CN113440534A - Application of verbascoside in preparation of medicines - Google Patents
Application of verbascoside in preparation of medicines Download PDFInfo
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- CN113440534A CN113440534A CN202010221601.0A CN202010221601A CN113440534A CN 113440534 A CN113440534 A CN 113440534A CN 202010221601 A CN202010221601 A CN 202010221601A CN 113440534 A CN113440534 A CN 113440534A
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- substance
- pharmaceutically acceptable
- medicament
- verbascoside
- acceptable salt
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention discloses an application of verbascoside in preparing a medicament. The invention provides an application of verbascoside in preparing a medicament. The verbascoside can remarkably inhibit liver cell liver cancer, and can be used for preparing medicines for treating liver cell liver cancer.
Description
Technical Field
The invention relates to application of verbascoside in preparation of a medicament.
Background
Primary liver cancer mainly refers to hepatocellular carcinoma (HCC), which is the 5 th most common cancer worldwide; the risk factors include chronic Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection, autoimmune hepatitis, long-term drinking, obesity, diabetes, etc. Primary liver cancer is highly malignant, difficult to diagnose early and has poor prognosis. In China, the incidence of liver cancer is increased by 1% per year on average, but the survival rate is still low. According to a Barcelona Clinical Liver Cancer (BCLC) staging system, radical treatment (including surgical resection, liver transplantation and local ablation treatment) can be carried out on a liver cancer patient with no symptoms at an extremely early stage and an early stage (both the A stage); but most patients have a chance of therapeutic surgical treatment at an advanced stage when the diagnosis is confirmed for the first time, and the recurrence rate exceeds 70% within 5 years at the risk of recurrence. Orthotopic liver transplantation is considered as the ultimate treatment for liver cancer because it can eliminate not only malignant tumors but also the entire diseased liver, however, due to the availability of liver resources and its difficulties, the number of patients whose liver transplantation surgery is affordable is far less than that of patients who are surgically resected. Local ablation therapy is usually performed by radiofrequency ablation or percutaneous injection of ethanol for the treatment of small tumors < 3cm in diameter. Transcatheter arterial catheterization chemoembolization (TACE) is a local treatment for asymptomatic, multinodular (mid-clinical or BCLC phase B) liver cancer patients. The whole-body treatment of liver cancer comprises radiotherapy, chemotherapy, gene therapy, immunotherapy and the like, and the methods can improve the life quality of patients to a certain extent and prolong the life cycle of the patients. Molecularly targeted drugs such as sorafenib (sorafenib) and regorafenib (regorafenib) are recommended treatment methods for patients with advanced clinical (BCLC C-stage) liver cancer (with invasive or extrahepatic tumors), but the effective rate is still less than 50%, and half of patients need to bear adverse drug reactions and huge economic burden and also need to face final drug tolerance risk. Based on the above severe situation, researchers need to pay attention to new intervention targets and develop more effective drugs and treatment strategies for treating liver cancer with less adverse reactions.
Acteoside (A01) is a kind of phenylethanoid glycosides, widely exists in various medicinal plants such as flos Caryophylli, herba plantaginis, and Cistanchis herba, and has multiple physiological activities of resisting oxidation, resisting inflammation, killing bacteria, and regulating apoptosis. Previous studies have demonstrated that a01 has effects of inhibiting prostate cancer cell proliferation, enhancing colorectal cancer cell sensitivity to chemotherapeutic drugs, and inhibiting tumor growth in (melanoma) -bearing mice. However, a role of a01 in hepatocellular carcinoma has been rarely reported. Only one Master thesis (research on antitumor activity of baicalin metal complex and echinacoside, verbascoside, university of Tarim) mentions that verbascoside has a bidirectional effect on cell proliferation of hepatocarcinoma cell SMMC-7221, i.e., the effect of promoting cell proliferation at low dose and the effect of inhibiting cell proliferation at high dose. However, it is clear that a single positive screening result (i.e. inhibition of cell proliferation) of a test substance at the cellular level does not naturally confer/suggest the property of the test substance to have an anti-tumor effect; indeed, screening of effective compounds at the cellular level has not demonstrated efficacy in animal models (screening of novel compounds for antitumor activity, king, et al, proceedings of the eleventh chinese co-annual meeting, 2009/9/1).
Furthermore, chemopregention of Colon Carcinogenesis by Dietary Alcohol, CANCER RESEARCH 57.420-425 and Phase II Trial of Perilliyl Alcohol in Patients with Metastic color CANCER, International Journal of gastric CANCER, vol.32, No. 2-3, 125-128 indicate that Perillyl Alcohol can significantly inhibit Colon invasive adenocarcinoma, but oral administration of Perillyl Alcohol to Patients with advanced Colorectal CANCER does not have clinical anti-tumor activity. That is, some drugs are active on animal cancer cells, but not on human cancer cells.
Folic Acid (FA) can prevent the occurrence of colorectal cancer in mice induced by 1, 2-Dimethylhydrazine (DMH) (Lu R et al, Folic acid and sodium butyl predictive in a mouse model of colorectal cancer. epitopes 2008, Vol3(6): 330-. That is, some drugs have a cancer-preventing effect, but not necessarily a cancer-treating effect.
Disclosure of Invention
The invention aims to solve the technical problem that the types of medicines for treating hepatocellular carcinoma with difficult early diagnosis, high malignancy and poor prognosis are few, and therefore, the invention provides the application of verbascoside in preparing medicines. The verbascoside can remarkably inhibit liver cell liver cancer, and can be used for preparing medicines for treating liver cell liver cancer.
The invention provides an application of a substance X in preparing a medicament;
the substance X is acteoside
Or a pharmaceutically acceptable salt thereof;
the medicine is used for treating hepatocellular carcinoma.
In the application, the medicine can be used for treating human hepatocellular carcinoma.
In the application, the medicine can be combined with other medicines for treating hepatocellular carcinoma. The other medicines for treating the hepatocellular carcinoma can be medicines containing sorafenib or pharmaceutically acceptable salts thereof. The other medicines for treating the hepatocellular carcinoma can be composed of a substance Y and pharmaceutic adjuvants; the substance Y is sorafenib or pharmaceutically acceptable salt thereof.
In the application, the medicament can be used in combination with a medicament containing sorafenib or a pharmaceutically acceptable salt thereof, and can also be used in combination with a medicament consisting of a substance Y and a pharmaceutic adjuvant, wherein the substance Y is sorafenib or a pharmaceutically acceptable salt thereof.
The invention also provides a pharmaceutical composition A, which consists of the substance X and pharmaceutic adjuvant; the substance X is verbascoside or pharmaceutically acceptable salt thereof.
The pharmaceutical composition A can be used for treating hepatocellular carcinoma.
The pharmaceutical composition A can be used for treating human hepatocellular carcinoma.
The invention also provides the application of the substance Y in preparing medicaments;
the substance Y is sorafenib or a pharmaceutically acceptable salt thereof;
the medicine is used for treating hepatocellular carcinoma;
the said medicament is used in combination with a medicament containing verbascoside or a pharmaceutically acceptable salt thereof.
In the application, the medicine for treating the hepatocellular carcinoma can be a medicine for treating the human hepatocellular carcinoma.
In the application, the medicine containing verbascoside or pharmaceutically acceptable salt thereof can be a medicine consisting of a substance X and a pharmaceutical adjuvant; the substance X is verbascoside or pharmaceutically acceptable salt thereof.
The invention also provides a pharmaceutical composition C, which consists of the substance X and other substances for treating hepatocellular carcinoma; the substance X is verbascoside or pharmaceutically acceptable salt thereof.
In the pharmaceutical composition C, the other substances for treating hepatocellular carcinoma can be sorafenib or pharmaceutically acceptable salts thereof.
The pharmaceutical composition C can be used for treating hepatocellular carcinoma.
The pharmaceutical composition C can be used for treating human hepatocellular carcinoma.
The invention also provides a pharmaceutical composition D, which consists of a substance X and a substance Y; the substance X is verbascoside or pharmaceutically acceptable salt thereof; the substance Y is sorafenib or pharmaceutically acceptable salt thereof.
The pharmaceutical composition D can be used for treating hepatocellular carcinoma.
The pharmaceutical composition D can be used for treating human hepatocellular carcinoma.
The invention also provides an application of the pharmaceutical composition C or the pharmaceutical composition D in preparation of a medicament for treating hepatocellular carcinoma.
In the application, the medicine can be used for treating human hepatocellular carcinoma.
The invention also provides a medicine composition B, which consists of a medicine composition and pharmaceutic adjuvants; the drug combination is the drug combination C or the drug combination D.
The pharmaceutical composition B can be used for treating hepatocellular carcinoma.
The pharmaceutical composition B can be used for treating human hepatocellular carcinoma.
Unless otherwise specified, the terms in this application have the following meanings:
the term "treatment" refers to therapeutic therapy. Where specific conditions are involved, treatment refers to: (1) relieving one or more biological manifestations of a disease or disorder, (2) interfering with (a) one or more points in a biological cascade that causes or leads to a disorder or (b) one or more biological manifestations of a disorder, (3) ameliorating one or more symptoms, effects, or side effects associated with a disorder, or one or more symptoms, effects, or side effects associated with a disorder or treatment thereof, or (4) slowing the progression of one or more biological manifestations of a disorder or disorder.
The term "pharmaceutical excipient" refers to excipients and additives used in the manufacture of pharmaceutical products and in the formulation of pharmaceutical formulations, and is intended to include all substances in a pharmaceutical formulation, except for the active ingredient. See the pharmacopoeia of the people's republic of China (2015 Edition), or Handbook of Pharmaceutical Excipients (Raymond C Rowe,2009Sixth Edition).
The above preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention without departing from the common general knowledge in the art.
The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows: the verbascoside can remarkably inhibit liver cell liver cancer, and can be used for preparing medicines for treating liver cell liver cancer.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
A sample to be tested: verbascoside was purchased from Jiangsu Yongtai pharmaceuticals, Inc., batch number: 100581, respectively; the purity is more than or equal to 99 percent (HPLC).
The instrument equipment comprises: clean bench, Suzhou clean plant, Inc., model SW-CJ-2 FD.
Experimental animals: BALB/C nude mice, male, weighing 18-20g, purchased from Shanghai Slek laboratory animals Co., Ltd, production license number: SCXK (Shanghai) 2017 and 0002; use of license number: SYXK (Shanghai) 2014-0018; grade: an SPF level; the animal is raised in a positive pressure purification ventilation animal house, the room temperature is 23 +/-2 ℃, the humidity is 40-70%, the day and night change is simulated by artificial illumination, and the animal can freely eat and drink water.
Bel7404 cells and JHH-7 cells were purchased from Shanghai Fuxiang Biotech, Inc.
Example 1
1.1 preparation of human hepatoma nude mouse transplantation tumor model
1.1.1 Bel7404 nude mouse transplantation tumor model preparation
Preparation of Bel7404 cell suspension (3X 10) under sterile conditions6) The mice were inoculated subcutaneously in the right axilla of BALB/C nude mice with a trocar. After 10 days of inoculation, the tumor-bearing nude mice are divided into 7 groups according to the tumor mass volume in a layering way, so that the average tumor volume of each group is basically consistent.
1.1.2 JHH-7 nude mouse transplantation tumor model preparation
Preparation of JHH-7 cell suspension (3X 10) under aseptic conditions6) The mice were inoculated subcutaneously in the right axilla of BALB/C nude mice with a trocar. After 7 days of inoculation, the tumor-bearing nude mice are divided into 4 groups according to the tumor mass volume, so as to ensure that the average tumor volume of each group is basically consistent.
1.2 test grouping and drug intervention
1.2.1 Bel7404 nude mouse transplantation tumor model grouping and drug intervention
Male BALB/C nude mice were divided into 7 groups in total, 5 per group except for the model group (n ═ 8), according to tumor mass volume. Namely, a model group (i.g. administration of an equal amount of physiological saline; n ═ 8), a 01-low dose group (i.g. administration of 12.5mg/kg of acteoside, preparation of physiological saline, the following groups being the same; n ═ 5), a 01-medium dose group (i.g. administration of 25mg/kg of acteoside; n ═ 5), a 01-high dose group (i.g. administration of 50mg/kg of acteoside; n ═ 5), sorafenib group (i.g. administration of 50mg/kg of sorafenib; n ═ 5), a01+ sorafenib group (i.g. administration of 50mg/kg of acteoside + i.g. administration of 50mg/kg of sorafenib; n ═ 5), a01 intravenous administration group (i.v. administration of 20mg/kg of acteoside; n ═ 5). Each group was administered with the drug 10 days after cell inoculation, with an intravenous administration volume of 0.1ml/10g body weight and an oral gavage administration volume of 0.1ml/10g body weight.
1.2.2 JHH-7 nude mouse transplanted tumor model grouping and drug intervention
Male BALB/C nude mice were divided into 4 groups in total, with 5 mice per group except for the model group (n ═ 8), according to tumor mass volume. Namely, a model group (i.v. administration of an equal amount of physiological saline; n ═ 8), an A01 group (i.v. administration of 20mg/kg of verbascoside, preparation of physiological saline, and the same in the following groups; n ═ 5), an A01+ sorafenib group (i.v. administration of 20mg/kg of verbascoside + i.g. administration of 50mg/kg of sorafenib; n ═ 5), and a sorafenib group (i.g. administration of 50mg/kg of sorafenib; n ═ 5), each group was administered with drugs 7 days after JHH-7 cell inoculation, the intravenous administration volume was 0.1ml/10g of body weight, and the oral gavage administration volume was 0.1ml/10g of body weight.
1.3 detection indices and methods
1.3.1 Bel7404 nude mouse transplantation tumor model
The administration is continued for 22 days, 1 time daily. The major diameter a (mm) and the perpendicular minor diameter b (mm) of the tumor are measured by a digital display electronic caliper 2 times a week from the administration, and the tumor volume is calculated by the following formula: TV ═ ab2The relative tumor volume calculation formula is: the resulting tumor volume was measured at caging (i.e., d1) for RTV versus Vo, Vt being the tumor volume at each measurement. Animals were sacrificed 32 days after inoculation (d22)Weighing, dissecting and taking tumor mass, weighing tumor weight, and judging the result according to the following formula:
tumor inhibition (%) - (control mean RTV-administration mean RTV)/control mean RTV × 100%.
1.3.2 JHH-7 nude mouse transplantation tumor model
The administration is continued for 14 days, 1 time daily. The major diameter a (mm) and the perpendicular minor diameter b (mm) of the tumor are measured by a digital display electronic caliper 2 times a week from the administration, and the tumor volume is calculated by the following formula: TV ═ ab2The relative tumor volume calculation formula is: the resulting tumor volume was measured at caging (i.e., d1) for RTV versus Vo, Vt being the tumor volume at each measurement. Animals were sacrificed 21 days after inoculation (d14), weighed, tumor masses dissected, and tumor weights were weighed, and the results were determined according to the following formula:
tumor inhibition (%) - (control mean RTV-administration mean RTV)/control mean RTV × 100%.
1.4 technical effects
1.4.1 Bel7404 nude mouse transplantation tumor model
After nude mice are continuously administrated for 22 days, the tumor inhibition rates of the A01 medium dose group (25mg/kg), the A01 high dose group (50mg/kg), the A01 intravenous administration group (20mg/kg), the sorafenib group and the A01+ sorafenib group are respectively 37.2%, 39.8%, 33.4%, 21.1% and 45.7% (P values are all less than 0.01, and a two-factor analysis of variance method is adopted for comparison among experimental data groups, and P <0.05 is taken as a statistical significance), so that verbascoside has an obvious inhibition effect on human hepatoma cell Bel7404 transplantable tumor.
1.4.2 JHH-7 nude mouse transplantation tumor model
After the nude mice are continuously administrated for 14 days, the tumor inhibition rates of the A01 group, the A01+ sorafenib group and the sorafenib group are respectively 54.7%, 69.4% and 50.8% (P values are all less than 0.01, and P <0.05 is statistically significant by adopting a two-factor anova method in comparison among experimental data groups), which indicates that verbascoside has obvious inhibition effect on human hepatoma cell JHH-7 transplanted tumor.
In conclusion, verbascoside has obvious inhibition effect on the growth of human liver cancer nude mouse transplanted tumor (Bel7404 tumor bearing nude mouse or JHH-7 tumor bearing nude mouse), has obvious difference compared with a model group, and can be applied to treating liver cell liver cancer. Has important research value and application prospect for treating the hepatocellular carcinoma.
Claims (10)
1. Use of a substance X for the manufacture of a medicament;
the substance X is verbascoside or pharmaceutically acceptable salt thereof;
the medicine is used for treating hepatocellular carcinoma.
2. The use of claim 1, wherein the medicament is a medicament for the treatment of human hepatocellular carcinoma;
the medicament is used in combination with a medicament containing sorafenib or a pharmaceutically acceptable salt thereof.
3. The use of claim 2, wherein the medicament is used in combination with a medicament consisting of substance Y and a pharmaceutically acceptable excipient, wherein substance Y is sorafenib or a pharmaceutically acceptable salt thereof.
4. The use of claim 1, wherein the medicament is for use in combination with other medicaments for the treatment of hepatocellular carcinoma;
the other medicines for treating the hepatocellular carcinoma include, for example, a medicine containing sorafenib or a pharmaceutically acceptable salt thereof; the pharmaceutical composition also comprises a substance Y and a pharmaceutical excipient, wherein the substance Y is sorafenib or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition A comprises substance X and medicinal adjuvants; the substance X is verbascoside or pharmaceutically acceptable salt thereof.
6. Use of a substance Y for the preparation of a medicament;
the substance Y is sorafenib or a pharmaceutically acceptable salt thereof;
the medicine is used for treating hepatocellular carcinoma;
the said medicament is used in combination with a medicament containing verbascoside or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical combination C consisting of substance X and other substances for the treatment of hepatocellular carcinoma; the substance X is verbascoside or pharmaceutically acceptable salt thereof.
8. A pharmaceutical combination D consisting of substance X and substance Y; the substance X is verbascoside or pharmaceutically acceptable salt thereof; the substance Y is sorafenib or pharmaceutically acceptable salt thereof.
9. Use of the pharmaceutical combination C according to claim 7 or the pharmaceutical combination D according to claim 8 for the preparation of a medicament for the treatment of hepatocellular carcinoma.
10. A pharmaceutical composition B comprises a pharmaceutical composition and a pharmaceutical adjuvant; the pharmaceutical combination is the pharmaceutical combination C according to claim 7 or the pharmaceutical combination D according to claim 8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010221601.0A CN113440534A (en) | 2020-03-26 | 2020-03-26 | Application of verbascoside in preparation of medicines |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010221601.0A CN113440534A (en) | 2020-03-26 | 2020-03-26 | Application of verbascoside in preparation of medicines |
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| CN202010221601.0A Withdrawn CN113440534A (en) | 2020-03-26 | 2020-03-26 | Application of verbascoside in preparation of medicines |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116392521A (en) * | 2023-05-06 | 2023-07-07 | 新疆医科大学第一附属医院 | Application of acteoside combined anticancer therapeutic agent in medicine and pharmaceutical composition |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1478479A (en) * | 2003-01-16 | 2004-03-03 | 兰州大学 | New use of verbascum glycoside |
| CN110754431A (en) * | 2019-11-21 | 2020-02-07 | 中国药科大学 | Building method and application of osteoporosis and Alzheimer's disease combined animal model |
-
2020
- 2020-03-26 CN CN202010221601.0A patent/CN113440534A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1478479A (en) * | 2003-01-16 | 2004-03-03 | 兰州大学 | New use of verbascum glycoside |
| CN110754431A (en) * | 2019-11-21 | 2020-02-07 | 中国药科大学 | Building method and application of osteoporosis and Alzheimer's disease combined animal model |
Non-Patent Citations (1)
| Title |
|---|
| 马鑫 等: "无法手术的肝细胞性肝癌的分子靶向治疗", 《分子诊断与治疗杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116392521A (en) * | 2023-05-06 | 2023-07-07 | 新疆医科大学第一附属医院 | Application of acteoside combined anticancer therapeutic agent in medicine and pharmaceutical composition |
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Address after: 200040 No. 1320 West Beijing Road, Shanghai, Jingan District Applicant after: Shanghai Pharmaceutical Industry Research Institute Co.,Ltd. Applicant after: China Pharmaceutical Industry Research Institute Co.,Ltd. Address before: 200040 No. 1320 West Beijing Road, Shanghai, Jingan District Applicant before: SHANGHAI INSTITUTE OF PHARMACEUTICAL INDUSTRY Applicant before: CHINA STATE INSTITUTE OF PHARMACEUTICAL INDUSTRY |
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