CN108653265A - A kind of compound anti-cancer medicine - Google Patents
A kind of compound anti-cancer medicine Download PDFInfo
- Publication number
- CN108653265A CN108653265A CN201810387128.6A CN201810387128A CN108653265A CN 108653265 A CN108653265 A CN 108653265A CN 201810387128 A CN201810387128 A CN 201810387128A CN 108653265 A CN108653265 A CN 108653265A
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- CN
- China
- Prior art keywords
- dtc
- drug
- tpa
- cancer
- diethyldithiocarbamate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- 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
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
-
- 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
Abstract
The present invention relates to a kind of compound anti-cancer medicines, the drug is made of diethyldithiocarbamate (DTC) and 12 oxygen Tetradecanoylphorbol, 13 acetic acid esters (TPA), the present invention is by using phorbol exters compound (TPA) and dithio carbamate compounds (DTC) use in conjunction as a kind of new antitumor drug, optimization treatment is achieved the effect that cancer, drug effect is better than independent medication, to inhibiting myelogenous leukemia to have good inhibition；In addition, combination drug provided by the invention dosage in treatment of cancer is low, the concentration of independent medication is reduced, to reduce the toxic side effect of drug, reduces the injury to human body, price is relatively cheap, alleviates the financial burden of patient.
Description
Technical field
The present invention relates to a kind of biomedicine technical field, especially a kind of compound anti-cancer medicine.
Background technology
Cancer seriously threatens the life and health of people, the latest edition of the World Health Organization (WHO) publication in 2014《The world
Cancer is reported》Swift and violent growing trend will be presented in prediction cases of cancer, and by 14,000,000 people in 2012, cumulative year after year was to 2025
19000000 people were up to 24,000,000 people by 2035.With people's life, the increase of operating pressure, the change of dietary structure, the people
Many cancered probabilities increase substantially, 2017 daily about 10,000 people in the newest tumour present situation display whole nation of National Cancer Center publication
Cancer is made a definite diagnosis, incidence occupies 74 of the whole world, the number of the infected whole world first；The death rate occupies 29 of the whole world.Cancer is
Seriously threaten the quality of life and life security of the common people.
Leukaemia (Leukemia) is the Clonal malignant disease of a kind of candidate stem cell exception.According to ASSOCIATE STATISTICS, white blood
Disease accounts for about 3% of tumor incidence or so, is apt to occur in children and youth, and male patient is more than women；It is in each age group in China
The 6th (male) and the 8th (women) are accounted in the death rate of malignant tumour respectively, is accounted in the death rate below in children and 35 years old
1st.It can be seen that allowing of no optimist in the case where China's leukaemia.Acute promyelocytic leukemia (Acute
Promyelocyticleukemia, APL) it is acute myeloid leukemia (Acute myelogenous leukemia, AML)
A kind of specific type accounts for the 10%~15% of AML.APL breaks with tremendous force, the state of an illness is dangerous, and clinically main utilize is all-trans certainly at present
Formula vitamin A acid (ATRA) combines arsenic trioxide (ATO) and treats APL, and complete remission rate is up to 80% or more.However, for non-
This therapy of the AML patient of APL is unsatisfactory, and medicine is mainly with cytarabine (Cytarabine) class drug
It is main.Breakthrough progress i.e. clinically there has been for the treatment of acute myeloid leukemia, but due to the difference of curative effect individual,
Drug resistance, recurrence rate etc. are intractable, and the effective drug of research and development low toxicity is made to become a weight for controlling and reducing leukemia mortality
Big challenge.
Invention content
In view of the deficiencies of the prior art, a kind of use concentration of present invention offer is low, secondary toxic action is small, to tumour especially marrow
Property leukaemia have good therapeutic effect compound anti-cancer medicine.
The technical scheme is that：A kind of compound anti-cancer medicine, the drug is by diethyldithiocar bamic acid
Ester (DTC) and 12- oxygen-tetradecanoylphorbol-13-acetate (TPA) composition.
Preferably, the 12- oxygen-tetradecanoylphorbol-13-acetate (TPA) and diethyldithiocar bamic acid
The amount of substance ratio of ester (DTC) is 1:100-1000.
More preferably, 12- oxygen-tetradecanoylphorbol-13-acetate (TPA) and diethyl-dithio ammonia
The amount of substance ratio of carbamate (DTC) is 1:600.
Further, the anticancer drug is for treating myelogenous leukemia tumour.
Beneficial effects of the present invention are：12- oxygen-tetradecanoylphorbol-13-acetate (TPA) is phorbol exters class chemical combination
Higher one kind of activity in object, under low concentration to blood tumor cell and a variety of solid tumors have apparent Inhibit proliferaton,
Apoptosis-induced and differentiation effect, diethyldithiocarbamate (DTC) is dithiocarbamates compound
A member is effective inhibitor of NF- κ B, is clinically mainly used for metal poisoning and the treatment of cancer, the present invention by using
Phorbol exters compound (TPA) and dithio carbamate compounds (DTC) use in conjunction as a kind of new antitumor drug,
Optimization treatment, drug effect, which are better than independent medication, to be achieved the effect that cancer, to inhibiting myelogenous leukemia that there is good inhibition；
In addition, combination drug provided by the invention dosage in treatment of cancer is low, the concentration of independent medication is reduced, to reduce medicine
The toxic side effect of object reduces the injury to human body, and price is relatively cheap, alleviates the financial burden of patient.
Description of the drawings
The growth inhibition effect of HL-60 cells is compared when Fig. 1 is the TPA of 0.2nM and the DTC of various concentration is used in combination
Scheme, in figure, TPA and the DTC drug combinations of various concentration and the DTC independent medications pair of various concentration that figure A is 0.2nM
The inhibiting effect comparison diagram of HL-60 cell growths, figure B are the DTC drug combinations and difference of 0.2nMTPA and various concentration
The DTC independent medications of concentration cause the comparison diagram of HL-60 cell deaths；
Fig. 2 is the influence diagram to SCID mice when TPA and DTC are used in combination, and in figure, figure A is that TPA and DTC is used in combination
When SCID mice is formed tumor size influence comparison diagram, figure B is when TPA and DTC are used in combination to SCID nude mice bodies
The influence comparison diagram of weight.
Specific implementation mode
The specific implementation mode of the present invention is described further below in conjunction with the accompanying drawings：
Embodiment 1
A kind of compound anti-cancer medicine, the drug are 1 by amount of substance ratio：100 12- oxygen-Tetradecanoylphorbol-
13- acetic acid esters (TPA) and diethyldithiocarbamate (DTC) composition.
Embodiment 2
A kind of compound anti-cancer medicine, the drug are 1 by amount of substance ratio：250 12- oxygen-Tetradecanoylphorbol-
13- acetic acid esters (TPA) and diethyldithiocarbamate (DTC) composition.
Embodiment 3
A kind of compound anti-cancer medicine, the drug are 1 by amount of substance ratio：500 12- oxygen-Tetradecanoylphorbol-
13- acetic acid esters (TPA) and diethyldithiocarbamate (DTC) composition.
Embodiment 4
A kind of compound anti-cancer medicine, the drug are 1 by amount of substance ratio：1000 12- oxygen-Tetradecanoylphorbol-
13- acetic acid esters (TPA) and diethyldithiocarbamate (DTC) composition.
Embodiment 5
The growth analysis of independent medication and drug combination to myelogenous leukemia HL-60 cells
By culture property myelogenous leukemia HL-60 cell inoculations in RPMI culture mediums, kind plate density 2 × 105A/ml, culture
For 24 hours, with the 12- oxygen of a concentration of 0.2nM-tetradecanoylphorbol-13-acetate (TPA) and concentration be respectively 20nM,
The culture medium of the diethyldithiocarbamate (DTC) of 50nM, 100nM, 200nM cultivates 48h, and individually uses a concentration of
The culture medium of the diethyldithiocarbamate (DTC) of 20nM, 50nM, 100nM, 200nM cultivates 48h as a contrast, takes
Cell suspending liquids and 20 μ l 0.4% trypan blue solution of the 80 μ l after drug-treated are uniformly mixed processing 2min, under the microscope
Remember that viable count (colourless) and dead cell number (blue), Fig. 1 (A) are 0.2nM12- oxygen-tetradecane respectively with blood red ball count plate
The diethyl-dithio amino of acyl phorbol -13- acetic acid esters (TPA) and various concentration (20nM, 50nM, 100nM, 200nM)
Diethyldithiocarbamate (DTC) independent medication of formic acid esters (DTC) drug combination and various concentration is to HL-60
The inhibiting effect comparison diagram of cell growth, it can be seen from the figure that the inhibiting effect of drug combination is better than the inhibition of independent medication
Effect, and with the increase of diethyldithiocarbamate (DTC) concentration, inhibiting effect constantly increases, and Fig. 1 (B) is
0.2nM12- oxygen-tetradecanoylphorbol-13-acetate (TPA) and various concentration (20nM, 50nM, 100nM, 200nM)
The diethyldithiocarbamate (DTC) of diethyldithiocarbamate (DTC) drug combination and various concentration
Independent medication causes the comparison diagram of HL-60 cell deaths, it can be seen from the figure that drug combination comparison independent medication causes HL-
The death rate higher of 60 cells, and with the increase of diethyldithiocarbamate (DTC) concentration, the death rate is higher, into
One step proves 12- oxygen-tetradecanoylphorbol-13-acetate (TPA) and diethyldithiocarbamate (DTC) joint
The effect of medication HL-60 cell growth inhibitions and inducing cell apoptosis is applied alone effect stronger than drug, or even more highly concentrated than height
Single drug effect fruit of degree is more preferable.
Embodiment 6
The analysis of drug combination and independent medication to immunodeficient mouse cancer resistant effect
Male immunization defect (SCID) mouse (6-7 weeks) is placed in and is sterile filtered in the isolation cage of net, and disinfection is provided
Food drink water, HL-60 cells and 50%Matrigel are mixed into cell suspension, are injected into the right side subcutaneous (2 of SCID mice
×106Cells/ mouse), when tumour reaches median size, i.e. width is：0.5-0.8cm, it is long：0.5-0.8cm divides mouse at random
It is made into 4 groups, respectively control group, DTC treatment groups, TPA treatment groups, administering drug combinations group, wherein control group volume injected ratio is
40：0.5：1：10：DTC (30 injects in 48.5 propylene glycol, Polysorbate 80, methanol, the lysate of second alcohol and water, DTC treatment groups
μ g/g body weight/day), TPA (50ng/g body weight/day), the injection of administering drug combinations group are injected by TPA treatment groups
DTC and TPA (DTC is 30 μ g/g/day, TPA 50ng/g/day), continues 28 days, measures tumor size and SCID mice weekly
Weight is primary.
From Fig. 2 (A) as can be seen that compared with being administered alone group (DTC or PTA), combination therapy injection can be effectively
The growth for inhibiting HL-60 cell xenograft tumors in SCID mice body carries out variance with the experiment of Tukey-Kramer Multiple range tests
Analysis shows tumor size difference significant difference (p between control group and administering drug combinations group<0.05), in administering drug combinations
Tumor size is significantly less than TPA treatment groups (p in group<Or DTC treatment groups (p 0.05)<0.05) it, can be seen that from Fig. 2 (B)
The variance analysis carried out using the experiment of Tukey-Kramer Multiple range tests shows that TPA or DTC or combination therapy pair is used alone
The weight of SCID nude mices does not influence (p>0.05), it can be seen that, TPA and DTC use in conjunction is expected to become a kind of effective low toxicity
The compound medicine of acute myeloid leukaemia is treated, TPA and DTC amount of substance ratios are 1 in drug combination:600.
The above embodiments and description only illustrate the principle of the present invention and most preferred embodiment, is not departing from this
Under the premise of spirit and range, various changes and improvements may be made to the invention, these changes and improvements both fall within requirement and protect
In the scope of the invention of shield.
Claims (4)
1. a kind of compound anti-cancer medicine, it is characterised in that：The drug by diethyldithiocarbamate (DTC) and
12- oxygen-tetradecanoylphorbol-13-acetate (TPA) composition.
2. a kind of compound anti-cancer medicine according to claim 1, it is characterised in that：The 12- oxygen-myristoyl Buddhist wave
Alcohol -13- acetic acid esters (TPA) and the amount of substance ratio of diethyldithiocarbamate (DTC) are 1:100-1000.
3. a kind of compound anti-cancer medicine according to claim 1, it is characterised in that：The 12- oxygen-myristoyl Buddhist wave
Alcohol -13- acetic acid esters (TPA) and the amount of substance ratio of diethyldithiocarbamate (DTC) are 1:600.
4. a kind of application of compound anti-cancer medicine according to claim 1, it is characterised in that：The compound anti-cancer medicine
For treating myelogenous leukemia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810387128.6A CN108653265A (en) | 2018-04-26 | 2018-04-26 | A kind of compound anti-cancer medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810387128.6A CN108653265A (en) | 2018-04-26 | 2018-04-26 | A kind of compound anti-cancer medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108653265A true CN108653265A (en) | 2018-10-16 |
Family
ID=63780238
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810387128.6A Pending CN108653265A (en) | 2018-04-26 | 2018-04-26 | A kind of compound anti-cancer medicine |
Country Status (1)
| Country | Link |
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| CN (1) | CN108653265A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2286557A1 (en) * | 1997-04-14 | 1998-10-22 | Rich Industries, Inc. | Phorbol esters as anti-neoplastic agents |
| TW200522938A (en) * | 2004-01-07 | 2005-07-16 | Biosuccess Biotech Co Ltd | Pharmaceutical composition for elevating white blood cells |
| US20110034425A1 (en) * | 2009-08-04 | 2011-02-10 | University Of Medicine And Dentistry Of New Jersey | Method of Treatment for Acute Myelogenous Leukemia |
| CN102274347A (en) * | 2011-07-15 | 2011-12-14 | 陈迪 | Anticancer composition and application thereof |
| CN107206053A (en) * | 2014-11-03 | 2017-09-26 | 华鸿新药公司 | For treat cytopenia or reduce cytopenia duration phorbol ester composition and method |
-
2018
- 2018-04-26 CN CN201810387128.6A patent/CN108653265A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2286557A1 (en) * | 1997-04-14 | 1998-10-22 | Rich Industries, Inc. | Phorbol esters as anti-neoplastic agents |
| EP0986378A4 (en) * | 1997-04-14 | 2001-03-14 | Rich Ind Inc | Phorbol esters as anti-neoplastic agents |
| TW200522938A (en) * | 2004-01-07 | 2005-07-16 | Biosuccess Biotech Co Ltd | Pharmaceutical composition for elevating white blood cells |
| US20110034425A1 (en) * | 2009-08-04 | 2011-02-10 | University Of Medicine And Dentistry Of New Jersey | Method of Treatment for Acute Myelogenous Leukemia |
| CN102274347A (en) * | 2011-07-15 | 2011-12-14 | 陈迪 | Anticancer composition and application thereof |
| CN107206053A (en) * | 2014-11-03 | 2017-09-26 | 华鸿新药公司 | For treat cytopenia or reduce cytopenia duration phorbol ester composition and method |
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| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181016 |
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