WO2015090139A1 - Médicament antitumoral, procédé de préparation et utilisation associée - Google Patents

Médicament antitumoral, procédé de préparation et utilisation associée Download PDF

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Publication number
WO2015090139A1
WO2015090139A1 PCT/CN2014/092627 CN2014092627W WO2015090139A1 WO 2015090139 A1 WO2015090139 A1 WO 2015090139A1 CN 2014092627 W CN2014092627 W CN 2014092627W WO 2015090139 A1 WO2015090139 A1 WO 2015090139A1
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WIPO (PCT)
Prior art keywords
cancer
tumor
drug
antitumor drug
antitumor
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Application number
PCT/CN2014/092627
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English (en)
Chinese (zh)
Inventor
李徐钦
Original Assignee
李徐钦
马丹霞
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Application filed by 李徐钦, 马丹霞 filed Critical 李徐钦
Publication of WO2015090139A1 publication Critical patent/WO2015090139A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/65—Amphibians, e.g. toads, frogs, salamanders or newts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A61K36/748—Oldenlandia or Hedyotis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine

Definitions

  • the invention relates to the field of traditional Chinese medicine, in particular to an antitumor medicine, a preparation method and the use thereof.
  • Cancer is one of the major diseases that seriously threaten human health and social development. It is also a major disease that threatens the health of our residents. Recent statistics show that the incidence of cancer in China is increasing year by year. Among them, cancers such as gastric cancer and colon cancer account for more than 10% of all cancers, which are common tumors with greater harm. At present, the commonly used radiotherapy and chemotherapy methods in the treatment of tumors, while killing tumor cells, also cause the body's bone marrow suppression and immune function is low, and the side effects are large. Therefore, searching for high-efficiency and low-toxic anti-tumor drugs or active ingredients from natural animals, plants and minerals is a hot topic in recent years. Traditional Chinese medicine is a unique treasure house of traditional medicine in China. It has been used in disease prevention and treatment in China for more than 2,000 years and provides a very rich resource for the development of anticancer drugs.
  • the highest cancer cell inhibition rate detected by similar drugs in China is only about 50%, and the cancer suppression rate of the well-known valuable anti-cancer drug Taxus is only about 30%.
  • the method for preparing the antitumor drug is characterized in that each component is weighed, and each component is pulverized, sieved, and mixed.
  • the components of the anti-tumor drug obtained by the screening have a diameter of 300-800 mesh.
  • the specific steps can be carried out in accordance with a conventional method.
  • the invention also protects the use of the anti-tumor drug for anti-tumor.
  • the method includes feeding the antitumor drug with water or rice wine.
  • the tumor is liver cancer, gastric cancer, and esophageal cancer.
  • the anti-tumor drug of the present invention that is, "Li's glutinous food powder” is based on the experience of ancestral medical practice and absorbs various therapeutic esophagus of various generations. The theoretical essence of cancer, the formation of a unique experience of the experience side.
  • "Lishi ⁇ ” is made up of Chinese medicines such as Awei, ⁇ , Mabao, and Hedyotis diffusa according to the theory of traditional Chinese medicine. It has been used clinically for decades and has been observed to have significant effects on cancers of the digestive tract such as esophageal cancer and gastric cancer. It can effectively eliminate cancer lumps, alleviate the suffering of patients, and promote appetite and prolong the life of cancer patients.
  • the "Li's glutinous food” compound is mainly composed of traditional Chinese medicines such as A., A., and Hedyotis diffusa.
  • a Wei is a commonly used traditional Chinese medicine, as recorded in the "New Revision of the Materia Medica”.
  • Awei has a special odor, tastes bitter and pungent, has the effect of reducing qi, promoting blood circulation, sputum and excitatory nerves.
  • Zhao Bei et al. preliminarily proved that the ferulic medicinal liquor has certain anti-tumor effects through the three levels of whole body, cell and molecule, mainly by preventing the infiltration and metastasis of the tumor and improving the immunity of the body.
  • the dagger was contained in the “Medical Doctors", and the "Shen Nong's Herbal Classic” contained the sexual taste and indications of "Shrimp.”
  • Ancient and modern prescriptions are widely used in the treatment of phlegm, phlegm and phlegm, detoxification, swelling, pain, and diuretic. It has been used in the clinical anti-tumor, analgesic, diuretic swelling and other preparations such as Qishen Zhentong Ointment, Zhishen Injection, Huachansu Injection and Fufang Suede Capsule.
  • Hedyotis diffusa is sweet, light, cool, and belongs to the stomach, large intestine, small intestine, has the effect of clearing away heat and detoxification, reducing swelling and analgesia, and attending appendicitis, bronchitis, urinary tract infection, snake bite, tumor, intestinal wind and blood. Wait.
  • ethanol extract of Hedyotis diffusa on human poorly differentiated gastric adenocarcinoma cells (BGC), human oral epidermoid carcinoma cells (KB), human hepatoma cells (SMMC), human cervical cancer cells (HELA), human lung cancer cells ( A549) has a certain inhibitory effect.
  • ethanol extract of Hedyotis diffusa has a certain inhibitory effect on transplanted S180 solid tumor in mice.
  • the clinical preparation of the liver preparation in the middle and late stage of treatment of advanced liver cancer with the clinical preparation of Hedyotis diffusa as the medicinal herb can significantly improve the quality of life and prolong the survival time of patients with stage III primary liver cancer.
  • the main medicinal taste of "Li's glutinous food” has good anti-tumor effect both in clinical trials and experimental studies, indicating that the "Li's glutinous food” compound compatibility has the basis of theoretical and practical application.
  • “Li's glutinous food” compound has both animal and botanical drugs.
  • the main active ingredients of each drug are different.
  • the main active ingredient of cockroach anti-tumor is scorpion lactone, which is a cardiac glycoside, including Bufalin, resibufogenin, scorpion venom (also known as cinobufagin); the main active components of ferula are volatile oil, coumarin and phenylpropanoid, white flower snake tongue
  • the main active ingredients of grass are flavonoids, triterpenoids, organic acids and polysaccharides. Mabao can detoxify and remove sores. These different active ingredients play a role in different tumor targets, fully reflecting the multi-component and multi-target of traditional Chinese medicine. The characteristics of the action, from the overall adjustment of the body function to achieve the purpose of removing disease.
  • the "Li's glutinous food” clinical trial uses a powder, which is to smash, sift and mix the medicinal materials, which is used for the treatment of patients with digestive tract cancer such as gastric cancer and esophageal cancer.
  • the patient's taking method is usually served with rice wine. Since the medicinal material powder cannot enter the cell during in vitro cell experiments, the medicinal material must be extracted.
  • the invention provides two methods for water extraction and alcohol extraction of "Li's glutinous food powder", and the anti-tumor activity of both extracts is studied in vitro.
  • the results of the present invention preliminarily indicate that the "Li's glutinous food" fat-soluble component may have better anti-tumor activity. It also indirectly proves that there is a scientific basis for the use of rice wine in clinical trials.
  • the anti-tumor drug of the invention has been subjected to an in vitro anti-tumor test research report, and the test data shows that the "Li's glutinous powder" water extract and the ethanol extract are for liver cancer cells (HpeG-2), gastric cancer cells (MKN-45), Three digestive system cell lines of esophageal cancer cells (EC-109) have obvious anti-tumor effects in vitro.
  • the ethanol extract was more effective, with a maximum inhibition rate of nearly 90% for the three cell lines.
  • the maximum inhibition rate of liver cancer cells was 88.40%
  • the maximum inhibition rate to esophageal cancer cells was 91.88%
  • the maximum inhibition rate to gastric cancer cells was 93.98%.
  • the highest cancer cell inhibition rate detected by similar drugs in China is only about 50%, and the cancer suppression rate of the well-known valuable anti-cancer drug Taxus is only about 30%.
  • the maximum inhibition rate of the cancer cells of the present invention is much higher than this.
  • HepG-2 human hepatoma cells
  • MKN-45 gastric cancer cells
  • EC-109 esophageal cancer cells
  • Reagents 95% ethanol (analytical grade, Beijing Chemical Plant), DMSO (analytical grade, Beijing Chemical Plant), RPMI 1640 medium (Solarbio, China), trypsin (Solarbio, China), fetal bovine serum (Gibco) , USA), phosphate buffer (Thermo, Germany), MTT reagent (Gibco, USA);
  • Example 1 Preparation method of antitumor drug (Lee's glutinous food) of the present invention
  • Li's granules were granulated with powder 10g, added with 100ml of water and refluxed three times for 30min each time, filtered, and the filtrate was combined and dried in vacuo to obtain a water extract of Lishi glutinosa, the yield was 16.8%.
  • Li's glutinous food ethanol extract 10 g was weighed and added with 100 ml of 95% ethanol solution for three times, each time for 30 min, filtered, and the filtrate was combined and dried in vacuo to obtain a Li's glutinous food ethanol extract with a yield of 10.5%.
  • Hepatoma cell line (HepG-2), gastric cancer cell line (MKN-45) and esophageal cancer cell line (EC-109) in logarithmic growth phase were digested and counted in 96-well culture plates at a rate of approximately 8,000 per well. -10000 cells, incubate at 37 ° C for 12 hours, discard the culture solution, add 100 ⁇ L of different concentrations of drug-containing medium (configured with RPMI 1640 medium), continue to incubate at 37 ° C for 24 hours, aspirate the culture solution, and add 150 ⁇ L per well.
  • drug-containing medium Configured with RPMI 1640 medium
  • the formula of the experimental group is the formula in the first embodiment
  • Control 1 is ferul 20g ⁇ 25g Mabao 40g Hedyotis diffusa 140g;
  • Control 2 is Awei 40g ⁇ 35g Mabao 60g Hedyotis diffusa 160g;
  • Example 1 The extraction method is referred to in Example 1.
  • the extract of Lee's glutinous rice water in the range of 15.62-1000 ⁇ g/ml for liver cancer cell lines (HepG-2), gastric cancer cell lines (MKN-45) and esophageal cancer cell lines (EC- 109) has a certain inhibitory effect.
  • the inhibitory effect on Hepatoma cell line (HepG-2) was slightly stronger, and the half-inhibitory concentration was 143.59 ⁇ g/ml.
  • the inhibition rate of gastric cancer cell line (MKN-45) and esophageal cancer cell line (EC-109) in this concentration range was not more than 50%.
  • Example 1 shows that when the amount of each component is slightly changed, the effect is also greatly affected, and the anticancer effect is greatly reduced (see Table 7-12). Up to 50%. The formulation of Example 1 was up to 90% compared to this, and the formulation of Example 1 was effective.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicines Containing Plant Substances (AREA)
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Abstract

La présente invention concerne un médicament antitumoral, constitué de ferula asafoetida, de crapaud, de bézoard de cheval et d'hedyotis diffusa en un rapport en poids de 30/30/50/150. Le procédé de préparation du médicament comprend les étapes suivantes : pesage des matières premières, pulvérisation, criblage et mélange. Le médicament peut être utilisé pour le traitement du cancer, par exemple du cancer du foie, du cancer de l'estomac ou du cancer de l'œsophage. Le médicament présente un bon effet anti-cancer, et peut inhiber approximativement 90 % des cellules tumorales.
PCT/CN2014/092627 2013-12-20 2014-12-01 Médicament antitumoral, procédé de préparation et utilisation associée WO2015090139A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201310711596.1 2013-12-20
CN201310711596.1A CN103655822B (zh) 2013-12-20 2013-12-20 一种抗肿瘤药物、制备方法及其用途

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CN103655822B (zh) * 2013-12-20 2014-08-20 李徐钦 一种抗肿瘤药物、制备方法及其用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102283867A (zh) * 2011-08-04 2011-12-21 陈宥伯 一种治疗癌症的中药组合物
CN103655822A (zh) * 2013-12-20 2014-03-26 李徐钦 一种抗肿瘤药物、制备方法及其用途

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102283867A (zh) * 2011-08-04 2011-12-21 陈宥伯 一种治疗癌症的中药组合物
CN103655822A (zh) * 2013-12-20 2014-03-26 李徐钦 一种抗肿瘤药物、制备方法及其用途

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
WANG, WENPING ET AL.: "Research on the Application Regularity of Traditional Chinese Medicine on the External Treatment of Cancer Pain", LIAONING JOURNAL OF TRADITIONAL CHINESE MEDICINE, vol. 38, no. 8, 31 August 2011 (2011-08-31), pages 1477 - 1478 *
XIA, FANGBO ET AL.: "Studying on the Antitumor Effect of Chinese Herbal Prescription of ''Li Shi Ge Shi San'' in Vitro", CHINA MEDICAL HERALD, vol. 11, no. 5, 15 February 2014 (2014-02-15), pages 21 - 23 AND 27 *

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