CN101773499A - New applications of tetrahydropalmatine - Google Patents

New applications of tetrahydropalmatine Download PDF

Info

Publication number
CN101773499A
CN101773499A CN200910076383A CN200910076383A CN101773499A CN 101773499 A CN101773499 A CN 101773499A CN 200910076383 A CN200910076383 A CN 200910076383A CN 200910076383 A CN200910076383 A CN 200910076383A CN 101773499 A CN101773499 A CN 101773499A
Authority
CN
China
Prior art keywords
cancer
cell
carcinoma
tetrahydropalmatine
formula
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
Application number
CN200910076383A
Other languages
Chinese (zh)
Inventor
张虹
金雪
向俊锋
李骞
谭莉
唐亚林
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institute of Chemistry CAS
Original Assignee
Institute of Chemistry CAS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Institute of Chemistry CAS filed Critical Institute of Chemistry CAS
Priority to CN200910076383A priority Critical patent/CN101773499A/en
Priority to PCT/CN2009/000563 priority patent/WO2010081266A1/en
Publication of CN101773499A publication Critical patent/CN101773499A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses new applications f tetrahydropalmatine. The new application is an application that tetrahydropalmatine shown in formula I or salts thereof which are acceptable in pharmacy are used to prepare medicines used for inhibiting the proliferation of tumor cells and an application for preparing medicines used for preventing and/or curing tumors. The result of the in vivo experiment using nude mice shows that tetrahydropalmatine can effectively inhibit the growth of tumors, and the tumor volume is much smaller than the volume of the negative control group. Therefore, tetrahydropalmatine which is widely used for analgesia has good antitumor activity, and the result shows that tetrahydropalmatine can be used to prepare medicines for curing cancers, in particular to prepare medicines for curing the lung cancer. The invention broadens the medical application field of tetrahydropalmatine.

Description

New applications f tetrahydropalmatine
Technical field
The present invention relates to new applications f tetrahydropalmatine.
Background technology
Rhizoma Corydalis is the dry tuber of Papaveraceae Herba corydalis edulis plant Rhizoma Corydalis, have invigorate blood circulation, promoting the circulation of QI, analgesic effect.Its main chemical compositions is an alkaloid, and wherein tetrahydropalmatine (structural formula is shown in formula I) belongs to the tertiary amines alkaloid, and analgesic activity is the strongest, has analgesia, calmness, sleeping and stable effect, and especially the dull pain that gastronintestinal system is caused is effective.At present tetrahydropalmatine is as analgesia sleeping class nonprescription drugs medicine, and for example tetrahydropalmatine sulfate sheet, strong pain are peaceful etc.But there is no its report at anti-tumor aspect.
Formula I
Pulmonary carcinoma is a kind of common pulmonary malignant tumour, and its mortality rate accounts for first of the cancer mortality.Most pulmonary carcinoma originate from the bronchial mucosa epithelium, and in recent years, along with smoking and various Effect of Environmental, countries in the world are industrially developed country particularly, and the sickness rate of pulmonary carcinoma and case fatality rate all rise rapidly.Chemotherapy can be used for the advanced lung cancer case separately, with relief of symptoms or with operation, radiotherapy integrated application, to prevent cancerometastasis, recurrence, raising cure rate.Chemotherapeutics commonly used has cyclophosphamide, 5-fluorouracil, ametycin, amycin, procarbazine, vincristine, ammonia methylpurine, lomustine, cisplatin etc.But still lack a kind of safe and effective treatment lung cancer drugs at present clinically.
Summary of the invention
The purpose of this invention is to provide new applications f tetrahydropalmatine.
The purposes of tetrahydropalmatine provided by the present invention is: the application in preparation inhibition eukaryote tumor cell proliferation medicine of the tetrahydropalmatine shown in the formula I or its pharmaceutically acceptable salt.
Formula I
Described tetrahydropalmatine can be levo form, d-isomer or raceme, is preferably the rotundine shown in the formula II;
Figure G200910076383XD0000022
Formula II
The present invention also protects a kind of medicine that suppresses the eukaryote tumor cell proliferation, and its effective ingredient is the tetrahydropalmatine shown in the formula I or its pharmaceutically acceptable salt.
Eukaryote described in the present invention is a mammal.
Described tumor cell is a cancerous cell; Described cancerous cell specifically can be breast cancer cell, hepatoma carcinoma cell, pancreatic cancer cell, lung carcinoma cell, brain cancer cell, ovarian cancer cell, uterus carcinoma cell, testicular cancer cell, skin cancer cell, stomach cancer cell, nasopharyngeal carcinoma cell, colon cancer cell, transitional cell bladder carcinoma cell line, anus cancer cell or rectum cancer cell; Be preferably lung carcinoma cell.
New applications f tetrahydropalmatine provided by the invention also is: acceptable salt prevents and/or treats application in the tumour medicine in preparation on the tetrahydropalmatine shown in the formula I or its materia medica.
Described tetrahydropalmatine can be levo form, d-isomer or raceme, is preferably the rotundine shown in the formula II.
Described tumor cell is a cancerous cell; Described cancerous cell specifically can be breast cancer cell, hepatoma carcinoma cell, pancreatic cancer cell, lung carcinoma cell, brain cancer cell, ovarian cancer cell, uterus carcinoma cell, testicular cancer cell, skin cancer cell, stomach cancer cell, nasopharyngeal carcinoma cell, colon cancer cell, transitional cell bladder carcinoma cell line, anus cancer cell or rectum cancer cell; Be preferably lung carcinoma cell.
With the tetrahydropalmatine shown in the formula I or its pharmaceutically acceptable salt is the medicine that prevents and/or treats tumor of effective ingredient preparation, also belongs to protection scope of the present invention.
The described tumour medicine that prevents and/or treats can import body such as muscle, Intradermal, subcutaneous, vein, mucosal tissue by the method for injection, injection, collunarium, eye drip, infiltration, absorption, physics or chemistry mediation; Or mixed by other materials or wrap up the back and import body.
With tetrahydropalmatine or its pharmaceutically acceptable salt is the antitumor drug of active component, when needing, can also add one or more pharmaceutically acceptable carriers in said medicine.Described carrier comprises diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.
Preventing and/or treating tumour medicine and can make various ways such as injection, tablet, powder, granule, capsule, oral liquid, unguentum, cream with the preparation of tetrahydropalmatine or its pharmaceutically acceptable salt.The medicine of above-mentioned various dosage forms all can be according to the conventional method preparation of pharmaceutical field.
Utilize people's pulmonary carcinoma transplanted tumor model of nude mice that tetrahydropalmatine is carried out the vivo antitumor effect and studies show that tetrahydropalmatine can effectively suppress growth of tumor.And,, and be hopeful very much to develop the antitumor drug that becomes a kind of new and effective, low toxicity, especially anti-lung cancer drugs so the medicinal scope of tetrahydropalmatine has not only been widened in this discovery because tetrahydropalmatine is marketed drug, and its toxicity is lower.
Description of drawings
Fig. 1 is for respectively organizing the big logotype of nude mice in-vivo tumour on the 28th day after the administration, and wherein positive controls empty place represent the tumor disappearance.
The specific embodiment
Embodiment 1, tetrahydropalmatine are to the influence of human lung carcinoma cell multiplication capacity
Tumor cell line: human lung carcinoma cell line A549 (Shanghai Inst. of Cytobiology, Chinese Academy of Sciences);
Experimental animal: be the male BALB/c nude mouse (SPF level, Institute of Experimental Animals, Chinese Academy of Medical Sciences) in 4-6 week age in week, 24;
The weight of animals scope: 16-18g when administration begins, the initial body weight of animal is no more than or is lower than 20% of average weight;
Positive reference substance: cisplatin injection (FH section ancient cooking vessel medical treatment company limited, lot number: M071881);
Negative control product: 0.9% sodium chloride injection (normal saline).
The concrete operations step is as follows:
(1) cultivation of tumor cell
Human lung carcinoma cell line A549 suspension culture in RPMI 1640 culture medium that contain 10% calf serum (containing penicillin 100U/mL, streptomycin 100U/mL), is placed 37 ℃, 5%CO 2The cell incubator in cultivate.Went down to posterity once in per 3 days.Go down to posterity cultivate 24 hours after cell enter exponential phase and can carry out next step test.
(2) foundation of transplanted tumor in nude mice model
Exponential phase A549 cell harvesting is centrifugal, be 0.4% with the quality percentage composition and count after expecting blue solution-dyed.
Adjusting cell concentration with above-mentioned RPMI 1640 culture medium is 1 * 10 7Individual/ml, it is subcutaneous only to be inoculated in nude mice right side axillary fossa with 0.2ml/, preparation lotus tumor kind Mus.
Treat tumor growth to the 1g, the inoculation mice, F1 is for lotus tumor kind Mus in preparation.
The selection tumor growth is vigorous and do not have diabrosis, gets tumor under the tumor animal that health condition is good, aseptic condition, is prepared into 3mm 3, it is subcutaneous to be inoculated in each animal right side axillary fossa.
Observe the tumor growth situation behind the nude inoculation, treat that gross tumor volume is 100-300mm 3The time, to screen by tumor volume size and body weight, excessive the reaching into tumor person of tumor volume will not be selected in.
With the mice with tumor random packet: negative control group, positive controls and tetrahydropalmatine group, 8 every group, grouping gives different pharmaceutical then.
(3) preparation of test sample
Negative control group: give normal saline;
The tetrahydropalmatine group: rotundine (Chengdu Cisco China Bioisystech Co., Ltd), irritating stomach dosage is the 100mg/kg body weight;
Positive controls: give the cisplatin solution of 0.5mg/ml, intraperitoneal administration dosage is: the 0.1ml/10g body weight.
(4) medication
Route of administration and frequency: tetrahydropalmatine and negative control product gastric infusion, every day 1 time, positive reference substance intraperitoneal administration, 1 time/week.The administration time limit: 4 weeks
(5) experimental result:
In process of the test, from grouping, administration, 2 times with vernier caliper measurement and write down tumor major diameter, minor axis and body weight weekly, comprise first administration and last administration same day, calculate gross tumor volume and the difference of tumor growth curve between each group relatively, respectively organized nude mice in-vivo tumour size on the 28th day after the administration and see Fig. 1.
Calculate gross tumor volume according to following formula:
V=1/2 * major diameter * minor axis 2
Carry out therapeutic evaluation according to gross tumor volume
Calculate relative tumour volume (RTV) and relative tumor proliferation rate T/C% according to following formula:
RTV＝Vt/V 0
Vt: measure the tumor volume that tumor obtains every day
V 0: initial tumor volume (before the administration)
RTV meansigma methods * 100% of the RTV meansigma methods/matched group of T/C%=administration group
Utilize the T method of inspection among the biostatistics, each group nude mice experimental result is carried out sorting-out in statistics, the results are shown in Table 1.
Table 1 tetrahydropalmatine is to significant difference (P) result in people's pulmonary carcinoma relative tumour volume (RTV) and each group
Wherein, the significant difference of " P " value for comparing with negative control group.
Table 2 tetrahydropalmatine is to the relative tumor proliferation rate of people's pulmonary carcinoma (T/C%)
Time/sky ??3 ??7 ??10 ??14 ??18 ??22 ??25 ??28
Positive controls ??72.6543 ??49.3087 ??26.5509 ??24.3323 ??20.1204 ??18.2441 ??16.0161 ??16.6303
The tetrahydropalmatine group ??87.6830 ??73.4258 ??31.8297 ??21.2873 ??14.7811 ??21.5647 ??17.3453 ??21.9651
The above results shows that tetrahydropalmatine has the good restraining effect in vivo to people's pulmonary carcinoma.Experimental result shows that tetrahydropalmatine can effectively suppress growth of tumor in the nude mouse, and gross tumor volume is significantly less than negative control.This shows, be widely used in the tetrahydropalmatine of analgesic activity at present, have good antitumor activity, this result has shown that tetrahydropalmatine can be used for preparation treatment lung cancer drugs.The present invention has widened the medical applications field of tetrahydropalmatine.

Claims (10)

1. the tetrahydropalmatine shown in the formula I or its pharmaceutically acceptable salt application in preparation inhibition eukaryote tumor cell proliferation medicine;
Figure F200910076383XC0000011
(formula I).
2. application according to claim 1 is characterized in that: described tetrahydropalmatine is the rotundine shown in the formula II;
(formula II).
3. medicine that suppresses the eukaryote tumor cell proliferation, its effective ingredient is the tetrahydropalmatine shown in the formula I or its pharmaceutically acceptable salt.
4. application according to claim 1 and 2 or medicine according to claim 3 is characterized in that: described eukaryote is a mammal; Described tumor cell is a cancerous cell; Described cancerous cell is breast cancer cell, hepatoma carcinoma cell, pancreatic cancer cell, lung carcinoma cell, brain cancer cell, ovarian cancer cell, uterus carcinoma cell, testicular cancer cell, skin cancer cell, stomach cancer cell, nasopharyngeal carcinoma cell, colon cancer cell, transitional cell bladder carcinoma cell line, anus cancer cell or rectum cancer cell; Be preferably lung carcinoma cell.
5. acceptable salt prevents and/or treats application in the tumour medicine in preparation on the tetrahydropalmatine shown in the formula I or its materia medica.
6. application according to claim 5 is characterized in that: described tetrahydropalmatine is the rotundine shown in the formula II.
7. according to claim 5 or 6 described application, it is characterized in that: described tumor is a cancer.
8. application according to claim 7 is characterized in that: described cancer is breast carcinoma, hepatocarcinoma, cancer of pancreas, pulmonary carcinoma, the brain cancer, ovarian cancer, uterus carcinoma, carcinoma of testis, skin carcinoma, gastric cancer, nasopharyngeal carcinoma, colon cancer, bladder cancer, anus cancer or rectal cancer; Be preferably pulmonary carcinoma.
9. medicine that prevents and/or treats tumor, its effective ingredient is the tetrahydropalmatine shown in the formula I or its pharmaceutically acceptable salt.
10. medicine according to claim 9 is characterized in that: described tumor is a cancer; Described cancer is breast carcinoma, hepatocarcinoma, cancer of pancreas, pulmonary carcinoma, the brain cancer, ovarian cancer, uterus carcinoma, carcinoma of testis, skin carcinoma, gastric cancer, nasopharyngeal carcinoma, colon cancer, bladder cancer, anus cancer or rectal cancer; Be preferably pulmonary carcinoma.
CN200910076383A 2009-01-14 2009-01-14 New applications of tetrahydropalmatine Pending CN101773499A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN200910076383A CN101773499A (en) 2009-01-14 2009-01-14 New applications of tetrahydropalmatine
PCT/CN2009/000563 WO2010081266A1 (en) 2009-01-14 2009-05-22 A new use of tetrahydropalmatine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN200910076383A CN101773499A (en) 2009-01-14 2009-01-14 New applications of tetrahydropalmatine

Publications (1)

Publication Number Publication Date
CN101773499A true CN101773499A (en) 2010-07-14

Family

ID=42339387

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200910076383A Pending CN101773499A (en) 2009-01-14 2009-01-14 New applications of tetrahydropalmatine

Country Status (2)

Country Link
CN (1) CN101773499A (en)
WO (1) WO2010081266A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104327068A (en) * 2014-09-17 2015-02-04 深圳福山生物科技有限公司 Anticancer analgesic selenium-containing compound and preparation method and application thereof
CN104490877A (en) * 2014-12-10 2015-04-08 中国科学院化学研究所 New use of L-tetrahydropalmatine derivatives
WO2017080313A1 (en) * 2015-11-13 2017-05-18 Institute Of Chemistry, Chinese Academy Of Sciences Tetrahydropalmatine derivative, its preparation method and use

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020139999A1 (en) * 2018-12-28 2020-07-02 Addanki Pratap Kumar Pancreatic cancer treatment
CN112755045B (en) * 2021-02-04 2022-08-26 新疆医科大学 Application of turnip neutral polysaccharide in preparation of lung cancer A549 cell regulation and control medicine

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101327214B (en) * 2008-07-18 2011-01-12 中国药科大学 Medicine use of isoquinoline alkaloids as tissue factor inhibitor

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104327068A (en) * 2014-09-17 2015-02-04 深圳福山生物科技有限公司 Anticancer analgesic selenium-containing compound and preparation method and application thereof
CN104490877A (en) * 2014-12-10 2015-04-08 中国科学院化学研究所 New use of L-tetrahydropalmatine derivatives
WO2017080313A1 (en) * 2015-11-13 2017-05-18 Institute Of Chemistry, Chinese Academy Of Sciences Tetrahydropalmatine derivative, its preparation method and use

Also Published As

Publication number Publication date
WO2010081266A1 (en) 2010-07-22

Similar Documents

Publication Publication Date Title
CN101773499A (en) New applications of tetrahydropalmatine
CN102861284B (en) Traditional Chinese medicine compound preparation for treating non-small cell lung cancer and preparation method thereof
CN104398526A (en) Application of triptolide and tripterine in preparation of antitumor drugs
CN104434939B (en) Antitumor medicament composition of panax notoginseng saponins R7 and oridonin with capabilities of reducing toxicity and enhancing efficacy and application of antitumor medicament composition
CN102389559B (en) Traditional Chinese medicine composition and application as radiotherapy sensitizer
CN101342175A (en) Application of sildenafil in preparing antineoplastic medicament
CN102716320A (en) Medicinal composition for treating non-small cell lung cancer
CN102688489A (en) Pharmaceutical composition containing triptolide, triptolide derivative and Bc1-2 inhibitor and application thereof
CN104189782A (en) Anti-tumor medicament composition
CN105311004A (en) Curcumin and application of pharmaceutical salt thereof
CN103316035A (en) Use of sodium bicarbonate in preparation of medicines for treating cancer
CN103463098B (en) Application of hederagenin for preparing antineoplastic drugs
CN101926797A (en) New application of tetrahydropalmatine derivatives
CN111388665B (en) Compound for treating tumor and preparation and application thereof
CN105434432B (en) N-Hydroxyphthalimide class compound application in preparation of anti-tumor drugs
CN103432282A (en) Compound medicine for treating tumor
CN103656646A (en) Anti-tumor drug composition and application thereof
CN107019771A (en) A kind of antineoplastic Chinese medicine composition
CN104523698B (en) Application of the hederagenin in preparation anti-endometrial cancer cell HEC-1 tumour medicine
CN103830262A (en) Auxiliary drug used for treating cancer, and applications thereof
CN101190329B (en) Medicinal composition for regrouping human P43 protein and its application in medication
CN104398704A (en) Traditional Chinese medicine composition for treating stomach cancer and preparation method thereof
CN103142711B (en) Anti-cancer pharmaceutical composition, and preparation method as well as application thereof
CN105535141A (en) Application of radix aconiti lateralis praeparata and cortex cinnamomi bone pain preparation to preparing of medicine for preventing and treating tumor and complications thereof
CN102240298B (en) Pharmaceutical composition for resisting tumors

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C12 Rejection of a patent application after its publication
RJ01 Rejection of invention patent application after publication

Open date: 20100714