WO2016062265A1 - 莫诺苯宗药物在用于制备治疗癌症的医药组合物中的用途 - Google Patents

莫诺苯宗药物在用于制备治疗癌症的医药组合物中的用途 Download PDF

Info

Publication number
WO2016062265A1
WO2016062265A1 PCT/CN2015/092617 CN2015092617W WO2016062265A1 WO 2016062265 A1 WO2016062265 A1 WO 2016062265A1 CN 2015092617 W CN2015092617 W CN 2015092617W WO 2016062265 A1 WO2016062265 A1 WO 2016062265A1
Authority
WO
WIPO (PCT)
Prior art keywords
cancer
monobenzone
10min
cells
use according
Prior art date
Application number
PCT/CN2015/092617
Other languages
English (en)
French (fr)
Inventor
陈丘泓
庄秀美
魏宗德
萧乃文
Original Assignee
朗齐生物医学股份有限公司
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 朗齐生物医学股份有限公司 filed Critical 朗齐生物医学股份有限公司
Priority to US15/521,540 priority Critical patent/US10098852B2/en
Publication of WO2016062265A1 publication Critical patent/WO2016062265A1/zh

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
    • C07C211/27—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring having amino groups linked to the six-membered aromatic ring by saturated carbon chains
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
    • C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention is an application of a new indication for a monobenzone drug, in particular, the use of the monobenzone drug for inhibiting various cancers.
  • Monobenzone is a topical decolorizing agent used to treat hyperpigmentation, such as various pigmentation, senile plaques, melanoma, etc., and the effect is obvious. It can break down the melanin in the skin, prevent the formation of melanin in the skin, restore the skin to a healthy color, without destroying the melanocytes, the toxicity is very light, usually made into an ointment or tincture. Monobenzone is a drug that has long been approved by the FDA and has a large number of drug transfer and human research results.
  • cancer has long been the leading cause of death worldwide, and the number of cancer patients has increased year by year. Therefore, treating cancer has become an important issue.
  • cancer drug treatment whether it is chemotherapy or target treatment, is intended to prevent cancer cells from replicating and dividing to block the spread and spread of tumors. According to statistics, only about five out of every 10,000 new drugs can enter the first phase of clinical trials. Further, many cancer cells successively develop drug resistance, which greatly reduces the effectiveness of drug use, and ultimately leads to failure of cancer treatment. This shows that drug development has a certain degree of difficulty.
  • the present invention aims at the development of new indications for monotil drugs, and achieves the goal of new use of old drugs.
  • the experimental design results show that the Monobenzone drug has no or only minimal toxicity to normal cells, but Monobenzone has a selective effect on tumor cells.
  • the invention provides a pharmaceutical composition for preparing cancer for treating monoclofen
  • the use of the pharmaceutical composition comprising an effective amount of a monobenzone drug and a pharmaceutically acceptable salt.
  • the cancer is one or more selected from the group consisting of a chest-related cancer, an abdominal cavity-related cancer, an endocrine-related cancer, and a digestive tract-related cancer.
  • the cancer is one or more selected from the group consisting of an osteosarcoma-related cancer, a skin cancer-related cancer, and a blood cancer-related cancer.
  • chest cavity related cancer refers to lung cancer
  • the abdominal cavity-related cancer is selected from the group consisting of bladder cancer or/and cervical cancer.
  • the endocrine-related cancer is one or more selected from the group consisting of prostate cancer, breast cancer, and ovarian cancer.
  • the endocrine-related cancer is one or more selected from the group consisting of gastric cancer, liver cancer, colon cancer, pancreatic cancer, and tongue cancer.
  • the effective dose concentration of the monoxantine drug is 20 to 500 mg/kg/day.
  • Fig. 1 shows the results of application of the monoxantine of the present invention for inhibiting cancer cell analysis.
  • FIG. 2 shows the effect of monobenzone on tumor volume
  • Figure 3 shows the inhibitory effect of high-dose and low-dose monobenzone on tumor growth
  • Subculture of cell lines of different cancer types including cancerous lung cancer, gastric cancer, liver cancer, rectal cancer, skin cancer, cervical cancer, prostate cancer, bladder cancer, breast cancer, blood cancer, pancreatic cancer, ovarian cancer, tongue cancer Osteosarcoma, kidney cancer, and the control group also used normal cells of the kidney (HEK293 (Kidney)) and lung epithelial cells BEAS-2B (Lung Epithelial) for testing.
  • HEK293 Kidney
  • BEAS-2B Lung Epithelial
  • the cells corresponding to different species should be counted with the corresponding culture solution (Table 1), and the number of cells should be counted, and the number of cells should be 2 ⁇ 10 6 cells.
  • the culture medium in which the cell strain was cultured was added to a volume of 10 ml, and the culture was continued for 2-3 days. The cells were then counted and dispensed into 96-well plates where the number of cells per well was fixed at 3000 cells and the volume was 100 ul.
  • the original culture solution in the 96-well plate was aspirated, and a commercially available drug having a concentration of 10 ⁇ m and a volume of 100 ul was added to each well. After 72 hours, 100 ul of diluted WST-1 reagent was added to each well, and the dilution ratio was the culture solution and The volume ratio of the WST-1 stock solution is 9:1. Finally, the total volume of each well plate is 200 ul. Then, the 96-well plate is placed at 37 ° C for 30-90 minutes, using an elisa reader (ELISA) on the OD450. The absorbance values were detected and the survival rate of each cancer cell line was calculated.
  • ELISA elisa reader
  • the analysis of the inhibitory effect of monoxantine on the cells of the abdominal cavity-related cancer was mainly tested on two types of cells of the abdominal cavity-related cancer.
  • the bladder cancer cell lines were TSGH and T24, respectively (Table 3), cervical cancer cells.
  • the strains were HeLa cell line (Table 4), and kidney cancer was 786-O cell strain (Table 5).
  • the results of cancer cell inhibition experiments were performed 4 times each, and the average value was calculated. The results are shown below.
  • the analysis of the inhibitory effect of monoxantine on the cells of the abdominal cavity-related cancer was mainly tested against three types of endocrine-related cancer cells, which were PC-3 and LNCap, respectively (Table 6), breast cancer cells.
  • the strains were MCF7 and MDA-MB-231, respectively (Table 7), and the ovarian cancer cell lines were NIH-OVCAR-3 cell line and TOV-21G (Table 8), respectively.
  • the results are calculated and their average values are calculated, and the results are listed below.
  • the gastric cancer cell lines are AGS and MKN-45, respectively (Table 9), liver cancer cells.
  • the strains were HepG2 and Hep3B, respectively (Table 10)
  • the colorectal cancer cell lines were HCT116-wt and LoVo cell lines (Table 11)
  • the pancreatic cancer cell lines were AsPC and BxPC cell lines, respectively (Table 12).
  • the tongue cancer cell line was a SAS cell strain (Table 13), and the results of the cancer cell inhibition experiments were performed four times each, and the average value was calculated, and the results are shown below.
  • the osteosarctic cancer cell line was U2OS cell line (Table 14)
  • the skin cancer cell lines were A375 and BCC cell lines (Table 15)
  • the normal kidney cell line is HEK293 cell line (Table 16)
  • the normal fibroblast cell line is HFW cell line (Table 17)
  • the normal lung epithelial cell line is HEK293 cell line (Table 18)
  • the results of the cancer cell inhibition experiments were performed 4 times each, and the average value was calculated, and the results are shown below.
  • mice Female BALB/cAnN.Cg-Foxn1nu/CrlNarl mice were used as samples (purchased from National Laboratory Animal Center), weighing 21 ⁇ 1g, subcutaneously injected into gastric cancer cells (AGS) and randomly divided into cages.
  • the test drugs were divided into three groups: Normal control group, low dose (100 mg/kg/day), high dose (200 mg/kg/day).
  • the tumor formed more than 100 mm 3
  • the drug was administered by intraperitoneal injection every day; the tumor size was measured twice a week, and the tumor volume measurement formula was as follows: (L ⁇ W2); L represents the longest diameter of the tumor; W represents the shortest diameter of the tumor.
  • the test results are shown in Table 20.
  • both low-dose and high-dose monobenzone have good inhibitory effects on tumors, and the weight of mice in each group did not decrease significantly during the experiment. Both the high and low doses can make the tested mice have good health without death during the treatment.
  • high and low doses of monobenzone can effectively reduce tumor volume growth and simultaneously reduce tumor volume, with high doses of monobenzone having better effects.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Emergency Medicine (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Communicable Diseases (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Steroid Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

本发明提供了莫诺苯宗在制备治疗癌症的医药组合物中的用途。

Description

莫诺苯宗药物在用于制备治疗癌症的医药组合物中的用途 技术领域
本发明为莫诺苯宗药物的新适应症的应用，尤其该莫诺苯宗药物具有抑制多种癌症的用途。
背景技术
莫诺苯宗(Monobenzone)是一种局部使用的脱色剂，用于治疗色素沉着过度，如各种色斑、老年斑、黑色素瘤等，效果很明显。它能分解皮肤中的黑色素，阻止皮肤中黑色素的生成，使皮肤恢复健康的色泽，而并不破坏黑色素细胞，毒性很轻，通常制成软膏或搽剂。莫诺苯宗是早已被FDA所认可的用药，具有大量药物机转及人体研究成果资料。
由于临床应用上的明显差异，因此从来没有人认为莫诺苯宗具有抑制癌症细胞的可能性。
癌症长期高居全球死因之首，且罹患癌症人数更是逐年攀升，因此治疗癌症俨然成为重要的课题。一般来说，癌症药物治疗无论是化学治疗或标靶治疗，目的多是让癌细胞无法复制、分裂，来阻断肿瘤的蔓延扩张。根据统计，平均每一万个新药约只有五个能够进入第一期临床试验。进一步，许多癌细胞相继产生抗药性，使药物的使用成效大幅降低，最终导致癌症治疗失败。由此可见药物开发具有一定的困难程度。
因此，如何能让癌症药物的快速的可以被开发出来，并且尽可能的减少临床失败的机率，在癌症病学上是一个非常急迫又重要的课题。
发明内容
为解决上述的问题，本发明针对莫诺苯宗药物进行新适应症的研发，而达到老药新用的目标。
经过实验设计结果显示莫诺苯宗药物对正常细胞没有或仅有微小的毒性，但莫诺苯宗在肿瘤细胞之间具有选择性的影响。
本发明提供一种莫诺苯宗药物在用于制备治疗癌症的医药组合物 中用途，其中所述医药组合物包含有效剂量的莫诺苯宗药物及药学上可接受的盐类所组成。
本发明一实施例中，其中所述癌症是选自由胸腔相关癌症、腹腔相关癌症、内分泌相关癌症、消化道相关癌症中的一种或多种。
本发明一实施例中，其中所述癌症是选自由骨肉瘤相关癌症、皮肤癌相关癌症、血癌相关癌症中的一种或多种。
本发明一实施例中，其中所述胸腔相关癌症是指肺癌。
本发明一实施例中，其中所述腹腔相关癌症是选自由膀胱癌或/和子宫颈癌。
本发明一实施例中，其中所述内分泌相关癌症是选自由前列腺癌、乳癌及卵巢癌中的一种或多种。
本发明一实施例中，其中所述内分泌相关癌症是选自由胃癌、肝癌、大肠癌、胰脏癌及舌癌中的一种或多种。
本发明一实施例中，其中所述莫诺苯宗药物的有效剂量浓度为20～500mg/kg/天。
附图说明
图1显示本发明莫诺苯宗用药应用于抑制癌细胞分析结果。
图2显示莫诺苯宗用药可对肿瘤体积的效果
图3显示高剂量及低剂量莫诺苯宗对肿瘤生长的抑制效果
具体实施方式
各种癌症细胞株建立
将不同癌症类型的细胞株进行继代培养，癌症细胞种类包含肺癌、胃癌、肝癌、直肠癌、皮肤癌、子宫颈癌、前列腺癌、膀胱癌、乳癌、血癌、胰腺癌、卵巢癌、舌癌、骨肉瘤、肾脏癌，并且对照组亦使用肾脏(HEK293(Kidney))、肺部上皮细胞BEAS-2B(Lung Epithelial)的正常细胞做测试。(表一)
先将各细胞于培养液培养后，由于各细胞的属性不同，因此针对不同种的细胞也要用相对应的培养液(表一)，计算细胞数目，将2×106细胞数至入培养皿中，然后加入培养该细胞株的培养液补至体积为10ml，继续培养2-3天。之后将细胞计数，并分装至96孔盘，其中每孔的细胞数目固定为3000个细胞，且体积为100ul。
表一、癌症测试细胞株及其培养所用的培养液
Figure PCTCN2015092617-appb-000001
Figure PCTCN2015092617-appb-000002
细胞存活分析方法
将96孔盘中原有的培养液吸掉，每孔加入浓度10um、体积100ul的市售药物，放置72小时后，每孔再加入100ul已稀释的WST-1试剂，该稀释比例为培养液与WST-1原液的体积比为9：1，最后每个孔盘的总体积为200ul，然后将96孔盘放置于37℃，30～90分钟，利用elisa reader(酶联免疫检测仪)于OD450侦测吸光值，并计算各癌症细胞株的存活率。
莫诺苯宗药对于各种癌细胞分析结果
莫诺苯宗对胸腔相关癌症细胞抑制效果的测试
本分析莫诺苯宗对胸腔相关癌症细胞抑制效果的测试，主要针对两种肺癌细胞进行测试，癌细胞株分别为A549和H1650两个细胞株，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。(表二)
表二、莫诺苯宗对肺癌相关癌症细胞抑制测试
  0524-10min 0526-10min 0529-10min 0531-10min 平均
A549 80.8 111.1 80.8 100.9 93.4
  1-10min 2-20min 3-20min 4-20min 平均
H1650 90.1 66.6 86.7 101.8 86.3
莫诺苯宗对腹腔相关癌症细胞抑制效果的测试
本分析莫诺苯宗对腹腔相关癌症细胞抑制效果的测试，主要针对两种腹腔相关癌症种类细胞进行测试，膀胱癌细胞株分别为TSGH和T24两个细胞株(表三)，子宫颈癌细胞株分别为HeLa细胞株(表四)，肾脏癌为786-O细胞株(表五)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。
表三、莫诺苯宗对膀胱癌相关癌症细胞抑制测试
Figure PCTCN2015092617-appb-000003
表四、莫诺苯宗对子宫颈癌相关癌症细胞抑制测试
  0524-10min 0526-10min 0529-10min 0531-10min 平均
HeLa 82.8 72.8 82.7 81.9 80.1
  1 2 3 4 平均
C-33A 57.9 66.2 61.0 64.3 62.3
表五、莫诺苯宗对肾脏癌相关癌症细胞抑制测试
  1 2 3 4 平均
786-O 39.8 32.4 21.2 23.4 29.2
莫诺苯宗对内分泌相关癌症细胞抑制效果的测试
本分析莫诺苯宗对腹腔相关癌症细胞抑制效果的测试，主要针对三种内分泌相关癌症种类细胞进行测试，前列腺癌细胞株分别为PC-3和LNCap两个细胞株(表六)，乳癌细胞株分别为MCF7和MDA-MB-231两个细胞株(表七)，卵巢癌细胞株分别为NIH-OVCAR-3细胞株和TOV-21G(表八)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。
表六、莫诺苯宗对前列腺癌相关癌症细胞抑制测试
Figure PCTCN2015092617-appb-000004
表七、莫诺苯宗对乳癌相关癌症细胞抑制测试
Figure PCTCN2015092617-appb-000005
Figure PCTCN2015092617-appb-000006
表八、莫诺苯宗对卵巢癌相关癌症细胞抑制测试
Figure PCTCN2015092617-appb-000007
莫诺苯宗对消化道相关癌症细胞抑制效果的测试
分析莫诺苯宗对消化道相关癌症细胞抑制效果的测试，主要针对五种消化道相关癌症种类细胞进行测试，胃癌细胞株分别为AGS和MKN-45两个细胞株(表九)，肝癌细胞株分别为HepG2和Hep3B两个细胞株(表十)，大肠癌细胞株分别为HCT116-wt和LoVo细胞株(表十一)，胰脏癌细胞株分别为AsPC和BxPC细胞株(表十二)，舌癌细胞株为SAS细胞株(表十三)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。
表九、莫诺苯宗对胃癌相关癌症细胞抑制测试
Figure PCTCN2015092617-appb-000008
表十、莫诺苯宗对肝癌相关癌症细胞抑制测试
  0524-20min 0526-20min 0529-20min 0531-20min 平均
HepG2 88.2 85.6 90.8 74.3 84.7
  0612-20min 0614-20min 0616-20min 0619-20min 平均
Hep3B 110.6 116.2 96.8 100.6 106.1
表十一、莫诺苯宗对大肠癌相关癌症细胞抑制测试
  0602-30min 0605-10min 0607-10min 0609-10min 平均
HCT116-wt 91.12 103.66 99.94 85.3 95.0
  0616-10min 0619-10min 0621-10min 0623-10min 平均
LoVo 82.29 73.94 94.7 81.3 83.0
表十二、莫诺苯宗对胰脏癌相关癌症细胞抑制测试
  1-7-3-30min 1-7-4-30min 1-7-7-30min 1-4-30min 平均
AsPC 88.7 116.5 81.7 93.7 95.1
  3-7-3-30min 3-7-4-30min 3-7-7-30min 3-4-30min 平均
BxPC 57.4 100.0 70.7 86.3 78.6
表十三、莫诺苯宗对舌癌相关癌症细胞抑制测试
  6-26-10min 6-28-10min 6-30-10min 7-3-10min 平均
SAS 97.29 59.36 89.56 115.2 90.3
莫诺苯宗对其他癌症细胞抑制效果的测试
分析莫诺苯宗对其他类型癌正进行测试，骨肉癌细胞株为U2OS细胞株(表十四)，皮肤癌细胞株分别为A375和BCC两个细胞株(表十五)，各做3～4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。
表十四、莫诺苯宗对骨肉瘤相关癌症细胞抑制测试
  6-26-10min 6-28-10min 6-30-10min 7-3-10min 平均
U2OS 69.3 66.7 73.0 81.7 72.7
表十五、莫诺苯宗对皮肤癌相关癌症细胞抑制测试
  0602-30min 0605-10min 0607-10min 0609-10min 平均
A375 56.7 64.8 77.3 106.8 76.4
  0602-30min 0605-10min 0607-10min 0609-10min 平均
BCC 48.2 59.8 38.6 53.80 50.1
对照组实验设计
莫诺苯宗对正常细胞抑制效果的测试
分析莫诺苯宗对多种正常细胞进行测试，正常肾脏细胞株为HEK293细胞株(表十六)，正常纤维母细胞细胞株为HFW细胞株(表十七)，正常肺部上皮细胞细胞株为BEAS-2B细胞株(表十八)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。
表十六、莫诺苯宗对正常肾脏细胞抑制测试
  0602-30min 0605-30min 0607-30min 0609-30min 平均
HEK293 82.7 99.43 97.88 91.84 93.0
表十七、莫诺苯宗对正常纤维母细胞抑制测试
  0612-10min 0614-10min 0616-10min 0619-10min 平均
HFW 119.66 74.93 68.08 79.13 85.4
表十八、莫诺苯宗对正常肺部上皮细胞抑制测试
  0510-10min 0512-10min 0515-10min 0517-10min 平均
BEAS-2B 84.7 79.5 74.9 56.2 73.8
针对莫诺苯宗对各种癌症细胞抑制效果汇整于表十九中，清楚看 出莫诺苯宗对于多项癌症有明显的抑制效果。经过发明人实验结果，莫诺苯宗药物对于不同的癌症细胞有明显的抑制效果。(图一)
表十九、莫诺苯宗对各种癌症细胞抑制效果的汇整
癌症细胞 抑制效果
肺癌 89.85
膀胱癌 85.80
子宫颈癌 71.20
肾脏癌 29.20
前列腺癌 65.20
乳癌 87.90
卵巢癌 84.95
胃癌 82.80
肝癌 95.40
大肠癌 89.00
胰脏癌 86.85
舌癌 90.30
骨肉癌 72.70
皮肤癌 63.25
正常细胞 抑制效果
肾脏 93.00
肺部上皮细胞 73.80
动物实验分析
本实验使用雌性BALB/cAnN.Cg-Foxn1nu/CrlNarl小鼠为样本(购自国家实验动物中心)，体重为21±1g，皮下注射胃癌细胞(AGS)后随机分笼，测试药物分成三组:正常对照组、低剂量(100mg/kg/天)、高剂量(200mg/kg/天)。肿瘤形成超过100mm3后，每天采取腹腔注射方式给予药物；每周测量肿瘤大小两次，肿瘤体积测量公式如下：(L×W2)；L代表肿瘤最长直径；W代表肿瘤最短直径。试验结果如表二十所示。
Figure PCTCN2015092617-appb-000009
Figure PCTCN2015092617-appb-000010
Figure PCTCN2015092617-appb-000011
依据第2图的结果，低剂量与高剂量的莫诺苯宗均对肿瘤具有良好的抑制效果，且于实验过程中各组小鼠的重量均未出现明显降低的现象，因此表示莫诺苯宗不论高低剂量在治疗过程均能使受测小鼠具有良好的健康状态而不死亡。
依据第3图的结果，高低剂量的莫诺苯宗可有效减缓肿瘤体积增长，并可同时减少肿瘤体积，其中以高剂量的莫诺苯宗具有较佳的效果。
上列详细说明是针对本发明之一可行实施例的具体说明，惟该实施例并非用以限制本发明的专利范围，凡未脱离本发明技艺精神所为的等效实施或变更，均应包含于本发明的专利范围中。

Claims (8)

  1. 一种莫诺苯宗药物在用于制备治疗癌症的医药组合物中的用途，其特征是，所述医药组合物是选自由有效剂量的莫诺苯宗(Monobenzone)及药学上可接受的盐类所组成。
  2. 如权利要求1所述的用途，其特征是，所述癌症为胸腔相关癌症、腹腔相关癌症、内分泌相关癌症、消化道相关癌症中的一种或多种。
  3. 如权利要求1所述的用途，其特征是，所述癌症是选自骨肉瘤相关癌症、皮肤癌相关癌症中的一种或多种。
  4. 如权利要求2所述的用途，其特征是，所述胸腔相关癌症是指肺癌。
  5. 如权利要求2所述的用途，其特征是，所述腹腔相关癌症是选自膀胱癌、子宫颈癌、肾脏癌中的一种或多种。
  6. 如权利要求2所述的用途，其特征是，所述内分泌相关癌症系选自由前列腺癌、乳癌、卵巢癌中的一种或多种。
  7. 如权利要求2所述的用途，其特征是，所述消化道相关癌症系选自由胃癌、肝癌、大肠癌、胰脏癌、舌癌中的一种或多种。
  8. 如权利要求1所述的用途，其特征是，所述有效剂量浓度为每日20mg/kg～500mg/kg。
PCT/CN2015/092617 2014-10-24 2015-10-23 莫诺苯宗药物在用于制备治疗癌症的医药组合物中的用途 WO2016062265A1 (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US15/521,540 US10098852B2 (en) 2014-10-24 2015-10-23 Indication of monobenzone pharmaceutical composition for treating cancer

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462068298P 2014-10-24 2014-10-24
US62/068,298 2014-10-24

Publications (1)

Publication Number Publication Date
WO2016062265A1 true WO2016062265A1 (zh) 2016-04-28

Family

ID=55760314

Family Applications (21)

Application Number Title Priority Date Filing Date
PCT/CN2015/092697 WO2016062272A1 (zh) 2014-10-24 2015-10-23 免疫疾病用药物在制备抑制癌症的医药组合物中的应用
PCT/CN2015/092686 WO2016062271A1 (zh) 2014-10-24 2015-10-23 抗生素药物用于制备治疗癌症的医药组合物的用途
PCT/CN2015/092677 WO2016062270A1 (zh) 2014-10-24 2015-10-23 呼吸系统疾病用药用于制备抗癌医药组合物的用途
PCT/CN2015/092746 WO2016062277A1 (zh) 2014-10-24 2015-10-23 驱虫药用于制备抗癌医药组合物中的应用
PCT/CN2015/092775 WO2016062285A1 (zh) 2014-10-24 2015-10-23 神经系统疾病用药在制备抗癌医药组合物中的应用
PCT/CN2015/092771 WO2016062283A1 (zh) 2014-10-24 2015-10-23 抗发炎用药物在制备抑制癌症的医药组合物中的应用
PCT/CN2015/092776 WO2016062286A1 (zh) 2014-10-24 2015-10-23 脱克钙药物在用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092782 WO2016062291A1 (zh) 2014-10-24 2015-10-23 千忧解药物在用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092761 WO2016062279A1 (zh) 2014-10-24 2015-10-23 苹果酸丙氯陪拉辛锭用于制备治疗癌症药物的用途
PCT/CN2015/092666 WO2016062269A1 (zh) 2014-10-24 2015-10-23 阿那格雷在用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092617 WO2016062265A1 (zh) 2014-10-24 2015-10-23 莫诺苯宗药物在用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092777 WO2016062287A1 (zh) 2014-10-24 2015-10-23 山喜多药物在用于制备抑制癌症的医药组合物中的用途
PCT/CN2015/092781 WO2016062290A1 (zh) 2014-10-24 2015-10-23 氨苯蝶啶药物在用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092780 WO2016062289A1 (zh) 2014-10-24 2015-10-23 帕罗西汀药物用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092779 WO2016062288A1 (zh) 2014-10-24 2015-10-23 代谢性疾病药物用于制备抑制癌症的医药组合物的用途
PCT/CN2015/092768 WO2016062281A1 (zh) 2014-10-24 2015-10-23 心血管疾病用药物在制备抑制癌症的医药组合物中的应用
PCT/CN2015/092753 WO2016062278A1 (zh) 2014-10-24 2015-10-23 内分泌疾病用药在制备抑制癌症的医药组合物中的应用
PCT/CN2015/092653 WO2016062267A1 (zh) 2014-10-24 2015-10-23 奈必洛尔在制备抑制癌症的医药组合物中的用途
PCT/CN2015/092714 WO2016062275A1 (zh) 2014-10-24 2015-10-23 阿折地平在制备治疗癌症的医药组合物中的用途
PCT/CN2015/092632 WO2016062266A1 (zh) 2014-10-24 2015-10-23 氨氯地平在制备抑制癌症的医药组合物中的用途
PCT/CN2015/092702 WO2016062274A1 (zh) 2014-10-24 2015-10-23 消化系统疾病用药物在制备抑制癌症的医药组合物中的应用

Family Applications Before (10)

Application Number Title Priority Date Filing Date
PCT/CN2015/092697 WO2016062272A1 (zh) 2014-10-24 2015-10-23 免疫疾病用药物在制备抑制癌症的医药组合物中的应用
PCT/CN2015/092686 WO2016062271A1 (zh) 2014-10-24 2015-10-23 抗生素药物用于制备治疗癌症的医药组合物的用途
PCT/CN2015/092677 WO2016062270A1 (zh) 2014-10-24 2015-10-23 呼吸系统疾病用药用于制备抗癌医药组合物的用途
PCT/CN2015/092746 WO2016062277A1 (zh) 2014-10-24 2015-10-23 驱虫药用于制备抗癌医药组合物中的应用
PCT/CN2015/092775 WO2016062285A1 (zh) 2014-10-24 2015-10-23 神经系统疾病用药在制备抗癌医药组合物中的应用
PCT/CN2015/092771 WO2016062283A1 (zh) 2014-10-24 2015-10-23 抗发炎用药物在制备抑制癌症的医药组合物中的应用
PCT/CN2015/092776 WO2016062286A1 (zh) 2014-10-24 2015-10-23 脱克钙药物在用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092782 WO2016062291A1 (zh) 2014-10-24 2015-10-23 千忧解药物在用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092761 WO2016062279A1 (zh) 2014-10-24 2015-10-23 苹果酸丙氯陪拉辛锭用于制备治疗癌症药物的用途
PCT/CN2015/092666 WO2016062269A1 (zh) 2014-10-24 2015-10-23 阿那格雷在用于制备治疗癌症的医药组合物中的用途

Family Applications After (10)

Application Number Title Priority Date Filing Date
PCT/CN2015/092777 WO2016062287A1 (zh) 2014-10-24 2015-10-23 山喜多药物在用于制备抑制癌症的医药组合物中的用途
PCT/CN2015/092781 WO2016062290A1 (zh) 2014-10-24 2015-10-23 氨苯蝶啶药物在用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092780 WO2016062289A1 (zh) 2014-10-24 2015-10-23 帕罗西汀药物用于制备治疗癌症的医药组合物中的用途
PCT/CN2015/092779 WO2016062288A1 (zh) 2014-10-24 2015-10-23 代谢性疾病药物用于制备抑制癌症的医药组合物的用途
PCT/CN2015/092768 WO2016062281A1 (zh) 2014-10-24 2015-10-23 心血管疾病用药物在制备抑制癌症的医药组合物中的应用
PCT/CN2015/092753 WO2016062278A1 (zh) 2014-10-24 2015-10-23 内分泌疾病用药在制备抑制癌症的医药组合物中的应用
PCT/CN2015/092653 WO2016062267A1 (zh) 2014-10-24 2015-10-23 奈必洛尔在制备抑制癌症的医药组合物中的用途
PCT/CN2015/092714 WO2016062275A1 (zh) 2014-10-24 2015-10-23 阿折地平在制备治疗癌症的医药组合物中的用途
PCT/CN2015/092632 WO2016062266A1 (zh) 2014-10-24 2015-10-23 氨氯地平在制备抑制癌症的医药组合物中的用途
PCT/CN2015/092702 WO2016062274A1 (zh) 2014-10-24 2015-10-23 消化系统疾病用药物在制备抑制癌症的医药组合物中的应用

Country Status (9)

Country Link
US (7) US10105357B2 (zh)
EP (3) EP3222278B1 (zh)
JP (1) JP6539345B2 (zh)
KR (1) KR102490334B1 (zh)
CN (3) CN107106550A (zh)
AU (2) AU2015335375B2 (zh)
ES (1) ES2954860T3 (zh)
TW (21) TW201615195A (zh)
WO (21) WO2016062272A1 (zh)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5409010B2 (ja) 2005-12-28 2014-02-05 バーテックス ファーマシューティカルズ インコーポレイテッド Ｎ−［２，４−ビス（１，１−ジメチルエチル）−５−ヒドロキシフェニル］−１，４−ジヒドロ−４−オキソキノリン−３−カルボキサミドの固体形態
WO2016062272A1 (zh) * 2014-10-24 2016-04-28 朗齐生物医学股份有限公司 免疫疾病用药物在制备抑制癌症的医药组合物中的应用
PL3236967T3 (pl) 2014-12-22 2020-04-30 Suda Pharmaceuticals Ltd Zapobieganie i leczenie przerzutów u pacjentów z nadpłytkowością typu nowotworowego
WO2017116049A1 (ko) * 2015-12-31 2017-07-06 경북대학교 산학협력단 설폰아마이드계 화합물을 유효성분으로 포함하는 암의 치료 및 전이 억제용 약학적 조성물
EP3241562A1 (en) * 2016-05-02 2017-11-08 Fundació Institut Mar d'Investigacio Medica Zonisamide for use in the treatment of breast cancer
CN106074474A (zh) * 2016-06-15 2016-11-09 中南大学湘雅医院 羟苄丝肼及其在药学上可接受的盐在制备抗肿瘤药物方面的应用
WO2018072135A1 (zh) * 2016-10-19 2018-04-26 微菌方舟生物科技股份有限公司 二氢吡啶类钙拮抗剂用于治疗癌症的用途
CN108066345A (zh) * 2016-11-14 2018-05-25 武汉华杰世纪生物医药有限公司 一种具有抗肿瘤作用的化合物
WO2018115001A1 (en) 2016-12-20 2018-06-28 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system containing asenapine
BR112019012573A2 (pt) 2016-12-20 2019-11-19 Lts Lohmann Therapie Systeme Ag sistema terapêutico transdérmico que contém asenapina e polissiloxano ou poli-isobutileno
US20200179404A1 (en) * 2017-06-09 2020-06-11 Regents Of The University Of Minnesota Skin care formulations and skin cancer treatment
ES2881783T3 (es) 2017-06-26 2021-11-30 Lts Lohmann Therapie Systeme Ag Sistema terapéutico transdérmico que contiene asenapina y polímero de acrílico y silicona
WO2019008516A2 (en) * 2017-07-03 2019-01-10 Menri Group Ltd. TREATMENT OF CANCER WITH DIHYDROPYRIDINES
JP2019064976A (ja) * 2017-10-03 2019-04-25 国立大学法人 熊本大学 抗がん剤
KR101933805B1 (ko) 2017-10-17 2018-12-28 성균관대학교산학협력단 옥셀라딘시트레이트를 유효성분으로 포함하는 뇌암 예방 또는 치료용 약학적 조성물
CN108186652A (zh) * 2017-12-28 2018-06-22 深圳大学 缝隙连接细胞间通迅抑制剂甘珀酸在制备预防和治疗肝细胞癌药物中的应用
AU2019214891A1 (en) 2018-01-30 2020-08-20 Apnimed, Inc. (Delaware) Methods and compositions for treating sleep apnea
WO2019204764A1 (en) * 2018-04-19 2019-10-24 Washington University Compositions and methods of use thereof for treatment of proteinopathies
CN112704672A (zh) 2018-06-20 2021-04-27 罗曼治疗系统股份公司 含有阿塞那平的透皮治疗系统
FR3090084B1 (fr) 2018-12-18 2023-10-13 Securengy Projectile pour armes à feu ou air comprimé pour emport liquide ou pulvérulent.
WO2020132253A1 (en) * 2018-12-19 2020-06-25 University Of Vermont And State Agricultural College Cancer therapeutic compositions and methods
US20220193020A1 (en) * 2019-04-04 2022-06-23 Daegu-Gyeongbuk Medical Innovation Foundation Pharmaceutical Composition Comprising Trimebutine or Pharmaceutically Acceptable Salt Thereof as an Active Ingredient For Prevention or Treatment of Cancer
US20220202771A1 (en) * 2019-04-05 2022-06-30 University Of North Texas Health Science Center At Fort Worth Antidepressants for the Treatment or Prevention of Memory Loss and/or Cognitive Decline or Dysfunction in Aging
WO2020210643A1 (en) * 2019-04-11 2020-10-15 Ian Basil Shine Cell membrane permeability restoring therapy
CN110179803A (zh) * 2019-05-31 2019-08-30 天津科技大学 一种噻吨溴类化合物的应用
CN110742890A (zh) * 2019-10-24 2020-02-04 暨南大学 洛美利嗪在制备抗结肠癌药物中的应用
CN110840887A (zh) * 2019-11-18 2020-02-28 杭州彗搏科技有限公司 三氯苯达唑在制备治疗乳腺癌的药物中的应用
CN110876800B (zh) * 2019-11-18 2023-06-27 中南大学 米卡芬净在制备抗肿瘤药物中的应用及抗肿瘤药物
CN111067899B (zh) * 2020-01-08 2021-03-05 温州医科大学 一种抗疟药物磷酸伯氨喹在制备治疗白血病药物上的应用
US11304969B2 (en) * 2020-01-24 2022-04-19 The Florida International Univeristy Board Of Trustees Treatments of prostate cancer
CN111973593A (zh) * 2020-05-09 2020-11-24 深圳市罗湖区人民医院 硝唑尼特及其药学上可接受的盐在制备治疗膀胱癌药物中的用途
CN111557941A (zh) * 2020-06-15 2020-08-21 浙江大学 Plod2的小分子抑制剂米诺地尔在肿瘤治疗中的应用
CN111848717A (zh) * 2020-08-07 2020-10-30 四川大学 靶向调控线粒体能量代谢的化合物及其应用和药物
WO2022033465A1 (zh) * 2020-08-10 2022-02-17 萧乃文 具有协同抗癌功效的氯硝柳胺和双硫仑医药组合物及其用途
CN112274525B (zh) * 2020-12-04 2022-04-08 遵义医科大学 一种化疗药物组合物及其应用
CN112336725A (zh) * 2020-12-11 2021-02-09 吴照球 甲氧苄啶的医药新用途
CN112569342A (zh) * 2020-12-21 2021-03-30 中南大学 卡泊芬净和/或其可药用盐在制备抗肿瘤药物中的应用及抗肿瘤药物
CN112569215A (zh) * 2020-12-30 2021-03-30 东莞市人民医院 度米芬在制备防治结直肠癌的药物中的应用
EP4108244A1 (en) * 2021-06-25 2022-12-28 Universität Regensburg Ss-lactam antibiotic with significant activity against cancer e.g. colon malignancies
CN113663071B (zh) * 2021-06-28 2022-12-30 四川大学 Fbxl2激活剂在制备治疗egfr驱动的肺癌的药物中的用途
WO2023006954A1 (en) 2021-07-30 2023-02-02 Fundació Institut D'investigació Biomèdica De Bellvitge (Idibell) Asenapine for use in cancer
WO2023035200A1 (zh) * 2021-09-09 2023-03-16 中国福利会国际和平妇幼保健院 五氟利多在制备治疗子宫内膜癌的药物中的应用
CN115887455B (zh) * 2022-08-04 2024-04-05 北京大学人民医院 钙离子通道阻滞剂阿折地平在制备治疗子宫内膜癌的药物中的应用
CN116570579A (zh) * 2023-06-13 2023-08-11 深圳市泛谷药业股份有限公司 一种含有阿戈美拉汀和氟伏沙明的药物组合物及其应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007013793A1 (en) * 2005-07-28 2007-02-01 Color Foundation (Stichting Color) Sensitization of immune system against haptenized melanoma antigens

Family Cites Families (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2150942C1 (ru) * 1993-10-01 2000-06-20 Синтекс (Ю.ЭС.ЭЙ.) Инк. Оральные суспензии, содержащие высокие дозы мофетила микофенолята
KR100264348B1 (ko) * 1994-12-28 2000-08-16 디르크 반테 항-죽종형성제로서 네비볼롤을 함유하는 조성물
ATE449603T1 (de) * 1998-09-15 2009-12-15 Lilly Co Eli Verwendung von duloxetine zur behandlung von fibromyalgie
US6927223B1 (en) * 2000-05-26 2005-08-09 Washington State University Research Foundation Use of serotonin agents for adjunct therapy in the treatment of cancer
US6846939B2 (en) * 2000-07-07 2005-01-25 Paratek Pharmaceuticals, Inc. 9-substituted minocycline compounds
IL139975A0 (en) * 2000-11-29 2002-02-10 Univ Ramot Anti proliferative drugs
US20040072824A1 (en) * 2001-06-01 2004-04-15 Adam Telerman Methods and compositions for the treatment of cancer
GB0202337D0 (en) * 2002-02-01 2002-03-20 Univ Birmingham Cancer treatment
US7135575B2 (en) * 2003-03-03 2006-11-14 Array Biopharma, Inc. P38 inhibitors and methods of use thereof
RU2006112834A (ru) * 2003-09-18 2007-10-27 Комбинаторкс, Инкорпорейтед (Us) Сочетание лекарственных средств для лечения новообразований
OA13284A (en) * 2003-11-06 2007-01-31 Corporation Celgene Methods and compositions using thalidomide for thetreatment and management of cancers and other dis eases.
JP2007537246A (ja) * 2004-05-12 2007-12-20 バイオランクス カンパニー リミテッド ニコチン酸誘導体を有効成分として含む癌予防及び治療剤
KR101336462B1 (ko) * 2004-05-21 2013-12-04 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 테트라사이클린 및 이의 유사체의 합성
CN1279980C (zh) * 2004-10-14 2006-10-18 孔庆忠 一种抗实体肿瘤药物组合物
JP2006298781A (ja) * 2005-04-15 2006-11-02 Geno Membrane:Kk エストロン３硫酸トランスポーター活性阻害剤
TW200716141A (en) * 2005-05-05 2007-05-01 Combinatorx Inc Compositions and methods for treatment for neoplasms
CN101223149A (zh) * 2005-07-05 2008-07-16 特瓦制药工业有限公司 制备缬沙坦的方法
US8148356B2 (en) * 2005-08-24 2012-04-03 Cumberland Pharmaceuticals, Inc. Acetylcysteine composition and uses therefor
EP2001832A1 (en) * 2006-03-23 2008-12-17 Amgen Inc. Methods and compositions for making and using polymorphs of cinacalcet
CN101099724A (zh) * 2006-07-07 2008-01-09 上海复旦复华药业有限公司 一种微粉化来曲唑及其组合物
CN101103976A (zh) * 2006-07-14 2008-01-16 海南盛科生命科学研究院 一种含阿那曲唑的口服药物组合物及其制备工艺
EP2114399A2 (en) * 2007-01-05 2009-11-11 Cornerstone Therapeutics Inc. R-zileuton for use in conditions associated with increased 5-lipoxygenase and/or leukotriene activity (eg asthma)
CN101730526A (zh) * 2007-03-07 2010-06-09 阿布拉科斯生物科学有限公司 作为抗癌剂的包含雷帕霉素和白蛋白的纳米颗粒
EP2170805B1 (en) * 2007-06-21 2016-03-16 Amgen Inc. Methods of synthesizing cinacalcet and salts thereof
WO2009025854A1 (en) * 2007-08-22 2009-02-26 Burnham Institute For Medical Research Smips: small molecule inhibitors of p27 depletion in cancers and other proliferative diseases
US20120082659A1 (en) * 2007-10-02 2012-04-05 Hartmut Land Methods And Compositions Related To Synergistic Responses To Oncogenic Mutations
CN100563645C (zh) * 2007-12-06 2009-12-02 济南帅华医药科技有限公司 一种治疗实体肿瘤的蓓萨罗丁缓释植入剂
US20090270397A1 (en) * 2008-04-08 2009-10-29 Orlow Seth J Methods and compositions for the treatment of cancers, such as melanomas and gliomas
CN101569624A (zh) * 2008-04-29 2009-11-04 石药集团中奇制药技术（石家庄）有限公司 氨氯地平在制备治疗细胞增生性疾病药物中的用途
EP2123626A1 (en) * 2008-05-21 2009-11-25 Laboratorios del Dr. Esteve S.A. Co-crystals of duloxetine and co-crystal formers for the treatment of pain
WO2009147169A1 (en) * 2008-06-03 2009-12-10 Universite Paris Diderot-Paris 7 Pharmaceuticl compositions useful for the treatment of cancers, in particular acute myeloid leukemia and acute promyelocytic leukemia
CN101612400A (zh) * 2009-07-22 2009-12-30 陈志龙 血管紧张素ⅱ的1型受体拮抗剂在抗肿瘤中的应用
CN101690816A (zh) * 2009-08-16 2010-04-07 王丽燕 含钙拮抗剂、aⅱ受体拮抗剂和他汀类药的药物组合物
CN101991553B (zh) * 2009-08-21 2015-02-25 北京以岭生物工程技术有限公司 一种依西美坦片及其制备方法
CN101863806B (zh) * 2010-03-18 2013-02-13 湖北省医药工业研究院有限公司 抗前列腺癌药物(r)-比卡鲁胺的制备方法
US9012511B2 (en) * 2010-05-19 2015-04-21 Alkermes Pharma Ireland Limited Nanoparticulate cinacalcet compositions
WO2012015023A1 (ja) * 2010-07-29 2012-02-02 国立大学法人京都大学 抗がん剤のスクリーニング方法
CN103429235A (zh) * 2010-12-15 2013-12-04 赖鸿政 用于治疗癌症的化合物及其应用
CN102631354B (zh) * 2011-02-11 2015-01-21 广东泰禾医药科技有限公司 含维生素d3和二甲双胍的药物组合物
CN102688493B (zh) * 2011-03-25 2014-09-10 鼎泓国际投资（香港）有限公司 含有白藜芦醇及白藜芦醇类衍生物和Bc1-2抑制剂的药物组合物及其应用
CN102813643B (zh) * 2011-06-10 2014-09-24 北京蛋白质组研究中心 bumetanide在抑制肝癌细胞转移中的应用
WO2013049045A1 (en) * 2011-09-27 2013-04-04 Biomed Valley Discoveries, Inc. Compositions and methods of treating gliomas
CN109985228A (zh) * 2011-11-10 2019-07-09 凯伊药品公司 拟钙剂及其使用方法
ES2384069B1 (es) * 2012-03-29 2013-07-04 Hospital Sant Joan De Déu Cinacalcet y tumores neuroblásticos
CN102600077B (zh) * 2012-03-29 2013-06-05 江苏豪森药业股份有限公司 吉西他滨或其盐纳米乳剂注射液及其制备方法
CN103536607A (zh) * 2012-07-10 2014-01-29 邵金辉 土霉素，普罗帕酮和安乃近的抗肿瘤作用
WO2014018563A2 (en) * 2012-07-23 2014-01-30 The Board Of Trustees Of The Leland Stanford Junior University Methods for the treatment of cancer
WO2014036654A1 (en) * 2012-09-06 2014-03-13 Mcmaster University Compounds and methods for selectively targeting cancer stem cells
WO2014046983A1 (en) * 2012-09-21 2014-03-27 Intensity Therapeutic Method of treating cancer
SI2903616T1 (en) * 2012-10-04 2018-02-28 Ab Science The use of masitinib in combination with gemcitabine for the treatment of a subgroup of patients suffering from foot-and-mouth disease
CN103356687B (zh) * 2012-10-19 2016-06-01 厦门大学 一种伊维菌素及其衍生物的用途
US9622982B2 (en) * 2013-01-14 2017-04-18 Health Clinics Limited Cancer drug and uses
CN103933569B (zh) * 2013-01-22 2017-01-11 复旦大学 一种抗肺癌药物组合物及其应用、药盒和包装件
US9890127B2 (en) * 2013-03-11 2018-02-13 The Broad Institute, Inc. Compounds and compositions for the treatment of cancer
US20140271727A1 (en) * 2013-03-18 2014-09-18 National Yang-Ming University Method of using an antidepressant for increasing immunity of a subject and treating cancer
CN104161759B (zh) * 2013-05-16 2019-10-08 中国科学院上海药物研究所 阿那格雷及其衍生物的抗肿瘤用途
CN103396419A (zh) * 2013-08-13 2013-11-20 海宁市绿升医药科技有限公司 肿瘤光动力治疗药二氢卟吩e6-15-乙酯及其制备方法
CN103536925B (zh) * 2013-10-28 2015-07-01 中国医学科学院基础医学研究所 强心苷化合物在非小细胞肺癌治疗中的应用
CN103622975B (zh) * 2013-11-07 2016-06-15 广东药学院 格列吡嗪在制备治疗肿瘤药物中的应用
CA2979530C (en) * 2014-04-08 2023-10-03 The Methodist Hospital Inos-inhibitory compositions and their use as breast cancer therapeutics
WO2016062272A1 (zh) * 2014-10-24 2016-04-28 朗齐生物医学股份有限公司 免疫疾病用药物在制备抑制癌症的医药组合物中的应用

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007013793A1 (en) * 2005-07-28 2007-02-01 Color Foundation (Stichting Color) Sensitization of immune system against haptenized melanoma antigens

Also Published As

Publication number Publication date
AU2015335375A1 (en) 2017-05-18
EP3222278A4 (en) 2018-06-20
EP3210604A4 (en) 2018-06-27
TW201615220A (zh) 2016-05-01
WO2016062279A1 (zh) 2016-04-28
US20170304387A1 (en) 2017-10-26
EP3210604C0 (en) 2024-02-14
TW201615186A (zh) 2016-05-01
TW201615226A (zh) 2016-05-01
TW201615184A (zh) 2016-05-01
WO2016062290A1 (zh) 2016-04-28
EP3235497A1 (en) 2017-10-25
TW201615219A (zh) 2016-05-01
EP3222278C0 (en) 2023-06-14
ES2954860T3 (es) 2023-11-27
WO2016062286A1 (zh) 2016-04-28
WO2016062267A1 (zh) 2016-04-28
TW201615197A (zh) 2016-05-01
EP3222278B1 (en) 2023-06-14
US20170304286A1 (en) 2017-10-26
WO2016062281A1 (zh) 2016-04-28
US20170216247A1 (en) 2017-08-03
TW201615194A (zh) 2016-05-01
TWI672150B (zh) 2019-09-21
WO2016062266A1 (zh) 2016-04-28
CN107106523A (zh) 2017-08-29
WO2016062278A1 (zh) 2016-04-28
TW201615189A (zh) 2016-05-01
WO2016062289A1 (zh) 2016-04-28
AU2015335391A1 (en) 2017-06-01
CN106999470A (zh) 2017-08-01
TW201615217A (zh) 2016-05-01
TWI663969B (zh) 2019-07-01
AU2015335375B2 (en) 2020-09-10
WO2016062287A1 (zh) 2016-04-28
TWI652060B (zh) 2019-03-01
WO2016062288A1 (zh) 2016-04-28
CN107106550A (zh) 2017-08-29
US10098852B2 (en) 2018-10-16
WO2016062272A1 (zh) 2016-04-28
US20170312260A1 (en) 2017-11-02
EP3210604B1 (en) 2024-02-14
KR102490334B1 (ko) 2023-01-18
TW201615222A (zh) 2016-05-01
TW201615195A (zh) 2016-05-01
US20170304218A1 (en) 2017-10-26
WO2016062270A1 (zh) 2016-04-28
EP3235497A4 (en) 2018-06-13
WO2016062269A1 (zh) 2016-04-28
TW201615193A (zh) 2016-05-01
US20170304388A1 (en) 2017-10-26
JP6539345B2 (ja) 2019-07-03
JP2017532351A (ja) 2017-11-02
TW201615224A (zh) 2016-05-01
EP3210604A1 (en) 2017-08-30
AU2015335391B2 (en) 2018-06-21
US10045962B2 (en) 2018-08-14
WO2016062291A1 (zh) 2016-04-28
WO2016062277A1 (zh) 2016-04-28
WO2016062285A1 (zh) 2016-04-28
TW201615191A (zh) 2016-05-01
TW201615225A (zh) 2016-05-01
TW201615218A (zh) 2016-05-01
US10105357B2 (en) 2018-10-23
US20170304228A1 (en) 2017-10-26
WO2016062275A1 (zh) 2016-04-28
WO2016062271A1 (zh) 2016-04-28
WO2016062283A1 (zh) 2016-04-28
TW201615196A (zh) 2016-05-01
TWI621434B (zh) 2018-04-21
TW201615223A (zh) 2016-05-01
EP3222278A1 (en) 2017-09-27
TW201615221A (zh) 2016-05-01
TW201615188A (zh) 2016-05-01
KR20170084034A (ko) 2017-07-19
TWI663984B (zh) 2019-07-01
WO2016062274A1 (zh) 2016-04-28
TW201615192A (zh) 2016-05-01

Similar Documents

Publication Publication Date Title
WO2016062265A1 (zh) 莫诺苯宗药物在用于制备治疗癌症的医药组合物中的用途
Chen et al. Chinese herbal prescription QYSL prevents progression of lung cancer by targeting tumor microenvironment
Xu et al. Effect of oxaliplatin combined with 5-fluorouracil on treatment efficacy of radiotherapy in the treatment of elderly patients with rectal cancer
CN105517558A (zh) 土庄绣线菊提取物及其用途
Jiang et al. Evodiamine Inhibits the Progression of Esophageal Aquamous Cell Carcinoma via Modulating PI3K/AKT/mTOR Pathway
CN115282142A (zh) 一种木犀草素在制备治疗胃癌前疾病的药物中的应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15852492

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 15521540

Country of ref document: US

122 Ep: pct application non-entry in european phase

Ref document number: 15852492

Country of ref document: EP

Kind code of ref document: A1