio of radiotherapy by preferentially enhancing tumor radioresponse | |
| Johnson et al. | Caffeine potentiates the enhancement by choline of striatal acetylcholine release | |
| EP1944030A1 (en) | Agent for treatment of schizophrenia | |
| CN101574339A (en) | Application of beta-anhydroicaritin in preparation of medicine capable of preventing and treating cardiovascular and cerebrovascular diseases | |
| CN106619613A (en) | Application of bilobalide serving as brain-targeting synergist to preparation of drug for preventing brain tumor | |
| CN110613716B (en) | Pharmaceutical composition for treating cancer and application thereof | |
| CN110063988A (en) | A kind of pharmaceutical composition and preparation method thereof for treating neuroblastoma | |
| CN110403924A (en) | A kind of pharmaceutical composition and preparation method thereof for treating cutaneous melanoma | |
| Muresanu et al. | Psychopharmacotherapy of pain | |
| Iqubal et al. | Combination therapy: past, present, and future | |
| Moncrieff et al. | Antipsychotics as particular types of sedatives | |
| WO2014081029A1 (en) | Prophylactic, therapeutic or alleviating agent for peripheral nerve disorders caused by anti-cancer agents | |
| WO2024101207A1 (en) | Quercetin- or quercetin-glycoside-containing composition for suppressing or ameliorating any reduction in cognitive function | |
| CN110151824A (en) | A kind of pharmaceutical composition and preparation method thereof for treating hypopharyngeal cancer | |
| Stamenkovic | tWo PoSt-ICU SECREtS thAt StILL NEED to bE REVEALED: ChRONIC PAIN AND OPIOID DEPENDENCE |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20070808 |